| Trial | Phase | Enrollment | Study Type | Start Date | Status |
|---|
| A Phase III, Open-Label, Single Arm, Rollover Trial of TMC435 in Combination With Peginterferon Alpha-2A and Ribavirin for HCV Genotype-1 Infected Subjects Who Participated in the Placebo Group of a Phase II/III TMC435 Study, or Who Received DAA Treatment [NCT01323244] | Phase 3 | 142 participants (Actual) | Interventional | 2011-12-31 | Completed |
| A Phase I, 2-panel, Open-label, Randomized, Crossover Trial in Healthy Subjects to Investigate the Pharmacokinetic Interaction Between TMC435 and Transporter Substrates, Digoxin and Rosuvastatin [NCT01288742] | Phase 1 | 33 participants (Actual) | Interventional | 2011-01-31 | Completed |
| A Double-blind, Double-dummy, Randomized, 4-period Cross-over, Placebo- and Positive-controlled Study to Evaluate the Effect of TMC435 on the QTc Interval in Healthy Subjects [NCT01269294] | Phase 1 | 60 participants (Actual) | Interventional | 2011-01-31 | Completed |
| A Phase I, Open-label, Randomized, Single-dose, 2-panel, Crossover Trial in Healthy Subjects to Assess the Relative Bioavailability of TMC435 HPMC Capsule Compared to the TMC435 Gelatin Capsule and to Assess the Effect of Different Meal Types on the Bioav [NCT01308606] | Phase 1 | 48 participants (Actual) | Interventional | 2011-03-31 | Completed |
| Photosensitivity Trial. A Randomized, Double-blind, Double Dummy, Placebo- and Positive Controlled Phase I Trial to Evaluate the Photosensitizing Potential of TMC435 in Healthy Subjects. [NCT01124799] | Phase 1 | 49 participants (Actual) | Interventional | 2010-07-31 | Completed |
| A Phase I, 2-panel, Open-label, Randomized, Cross-over Trial in Healthy Subjects to Investigate the Pharmacokinetic Interaction Between TMC435 and Antiretroviral Agents, TMC278 and Tenofovir Disoproxil Fumarate (TDF), at Steady State [NCT01205139] | Phase 1 | 48 participants (Actual) | Interventional | 2010-11-30 | Completed |
| A Phase 2a, Multicenter, Open-label Study to Investigate the Safety, Pharmacokinetics, and Efficacy of Combination Treatment of AL-335, Odalasvir, and Simeprevir in Japanese Subjects With Chronic Hepatitis C Genotype 1 or 2 Virus Infection, With or Withou [NCT02993250] | Phase 2 | 33 participants (Actual) | Interventional | 2016-12-21 | Completed |
| Sofosbuvir /Simeprevir/ Daclatasvir/Ribavirin Versus Sofosbuvir /Ombitasvir/ Paritaprevir /Ritonavir/Ribavirin in the Management of Hepatitis C Patients Fauilre to Prior Sofosbuvir/ Daclatasvir (An Open-labeled Randomized Trial) [NCT03549832] | | 40 participants (Actual) | Interventional | 2018-01-01 | Completed |
| A Phase 2, Open-Label Study to Investigate the Efficacy and Safety of an 8-Week and 12-Week Regimen of Simeprevir in Combination With Sofosbuvir in Treatment-Naïve or -Experienced Subjects With Chronic Genotype 4 Hepatitis C Virus Infection With and Witho [NCT02253550] | Phase 2 | 30 participants (Anticipated) | Interventional | 2014-10-31 | Completed |
| A Phase 1, Double-blind, Placebo-controlled, Randomized, Single Ascending Dose Study to Investigate the Safety, Tolerability, and Pharmacokinetics of TMC647055 in Combination With a Pharmacokinetic Enhancer (Part 1) Followed by an Open-label, Randomized, [NCT02064842] | Phase 1 | 24 participants (Actual) | Interventional | 2014-02-28 | Completed |
| An Open-Label, Single-Arm Phase III Study to Evaluate the Efficacy, Safety and Tolerability of TMC435 in Combination With PegIFN Alfa-2a (Pegasys) and Ribavirin (Copegus) in Treatment-Naïve or Treatment-Experienced, Chronic Hepatitis C Virus Genotype-4 In [NCT01567735] | Phase 3 | 107 participants (Actual) | Interventional | 2012-03-27 | Completed |
| Phase I, Open-label Trial to Investigate the Effect of Severe Renal Impairment on the Pharmacokinetics and Safety of TMC435 [NCT01381835] | Phase 1 | 16 participants (Actual) | Interventional | 2011-07-31 | Completed |
| A Phase I, Open-label, Randomized, 3-way Crossover Trial in Healthy Subjects to Investigate the Pharmacokinetic Interaction Between TMC435 and Escitalopram at Steady-state [NCT01090700] | Phase 1 | 20 participants (Actual) | Interventional | 2010-05-31 | Completed |
| A Phase-1, Open-label, Two Group, Fixed-Sequence Study to Evaluate the Effect of ACH-3102 and Simeprevir on AL-335 Pharmacokinetics in Healthy Volunteers [NCT02512562] | Phase 1 | 32 participants (Actual) | Interventional | 2015-07-31 | Completed |
| Outcome of New Direct Acting Agents For Hepatitis C [NCT02485262] | | 340 participants (Anticipated) | Observational [Patient Registry] | 2013-11-30 | Recruiting |
| A Phase III, Open-Label Study in Japan to Assess the Efficacy and Safety of TMC435 as Part of a Treatment Regimen Including Peginterferon Alfa-2b and Ribavirin in Hepatitis C, Genotype 1 Infected Subjects [NCT01366638] | Phase 3 | 79 participants (Actual) | Interventional | 2011-05-31 | Completed |
| A Phase 2b, Multicenter, Randomized, Open-label Study to Investigate the Efficacy, Safety and Pharmacokinetics of Different Treatment Regimens of AL-335, Odalasvir, and Simeprevir in Treatment-naive and Treatment-experienced Subjects With Chronic Hepatiti [NCT02765490] | Phase 2 | 365 participants (Actual) | Interventional | 2016-11-09 | Completed |
| An Open Label, Pilot Study to Investigate the Safety and Efficacy of 12 Weeks of Simeprevir and Sofosbuvir, for HIV-infected, HCV Genotype 1 Patients With Advanced Fibrosis [NCT02206932] | Phase 4 | 0 participants (Actual) | Interventional | 2014-08-31 | Withdrawn(stopped due to never opened) |
| Pilot BA Study With Phase III/Commercial Versus Phase IIB Formulation. A Phase I, Open Label, Randomized, Single Dose, Crossover Study in Healthy Subjects to Assess the Relative Bioavailability of TMC435 Following Administration of Potential Phase III For [NCT01134718] | Phase 1 | 24 participants (Actual) | Interventional | 2010-06-30 | Completed |
| Phase I, Open Label, Randomized Study to Examine the Pharmacokinetics, Safety and Tolerability of Different Oral Doses of TMC435 After Single and Repeated Dosing in Healthy Chinese Subjects [NCT01224197] | Phase 1 | 32 participants (Actual) | Interventional | 2010-10-31 | Completed |
| Phase I, Double Blind, Randomized, Placebo-controlled Trial in Healthy Subjects to Examine the Safety, Tolerability and Pharmacokinetics of Increasing Oral Doses of TMC435350 After Single and Repeated Dosing, Followed by an Open Label Repeated Dosing Sess [NCT00938899] | Phase 1 | 55 participants (Actual) | Interventional | 2007-01-31 | Completed |
| Phase I, First-in-human Trial in Healthy Volunteers to Examine Increasing Single and Repeated Oral Doses of TMC647055, Followed by a Repeated-dose Part in Chronic HCV-genotype 1 Infected Patients to Examine TMC647055 Given Alone or in Combination With TMC [NCT01202825] | Phase 1 | 72 participants (Actual) | Interventional | 2010-04-30 | Completed |
| A Phase III, Randomized, Open-label, Two-arm Trial in Japan to Investigate the Efficacy and Safety of TMC435 as Part of a Treatment Regimen Including Peginterferon Alfa-2a and Ribavirin in Hepatitis C, Genotype 1-Infected Subjects Who Failed to Respond to [NCT01288209] | Phase 3 | 106 participants (Actual) | Interventional | 2011-02-28 | Completed |
| A Phase II, Randomized, Open-label Study in Japan to Investigate the Efficacy, Safety and Pharmacokinetics of TMC435 as Part of a Treatment Regimen Including Peginterferon Alfa-2a and Ribavirin in Treatment naïve, Genotype 1, Chronic Hepatitis C Subjects [NCT00996476] | Phase 2 | 92 participants (Actual) | Interventional | 2009-07-31 | Completed |
| Phase I, Open-label, 3-way Crossover Trial in Healthy Volunteers to Determine the Drug-drug Interaction Between TMC435350 and Rifampin After Multiple Dosing. [NCT00741169] | Phase 1 | 21 participants (Actual) | Interventional | 2008-06-30 | Completed |
| An Open-label Trial in Genotype 2, 3, 4, 5 and 6 Hepatitis C-infected Subjects to Evaluate the Antiviral Activity, Safety, Tolerability and Pharmacokinetics of TMC435350 Following 7 Days Once Daily Dosing as Monotherapy. [NCT00812331] | Phase 2 | 37 participants (Actual) | Interventional | 2009-03-31 | Completed |
| A Phase 2 Open-Label Study in Patients With Recurrent Genotype 1 Hepatitis C Post-Orthotopic Liver Transplant to Explore the Safety And Efficacy of Simeprevir and Sofosbuvir With and Without Ribavirin [NCT02165189] | Phase 2 | 46 participants (Actual) | Interventional | 2014-08-31 | Completed |
| Security and Efficacy of Triple Therapy Including Direct-Acting Antivirals Against Chronic Hepatitis C Infection In HIV-Coinfected Patients In Real-Life Conditions: The Prospective HEPAVIR Cohort. [NCT02057003] | | 1,000 participants (Anticipated) | Observational | 2012-01-31 | Recruiting |
| Phase I, Open Label Study to Examine the Pharmacokinetics, Safety and Tolerability of TMC435 Following Multiple Oral Doses of 100 and 150 mg q.d. in Healthy Chinese Subjects [NCT02071355] | Phase 1 | 32 participants (Actual) | Interventional | 2014-04-30 | Completed |
| A Phase I, 2-panel, Open-label, Randomized, Crossover Trial in Healthy Subjects to Investigate the Pharmacokinetic Interaction Between TMC435 and CYP3A Inhibitors, Erythromycin and Darunavir/Ritonavir (DRV/r) [NCT01323257] | Phase 1 | 49 participants (Actual) | Interventional | 2011-03-31 | Completed |
| Impact of Interferon Free Regimens in Patients With Chronic HCV and Successfully Treated HCC [NCT02771405] | Phase 3 | 150 participants (Anticipated) | Interventional | 2016-03-31 | Recruiting |
| A Blinded, Randomized, Placebo-controlled Trial in Genotype 1 Hepatitis C-Infected Subjects to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of Repeated Doses of TMC435350, With or Without Peginterferon Alpha-2a and Ribavirin [NCT00561353] | Phase 2 | 121 participants (Actual) | Interventional | 2008-01-31 | Completed |
| A Phase I, Open-Label, Single-Sequence Drug-Drug Interaction Trial in Subjects On Stable Methadone Maintenance Therapy, to Investigate the Potential Pharmacokinetic Interaction Between TMC435 and Methadone, at Steady-State [NCT00915564] | Phase 1 | 13 participants (Actual) | Interventional | 2009-09-30 | Completed |
| Randomized Clinical Trial to Assess the Effectiveness of Sofosbuvir in Combination With Daclatasvir or Simeprevir for 12 Weeks in Non-cirrhotic Subjects Infected With Chronic Hepatitis C Virus (HCV) Genotype 1 (TNT-1 Study) [NCT02624063] | Phase 4 | 121 participants (Actual) | Interventional | 2015-12-31 | Completed |
| A Phase I Study in Healthy Subjects to Assess the Relative Bioavailability of TMC435 Following Administration of Potential Phase III Formulations Compared to the Phase IIb Capsule and to Assess the Effect of Food on the Bioavailability of TMC435 Following [NCT01022125] | Phase 1 | 28 participants (Actual) | Interventional | 2010-01-31 | Completed |
| Phase I, Double-blind, Randomized, Placebo-controlled Trial to Examine the Safety, Tolerability and Plasma Pharmacokinetics of Ascending Oral Doses of TMC435350 After Single and Repeated Dosing in Healthy Japanese Male Subjects [NCT00752544] | Phase 1 | 30 participants (Actual) | Interventional | 2008-08-31 | Completed |
| A Phase I, Open Label, 2-period, Randomized, Crossover Trial in 16 Healthy Subjects to Assess the Drug Interaction Potential of TMC435 With Oral Midazolam and With a Drug Cocktail Representative of CYP1A2, CYP2C9, CYP2D6, CYP3A4, and CYP2C19 Substrates. [NCT00866853] | Phase 1 | 16 participants (Actual) | Interventional | 2009-03-31 | Completed |
| A Phase I, 2-panel, Open-label, Randomized, Cross-over Trial in Healthy Subjects to Investigate the Effect of TMC435 at Steady-state on the Pharmacokinetics of the Immunosuppressants Cyclosporine and Tacrolimus [NCT01479881] | Phase 1 | 29 participants (Actual) | Interventional | 2011-10-31 | Completed |
| A Phase I, Open-label, 3-way Crossover Trial in Healthy Subjects to Compare the Bioavailability of a Single Oral Dose of TMC435350 Formulated as 2 Different Solid Formulations to That of a Single Oral Dose of TMC435350 Formulated as a Powder Blend Capsule [NCT00752648] | Phase 1 | 24 participants (Actual) | Interventional | 2008-07-31 | Completed |
| Efficacy and Safety of Interferon Based Therapy and Interferon-free Direct-acting Antivirals in Cirrhotic Patients With Hepatitis C. Impact of Antiviral Therapy on Gastroesophageal Varices. [NCT02758509] | | 237 participants (Actual) | Observational | 2010-01-01 | Completed |
| Efficacy and Safety of Sofosbuvir/Simeprevir Plus a Flat Dose of Ribavirin in Genotype 1 Elderly Cirrhotic Patients: a Real Life Study [NCT02702739] | Phase 4 | 270 participants (Actual) | Interventional | 2015-01-31 | Completed |
| A Randomized Study to Evaluate the Safety and Efficacy of IDX719 in Combinations With Simeprevir and/or TMC647055/Ritonavir With or Without Ribavirin for 12 Weeks in Subjects With Chronic Hepatitis C Infection [NCT01852604] | Phase 2 | 143 participants (Actual) | Interventional | 2013-03-31 | Completed |
| A Phase 1, Double-blind, Placebo-controlled, Randomized, Single Ascending Dose Study to Investigate the Safety, Tolerability, and Pharmacokinetics of GSK2336805 (Part 1), Followed by an Open-label, Randomized, 4-way Crossover Study to Evaluate Short-term [NCT02018536] | Phase 1 | 48 participants (Actual) | Interventional | 2013-10-31 | Completed |
| A Phase 1, Open-label, Sequential Study to Investigate the Pharmacokinetic Interaction Between Odalasvir, Given as a Single Agent or in Combination With Simeprevir, and Dabigatran Etexilate Mesylate in Healthy Subjects [NCT02945020] | Phase 1 | 15 participants (Actual) | Interventional | 2016-11-10 | Completed |
| A Phase I, Open-label, Sequential Trial to Investigate the Pharmacokinetics, Safety, and Tolerability of TMC435 in Subjects With Moderately or Severely Impaired Hepatic Function [NCT01046058] | Phase 1 | 23 participants (Actual) | Interventional | 2010-01-31 | Completed |
| A Phase I, Randomized, Multiple-Dose Study to Evaluate the Pharmacokinetic Drug-Drug Interaction Between IDX719, Simeprevir, TMC647055 and Ritonavir When Administered in Combination in Healthy Subjects [NCT01907724] | Phase 1 | 34 participants (Actual) | Interventional | 2013-05-31 | Completed |
| A Phase III, Open-label Trial in Japan to Investigate the Efficacy and Safety of TMC435 as Part of a Treatment Regimen Including Peginterferon Alfa-2a and Ribavirin in Genotype 1, Hepatitis C-infected Subjects Who Relapsed After Previous IFN-based Therapy [NCT01290731] | Phase 3 | 49 participants (Actual) | Interventional | 2011-01-31 | Completed |
| A Phase 2a, Partly Randomized, Open-label Trial to Investigate the Efficacy and Safety of an 8 or 12-Week Treatment Regimen of Simeprevir in Combination With Sofosbuvir in Treatment-Naive and Experienced Subjects With Chronic Genotype 4 Hepatitis C Infect [NCT02278419] | Phase 2 | 63 participants (Actual) | Interventional | 2014-12-31 | Completed |
| A Phase I, 2-Panel, Open-Label Study in Healthy Subjects to Investigate the Pharmacokinetic Interaction Between TMC435 and the HMG-CoA Reductase Inhibitors Atorvastatin and Simvastatin [NCT01689623] | Phase 1 | 36 participants (Actual) | Interventional | 2012-06-30 | Completed |
| A Phase IIb, Randomized, Double-Blind, Placebo-Controlled Trial to Investigate the Efficacy, Tolerability, Safety and Pharmacokinetics of TMC435 as Part of a Treatment Regimen Including Peginterferon Alfa-2a and Ribavirin In Treatment-Naive Genotype 1 Hep [NCT00882908] | Phase 2 | 386 participants (Actual) | Interventional | 2009-06-30 | Completed |
| A Phase 1, Open-label Study in Healthy Female Subjects to Investigate the Effects of Odalasvir and AL-335 at Steady-state, Given as Single Agents and in Combination With Simeprevir, on the Single-dose Pharmacokinetics of Ethinylestradiol and Drospirenone [NCT02885454] | Phase 1 | 24 participants (Actual) | Interventional | 2016-08-31 | Completed |
| A Phase 1, Open-label, Fixed Sequence Study to Investigate the Pharmacokinetic Interaction Between 2 Direct Acting Antiviral Agents Odalasvir and AL-335 and Between 3 Direct Acting Antiviral Agents Simeprevir, Odalasvir and AL-335 at Steady State in Healt [NCT02824315] | Phase 1 | 22 participants (Actual) | Interventional | 2016-05-31 | Completed |
| Efficacy and Safety of Switching From Pegylated Interferon/Ribavirin (PR) to Direct-acting Antiviral Agents (DAAs) for Chinese With CHC Genotype 1b Infection (SWITCH-1) [NCT02583685] | Phase 2 | 160 participants (Anticipated) | Interventional | 2015-05-31 | Recruiting |
| A Phase III, Randomized, Double-blind, Placebo-controlled Trial in Japan to Investigate the Efficacy and Safety of TMC435 vs. Placebo as Part of a Treatment Regimen Including Peginterferon Alfa-2a and Ribavirin in Treatment-Naive, Genotype 1, Hepatitis C- [NCT01292239] | Phase 3 | 183 participants (Actual) | Interventional | 2011-02-28 | Completed |
| A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy, Safety and Tolerability of TMC435 vs Placebo as Part of a Treatment Regimen Including Peginterferon α-2a and Ribavirin in Treatment-naïve, Genotype 1 Hepatitis Cinf [NCT01289782] | Phase 3 | 395 participants (Actual) | Interventional | 2011-02-28 | Completed |
| A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy, Safety and Tolerability of TMC435 Versus Placebo as Part of a Treatment Regimen Including Peginterferon α-2a (Pegasys®) and Ribavirin (Copegus®) or Peginterferon α- [NCT01290679] | Phase 3 | 393 participants (Actual) | Interventional | 2011-03-31 | Completed |
| The SIM-SOF Trial: A Randomized Trial Comparing Simeprevir-Sofosbuvir Versus Peginterferon/Ribavirin/Sofosbuvir for the Treatment of Chronic Hepatitis C Genotype-1a-infected Patients With Cirrhosis [NCT02168361] | Phase 4 | 93 participants (Actual) | Interventional | 2013-12-31 | Completed |
| A Phase-I, Open-label Trial in Healthy Female Subjects to Investigate the Effect of TMC435 at Steady-state on the Steady-state Pharmacokinetics of Ethinylestradiol and Norethindrone [NCT01486004] | Phase 1 | 18 participants (Actual) | Interventional | 2011-11-30 | Completed |
| A Phase I, 2-panel, Open-label, Randomized, Crossover Trial in Healthy Subjects to Investigate the Pharmacokinetic Interaction Between TMC435 and Antiretroviral Agents, Efavirenz and Raltegravir, at Steady State [NCT01241773] | Phase 1 | 48 participants (Actual) | Interventional | 2010-10-31 | Completed |
| A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy, Safety and Tolerability of TMC435 vs Placebo as Part of a Treatment Regimen Including Peginterferon α-2a and Ribavirin in Hepatitis C, Genotype 1 Infected Subjects [NCT01281839] | Phase 3 | 394 participants (Actual) | Interventional | 2011-02-28 | Completed |
| A Phase 1, Open-label, Randomized, 2-panel, 3-way Crossover Study in Healthy Adult Subjects to Assess the Relative Bioavailability of Simeprevir Following Single Dose Administration of Age-appropriate Oral Formulation Candidates, Compared to the 150-mg Or [NCT02385071] | Phase 1 | 48 participants (Actual) | Interventional | 2015-04-28 | Completed |
| Sofosbuvir in Combination With Ribavirin or Simeprevir: Real-life Study of Patients With Hepatitis C Genotype 4 [NCT04385407] | Phase 2 | 203 participants (Actual) | Interventional | 2015-04-30 | Completed |
| A Single-dose, Open-label, Randomized, Two-way Crossover Study to Assess the Effect of Food on the Pharmacokinetics of TMC435 in Japanese Healthy Adult Male Subjects [NCT01799603] | Phase 1 | 24 participants (Actual) | Interventional | 2012-05-31 | Completed |
| Simeprevir (SMV) + Sofosbuvir (SOF) With or Without Ribavirin (RBV) for Interferon-intolerant or Ineligible (IFN-II) Patients With Chronic Hepatitis C (CHC) [NCT02214420] | Phase 4 | 24 participants (Actual) | Interventional | 2014-10-31 | Completed |
| Phase III in Partial and Null Responders [NCT01485991] | Phase 3 | 771 participants (Actual) | Interventional | 2012-02-29 | Completed |
| Efficacy and Safety of Treatment Against Hepatitis C Virus Infection Based on Direct-acting Antivirals in Real-life Conditions: The GEHEP Cohort [NCT02333292] | | 1,128 participants (Actual) | Observational | 2014-12-31 | Completed |
| A Phase I, Open-Label, Sequential, Single-Dose Study to Assess the Absolute Bioavailability and Pharmacokinetics of TMC435 Administered as Single Oral Doses of 50 mg and 150 mg and an Intravenous Microdose of 100 μg [3H]-TMC435 in Healthy Male Subjects [NCT01707342] | Phase 1 | 6 participants (Actual) | Interventional | 2012-10-31 | Completed |
| A Phase I, Randomized, Multiple-Dose Study to Evaluate the Pharmacokinetic Drug-Drug Interaction Between IDX719 and Simeprevir in Healthy Subjects [NCT01813513] | Phase 1 | 42 participants (Actual) | Interventional | 2013-01-31 | Completed |
| A Phase 3, Open-Label, Single-Arm Study to Evaluate the Safety and Efficacy of TMC435 Plus Pegylated Interferon Alfa-2a and Ribavirin Administered for 12 Weeks in Treatment-Naïve Subjects With Chronic Genotype 1 or Genotype 4 HCV Infection [NCT01846832] | Phase 3 | 232 participants (Actual) | Interventional | 2013-09-30 | Completed |
| A Phase 2, Randomized, Open-label Study to Investigate the Efficacy, Safety, Tolerability and Pharmacokinetics of 6 or 8 Weeks of Treatment With Simeprevir, Daclatasvir and Sofosbuvir in Treatment-naive Subjects With Chronic Hepatitis C Virus Genotype 1 I [NCT02349048] | Phase 2 | 68 participants (Actual) | Interventional | 2015-01-31 | Completed |
| An Exploratory Phase IIa, Randomized, Open-Label Trial to Investigate the Efficacy and Safety of 12 Weeks or 24 Weeks of TMC435 in Combination With PSI-7977 (GS7977) With Or Without Ribavirin in Chronic Hepatitis C Genotype 1-Infected Prior Null Responder [NCT01466790] | Phase 2 | 168 participants (Actual) | Interventional | 2012-01-31 | Completed |
| A Phase IIb, Randomized, Double-Blind, Placebo-Controlled Trial to Investigate the Efficacy, Tolerability, Safety and Pharmacokinetics of TMC435 as Part of a Treatment Regimen Including PegIFNa-2a and Ribavirin in HCV Genotype 1 Infected Subjects Who Fail [NCT00980330] | Phase 2 | 463 participants (Actual) | Interventional | 2009-10-31 | Completed |
| A Phase 2a, Open-Label Study to Evaluate the Safety, Pharmacokinetics and Efficacy of the Combination of AL-335 and Odalasvir, With or Without Simeprevir, in Treatment-Naïve Subjects With Genotype 1, 2 or 3 Chronic Hepatitis C Infection With or Without Co [NCT02569710] | Phase 2 | 161 participants (Actual) | Interventional | 2015-10-31 | Completed |
| Effect of New Oral Treatment for Hepatitis C Virus on Seminal Parameters [NCT05616598] | Phase 2/Phase 3 | 200 participants (Actual) | Interventional | 2022-03-01 | Completed |
| A Phase 3, Multicenter, Open-Label, Single-Arm Study to Investigate the Efficacy and Safety of a 12-Week Regimen of Simeprevir in Combination With Sofosbuvir in Treatment-Naive or -Experienced Subjects With Chronic Genotype 4 Hepatitis C Virus Infection [NCT02250807] | Phase 3 | 40 participants (Actual) | Interventional | 2015-01-31 | Completed |
| A Phase I, Open-Label, Randomized, 3-Panel, 3-way Crossover Trial in Healthy Adult Subjects to Assess the Relative Bioavailability of TMC435 Following Administration of 2 Liquid Formulations or 2 Different Capsule Concept Formulations Compared ot the Phas [NCT01571570] | Phase 1 | 72 participants (Actual) | Interventional | 2012-03-31 | Completed |
| Non-interventional Study to Observe Triple Combination Therapy With Boceprevir or Simeprevir Plus Peginterferon Alfa-2a Plus Ribavirin for Re-treatment of Chronic Hepatitis C in Hungary (IMPERIAL) [NCT02118597] | | 19 participants (Actual) | Observational | 2014-05-31 | Terminated(stopped due to Study terminated due to the Sponsor's decision.) |
| A Phase 3, Multicenter, Open-Label, Single-Arm Study to Investigate the Efficacy and Safety of a 12-Week Regimen of Simeprevir in Combination With Sofosbuvir in Treatment-Naïve or -Experienced Subjects With Chronic Genotype 1 Hepatitis C Virus Infection a [NCT02114151] | Phase 3 | 103 participants (Actual) | Interventional | 2014-04-30 | Completed |
| Drug Interaction Potential Between Dolutegravir and Simeprevir in HIV/Hepatitis C Virus (HCV) Seronegative Volunteers [NCT02404805] | | 25 participants (Actual) | Interventional | 2016-02-29 | Completed |
| A Phase 2, Open-label Study to Investigate the Efficacy and Safety of the Combination of Simeprevir and Daclatasvir in Chronic Hepatitis C Genotype 1b-Infected Subjects [NCT02268864] | Phase 2 | 106 participants (Actual) | Interventional | 2015-01-31 | Completed |
| Safety, Tolerability, and Efficacy of Simeprevir 150 mg Daily Plus Sofosbuvir 400 mg Daily for 24 Weeks in Patients With Chronic Hepatitis C Genotype 1 With CPT Score of 6 or Lower Who Are IFN-Intolerant or Unwilling to be Treated With IFN [NCT02485080] | Phase 4 | 0 participants (Actual) | Interventional | 2015-09-30 | Withdrawn(stopped due to Withdrawn due to lack of resources) |
| A Phase 2, 2-panel, Open-label Randomized Study in Hepatitis C Virus Infected Subjects to Investigate the Pharmacokinetic Interactions Between Simeprevir and Ledipasvir in a Treatment Regimen Consisting of Simeprevir, Sofosbuvir and Ledipasvir in Treatmen [NCT02421211] | Phase 2 | 41 participants (Actual) | Interventional | 2015-05-19 | Completed |
| A Phase 2, Open-Label Study of Daclatasvir (BMS-790052) and TMC435 in Combination With or Without Ribavirin (RBV) For Treatment-Naive Subjects or Null Responders to Prior Peginterferon Alfa (PegIFN)/RBV Therapy With Genotype 1 Chronic Hepatitis C [NCT01628692] | Phase 2 | 230 participants (Actual) | Interventional | 2012-07-31 | Completed |
| A Phase 2, Open-label, Single-arm Study to Investigate the Efficacy, Safety, Tolerability and Pharmacokinetics of 12 Weeks Treatment With Simeprevir and Daclatasvir in Subjects With Chronic Hepatitis C Virus Genotype 1b or 4 Infection and Either Severe Re [NCT02397395] | Phase 2 | 0 participants (Actual) | Interventional | 2015-05-31 | Withdrawn(stopped due to Trial has been cancelled due to availability of new therapeutic options for patient population) |
| A Sofosbuvir-based Quadruple Regimen is Highly Effective in HCV Type 4-infected Egyptian Patients With DAA Treatment Failure [NCT04387539] | Phase 1/Phase 2 | 94 participants (Actual) | Interventional | 2017-03-01 | Completed |
| A Phase III, Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Efficacy, Pharmacokinetics, Safety and Tolerability of TMC435 vs. Placebo as Part of a Treatment Regimen Including Peginterferon Alfa-2a and Ribavirin in Treatment-Naïve, G [NCT01725529] | Phase 3 | 457 participants (Actual) | Interventional | 2012-11-30 | Completed |
| A Phase IIa, Open-label Trial to Evaluate the Safety, Tolerability and Efficacy of a 12 Weeks Combination Therapy of TMC647055 and TMC435 With and Without GSK23336805 With a Pharmacokinetic Enhancer With and Without Ribavirin in Chronic Genotype 1 Hepatit [NCT01724086] | Phase 2 | 90 participants (Actual) | Interventional | 2012-10-31 | Completed |
| Phase 1, Open-label, Partially Randomized, Parallel-group Study in Healthy Adult Subjects to Assess the Relative Bioavailability of Single-dose Simeprevir (SMV), Odalasvir (ODV), and AL-335 Administered as a Fixed-dose Combination (FDC) Compared With the [NCT03059303] | Phase 1 | 72 participants (Actual) | Interventional | 2017-02-20 | Terminated(stopped due to Decision to discontinue development of investigational Hep C treatment regimen JNJ-4178: 3 direct acting antivirals - AL-335, ODV & SMV.) |
| Sofosbuvir and Simeprevir Versus Sofosbuvir and Ribavirin in Egyptian Patients With HCV [NCT03069001] | Phase 4 | 90 participants (Actual) | Interventional | 2015-06-30 | Completed |
| Phase 2, Open-Label Study to Investigate the Pharmacokinetics, Efficacy, Safety, and Tolerability of the Combination of Simeprevir (TMC435), Daclatasvir (BMS-790052) and Ribavirin (RBV) in Subjects With Recurrent Chronic Hepatitis C Genotype 1b Infection [NCT01938625] | Phase 2 | 35 participants (Actual) | Interventional | 2013-12-12 | Completed |
| Phase I, Open-label Trial in Healthy Subjects to Evaluate the Drug-drug Interaction Between Ritonavir at Steady-state and TMC435350, a Viral Protease Inhibitor Against Hepatitis C Virus, After the First and the Last Dose of a Multiple Dosing Regimen [NCT01891851] | Phase 1 | 12 participants (Actual) | Interventional | 2007-10-31 | Completed |
| Study of the Safety and Efficacy of Sofosbuvir-Based Regimens in the Treatment of Egyptian Patients With and Without Post-hepatitis C Cirrhosis [NCT02992457] | Phase 4 | 10,000 participants (Actual) | Interventional | 2015-01-31 | Completed |
| A Phase III Open-Label Study to Evaluate the Safety, Tolerability and Efficacy of TMC435 Plus PegIFNα-2a (Pegasys) and Ribavirin (Copegus) Triple Therapy in Chronic Hepatitis C Genotype-1 Infected Subjects Who Are Co-infected With Human Immunodeficiency V [NCT01479868] | Phase 3 | 109 participants (Actual) | Interventional | 2011-10-31 | Completed |
| A Phase 3, Multicenter, Randomized, Open-Label Study to Investigate the Efficacy and Safety of a 12- or 8-Week Treatment Regimen of Simeprevir in Combination With Sofosbuvir in Treatment-Naïve and -Experienced Subjects With Chronic Genotype 1 Hepatitis C [NCT02114177] | Phase 3 | 310 participants (Actual) | Interventional | 2014-04-30 | Completed |
| A Phase 2 Open-label Study to Investigate the Efficacy, Safety and Pharmacokinetics of 12 Weeks of Treatment With Simeprevir, Daclatasvir and Sofosbuvir, Followed by a 5-Year Post-treatment Long-term Follow-up, in Treatment-naïve and Treatment-experienced [NCT02262728] | Phase 2 | 40 participants (Actual) | Interventional | 2014-09-30 | Completed |
| [information is prepared from clinicaltrials.gov, extracted Sep-2024] |
| Trial | Outcome |
|---|
| NCT00561353 (28) [back to overview] | Virologic Response Parameters Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) |
| NCT00561353 (28) [back to overview] | Viral Breakthrough in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) |
| NCT00561353 (28) [back to overview] | Viral Breakthrough in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1, Panel A and B) |
| NCT00561353 (28) [back to overview] | Viral Relapse in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) |
| NCT00561353 (28) [back to overview] | Viral Relapse in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) |
| NCT00561353 (28) [back to overview] | Sustained Virologic Response (SVR) in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) |
| NCT00561353 (28) [back to overview] | Virologic Response Parameters in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) |
| NCT00561353 (28) [back to overview] | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) |
| NCT00561353 (28) [back to overview] | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) |
| NCT00561353 (28) [back to overview] | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) |
| NCT00561353 (28) [back to overview] | Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) |
| NCT00561353 (28) [back to overview] | Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) at Week 4 in Treatment-Naïve HCV-Infected Participants (Cohort 1 and 2, Panel B) |
| NCT00561353 (28) [back to overview] | Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) at Week 4 in Treatment-Naïve HCV-Infected Participants (Cohort 1 and 2, Panel A) |
| NCT00561353 (28) [back to overview] | Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) at Week 4 in Treatment-Experienced HCV-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) |
| NCT00561353 (28) [back to overview] | Average Steady-state Plasma Concentration (Css,av) of TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) |
| NCT00561353 (28) [back to overview] | Average Steady-state Plasma Concentration (Css,av) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B) |
| NCT00561353 (28) [back to overview] | Initial Suboptimal Responses Following Treatment With TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) |
| NCT00561353 (28) [back to overview] | Maximum Plasma Concentration (Cmax) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B) |
| NCT00561353 (28) [back to overview] | Predose Plasma Concentration (C0h) of TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) |
| NCT00561353 (28) [back to overview] | Predose Plasma Concentration (C0h) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B) |
| NCT00561353 (28) [back to overview] | Sustained Virologic Response (SVR) in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) |
| NCT00561353 (28) [back to overview] | Maximum Plasma Concentration (Cmax) of TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) |
| NCT00561353 (28) [back to overview] | Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) on Day 7 in Treatment-Experienced HCV-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) |
| NCT00561353 (28) [back to overview] | Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) on Day 7 in Treatment-Naïve HCV-Infected Participants (Cohort 1 and 2, Panel A) |
| NCT00561353 (28) [back to overview] | Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) on Day 7 in Treatment-Naïve HCV-Infected Participants (Cohort 1 and 2, Panel B) |
| NCT00561353 (28) [back to overview] | Initial Suboptimal Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) |
| NCT00561353 (28) [back to overview] | Initial Suboptimal Responses Following Treatment With TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) |
| NCT00561353 (28) [back to overview] | Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B) |
| NCT00812331 (14) [back to overview] | Area Under the Plasma Concentration-time Curve From Time of Administration up to the Last Time Point With a Measurable Concentration After Dosing (AUClast) of TMC435 |
| NCT00812331 (14) [back to overview] | Number of Participants With Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels Below the Limit of Quantification (Less Than 25 IU/mL) and Limit of Detection (Less Than 25 IU/mL Undetectable) During the TMC435 Treatment Period |
| NCT00812331 (14) [back to overview] | Change From Baseline in log10 Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels |
| NCT00812331 (14) [back to overview] | Time to Reach the Maximum Plasma Concentration (Tmax) of TMC435 |
| NCT00812331 (14) [back to overview] | Maximum Plasma Concentration (Cmax) of TMC435 |
| NCT00812331 (14) [back to overview] | Terminal Elimination Half-life (t1/2,Term) of TMC435 |
| NCT00812331 (14) [back to overview] | Elimination Rate Constant of TMC435 |
| NCT00812331 (14) [back to overview] | Average Steady-State Plasma Concentration (Css,av) of TMC435 |
| NCT00812331 (14) [back to overview] | Fluctuation Index (FI) of TMC435 |
| NCT00812331 (14) [back to overview] | Area Under the Plasma Concentration-time Curve From the Time of Administration up to 24 Hours After Dosing (AUC24h) of TMC435 |
| NCT00812331 (14) [back to overview] | Predose Plasma Concentration (C0h) of TMC435 |
| NCT00812331 (14) [back to overview] | Number of Participants Who Experienced Viral Breakthrough During TMC435 Treatment Period |
| NCT00812331 (14) [back to overview] | Minimum Plasma Concentration (Cmin) of TMC435 |
| NCT00812331 (14) [back to overview] | Number of Participants With a Decrease From Baseline of Greater Than or Equal to 2 log10 IU/mL in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) During the TMC435 Treatment Period |
| NCT00882908 (14) [back to overview] | Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24h) for TMC435 |
| NCT00882908 (14) [back to overview] | The Number of Participants With Abnormal Alanine Aminotransferase (ALT) Levels at Baseline Who Achieved Normalized ALT Levels at the End of Treatment (EOT) |
| NCT00882908 (14) [back to overview] | The Number of Participants With Viral Relapse |
| NCT00882908 (14) [back to overview] | The Percentage of Participants Achieving a Complete Early Virologic Response (cEVR) |
| NCT00882908 (14) [back to overview] | The Percentage of Participants Achieving a Rapid Virologic Response (RVR) |
| NCT00882908 (14) [back to overview] | The Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12) |
| NCT00882908 (14) [back to overview] | The Percentage of Participants Achieving a Sustained Virologic Response at Week 72 (SVRW72) |
| NCT00882908 (14) [back to overview] | The Percentage of Participants Achieving an Early Virologic Response (EVR) |
| NCT00882908 (14) [back to overview] | The Percentage of Participants Who Achieved a Sustained Virologic Response 24 Weeks After the Planned End of Treatment (SVR24) |
| NCT00882908 (14) [back to overview] | Plasma Concentrations of TMC435 |
| NCT00882908 (14) [back to overview] | The Percentage of Participants Achieving Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels of Greater Than or Equal to 2 log10 Drop During Treatment |
| NCT00882908 (14) [back to overview] | The Percentage of Participants Achieving Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels of Less Than 25 IU/mL Undetectable During Treatment and Follow-up |
| NCT00882908 (14) [back to overview] | The Percentage of Participants Who Achieved Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels of Less Than 25 IU/mL Detectable or Undetectable During Treatment and Follow-up |
| NCT00882908 (14) [back to overview] | Number of Participants With Viral Breakthrough |
| NCT00980330 (13) [back to overview] | The Percentage of Participants Achieving a Complete Early Virologic Response (cEVR) |
| NCT00980330 (13) [back to overview] | The Percentage of Participants Achieving a Rapid Virologic Response (RVR) |
| NCT00980330 (13) [back to overview] | The Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12) |
| NCT00980330 (13) [back to overview] | The Percentage of Participants Achieving Plasma Levels of Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Undetectable During Treatment and Follow-up |
| NCT00980330 (13) [back to overview] | The Percentage of Participants Achieving a Sustained Virologic Response at the End of Treatment (EOT) and 24 Weeks After the EOT (SVR24) |
| NCT00980330 (13) [back to overview] | The Percentage of Participants Achieving an Early Virologic Response (EVR) |
| NCT00980330 (13) [back to overview] | The Percentage of Participants With Viral Breakthrough |
| NCT00980330 (13) [back to overview] | The Percentage of Participants With Viral Relapse |
| NCT00980330 (13) [back to overview] | Plasma Concentrations of TMC435 |
| NCT00980330 (13) [back to overview] | The Percentage of Participants Achieving Plasma Levels of Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Detectable or Undetectable During Treatment and Follow-up |
| NCT00980330 (13) [back to overview] | The Percentage of Participants With a Greater Than 2 log10 Drop in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels at Time Points During Treatment |
| NCT00980330 (13) [back to overview] | Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24h) for TMC435 |
| NCT00980330 (13) [back to overview] | The Number of Participants Who Achieved Normalized Alanine Aminotransferase (ALT) Levels at the End of Treatment (EOT) |
| NCT00996476 (14) [back to overview] | Time to Reach the Maximum Plasma Concentration (Tmax) of TMC435 |
| NCT00996476 (14) [back to overview] | Actual Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Values up to Week 24 in the Post-treatment Follow-up Period |
| NCT00996476 (14) [back to overview] | Predose Plasma Concentrations (C0h) of TMC435 (Sparse Blood Sampling) |
| NCT00996476 (14) [back to overview] | The Number of Participants With Alanine Aminotransaminase (ALT) Values Within the Normal Range at the End-of-treatment (EOT) |
| NCT00996476 (14) [back to overview] | The Percentage of Participants With a Decrease of Greater Than or Equal to 2 log10 IU/mL From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Through the Post-treatment Follow-up Period |
| NCT00996476 (14) [back to overview] | The Percentage of Participants With Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels Undetectable or Below the Limit of Quantification (<1.2 log10 IU/mL Detectable) During Treatment and During Post Treatment Follow-up |
| NCT00996476 (14) [back to overview] | The Percentage of Participants With Sustained Virologic Response (SVR) |
| NCT00996476 (14) [back to overview] | The Percentage of Participants With Undetectable Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels During the Study |
| NCT00996476 (14) [back to overview] | The Number of Participants With Viral Breakthrough |
| NCT00996476 (14) [back to overview] | The Percentage of Participants With Viral Relapse |
| NCT00996476 (14) [back to overview] | The Number of Participants Who Met Virologic Stopping/Continuation Rules and Completed All Study Medications |
| NCT00996476 (14) [back to overview] | The Area Under the Plasma Concentration-time Curve From the Time of Administration up to 24 Hours After Dosing (AUC24) for TMC435 |
| NCT00996476 (14) [back to overview] | Predose Plasma Concentrations (C0h) of TMC435 (Intensive Blood Sampling) |
| NCT00996476 (14) [back to overview] | Change in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels From Baseline to Week 4 |
| NCT01281839 (30) [back to overview] | The Percentage of Participants Achieving a Rapid Virologic Response (RVR) |
| NCT01281839 (30) [back to overview] | The Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12) |
| NCT01281839 (30) [back to overview] | The Percentage of Participants Achieving a Sustained Virologic Response at Week 72 (SVRW72) |
| NCT01281839 (30) [back to overview] | The Percentage of Participants Who Achieved a Sustained Virologic Response 24 Weeks After the Planned End of Treatment (SVR24) |
| NCT01281839 (30) [back to overview] | The Percentage of Participants Who Achieved a Sustained Virologic Response 4 Weeks After the Planned End of Treatment (SVR4) |
| NCT01281839 (30) [back to overview] | The Percentage of Participants Who Completed All Study Treatment at Week 24 Because of the Treatment Duration Rule |
| NCT01281839 (30) [back to overview] | The Percentage of Participants With <1 log10 Decrease in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) From Baseline at Week 4 |
| NCT01281839 (30) [back to overview] | The Percentage of Participants With Normalization of Alanine Aminotransferase (ALT) |
| NCT01281839 (30) [back to overview] | The Percentage of Participants With Null Response |
| NCT01281839 (30) [back to overview] | The Percentage of Participants With On-treatment Failure |
| NCT01281839 (30) [back to overview] | The Percentage of Participants With Partial Response |
| NCT01281839 (30) [back to overview] | The Percentage of Participants With Viral Breakthrough |
| NCT01281839 (30) [back to overview] | The Percentage of Participants With Viral Relapse |
| NCT01281839 (30) [back to overview] | Time From End-of-treatment to Viral Relapse |
| NCT01281839 (30) [back to overview] | Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <100 IU/mL |
| NCT01281839 (30) [back to overview] | Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <1000 IU/mL |
| NCT01281839 (30) [back to overview] | Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Undetectable |
| NCT01281839 (30) [back to overview] | Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Undetectable or Detectable |
| NCT01281839 (30) [back to overview] | Actual Values of log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) |
| NCT01281839 (30) [back to overview] | Change From Baseline in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) |
| NCT01281839 (30) [back to overview] | The Percentage of Participants With On-treatment Virologic Response at All Time Points |
| NCT01281839 (30) [back to overview] | The Percentage of Participants With Viral Breakthrough at Different Time Points |
| NCT01281839 (30) [back to overview] | Median Time to Normalization of Alanine Aminotransferase (ALT) Levels |
| NCT01281839 (30) [back to overview] | Percentage of Participants With in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels >1000 IU/mL at Week 4 |
| NCT01281839 (30) [back to overview] | Plasma Concentration of TMC435: Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h) |
| NCT01281839 (30) [back to overview] | Plasma Concentration of TMC435: Predose Plasma Concentration (C0h) |
| NCT01281839 (30) [back to overview] | Plasma Concentration of TMC435: Systemic Clearance (CL) |
| NCT01281839 (30) [back to overview] | The Percentage of Participants Achieving a Complete Early Virologic Response (cEVR) |
| NCT01281839 (30) [back to overview] | The Percentage of Participants Achieving a Early Virologic Response (EVR) |
| NCT01281839 (30) [back to overview] | The Percentage of Participants Achieving a Extended Rapid Virologic Response (eRVR) |
| NCT01288209 (11) [back to overview] | The Percentage of Participants With Undetectable Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels During Treatment for Participants Who Did Not Achieve Undetectable Plasma HCV RNA Levels at Week 12 |
| NCT01288209 (11) [back to overview] | The Percentage of Participants With Undetectable Plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) During Treatment and at the End of Treatment (EOT) |
| NCT01288209 (11) [back to overview] | The Number of Participants Demonstrating Viral Relapse During the Study |
| NCT01288209 (11) [back to overview] | The Number of Participants With Viral Breakthrough During the Study |
| NCT01288209 (11) [back to overview] | The Number Participants With Abnormal Alanine Aminotransferase (ALT) Levels at Baseline Who Achieved Normal ALT Levels at the End of Treatment (EOT) |
| NCT01288209 (11) [back to overview] | The Percentage of Participants Who Met Response Guided Treatment (RGT) Criteria and Completed Treatment With Peginterferon Alpha-2a (PegIFNα-2a) and Ribavirin (RBV) at Week 24 |
| NCT01288209 (11) [back to overview] | The Percentage of Participants With a Sustained Virologic Response 24 Weeks After the End of Treatment (EOT) and 24 Weeks After the Last Dose of Treatment (SVR24) |
| NCT01288209 (11) [back to overview] | The Percentage of Participants With a Sustained Virologic Response at the End of Treatment (EOT) and 12 Weeks After the Last Dose of Treatment (SVR12) |
| NCT01288209 (11) [back to overview] | Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24h) for TMC435 |
| NCT01288209 (11) [back to overview] | Plasma Concentrations of TMC435 |
| NCT01288209 (11) [back to overview] | The Percentage of Participants Who Achieved a Greater Than or Equal to 2 log10 IU/mL Drop From Baseline in Plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) at Each Time Point During Treatment and Follow-up |
| NCT01289782 (34) [back to overview] | The Percentage of Participants With <1 log10 Decrease in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) From Baseline at Week 4 |
| NCT01289782 (34) [back to overview] | Percentage of Participants With On-treatment Virologic Response at All Time Points |
| NCT01289782 (34) [back to overview] | The Percentage of Participants With Viral Breakthrough at Different Time Points |
| NCT01289782 (34) [back to overview] | Percentage of Participants Who Completed All Study Treatment at Week 24 Because of the Treatment Duration Rule |
| NCT01289782 (34) [back to overview] | Percentage of Participants With in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels >1000 IU/mL at Week 4 |
| NCT01289782 (34) [back to overview] | Percentage of Participants With Null Response |
| NCT01289782 (34) [back to overview] | Percentage of Participants With On-treatment Failure |
| NCT01289782 (34) [back to overview] | Percentage of Participants With Partial Response |
| NCT01289782 (34) [back to overview] | Percentage of Participants With Viral Breakthrough |
| NCT01289782 (34) [back to overview] | Percentage of Participants With Viral Relapse |
| NCT01289782 (34) [back to overview] | Plasma Concentration of TMC435: Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h) |
| NCT01289782 (34) [back to overview] | Median Time to Normalization of Alanine Aminotransferase (ALT) Levels |
| NCT01289782 (34) [back to overview] | Plasma Concentration of TMC435: Predose Plasma Concentration (C0h) |
| NCT01289782 (34) [back to overview] | Plasma Concentration of TMC435: Systemic Clearance (CL) |
| NCT01289782 (34) [back to overview] | The Percentage of Participants Achieving a Complete Early Virologic Response (cEVR) |
| NCT01289782 (34) [back to overview] | The Percentage of Participants Achieving a Early Virologic Response (EVR) |
| NCT01289782 (34) [back to overview] | The Percentage of Participants Achieving a Extended Rapid Virologic Response (eRVR) |
| NCT01289782 (34) [back to overview] | The Percentage of Participants Achieving a Rapid Virologic Response (RVR) |
| NCT01289782 (34) [back to overview] | The Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12) |
| NCT01289782 (34) [back to overview] | The Percentage of Participants Achieving a Sustained Virologic Response at Week 72 (SVRW72) |
| NCT01289782 (34) [back to overview] | The Percentage of Participants Who Achieved a Sustained Virologic Response 24 Weeks After the Planned End of Treatment (SVR24) |
| NCT01289782 (34) [back to overview] | The Percentage of Participants Who Achieved a Sustained Virologic Response 4 Weeks After the Planned End of Treatment (SVR4) |
| NCT01289782 (34) [back to overview] | The Percentage of Participants With Normalization of Alanine Aminotransferase (ALT) |
| NCT01289782 (34) [back to overview] | Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <100 IU/mL |
| NCT01289782 (34) [back to overview] | Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <1000 IU/mL |
| NCT01289782 (34) [back to overview] | Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Undetectable |
| NCT01289782 (34) [back to overview] | Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Undetectable or Detectable |
| NCT01289782 (34) [back to overview] | Actual Values of log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) |
| NCT01289782 (34) [back to overview] | Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) for Impairment in Daily Activity Scores Due to Hepatitis C Virus (HCV) Infection and Its Treatment |
| NCT01289782 (34) [back to overview] | Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) for the Fatigue Severity Scale (FSS) Total Scores |
| NCT01289782 (34) [back to overview] | Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) in Work Productivity and Activity (WPAI) Absenteeism Scores Due to Hepatitis C Virus (HCV) Infection and Its Treatment |
| NCT01289782 (34) [back to overview] | Change From Baseline in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) |
| NCT01289782 (34) [back to overview] | Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) for Impairment in Overall Work Productivity Scores Due to Hepatitis C Virus (HCV) Infection and Its Treatment |
| NCT01289782 (34) [back to overview] | Time From End-of-treatment to Viral Relapse |
| NCT01290679 (34) [back to overview] | Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Undetectable or Detectable |
| NCT01290679 (34) [back to overview] | Actual Values of log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) |
| NCT01290679 (34) [back to overview] | Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) for Impairment in Daily Activities Due to Hepatitis C Virus (HCV) Infection and Its Treatment |
| NCT01290679 (34) [back to overview] | Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) for Impairment in Overall Work Productivity Due to Hepatitis C Virus (HCV) Infection and Its Treatment |
| NCT01290679 (34) [back to overview] | Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) for the Fatigue Severity Scale (FSS) Total Scores |
| NCT01290679 (34) [back to overview] | Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) for Time Missed From Work Due to Hepatitis C Virus (HCV) Infection and Its Treatment |
| NCT01290679 (34) [back to overview] | Change From Baseline in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) |
| NCT01290679 (34) [back to overview] | Percentage of Participants With On-treatment Virologic Response at All Time Points |
| NCT01290679 (34) [back to overview] | The Percentage of Participants With Viral Breakthrough at Different Time Points |
| NCT01290679 (34) [back to overview] | Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <1000 IU/mL |
| NCT01290679 (34) [back to overview] | Time From End-of-treatment to Viral Relapse |
| NCT01290679 (34) [back to overview] | The Percentage of Participants With Normalization of Alanine Aminotransferase (ALT) |
| NCT01290679 (34) [back to overview] | The Percentage of Participants With <1 log10 Decrease in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) From Baseline at Week 4 |
| NCT01290679 (34) [back to overview] | The Percentage of Participants Who Achieved a Sustained Virologic Response 4 Weeks After the Planned End of Treatment (SVR4) |
| NCT01290679 (34) [back to overview] | The Percentage of Participants Who Achieved a Sustained Virologic Response 24 Weeks After the Planned End of Treatment (SVR24) |
| NCT01290679 (34) [back to overview] | The Percentage of Participants Achieving a Sustained Virologic Response at Week 72 (SVRW72) |
| NCT01290679 (34) [back to overview] | The Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12) |
| NCT01290679 (34) [back to overview] | The Percentage of Participants Achieving a Rapid Virologic Response (RVR) |
| NCT01290679 (34) [back to overview] | The Percentage of Participants Achieving a Extended Rapid Virologic Response (eRVR) |
| NCT01290679 (34) [back to overview] | The Percentage of Participants Achieving a Early Virologic Response (EVR) |
| NCT01290679 (34) [back to overview] | The Percentage of Participants Achieving a Complete Early Virologic Response (cEVR) |
| NCT01290679 (34) [back to overview] | Percentage of Participants With Viral Relapse |
| NCT01290679 (34) [back to overview] | Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <100 IU/mL |
| NCT01290679 (34) [back to overview] | Median Time to Normalization of Alanine Aminotransferase (ALT) Levels |
| NCT01290679 (34) [back to overview] | Percentage of Participants Who Completed All Study Treatment at Week 24 Because of the Treatment Duration Rule |
| NCT01290679 (34) [back to overview] | Percentage of Participants With in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels >1000 IU/mL at Week 4 |
| NCT01290679 (34) [back to overview] | Percentage of Participants With Null Response |
| NCT01290679 (34) [back to overview] | Percentage of Participants With On-treatment Failure |
| NCT01290679 (34) [back to overview] | Percentage of Participants With Partial Response |
| NCT01290679 (34) [back to overview] | Percentage of Participants With Viral Breakthrough |
| NCT01290679 (34) [back to overview] | Plasma Concentration of TMC435: Systemic Clearance (CL) |
| NCT01290679 (34) [back to overview] | Plasma Concentration of TMC435: Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h) |
| NCT01290679 (34) [back to overview] | Plasma Concentration of TMC435: Predose Plasma Concentration (C0h) |
| NCT01290679 (34) [back to overview] | Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Undetectable |
| NCT01290731 (9) [back to overview] | The Number of Participants With Viral Breakthrough |
| NCT01290731 (9) [back to overview] | The Percentage of Participants With a Sustained Virologic Response 12 Weeks After the Actual End of Treatment (SVR12) |
| NCT01290731 (9) [back to overview] | The Percentage of Participants With a Sustained Virologic Response 24 Weeks After the Actual End of Treatment (SVR24) |
| NCT01290731 (9) [back to overview] | Plasma Concentrations of TMC435 |
| NCT01290731 (9) [back to overview] | The Percentage of Participants Who Achieved a Greater Than or Equal to 2 log10 IU/mL Drop From Baseline in Plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) at Each Time Point During Treatment and Follow-up |
| NCT01290731 (9) [back to overview] | The Percentage of Participants With Undetectable Plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) During Treatment and at the End of Treatment (EOT) |
| NCT01290731 (9) [back to overview] | Area Under the Plasma Concentration-time Curve From 0 to 24 Hrs (AUC24h) for TMC435 |
| NCT01290731 (9) [back to overview] | The Number of Participants Demonstrating Viral Relapse |
| NCT01290731 (9) [back to overview] | The Number of Participants With Abnormal Alanine Aminotransferase (ALT) Levels at Baseline Who Achieved Normal ALT Levels at the End of Treatment (EOT) |
| NCT01292239 (10) [back to overview] | The Number of Participants With Viral Breakthrough |
| NCT01292239 (10) [back to overview] | The Percentage of Participants in the TMC435 Treatment Group Who Met Response Guided Treatment (RGT) Criteria and Completed Treatment With Peginterferon Alpha-2a (PegIFN Alpha-2a) and Ribavirin (RBV) at Week 24 |
| NCT01292239 (10) [back to overview] | The Percentage of Participants With a Sustained Virologic Response at the End of Treatment (EOT) and 12 Weeks After the Last Dose of Treatment (SVR12) |
| NCT01292239 (10) [back to overview] | The Percentage of Participants With a Sustained Virologic Response at the End of Treatment (EOT) and 24 Weeks After the Last Dose of Treatment (SVR24) |
| NCT01292239 (10) [back to overview] | Plasma Concentrations of TMC435 |
| NCT01292239 (10) [back to overview] | The Percentage of Participants Who Achieved a Greater Than or Equal to 2 log10 IU/mL Drop From Baseline in Plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) at Each Time Point During Treatment and Follow-up |
| NCT01292239 (10) [back to overview] | The Percentage of Participants With Undetectable Plasma Levels of Hepatitis C Virus Ribonucleic Acid (HCV RNA) During Treatment and at the End of Treatment (EOT) |
| NCT01292239 (10) [back to overview] | The Number of Participants Demonstrating Viral Relapse |
| NCT01292239 (10) [back to overview] | Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24h) for TMC435 |
| NCT01292239 (10) [back to overview] | The Number of Participants With Abnormal Alanine Aminotransferase (ALT) Levels at Baseline Who Achieved Normal ALT Levels at the End of Treatment (EOT) |
| NCT01366638 (10) [back to overview] | The Percentage of Participants Who Met Response Guided Treatment (RGT) Criteria and Completed Treatment With Peginterferon Alpha-2b (PegIFNα-2b) and Ribavirin (RBV) at Week 24 |
| NCT01366638 (10) [back to overview] | The Number of Participants With Abnormal Alanine Aminotransferase (ALT) Levels at Baseline Who Achieved Normal Limit of ALT at the End of Treatment (EOT) |
| NCT01366638 (10) [back to overview] | The Percentage of Participants With a Sustained Virologic Response 12 Weeks After the Actual End of Treatment (SVR12) |
| NCT01366638 (10) [back to overview] | The Percentage of Participants With Undetectable Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) During Treatment and at the End of Treatment |
| NCT01366638 (10) [back to overview] | The Percentage of Participants Who Achieved a Greater Than or Equal to 2 log10 IU/mL Drop From Baseline in Plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) at Each Time Point During Treatment and Follow-up |
| NCT01366638 (10) [back to overview] | Plasma Concentrations of TMC435 |
| NCT01366638 (10) [back to overview] | The Percentage of Participants With a Sustained Virologic Response 24 Weeks After the Actual End of Treatment (SVR24) |
| NCT01366638 (10) [back to overview] | The Number of Participants With Viral Breakthrough |
| NCT01366638 (10) [back to overview] | The Number of Participants Demonstrating Viral Relapse |
| NCT01366638 (10) [back to overview] | The Area Under the Plasma Concentration-Time Curve (From 0 to 24 Hours) (AUC24h) |
| NCT01466790 (7) [back to overview] | Number of Participants With a Sustained Virologic Response (SVR) 4 Weeks After the Planned End of Treatment (EOT) |
| NCT01466790 (7) [back to overview] | Number of Participants With a Sustained Virologic Response (SVR) at Week 48 |
| NCT01466790 (7) [back to overview] | Number of Participants With a Sustained Virologic Response (SVR) 24 Weeks After the Planned End of Treatment (EOT) |
| NCT01466790 (7) [back to overview] | Number of Participants With a Sustained Virologic Response (SVR) 12 Weeks After the Planned End of Treatment (EOT) |
| NCT01466790 (7) [back to overview] | Number of Participants With Inadequate Virologic Response |
| NCT01466790 (7) [back to overview] | Number of Participants With Viral Breakthrough |
| NCT01466790 (7) [back to overview] | Number of Participants With Viral Relapse |
| NCT01479868 (12) [back to overview] | Percentage of Participants With Viral Relapse |
| NCT01479868 (12) [back to overview] | Percentage of Participants With Viral Breakthrough |
| NCT01479868 (12) [back to overview] | Percentage of Participants With Sustained Virologic Response at Week 12 (SVR 12) |
| NCT01479868 (12) [back to overview] | Percentage of Participants With On-treatment Failure |
| NCT01479868 (12) [back to overview] | Percentage of Participants With Normalized Alanine Aminotransferase Levels |
| NCT01479868 (12) [back to overview] | Percentage of Human Immunodeficiency Virus (HIV) Participants With Virologic Failure |
| NCT01479868 (12) [back to overview] | Percentage of Participants With Sustained Virologic Response at Week 24 (SVR 24) |
| NCT01479868 (12) [back to overview] | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) |
| NCT01479868 (12) [back to overview] | Mean Change From Baseline in Log10 Plasma Human Immunodeficiency Virus (HIV) Viral Load |
| NCT01479868 (12) [back to overview] | Mean Change From Baseline in CD4+ Cell Count |
| NCT01479868 (12) [back to overview] | Change From Baseline in CD4+ Cell Count in Percentage |
| NCT01479868 (12) [back to overview] | Percentage of Participants With Hepatitis C Virus Ribonucleic Acid (HCV-RNA) Less Than (<) 25 International Units (IU/mL) Undetectable or Detectable/Undetectable |
| NCT01485991 (3) [back to overview] | Percentage of Participants With Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12) |
| NCT01485991 (3) [back to overview] | Percentage of Participants With Viral Relapse |
| NCT01485991 (3) [back to overview] | Percentage of Participants With Sustained Virologic Response 24 Weeks After the Planned End of Treatment (SVR24) |
| NCT01628692 (7) [back to overview] | Percentage of Participants With Rapid Virologic Response (RVR) at Week 4 |
| NCT01628692 (7) [back to overview] | Percentage of Participants With Sustained Virologic Response at Week 12 (SVR12) by rs12979860 Single Nucleotide Polymorphisms in the IL-28B Gene Categories |
| NCT01628692 (7) [back to overview] | Percentage of Participants With Sustained Virologic Response Rate at Post-treatment Week 12 (SVR12) |
| NCT01628692 (7) [back to overview] | Percentage of Participants With Extended Rapid Virologic Response (eRVR) |
| NCT01628692 (7) [back to overview] | Percentage of Participants With Complete Early Virologic Response (cEVR) |
| NCT01628692 (7) [back to overview] | Percentage of Participants With End of Treatment Response (EOTR) |
| NCT01628692 (7) [back to overview] | Number of Participants With Serious Adverse Events (SAEs) and Discontinuations Due to Adverse Events (AEs) and Who Died |
| NCT01725529 (7) [back to overview] | Percentage of Participants With On-treatment Failure |
| NCT01725529 (7) [back to overview] | Percentage of Participants With Viral Breakthrough |
| NCT01725529 (7) [back to overview] | Percentage of Participants With Sustained Virologic Response at Week 72 (SVRW72) |
| NCT01725529 (7) [back to overview] | Percentage of Participants With Sustained Virologic Response 24 Weeks After End of Study Drug Treatment (SVR24) |
| NCT01725529 (7) [back to overview] | Percentage of Participants With Sustained Virologic Response 12 Weeks After End of Study Drug Treatment (SVR12) |
| NCT01725529 (7) [back to overview] | Percentage of Participants With On-treatment Normalization of Alanine Aminotransferase Level |
| NCT01725529 (7) [back to overview] | Percentage of Participants With Viral Relapse |
| NCT01938625 (8) [back to overview] | Percentage of Participants With HCV RNA (< 25 IU/mL Undetectable) and HCV RNA < 25 IU/mL Detectable |
| NCT01938625 (8) [back to overview] | Percentage of Participants With Sustained Virologic Response 4 Weeks After the End of Treatment (SVR 4) |
| NCT01938625 (8) [back to overview] | Number of Participants With On-Treatment Failure |
| NCT01938625 (8) [back to overview] | Number of Participants With Viral Breakthrough |
| NCT01938625 (8) [back to overview] | Number of Participants With Viral Relapse |
| NCT01938625 (8) [back to overview] | Percentage of Participants With Sustained Virologic Response 12 Weeks After the End of Treatment (SVR 12) |
| NCT01938625 (8) [back to overview] | Percentage of Participants With Sustained Virologic Response 24 Weeks After the End of Treatment (SVR 24) |
| NCT01938625 (8) [back to overview] | Percentage of Participants With HCV RNA (<) 100 IU/mL at Week 4 |
| NCT02114151 (12) [back to overview] | Percentage of Participants With Depression by Using Center for Epidemiologic Studies Depression Scale (CES-D) |
| NCT02114151 (12) [back to overview] | Number of Participants Not Achieving SVR Showing Emerging Mutation at Time of Failure in HCV NS3/4A Sequence and NS5B up to Follow-up Week 24 |
| NCT02114151 (12) [back to overview] | Change From Baseline in Hepatitis C Symptom and Impact Questionnaire Version 4 (HCV-SIQv4) Overall Body System Score (OBSS) up to Follow-up Week 12 |
| NCT02114151 (12) [back to overview] | Change From Baseline in Fatigue Severity Score (FSS) up to Follow-up Week 24 |
| NCT02114151 (12) [back to overview] | Change From Baseline in EuroQol 5 Dimension Questionnaire (EQ-5D) up to Follow-up Week 24 |
| NCT02114151 (12) [back to overview] | Percentage of Participants With a Sustained Virologic Response (SVR) 24 Weeks After the Actual End of Treatment (EOT) |
| NCT02114151 (12) [back to overview] | Percentage of Participants With a Sustained Virologic Response (SVR) 4 Weeks After the Actual End of Treatment (EOT) |
| NCT02114151 (12) [back to overview] | Percentage of Participants With On-treatment Failure |
| NCT02114151 (12) [back to overview] | Percentage of Participants With Viral Breakthrough |
| NCT02114151 (12) [back to overview] | Percentage of Participants With Viral Relapse |
| NCT02114151 (12) [back to overview] | Percentage of Participants With a Sustained Virologic Response (SVR) 12 Weeks After the Actual End of Treatment (EOT) |
| NCT02114151 (12) [back to overview] | Percentage of Participants With On-treatment Virologic Response |
| NCT02114177 (10) [back to overview] | Percentage of Participants Achieving a Sustained Virologic Response 24 Weeks After the Actual End of Treatment (SVR24) |
| NCT02114177 (10) [back to overview] | Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Actual End of Treatment (SVR12) |
| NCT02114177 (10) [back to overview] | Percentage of Participants Achieving a On-treatment Virologic Response |
| NCT02114177 (10) [back to overview] | Percentage of Participants Achieving a Sustained Virologic Response 4 Weeks After the Actual End of Treatment (SVR4) |
| NCT02114177 (10) [back to overview] | Percentage of Participants With Viral Breakthrough |
| NCT02114177 (10) [back to overview] | Percentage of Participants With Viral Relapse |
| NCT02114177 (10) [back to overview] | Change From Baseline in Center for Epidemiologic Studies Depression Scale (CES-D) Scores |
| NCT02114177 (10) [back to overview] | Change From Baseline in EuroQol 5 Dimension (EQ-5D) Visual Analogue Scale |
| NCT02114177 (10) [back to overview] | Change From Baseline in Fatigue Severity Scale (FSS) Score up to Follow-up Week 24 |
| NCT02114177 (10) [back to overview] | Change From Baseline in Hepatitis C Symptom and Impact Questionnaire 4 (HCV-SIQv4) Overall Body System Score (OBSS) |
| NCT02118597 (7) [back to overview] | Number of Participants With Treatment Discontinuation |
| NCT02118597 (7) [back to overview] | Number of Participants With Adverse Events |
| NCT02118597 (7) [back to overview] | Number of Participants With Treatment Discontinuation Due to Futility |
| NCT02118597 (7) [back to overview] | Number of Participants With Virological Breakthrough |
| NCT02118597 (7) [back to overview] | Number of Participants With Virological Relapse |
| NCT02118597 (7) [back to overview] | Sustained Virological Response 24 (SVR24) Rate |
| NCT02118597 (7) [back to overview] | Percentage of Participants With Virological Response |
| NCT02168361 (2) [back to overview] | Proportion of Participants With Sustained Virologic Response 12 (SVR-12) |
| NCT02168361 (2) [back to overview] | Serum HCV RNA Level |
| NCT02214420 (1) [back to overview] | Sustained Viral Response |
| NCT02250807 (7) [back to overview] | Percentage of Participants With Sustained Virologic Response 24 Weeks After End of Therapy (SVR24) |
| NCT02250807 (7) [back to overview] | Percentage of Participants With On-Treatment Failure |
| NCT02250807 (7) [back to overview] | Percentage of Participants With Sustained Virologic Response 12 Weeks After End of Treatment (EOT) (SVR12) |
| NCT02250807 (7) [back to overview] | Percentage of Participants With On-treatment Virologic Response of Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) |
| NCT02250807 (7) [back to overview] | Percentage of Participants With Viral Breakthrough |
| NCT02250807 (7) [back to overview] | Percentage of Participants With Viral Relapse |
| NCT02250807 (7) [back to overview] | Percentage of Participants With Sustained Virologic Response 4 Weeks After End of Therapy (SVR4) |
| NCT02262728 (11) [back to overview] | Time to Reach Maximum Plasma Concentration (Tmax) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) |
| NCT02262728 (11) [back to overview] | Percentage of Participants With On-treatment Failure |
| NCT02262728 (11) [back to overview] | Percentage of Participants With Sustained Virologic Response 12 Weeks After End of Study Drug Treatment (SVR12) |
| NCT02262728 (11) [back to overview] | Percentage of Participants With SVR12 Who Maintained to Have HCV RNA |
| NCT02262728 (11) [back to overview] | Absolute Values of Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) Levels at Follow-up Week 24 (Week 36) |
| NCT02262728 (11) [back to overview] | Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours After Dosing (AUC[0-24]) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) |
| NCT02262728 (11) [back to overview] | Maximum Plasma Concentration (Cmax) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) |
| NCT02262728 (11) [back to overview] | Minimum Plasma Concentration (Cmin) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) |
| NCT02262728 (11) [back to overview] | Percentage of Participants With On-Treatment Virologic Response |
| NCT02262728 (11) [back to overview] | Percentage of Participants With SVR 4 Weeks After End of Study Drug Treatment (SVR4) and SVR 24 Weeks After End of Study Drug Treatment (SVR24) |
| NCT02262728 (11) [back to overview] | Pre-dose (Trough) Concentration (C0h) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite) |
| NCT02268864 (6) [back to overview] | Percentage of Participants With Sustained Virologic Response 12 Weeks After End of Study Drug Treatment (SVR12) |
| NCT02268864 (6) [back to overview] | Number of Participants With Viral Breakthrough |
| NCT02268864 (6) [back to overview] | Number of Participants With Viral Relapse |
| NCT02268864 (6) [back to overview] | Percentage of Participants With On-treatment Failure |
| NCT02268864 (6) [back to overview] | Percentage of Participants With Sustained Virologic Response 4 Weeks After End of Study Drug Treatment (SVR4) |
| NCT02268864 (6) [back to overview] | Percentage of Participants With SVR 24 Weeks After End of Study Drug Treatment (SVR 24) |
| NCT02349048 (8) [back to overview] | Number of Participants With HCV Nonstructural Protein 3/4A (NS3/4A), NS5A and NS5B Sequence in Participants Not Achieving SVR |
| NCT02349048 (8) [back to overview] | Number of Participants With Late Viral Relapse |
| NCT02349048 (8) [back to overview] | Number of Participants With Viral Relapse |
| NCT02349048 (8) [back to overview] | Percentage of Participants With On-Treatment Failure |
| NCT02349048 (8) [back to overview] | Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After End of Study Drug Treatment (SVR12) |
| NCT02349048 (8) [back to overview] | Percentage of Participants With On-treatment Virologic Response |
| NCT02349048 (8) [back to overview] | Percentage of Participants With or Without an NS3 Q80K Polymorphism at Baseline Achieving SVR |
| NCT02349048 (8) [back to overview] | Percentage of Participants With Sustained Virologic Response at 4 Weeks (SVR4) and 24 Weeks (SVR24) After End of Study Drug Treatment |
| NCT02404805 (2) [back to overview] | Simeprevir AUC Pharmacokinetics |
| NCT02404805 (2) [back to overview] | Dolutegravir AUC Pharmacokinetics |
| NCT02421211 (19) [back to overview] | Percentage of Participants With Sustained Virologic Response (SVR) 4 Weeks After the Actual EOT (SVR4) and 12 Weeks After the Actual EOT (SVR12) |
| NCT02421211 (19) [back to overview] | Average Plasma Concentration at Steady State (Cavg,ss) of Ledipasvir |
| NCT02421211 (19) [back to overview] | Trough Plasma Concentration (Ctrough) of Simeprevir |
| NCT02421211 (19) [back to overview] | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
| NCT02421211 (19) [back to overview] | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Ledipasvir |
| NCT02421211 (19) [back to overview] | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Simeprevir |
| NCT02421211 (19) [back to overview] | Percentage of Participants With On-treatment Virologic Response |
| NCT02421211 (19) [back to overview] | Average Plasma Concentration at Steady State (Cavg,ss) of Simeprevir |
| NCT02421211 (19) [back to overview] | Fluctuation Index (FI) of Ledipasvir |
| NCT02421211 (19) [back to overview] | Fluctuation Index (FI) of Simeprevir |
| NCT02421211 (19) [back to overview] | Maximum Plasma Concentration (Cmax) of Ledipasvir |
| NCT02421211 (19) [back to overview] | Maximum Plasma Concentration (Cmax) of Simeprevir |
| NCT02421211 (19) [back to overview] | Minimum Plasma Concentration (Cmin) of Ledipasvir (LDV) |
| NCT02421211 (19) [back to overview] | Minimum Plasma Concentration (Cmin) of Simeprevir (SMV) |
| NCT02421211 (19) [back to overview] | Percentage of Participants With On-treatment Failure |
| NCT02421211 (19) [back to overview] | Percentage of Participants With Viral Relapse |
| NCT02421211 (19) [back to overview] | Time to Reach Maximum Plasma Concentration (Tmax) of Ledipasvir |
| NCT02421211 (19) [back to overview] | Time to Reach Maximum Plasma Concentration (Tmax) of Simeprevir |
| NCT02421211 (19) [back to overview] | Trough Plasma Concentration (Ctrough) of Ledipasvir |
| NCT02569710 (44) [back to overview] | AUC (0-last) of Odalasvir |
| NCT02569710 (44) [back to overview] | AUC (0-24) of Simeprevir |
| NCT02569710 (44) [back to overview] | AUC (0-24) for Odalasvir |
| NCT02569710 (44) [back to overview] | Cmin of Odalasvir |
| NCT02569710 (44) [back to overview] | Average Plasma Concentration at Steady State (Css,Avg) of Odalasvir |
| NCT02569710 (44) [back to overview] | Average Plasma Concentration at Steady State (Css,Avg) of Simeprevir |
| NCT02569710 (44) [back to overview] | Body Mass Index (BMI) at End of Treatment |
| NCT02569710 (44) [back to overview] | Body Weight at End of Treatment |
| NCT02569710 (44) [back to overview] | Clast of Odalasvir |
| NCT02569710 (44) [back to overview] | Clast of Simeprevir |
| NCT02569710 (44) [back to overview] | Cmax of Odalasvir |
| NCT02569710 (44) [back to overview] | Cmax of Simeprevir |
| NCT02569710 (44) [back to overview] | Percentage of Participants With Maximum Decrease From Baseline in Mean Ejection Fraction |
| NCT02569710 (44) [back to overview] | Cmin of Simeprevir |
| NCT02569710 (44) [back to overview] | Ctrough of Odalasvir |
| NCT02569710 (44) [back to overview] | Ctrough of Simeprevir |
| NCT02569710 (44) [back to overview] | Number of Participants With HCV Nonstructural Protein NS5A, NS5B, and NS3/4A Sequence in Participants With Virologic Failure |
| NCT02569710 (44) [back to overview] | Number of Participants With Treatment Emergent Adverse Event (TEAE) |
| NCT02569710 (44) [back to overview] | Percentage of Participants With On-treatment Failure |
| NCT02569710 (44) [back to overview] | Percentage of Participants With Virologic Relapse During the Follow-up Period |
| NCT02569710 (44) [back to overview] | Tlast of Odalasvir |
| NCT02569710 (44) [back to overview] | Average Plasma Concentration at Steady State (Css,Avg) of ALS-022227 |
| NCT02569710 (44) [back to overview] | Tlast of Simeprevir |
| NCT02569710 (44) [back to overview] | Tmax of Odalasvir |
| NCT02569710 (44) [back to overview] | Tmax of Simeprevir |
| NCT02569710 (44) [back to overview] | Area Under the Plasma Concentration Time-Curve at 24 Hours (AUC0-24) for AL-335 and Its Metabolites (ALS-022399 and ALS-022227) |
| NCT02569710 (44) [back to overview] | Area Under the Plasma Concentration-Time Curve From Time 0 to Last Measurable Plasma Concentration (AUC [0-last]) of AL-335 and Its Metabolites (ALS-022399 and ALS-022227) |
| NCT02569710 (44) [back to overview] | Last Measurable Plasma Concentration (Clast) of AL-335 and Its Metabolite (ALS-022399 and ALS-022227) |
| NCT02569710 (44) [back to overview] | Maximum Observed Plasma Concentration (Cmax) of AL-335 and Its Metabolites (ALS-022399 and ALS-022227) |
| NCT02569710 (44) [back to overview] | Minimum Observed Plasma Concentration (Cmin) of AL-335 and Its Metabolites (ALS-022399 and ALS-022227) |
| NCT02569710 (44) [back to overview] | Percentage of Participants by Treatment Emergent Toxicity Grade - Blood Chemistry Parameters |
| NCT02569710 (44) [back to overview] | Percentage of Participants by Treatment Emergent Toxicity Grade - Hematology Parameters |
| NCT02569710 (44) [back to overview] | Percentage of Participants by Treatment Emergent Toxicity Grade - Prothrombin International Normalized Ratio (INR) |
| NCT02569710 (44) [back to overview] | Percentage of Participants by Treatment Emergent Toxicity Grade - Urinalysis Parameter (Protein) |
| NCT02569710 (44) [back to overview] | Percentage of Participants Who Achieved HCV RNA |
| NCT02569710 (44) [back to overview] | Percentage of Participants Who Achieved HCV RNA Less Then (<) LLOQ Undetectable |
| NCT02569710 (44) [back to overview] | Percentage of Participants With Sustained Virologic Response (SVR) at Week 4, 12 and 24 After End of Treatment |
| NCT02569710 (44) [back to overview] | Percentage of Participants With Worst Post-Baseline Values of Vital Signs |
| NCT02569710 (44) [back to overview] | Percentage of Participants With Worst Treatment Emergent Abnormalities of Electrocardiogram (ECG) Parameters |
| NCT02569710 (44) [back to overview] | Time Corresponding to Last Measurable Plasma Concentration (Tlast) for AL-335 and Its Metabolites (ALS-022399 and ALS-022227) |
| NCT02569710 (44) [back to overview] | Time to Reach the Maximum Plasma Concentration (Tmax) of AL-335 and Its Metabolites (ALS-022399 and ALS-022227) |
| NCT02569710 (44) [back to overview] | Trough Plasma Concentration (Ctrough) for AL-335 and Its Metabolites (ALS-022399 and ALS-022227) |
| NCT02569710 (44) [back to overview] | Trough Plasma Concentration (Ctrough) for AL-335 and Its Metabolites (ALS-022399 and ALS-022227) |
| NCT02569710 (44) [back to overview] | AUC (0-last) of Simeprevir |
| NCT02765490 (6) [back to overview] | Percentage of Participants With Sustained Virologic Response 24 Weeks After End of Treatment (SVR24) |
| NCT02765490 (6) [back to overview] | Percentage of Participants With Sustained Virologic Response 12 Weeks After End of Treatment (EOT) (SVR12) |
| NCT02765490 (6) [back to overview] | Percentage of Participants With On-treatment Failure |
| NCT02765490 (6) [back to overview] | Percentage of Participants With Sustained Virologic Response 4 Weeks After End of Treatment (EOT) |
| NCT02765490 (6) [back to overview] | Number of Participants With Late Viral Relapse |
| NCT02765490 (6) [back to overview] | Number of Participants With Viral Relapse |
| NCT02993250 (9) [back to overview] | Percentage of Participants With Sustained Virologic Response 12 Weeks (SVR12) After Actual End-of-treatment |
| NCT02993250 (9) [back to overview] | Percentage of Participants With Sustained Virologic Response 4 Weeks (SVR4) After Actual End-of-Treatment |
| NCT02993250 (9) [back to overview] | Percentage of Participants With Viral Relapse |
| NCT02993250 (9) [back to overview] | Time to Achieve HCV RNA Not Detected or HCV RNA |
| NCT02993250 (9) [back to overview] | Percentage of Participants With On-treatment Virologic Response |
| NCT02993250 (9) [back to overview] | Percentage of Participants With On-treatment Virologic Response |
| NCT02993250 (9) [back to overview] | Percentage of Participants With On-treatment Failure |
| NCT02993250 (9) [back to overview] | Number of Participants With Adverse Events (AEs) |
| NCT02993250 (9) [back to overview] | Percentage of Participants With Sustained Virologic Response 24 Weeks (SVR24) After Actual End-of-treatment |
Virologic Response Parameters Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D)
The table below shows the number of treatment-experienced participants (non-responders and relapsers, see defined above) treated with TMC435 or placebo coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22 who met the following virologic response parameters: rapid virological response (RVR) defined as having undetectable plasma HCV ribonucleic acid (RNA) at Week 4; early virologic response (EVR) defined as change from baseline in plasma HCV RNA of greater than or equal to 2 log 10 at Week 12; a complete EVR (cEVR) defined as a EVR having undetectable plasma HCV RNA at Week 12; an extended RVR (eRVR) defined as undetectable plasma HCV RNA at Week 4 and 12; and a partial response defined as EVR but not reaching undetectability while on treatment. (NCT00561353)
Timeframe: Week 4 (RVR), Week 12 (EVR, cEVR, and partial response), and Week 4 and 12 (eRVR)
| Intervention | Participants (Number) |
|---|
| RVR | EVR | cEVR | eRVR | Partial response |
|---|
| Placebo (Cohort 4, Panel C) | 0 | 8 | 0 | 0 | 5 |
,| TMC435 150 mg (Cohort 4, Panel C) | 5 | 7 | 4 | 4 | 1 |
,| TMC435 200 mg (Cohort 4, Panel C) | 3 | 8 | 5 | 3 | 1 |
,| TMC435 200 mg (Cohort 5, Panel D) | 3 | 4 | 3 | 3 | 0 |
,| TMC435 75 mg (Cohort 4, Panel C) | 2 | 6 | 4 | 2 | 0 |
Viral Breakthrough in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D)
The table below shows the number of treatment-experienced participants (non-responders and relapsers, see defined above) with viral breakthrough, defined as a confirmed increase of greater than 1 log10 IU/mL in plasma HCV ribonucleic acid (RNA) level from the lowest level reached), or a confirmed plasma HCV RNA level of greater than 100 IU/mL in participants whose plasma HCV RNA had previously been below the limit of quantification (25 IU/mL detectable) or undetectable (less than 25 IU/mL undetectable) treated with TMC435 or placebo coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22. (NCT00561353)
Timeframe: 4 Weeks (Wks), 44 Wks, and 48 Wks
| Intervention | Participants (Number) |
|---|
| Entire treatment period (48 Wks) | During TMC435/Placebo treatment (4 Wks) | During treatment with RBV and PegIFNα-2a (44 Wks) |
|---|
| Placebo (TMC435 75/150/200 mg) (Cohort 4, Panel C) | 1 | 1 | 0 |
,| TMC435 150 mg (Cohort 4, Panel C) | 4 | 1 | 3 |
,| TMC435 200 mg (Cohort 4, Panel C) | 4 | 0 | 4 |
,| TMC435 200 mg (Cohort 5, Panel D) | 1 | 0 | 1 |
,| TMC435 75 mg (Cohort 4, Panel C) | 3 | 2 | 1 |
Viral Breakthrough in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1, Panel A and B)
The table below shows the number of treatment-naïve participants with viral breakthrough, defined as a confirmed increase of greater than 1 log10 IU/mL in plasma HCV ribonucleic acid (RNA) level from the lowest level reached, or a confirmed plasma HCV RNA level of greater than 100 IU/mL in participants whose plasma HCV RNA had previously been below the limit of quantification (25 IU/mL detectable) or undetectable (less than 25 IU/mL undetectable) after treatment with TMC435 or placebo for 7 days followed by TMC435 or placebo coadministered with ribavirin for 21 days + peginterferon alpha-2a (PegIFNα-2a) on days 8, 15, and 22 (Panel A) and after treatment with TMC435 or placebo coadministered with ribavirin for 28 days + PegIFNα-2a on Days 1, 8, 15, and 22 (Panel B). (NCT00561353)
Timeframe: 4 Weeks (Wks), 44 Wks, and 48 Wks
| Intervention | Participants (Number) |
|---|
| Entire treatment period (48 Wks) | During TMC435/Placebo treatment (4 Wks) | During treatment with RBV and PegIFNα-2a (44 Wks) |
|---|
| Placebo (Cohort 1, Panels A and B) | 0 | 0 | 0 |
,| Placebo (Cohort 2, Panels A and B) | 0 | 0 | 0 |
,| TMC435 200 mg (Cohort 2, Panels A and B) | 4 | 1 | 3 |
,| TMC435 25 mg (Cohort 1, Panels A and B) | 3 | 2 | 1 |
,| TMC435 75 mg (Cohort 1, Panels A and B) | 3 | 2 | 1 |
Viral Relapse in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D)
The table below shows the number of treatment-experienced participants combined (non-responders and relapsers, see defined above) with viral relapse, defined as having confirmed detectable plasma level of HCV ribonucleic acid (RNA) during the follow-up period in participants with undetectable plasma HCV RNA (less than 25 IU/mL undetectable) at the end of treatment who received TMC435 or placebo coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22. (NCT00561353)
Timeframe: Up to Week 72
| Intervention | Participants (Number) |
|---|
| Relapse | No relapse |
|---|
| Placebo (TMC435 75/150/200 mg) (Cohort 4, Panel C) | 3 | 0 |
,| TMC435 150 mg (Cohort 4, Panel C) | 0 | 3 |
,| TMC435 200 mg (Cohort 4, Panel C) | 1 | 5 |
,| TMC435 200 mg (Cohort 5, Panel D) | 0 | 3 |
,| TMC435 75 mg (Cohort 4, Panel C) | 3 | 3 |
Viral Relapse in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined)
"The table below shows the number of treatment-naïve participants with viral relapse (defined as having confirmed detectable plasma level of HCV ribonucleic acid [RNA] during the follow-up period in participants with undetectable plasma HCV RNA [less than 25 IU/mL undetectable] at the end of treatment) for the treatment groups in Cohort 1 (Panel A and B combined) and in Cohort 2 (Panel A and B combined). See treatment-naïve defined above." (NCT00561353)
Timeframe: Up to Week 72
| Intervention | Participants (Number) |
|---|
| Relapse | No relapse | Missing follow-up |
|---|
| Placebo (Cohort 1, Panel A and B) | 2 | 10 | 0 |
,| Placebo (Cohort 2, Panel A and B) | 0 | 5 | 0 |
,| TMC435 200 mg (Cohort 2, Panel A and B) | 1 | 13 | 0 |
,| TMC435 25 mg (Cohort 1, Panel A and B) | 2 | 12 | 1 |
,| TMC435 75 mg (Cohort 1, Panel A and B) | 1 | 17 | 0 |
Sustained Virologic Response (SVR) in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined)
"The table below shows the number of treatment-naïve participants with an SVR to treatment (defined as having an undetectable plasma level of HCV ribonucleic acid after the last planned dose of treatment) for the treatment groups in Cohort 1 (Panel A and B combined) and in Cohort 2 (Panel A and B combined). SVR was measured at 4, 8, 12, and 24 weeks after the last dose of treatment (SVR4, SVR8, SVR12, and SVR24, respectively). See treatment-naïve defined above." (NCT00561353)
Timeframe: SVR4 (Week 52), SVR8 (Week 56), SVR12 (Week 60), and SVR24 (Week 72)
| Intervention | Participants (Number) |
|---|
| SVR4 | SVR8 | SVR12 | SVR24 |
|---|
| Placebo (Cohort 1, Panel A and B) | 11 | 9 | 9 | 9 |
,| Placebo (Cohort 2, Panel A and B) | 5 | 5 | 5 | 5 |
,| TMC435 200mg (Cohort 2, Panel A and B) | 12 | 12 | 12 | 12 |
,| TMC435 25 mg (Cohort 1, Panel A and B) | 12 | 12 | 12 | 10 |
,| TMC435 75mg (Cohort 1, Panel A and B) | 16 | 14 | 15 | 15 |
Virologic Response Parameters in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined)
The table below shows the number of treatment-naïve participants in the treatment groups for Cohort 1 (Panel A and B combined) and in Cohort 2 (Panel A and B combined) who met the following virologic response parameters: rapid virological response (RVR) defined as having undetectable plasma HCV ribonucleic acid (RNA) at Week 4; early virologic response (EVR) defined as change from baseline in plasma HCV RNA of greater than or equal to 2 log 10 at Week 12); a complete EVR (cEVR) defined as a complete EVR having undetectable plasma HCV RNA at Week 12); an extended RVR (eRVR) defined as undetectable plasma HCV RNA at Week 4 and 12; and a partial response defined as EVR but not reaching undetectability while on treatment. (NCT00561353)
Timeframe: Week 4 (RVR), Week 12 (EVR, cEVR, and partial response), and Week 4 and 12 (eRVR)
| Intervention | Participants (Number) |
|---|
| RVR | EVR | cEVR | eRVR | Partial response |
|---|
| Placebo (Cohort 1, Panel A and B) | 3 | 12 | 7 | 3 | 0 |
,| Placebo (Cohort 2, Panel A and B) | 0 | 6 | 5 | 0 | 1 |
,| TMC435 200mg (Cohort 2, Panel A and B) | 13 | 16 | 16 | 13 | 0 |
,| TMC435 25 mg (Cohort 1, Panel A and B) | 8 | 16 | 13 | 8 | 0 |
,| TMC435 75mg (Cohort 1, Panel A and B) | 13 | 19 | 17 | 13 | 0 |
Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D)
The table below shows the number of treatment-experienced participants (non-responders and relapsers, see defined above) with the following virologic responses to treatment with TMC435 or placebo coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22: plasma levels of HCV ribonucleic acid (RNA) of greater than or equal to 2 log10 decline from Baseline; plasma levels of HCV RNA below the limit of quantification (ie, less than [<] 25 IU/mL detectable or undetectable); plasma levels of HCV RNA below the limit of detection (ie, <25 IU/mL undetectable); plasma levels of HCV RNA <100 IU/mL; and plasma levels of HCV RNA <1000 at the time points listed. Note: in the table below, the number of participants (n) analyzed in the TMC435 200 mg (Cohort 4, Panel B) on Day 28 (Week 4) was n=4. (NCT00561353)
Timeframe: Day 2 or 3, Day 7, and Day 28
| Intervention | Participants (Number) |
|---|
| Day 2/3: > or = 2 log10 change from baseline | Day 7: > or = 2 log10 change from baseline | Day 28: > or = 2 log10 change from baseline | Day 2/3: <25 IU/mL detectable or undetectable | Day 7: <25 IU/mL detectable or undetectable | Day 28: <25 IU/mL detectable or undetectable | Day 2/3: <25 IU/mL undetectable | Day 7: <25 IU/mL undetectable | Day 28: <25 IU/mL undetectable | Day 2/3: <100 IU/mL | Day 7: <100 IU/mL | Day 28: <100 IU/mL | Day 2/3: <1000 IU/mL | Day 7: <1000 IU/mL | Day 28: <1000 IU/mL |
|---|
| Placebo (Cohort 4, Panel C) | 1 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
,| TMC435 150 mg (Cohort 4, Panel C) | 9 | 9 | 9 | 0 | 2 | 7 | 0 | 0 | 5 | 0 | 4 | 8 | 3 | 7 | 8 |
,| TMC435 200 mg (Cohort 4, Panel C) | 10 | 10 | 10 | 0 | 3 | 7 | 0 | 0 | 3 | 0 | 5 | 7 | 5 | 8 | 10 |
,| TMC435 200 mg (Cohort 5, Panel D) | 4 | 5 | 4 | 0 | 0 | 4 | 0 | 0 | 3 | 0 | 0 | 4 | 0 | 3 | 4 |
,| TMC435 75 mg (Cohort 4, Panel C) | 8 | 8 | 8 | 0 | 0 | 4 | 0 | 0 | 2 | 0 | 2 | 6 | 3 | 5 | 6 |
Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A)
"The table below shows the number of treatment-naïve HCV-infected participants treated with TMC435 or placebo for 7 days followed by TMC435 or placebo coadministered with ribavirin for 21 days + peginterferon alpha-2a (PegIFNα-2a) on Days 8, 15, and 22 who had the following virologic responses: plasma levels of HCV ribonucleic acid (RNA) of greater than or equal to 2 log10 decline from Baseline; plasma levels of HCV RNA below the limit of quantification (ie, less than [<] 25 IU/mL detectable or undetectable); plasma levels of HCV RNA below the limit of detection (ie, <25 IU/mL undetectable); plasma levels of HCV RNA <100 IU/mL; and plasma levels of HCV RNA <1000 at the time points listed. See treatment-naive defined above." (NCT00561353)
Timeframe: Day 2 or 3, Day 7, and Day 28
| Intervention | Participants (Number) |
|---|
| Day 2/3: > or = 2 log10 change from baseline | Day 7: > or = 2 log10 change from baseline | Day 28: > or = 2 log10 change from baseline | Day 2/3: <25 IU/mL detectable or undetectable | Day 7: <25 IU/mL detectable or undetectable | Day 28: <25 IU/mL detectable or undetectable | Day 2/3: <25 IU/mL undetectable | Day 7: <25 IU/mL undetectable | Day 28: <25 IU/mL undetectable | Day 2/3: <100 IU/mL | Day 7: <100 IU/mL | Day 28: <100 IU/mL | Day 2/3: <1000 IU/mL | Day 7: <1000 IU/mL | Day 28: <1000 IU/mL |
|---|
| Placebo (Cohort 1, Panel A) | 0 | 0 | 4 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 2 |
,| Placebo (Cohort 2, Panel A) | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
,| TMC435 200 mg (Cohort 2, Panel A) | 9 | 9 | 8 | 1 | 1 | 7 | 0 | 0 | 7 | 1 | 4 | 7 | 6 | 7 | 7 |
,| TMC435 25 mg (Cohort 1, Panel A) | 6 | 7 | 7 | 1 | 1 | 5 | 0 | 0 | 5 | 1 | 1 | 6 | 2 | 3 | 7 |
,| TMC435 75 mg (Cohort 1, Panel A) | 9 | 9 | 9 | 1 | 0 | 8 | 0 | 0 | 5 | 1 | 3 | 8 | 5 | 6 | 8 |
Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B)
"The table below shows the number of treatment-naive HCV-Infected participants with the following virologic responses to treatment with TMC435 or placebo coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 8, 15, and 22: plasma levels of HCV ribonucleic acid (RNA) of greater than or equal to 2 log10 decline from Baseline; plasma levels of HCV RNA below the limit of quantification (ie, less than [<] 25 IU/mL detectable or undetectable); plasma levels of HCV RNA below the limit of detection (ie, <25 IU/mL undetectable); plasma levels of HCV RNA <100 IU/mL; and plasma levels of HCV RNA <1000 at the time points listed. See treatment-naive defined above." (NCT00561353)
Timeframe: Day 2 or 3, Day 7, and Day 28
| Intervention | Participants (Number) |
|---|
| Day 2/3: > or = 2 log10 change from baseline | Day 7: > or = 2 log10 change from baseline | Day 28: > or = 2 log10 change from baseline | Day 2/3: <25 IU/mL detectable or undetectable | Day 7: <25 IU/mL detectable or undetectable | Day 28: <25 IU/mL detectable or undetectable | Day 2/3: <25 IU/mL undetectable | Day 7: <25 IU/mL undetectable | Day 28: <25 IU/mL undetectable | Day 2/3: <100 IU/mL | Day 7: <100 IU/mL | Day 28: <100 IU/mL | Day 2/3: <1000 IU/mL | Day 7: <1000 IU/mL | Day 28: <1000 IU/mL |
|---|
| Placebo (Cohort 1, Panel B) | 2 | 2 | 6 | 0 | 0 | 3 | 0 | 0 | 2 | 0 | 0 | 3 | 0 | 0 | 4 |
,| Placebo (Cohort 2, Panel B) | 2 | 1 | 2 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 2 |
,| TMC435 200 mg (Cohort 2, Panel B) | 9 | 9 | 9 | 0 | 3 | 9 | 0 | 1 | 6 | 1 | 5 | 9 | 6 | 9 | 9 |
,| TMC435 25 (Cohort 1, Panel B) | 7 | 7 | 8 | 0 | 1 | 6 | 0 | 0 | 3 | 0 | 1 | 6 | 4 | 5 | 7 |
,| TMC435 75 mg (Cohort 1, Panel B) | 9 | 9 | 9 | 0 | 1 | 9 | 0 | 0 | 8 | 1 | 6 | 9 | 5 | 9 | 9 |
Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D)
The table below shows mean (standard deviation) values of the area under the plasma concentration-time curve from time of administration to 24 hours after dosing for TMC435 in treatment-experienced HCV-infected participants considered non-responders (participants who achieved less than a 2 log10 IU/mL decline from baseline in plasma HCV ribonucleic acid (RNA) levels after 12 weeks of previous interferon [IFN]-based therapy [pegylated or non-pegylated]) or relapsers (defined as a participant with undetectable plasma HCV RNA at the end of treatment of previous IFN-based therapy and subsequent confirmed detectable plasma HCV RNA levels during follow-up at selected time points following treatment with TMC435 coadministered with ribavirin (RBV) for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22. The number of participants analyzed at Day 28 in the 4 treatment groups listed below from left to right was 8, 7, 10, and 3. (NCT00561353)
Timeframe: Days 1 and 28 (predose and 0.5, 1, 2, 4, 6, 8, and 10 hours postdose)
| Intervention | ng.h/mL (Mean) |
|---|
| Day 1 | Day 28 |
|---|
| TMC435 150 mg (Cohort 4, Panel C) | 30920 | 57440 |
,| TMC435 200 mg (Cohort 4, Panel C) | 34410 | 152600 |
,| TMC435 200 mg (Cohort 5, Panel D) | 51300 | 231300 |
,| TMC435 75 mg (Cohort 4, Panel C) | 11150 | 20150 |
Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) at Week 4 in Treatment-Naïve HCV-Infected Participants (Cohort 1 and 2, Panel B)
The table below shows the change from Baseline in plasma levels of HCV RNA at Week 4 following treatment with TMC435 or placebo coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22 in treatment-naïve HCV-infected participants. (A treatment-naive participant is someone who has never taken drugs for their HCV infection). (NCT00561353)
Timeframe: Week 4
| Intervention | log10 IU/mL (Mean) |
|---|
| TMC435 25 mg (Cohort 1, Panel B) | -4.74 |
| TMC435 75 mg (Cohort 1, Panel B) | -5.52 |
| Placebo (Cohort 1, Panel B) | -3.74 |
| TMC435 200 mg (Cohort 2, Panel B) | -5.44 |
| Placebo (Cohort 2, Panel B) | -3.26 |
Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) at Week 4 in Treatment-Naïve HCV-Infected Participants (Cohort 1 and 2, Panel A)
The table below shows the change from Baseline in plasma levels of HCV RNA at Week 4 following treatment with TMC435 or placebo as for 7 days followed by TMC435 or placebo coadministered with ribavirin for 21 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22 in treatment-naïve HCV-infected participants. (A treatment-naive participant is someone who has never taken drugs for their HCV infection). (NCT00561353)
Timeframe: Week 4
| Intervention | log10 IU/mL (Mean) |
|---|
| TMC435 25 mg (Cohort 1, Panel A) | -4.26 |
| TMC435 75 mg (Cohort 1, Panel A) | -4.47 |
| Placebo (Cohort 1, Panel A) | -2.97 |
| TMC435 200 mg (Cohort 2, Panel A) | -4.70 |
| Placebo (Cohort 2, Panel A) | -1.92 |
Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) at Week 4 in Treatment-Experienced HCV-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D)
The table below shows the change from Baseline in plasma levels of HCV RNA at Week 4 following treatment with TMC435 or placebo coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22 in treatment-experienced participants considered non-responders (defined as participants who achieved less than a 2 log10 IU/mL decline from baseline in plasma HCV RNA levels after 12 weeks of previous interferon [IFN]-based therapy [pegylated or non-pegylated]) or relapsers (defined as a participant with undetectable plasma HCV RNA at the end of treatment of previous IFN-based therapy and subsequent confirmed detectable plasma HCV RNA levels during follow-up). (NCT00561353)
Timeframe: Week 4
| Intervention | log10 IU/mL (Mean) |
|---|
| TMC435 75 mg (Cohort 4, Panel C) | -4.28 |
| TMC435 150 mg (Cohort 4, Panel C) | -5.46 |
| TMC435 200 mg (Cohort 4, Panel C) | -5.26 |
| Placebo (Cohort 4, Panel C) | -1.53 |
| TMC435 200 mg (Cohort 5, Panel D) | -5.86 |
Average Steady-state Plasma Concentration (Css,av) of TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D)
The table below shows mean (standard deviation) of Css,av for TMC435 in treatment-experienced HCV-infected participants (non-responders and relapsers, see defined above) at selected time points following treatment with TMC435 coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22. (NCT00561353)
Timeframe: Day 28 (predose and 0.5, 1, 2, 4, 6, 8, and 10 hours postdose)
| Intervention | ng/ml (Mean) |
|---|
| TMC435 75 mg (Cohort 4, Panel C) | 820.8 |
| TMC435 150 mg (Cohort 4, Panel C) | 2435 |
| TMC435 200 mg (Cohort 4, Panel C) | 6353 |
| TMC435 200 mg (Cohort 5, Panel D) | 9613 |
Average Steady-state Plasma Concentration (Css,av) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B)
"The table below shows mean (standard deviation)of Css,av for TMC435 in treatment-naïve HCV-infected participants at selected time points administered TMC435 for 7 days followed by TMC435 coadministered with ribavirin for 21 days + peginterferon alpha-2a (PegIFNα-2a) on Days 8, 15, and 22 (Panel A) and with TMC435 coadministered with ribavirin for 28 days + PegIFNα-2a on Days 1, 8, 15, and 22 (Panel B). See treatment-naïve defined above. The number of participants analyzed at Day 28 in the 6 treatment groups listed below from left to right were 9, 8, 7, 9, 9, and 10." (NCT00561353)
Timeframe: Day 7 (predose); Day 28 (predose and 0.5, 1, 2, 4, 6, 8, and 10 hours postdose) (Panel A, Cohorts 1 and 2) and Day 28 (predose and 0.5, 1, 2, 4, 6, 8, and 10 hours postdose) (Panel B, Cohorts 1 and 2)
| Intervention | ng/ml (Mean) |
|---|
| Day 7 | Day 28 |
|---|
| TMC435 200 mg (Cohort 2, Panel B) | NA | 7182 |
,| TMC435 25 mg (Cohort 1, Panel A) | 180.9 | 170.4 |
,| TMC435 25 mg (Cohort 1, Panel B) | NA | 186.5 |
,| TMC435 75 mg (Cohort 1, Panel A) | 832.3 | 681.4 |
,| TMC435 75 mg (Cohort 1, Panel B) | NA | 986.0 |
,| TTMC435 200 mg (Cohort 2, Panel A) | 5714 | 7117 |
Initial Suboptimal Responses Following Treatment With TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A)
"The table below shows the number of treatment-naïve participants with an initial suboptimal response defined as less than 2 log10 change in plasma level of hepatitis C virus (HCV) ribonucleic acid (RNA) on Day 2 or 3 (depending when visit was scheduled) following treatment with TMC435 or placebo for 7 days followed by TMC435 or placebo coadministered with ribavirin for 21 days + peginterferon alpha-2a (PegIFNα-2a) on Days 8, 15, and 22. See treatment-naive defined above." (NCT00561353)
Timeframe: Day 2 or 3
| Intervention | Participants (Number) |
|---|
| TMC435 25 mg (Cohort 1, Panel A) | 3 |
| TMC435 75 mg (Cohort 1, Panel A) | 1 |
| Placebo (Cohort 1, Panel A) | 6 |
| TMC435 200 mg (Cohort 2, Panel A) | 0 |
| Placebo (Cohort 2, Panel A) | 3 |
Maximum Plasma Concentration (Cmax) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B)
"The table below shows the mean (standard deviation) Cmax for treatment-naïve participants at selected time points who were treated with TMC435 for 7 days followed by TMC435 coadministered with ribavirin for 21 days + peginterferon alpha-2a (PegIFNα-2a) on Days 8, 15, and 22 (Panel A) and with TMC435 coadministered with ribavirin for 28 days + PegIFNα-2a on Days 1, 8, 15, and 22 (Panel B). See treatment-naïve defined above. The number of participants analyzed at Day 28 in the 6 treatment groups listed below from left to right were 9, 8, 7, 9, 9, and 10." (NCT00561353)
Timeframe: Days 1 and 28 (predose and 0.5, 1, 2, 4, 6, 8, and 10 hours postdose)
| Intervention | ng/mL (Mean) |
|---|
| Day 1 | Day 28 |
|---|
| TMC435 200 mg (Cohort 2, Panel A) | 3369 | 11180 |
,| TMC435 200 mg (Cohort 2, Panel B) | 3945 | 10900 |
,| TMC435 25 mg (Cohort 1, Panel A) | 251.1 | 307.1 |
,| TMC435 25 mg (Cohort 1, Panel B) | 239.6 | 329.4 |
,| TMC435 75 mg (Cohort 1, Panel A) | 1008 | 1058 |
,| TMC435 75 mg (Cohort 1, Panel B) | 958.0 | 1609 |
Predose Plasma Concentration (C0h) of TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D)
The table below shows mean (standard deviation) of C0h for treatment-experienced participants (non-responders and relapsers, see defined above) following treatment with TMC435 coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22. The number of participants analyzed at Day 2 and Day 28 differed as follows: At Day 2, the number of participants in the 4 treatment groups (from left to right) were 8, 7, 10, and 5; the number of participants analyzed at Day 28 in the 4 treatment groups (from left to right) were 9, 8, 10, and 4. (NCT00561353)
Timeframe: Day 2 (predose) and Day 28 (predose and 0.5, 1, 2, 4, 6, 8, and 10 hours postdose)
| Intervention | ng/mL (Mean) |
|---|
| Day 2 | Day 28 |
|---|
| TMC435 150 mg (Cohort 4, Panel C) | 733.6 | 1431 |
,| TMC435 200 mg (Cohort 4, Panel C) | 669.8 | 4145 |
,| TMC435 200 mg (Cohort 5, Panel D) | 1280 | 5593 |
,| TMC435 75 mg (Cohort 4, Panel C) | 278.4 | 324.3 |
Predose Plasma Concentration (C0h) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B)
"The table below shows mean (standard deviation) of C0h of TMC435 at selected time points following treatment with TMC435 for 7 days followed by TMC435 coadministered with ribavirin for 21 days + peginterferon alpha-2a (PegIFNα-2a) on Days 8, 15, and 22 (Panel A) or with TMC435 coadministered with ribavirin for 28 days + PegIFNα-2a on Days 1, 8, 15, and 22 (Panel B) in treatment-naïve participants (see treatment-naïve defined above).The number of participants analyzed at Day 28 in the 6 treatment groups listed below from left to right were 9, 9, 8, 9, 9, and 10." (NCT00561353)
Timeframe: Day 2 (predose) and Day 28 (predose and 0.5, 1, 2, 4, 6, 8, and 10 hours postdose)
| Intervention | ng/ml (Mean) |
|---|
| Day 2 | Day 28 |
|---|
| TMC435 200 mg (Cohort 2, Panel A) | 1053 | 6913 |
,| TMC435 200 mg (Cohort 2, Panel B) | 821.7 | 4818 |
,| TMC435 25 mg (Cohort 1, Panel A) | 64.51 | 64.78 |
,| TMC435 25 mg (Cohort 1, Panel B) | 65.73 | 95.83 |
,| TMC435 75 mg (Cohort 1, Panel A) | 209.3 | 331.6 |
,| TMC435 75 mg (Cohort 1, Panel B) | 281.6 | 632.8 |
Sustained Virologic Response (SVR) in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D)
The table below shows the number of treatment-experienced participants (non-responders and relapsers, see defined above) in each treatment group in Cohort 4, Panel C and in Cohort 5, Panel D with an SVR to treatment defined as having an undetectable plasma level of HCV ribonucleic acid after the last planned dose of the entire treatment regimen. SVR was measured at 4, 8, 12, and 24 weeks after the last dose of treatment (SVR4, SVR8, SVR12, and SVR24, respectively). (NCT00561353)
Timeframe: SVR4 (Week 52), SVR8 (Week 56), SVR12 (Week 60), and SVR24 (Week 72)
| Intervention | Participants (Number) |
|---|
| SVR4 | SVR8 | SVR12 | SVR24 |
|---|
| Placebo (TMC435 75/150/200 mg) (Cohort 4, Panel C) | 1 | 0 | 0 | 0 |
,| TMC435 150 mg (Cohort 4, Panel C) | 3 | 3 | 3 | 3 |
,| TMC435 200 mg (Cohort 4, Panel C) | 4 | 4 | 5 | 5 |
,| TMC435 200 mg (Cohort 5, Panel D) | 3 | 3 | 3 | 3 |
,| TMC435 75 mg (Cohort 4, Panel C) | 2 | 1 | 1 | 1 |
Maximum Plasma Concentration (Cmax) of TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D)
The table below shows the mean (standard deviation) Cmax for treatment-experienced participants (non-responders and relapsers, see defined above) following treatment with TMC435 coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22. The number of participants analyzed at Day 28 in the 4 treatment groups listed below from left to right were 8, 8, 10, and 3. (NCT00561353)
Timeframe: Days 1 and 28 (predose and 0.5, 1, 2, 4, 6, 8, and 10 hours postdose)
| Intervention | ng/mL (Mean) |
|---|
| Day 1 | Day 28 |
|---|
| TMC435 150 mg (Cohort 4, Panel C) | 2422 | 4383 |
,| TMC435 200 mg (Cohort 4, Panel C) | 2877 | 8452 |
,| TMC435 200 mg (Cohort 5, Panel D) | 3870 | 12220 |
,| TMC435 75 mg (Cohort 4, Panel C) | 882.1 | 1481 |
Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) on Day 7 in Treatment-Experienced HCV-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D)
The table below shows the change from Baseline in plasma levels of HCV RNA on Day 7 (Week 1) following treatment with TMC435 or placebo coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22 in treatment-experienced participants considered non-responders (defined as participants who achieved less than a 2 log10 IU/mL decline from baseline in plasma HCV RNA levels after 12 weeks of previous interferon [IFN]-based therapy [pegylated or non-pegylated]) or relapsers (defined as a participant with undetectable plasma HCV RNA at the end of treatment of previous IFN-based therapy and subsequent confirmed detectable plasma HCV RNA levels during follow-up). (NCT00561353)
Timeframe: Day 7
| Intervention | log10 IU/mL (Mean) |
|---|
| TMC435 75 mg (Cohort 4, Panel C) | -3.80 |
| TMC435 150 mg (Cohort 4, Panel C) | -4.68 |
| TMC435 200 mg (Cohort 4, Panel C) | -4.49 |
| Placebo (Cohort 4, Panel C) | -0.50 |
| TMC435 200 mg (Cohort 5, Panel D) | -4.08 |
Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) on Day 7 in Treatment-Naïve HCV-Infected Participants (Cohort 1 and 2, Panel A)
The table below shows the change from Baseline in plasma levels of HCV RNA on Day 7 (at Week 1) following treatment with TMC435 or placebo for 7 days followed by TMC435 or placebo coadministered with ribavirin for 21 days + peginterferon alpha-2a (PegIFNα-2a) on Days 8, 15, and 22 in treatment-naïve HCV-infected participants. (A treatment-naive participant is someone who has never taken drugs for their HCV infection). (NCT00561353)
Timeframe: Day 7
| Intervention | log10 IU/mL (Mean) |
|---|
| TMC435 25 mg (Cohort 1, Panel A) | -2.63 |
| TMC435 75 mg (Cohort 1, Panel A) | -3.48 |
| Placebo (Cohort 1, Panel A) | -0.08 |
| TMC435 200 mg (Cohort 2, Panel A) | -4.18 |
| Placebo (Cohort 2, Panel A) | 0.30 |
Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) on Day 7 in Treatment-Naïve HCV-Infected Participants (Cohort 1 and 2, Panel B)
The table below shows the change from Baseline in plasma levels of HCV RNA on Day 7 (at Week 1) following treatment with TMC435 or placebo coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22 in treatment-naïve HCV-infected participants (A treatment-naive participant is someone who has never taken drugs for their HCV infection). (NCT00561353)
Timeframe: Day 7
| Intervention | log10 IU/mL (Mean) |
|---|
| TMC435 25 mg (Cohort 1, Panel B) | -3.47 |
| TMC435 75 mg (Cohort 1, Panel B) | -4.55 |
| Placebo (Cohort 1, Panel B) | -1.73 |
| TMC435 200 mg (Cohort 2, Panel B) | -4.68 |
| Placebo (Cohort 2, Panel B) | -1.64 |
Initial Suboptimal Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D)
The table below shows the number of treatment-experienced participants (non-responders and relapsers, see defined above) with an initial suboptimal response defined as less than 2 log10 change of plasma in plasma level of HCV ribonucleic acid (RNA) at Day 2 or 3 (depending when visit was scheduled) treated with TMC435 or placebo coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22. (NCT00561353)
Timeframe: Day 2 or 3
| Intervention | Participants (Number) |
|---|
| TMC435 75 mg (Cohort 4, Panel C) | 1 |
| TMC435 150 mg (Cohort 4, Panel C) | 0 |
| TMC435 200 mg (Cohort 4, Panel C) | 0 |
| Placebo (Cohort 4, Panel C) | 8 |
| TMC435 200 mg (Cohort 5, Panel D) | 1 |
Initial Suboptimal Responses Following Treatment With TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B)
"The table below shows the number of treatment-naïve participants with an initial suboptimal response defined as less than 2 log10 change in plasma plasma level of hepatitis C virus (HCV) ribonucleic acid (RNA) on Day 2 or 3 (depending when visit was scheduled) after treatment with TMC435 or placebo coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22. See treatment-naive defined above." (NCT00561353)
Timeframe: Day 2 or 3
| Intervention | Participants (Number) |
|---|
| TMC435 25 mg (Cohort 1, Panel B) | 2 |
| TMC435 75 mg (Cohort 1, Panel B) | 0 |
| Placebo (Cohort 1, Panel B) | 5 |
| TMC435 200 mg (Cohort 2, Panel B) | 0 |
| Placebo (Cohort 2, Panel B) | 1 |
Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B)
The table below shows mean (standard deviation) values of the area under the plasma concentration-time curve from time of administration to 24 hours after dosing for TMC435 in treatment-naïve HCV-infected participants administered TMC435 for 7 days followed by TMC435 coadministered with ribavirin for 21 days + peginterferon alpha-2a (PegIFNα-2a) on Days 8, 15, and 22 (Panel A) and with TMC435 coadministered with ribavirin for 28 days + PegIFNα-2a on Days 1, 8, 15, and 22 (Panel B).The number of participants analyzed at Day 28 in the 6 treatment groups listed below from left to right were 9, 8, 7, 9, 9, and 10. (NCT00561353)
Timeframe: Days 1 and 28 (predose and 0.5, 1, 2, 4, 6, 8, and 10 hours postdose)
| Intervention | ng.h/mL (Mean) |
|---|
| Day 1 | Day 28 |
|---|
| TMC435 200 mg (Cohort 2, Panel A) | 43430 | 167200 |
,| TMC435 200 mg (Cohort 2, Panel B) | 45700 | 169400 |
,| TMC435 25 mg (Cohort 1, Panel A) | 3035 | 3961 |
,| TMC435 25 mg (Cohort 1, Panel B) | 2853 | 4527 |
,| TMC435 75 mg (Cohort 1, Panel A) | 12240 | 16600 |
,| TMC435 75 mg (Cohort 1, Panel B) | 12790 | 23610 |
Area Under the Plasma Concentration-time Curve From Time of Administration up to the Last Time Point With a Measurable Concentration After Dosing (AUClast) of TMC435
The table below shows the area under the plasma concentration-time curve from time of administration up to the last time point with a measurable concentration after dosing (AUClast) on Day 7 for TMC435 by genotype of hepatitis C virus infection. (NCT00812331)
Timeframe: Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7
| Intervention | ng*h/mL (Median) |
|---|
| Genotype 2 | 268000 |
| Genotype 3 | 111500 |
| Genotype 4 | 365500 |
| Genotype 5 | 360000 |
| Genotype 6 | 411100 |
Number of Participants With Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels Below the Limit of Quantification (Less Than 25 IU/mL) and Limit of Detection (Less Than 25 IU/mL Undetectable) During the TMC435 Treatment Period
The table below shows the number of participants with plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels below limit of quantification (less than 25 IU/mL) and limit of detection (less than 25 IU/mL undetectable), respectively, during the 7-day TMC435 treatment period. (NCT00812331)
Timeframe: Baseline, Day 3, Day 5 and Day 7
| Intervention | Participants (Number) |
|---|
| Day 3 (less than 25 IU/mL) | Day 3 (less than 25 IU/mL undetectable) | Day 5 (less than 25 IU/mL) | Day 5 (less than 25 IU/mL undetectable) | Day 7 (less than 25 IU/mL) | Day 7 (less than 25 IU/mL undetectable) |
|---|
| Genotype 2 | 0 | 0 | 0 | 0 | 0 | 0 |
,| Genotype 3 | 0 | 0 | 0 | 0 | 0 | 0 |
,| Genotype 4 | 0 | 0 | 2 | 1 | 3 | 0 |
,| Genotype 5 | 0 | 0 | 0 | 0 | 0 | 0 |
,| Genotype 6 | 0 | 0 | 1 | 0 | 1 | 0 |
Change From Baseline in log10 Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels
The table below shows the mean changes from baseline in HCV RNA values (log10 IU/mL) per genotype on Day 3 and Day 7 during the TMC435 treatment period. (NCT00812331)
Timeframe: Baseline, Day 3, and Day 7
| Intervention | log10 IU/mL (Mean) |
|---|
| Day 3 | Day 7 |
|---|
| Genotype 2 | -2.02 | -2.46 |
,| Genotype 3 | 0.16 | -0.13 |
,| Genotype 4 | -3.43 | -3.66 |
,| Genotype 5 | -2.71 | -2.43 |
,| Genotype 6 | -3.57 | -4.40 |
Time to Reach the Maximum Plasma Concentration (Tmax) of TMC435
The table below shows the median time in hours for all participants (by genotype of hepatitis C virus infection) to reach the maximum plasma concentration (tmax) of TMC435 following treatment. (NCT00812331)
Timeframe: Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7
| Intervention | hours (Median) |
|---|
| Genotype 2 | 4.01 |
| Genotype 3 | 6.025 |
| Genotype 4 | 6.04 |
| Genotype 5 | 6.00 |
| Genotype 6 | 6.00 |
Maximum Plasma Concentration (Cmax) of TMC435
The table below shows the median maximum plasma concentration (Cmax) for all participants by genotype of hepatitis C virus infection on Day 7 of the TMC435 treatment period. (NCT00812331)
Timeframe: Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7
| Intervention | ng/mL (Median) |
|---|
| Genotype 2 | 11250 |
| Genotype 3 | 6580 |
| Genotype 4 | 13500 |
| Genotype 5 | 13600 |
| Genotype 6 | 14800 |
Terminal Elimination Half-life (t1/2,Term) of TMC435
The table below shows the terminal plasma half-life for TMC435 in participants analyzed by genotype of hepatitis C virus infection. The terminal plasma half-life of a drug is the time in hours required for the concentration of a drug in the body to fall to 50% after having reached a state of equilibrium following administration. (NCT00812331)
Timeframe: Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7
| Intervention | hours (Median) |
|---|
| Genotype 2 | 13.75 |
| Genotype 3 | 11.51 |
| Genotype 4 | 16.09 |
| Genotype 5 | 18.12 |
| Genotype 6 | 18.32 |
Elimination Rate Constant of TMC435
In the table below, median values for the elimination rate constant (the rate at which a drug is removed from the body expressed per unit of time, e.g., fraction/hour) for TMC435 are shown for participants by genotype of hepatitis C virus infection. (NCT00812331)
Timeframe: Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7
| Intervention | 1/hour (Median) |
|---|
| Genotype 2 | 0.05042 |
| Genotype 3 | 0.06024 |
| Genotype 4 | 0.04308 |
| Genotype 5 | 0.03826 |
| Genotype 6 | 0.03784 |
Average Steady-State Plasma Concentration (Css,av) of TMC435
The table below shows the average steady-state TMC435 plasma concentration (Css,av) for all participants by genotype of hepatitis C virus infection on Day 7 during the TMC435 treatment period. (NCT00812331)
Timeframe: Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7
| Intervention | ng/mL (Median) |
|---|
| Genotype 2 | 7115 |
| Genotype 3 | 3081 |
| Genotype 4 | 8843 |
| Genotype 5 | 7850 |
| Genotype 6 | 9354 |
Fluctuation Index (FI) of TMC435
The table below shows the percentage of fluctuation (FI) (defined as the variation between maximum and minimum TMC435 plasma concentrations at steady-state) of TMC435 on Day 7 for participants by genotype of hepatitis C virus infection. (NCT00812331)
Timeframe: Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7
| Intervention | % fluctuation (Median) |
|---|
| Genotype 2 | 130.2 |
| Genotype 3 | 149.4 |
| Genotype 4 | 95.38 |
| Genotype 5 | 93.12 |
| Genotype 6 | 88.16 |
Area Under the Plasma Concentration-time Curve From the Time of Administration up to 24 Hours After Dosing (AUC24h) of TMC435
The table below shows the area under the plasma concentration-time curve from the time of administration up to 24 hours after dosing (AUC24h) of TMC435 on Day 7 for all participants by genotype of hepatitis C virus infection. (NCT00812331)
Timeframe: Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7
| Intervention | ng*h/mL (Median) |
|---|
| Genotype 2 | 170100 |
| Genotype 3 | 74670 |
| Genotype 4 | 212000 |
| Genotype 5 | 189000 |
| Genotype 6 | 227100 |
Predose Plasma Concentration (C0h) of TMC435
The table below shows the median predose plasma concentration (C0h) for all participants on Day 7 of the TMC435 treatment period. (NCT00812331)
Timeframe: Predose on Day 7
| Intervention | ng/mL (Median) |
|---|
| Genotype 2 | 3720 |
| Genotype 3 | 1310 |
| Genotype 4 | 6270 |
| Genotype 5 | 4650 |
| Genotype 6 | 5440 |
Number of Participants Who Experienced Viral Breakthrough During TMC435 Treatment Period
The table below shows the number of participants who experienced viral breakthrough (defined as an increase greater than 1 log10 IU/mL in plasma level of hepatitis C virus [HCV] ribonucleic acid [RNA] from the lowest level reached, or a HCV RNA level greater than 100 IU/mL in participants who previously had HCV RNA levels undetectable [less than 25 IU/mL undetectable] or not quantifiable [less than 25 IU/mL detectable]) during the 7-day TMC435 treatment period. (NCT00812331)
Timeframe: During the 7-day of TMC435 treatment period
| Intervention | Participants (Number) |
|---|
| Genotype 2 | 0 |
| Genotype 3 | 1 |
| Genotype 4 | 2 |
| Genotype 5 | 3 |
| Genotype 6 | 0 |
Minimum Plasma Concentration (Cmin) of TMC435
The table below shows the median minimum plasma concentration (Cmin) for all participants on Day 7 of the TMC435 treatment period. (NCT00812331)
Timeframe: Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7
| Intervention | ng/mL (Median) |
|---|
| Genotype 2 | 3320 |
| Genotype 3 | 1110 |
| Genotype 4 | 5450 |
| Genotype 5 | 4230 |
| Genotype 6 | 4960 |
Number of Participants With a Decrease From Baseline of Greater Than or Equal to 2 log10 IU/mL in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) During the TMC435 Treatment Period
The table below shows the number of participants with a decrease from baseline of greater than or equal to 2 log10 IU/mL in HCV RNA during the 7-day TMC435 treatment period. (NCT00812331)
Timeframe: Baseline, Day 3, Day 5 and Day 7
| Intervention | Participants (Number) |
|---|
| Day 3 | Day 5 | Day 7 |
|---|
| Genotype 2 | 3 | 3 | 3 |
,| Genotype 3 | 0 | 0 | 0 |
,| Genotype 4 | 8 | 8 | 8 |
,| Genotype 5 | 6 | 5 | 5 |
,| Genotype 6 | 8 | 8 | 8 |
Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24h) for TMC435
The table below shows the median (range) AUC24h values for TMC435 for participants in each of the 4 TMC435 treatment groups. Two blood samples taken at least 2 hours apart from each other for determination of TMC435 plasma pharmacokinetics were obtained in all participants on Weeks 2, 4, 8, 12, 16, and 24 to obtain Bayesian estimates of TMC435 AUC24h (overall exposure). (NCT00882908)
Timeframe: Two random blood samples taken at least 2 hours apart at Weeks 2, 4, 8, 12, 16, and 24
| Intervention | ng*h/mL (Median) |
|---|
| TMC435 75 mg 12 Wks + PR 24/48 | 9926.4 |
| TMC435 75 mg 24 Wks + PR 24/48 | 8976.8 |
| TMC435 150 mg 12 Wks + PR 24/48 | 39884.0 |
| TMC435 150 mg 24 Wks + PR 24/48 | 36038.8 |
The Number of Participants With Abnormal Alanine Aminotransferase (ALT) Levels at Baseline Who Achieved Normalized ALT Levels at the End of Treatment (EOT)
The table below shows the number of participants with abnormal ALT levels at Baseline who achieved ALT levels within the normal range at the EOT. (NCT00882908)
Timeframe: Baseline (Day 1) up to Week 24 or 48
| Intervention | Participants (Number) |
|---|
| TMC435 75 mg 12 Wks + PR 24/48 | 39 |
| TMC435 75 mg 24 Wks + PR 24/48 | 37 |
| TMC435 150 mg 12 Wks + PR 24/48 | 39 |
| TMC435 150 mg 24 Wks + PR 24/48 | 35 |
| All TMC435 Treatment Groups | 150 |
The Number of Participants With Viral Relapse
The table below shows the number of participants who experienced viral relapse, defined as a confirmed detectable plasma Hepatitis C virus (HCV) ribonucleic acid (RNA) level during the follow-up period in participants with undetectable plasma HCV RNA (less than 25 IU/mL undetectable) at the end of treatment. (NCT00882908)
Timeframe: Up to Week 72
| Intervention | Participants (Number) |
|---|
| TMC435 75 mg 12 Wks + PR 24/48 | 8 |
| TMC435 75 mg 24 Wks + PR 24/48 | 14 |
| TMC435 150 mg 12 Wks + PR 24/48 | 6 |
| TMC435 150 mg 24 Wks + PR 24/48 | 6 |
| Placebo 24 Wks + PR48 | 11 |
The Percentage of Participants Achieving a Complete Early Virologic Response (cEVR)
The table below shows the percentage of participants in each treatment group who had a cEVR, defined as having undetectable plasma Hepatitis C Virus ribonucleic acid levels at Week 12. (NCT00882908)
Timeframe: Week 12
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 75 mg 12 Wks + PR 24/48 | 91.0 |
| TMC435 75 mg 24 Wks + PR 24/48 | 93.3 |
| TMC435 150 mg 12 Wks + PR 24/48 | 93.5 |
| TMC435 150 mg 24 Wks + PR 24/48 | 94.9 |
| Placebo 24 Wks + PR48 | 55.8 |
The Percentage of Participants Achieving a Rapid Virologic Response (RVR)
The table below shows the percentage of participants in each treatment group who achieved a RVR, defined as having undetectable plasma Hepatitis C virus ribonucleic acid levels after receiving 4 weeks of treatment. (NCT00882908)
Timeframe: Week 4
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 75 mg 12 Wks + PR 24/48 | 75.6 |
| TMC435 75 mg 24 Wks + PR 24/48 | 68.0 |
| TMC435 150 mg 12 Wks + PR 24/48 | 75.3 |
| TMC435 150 mg 24 Wks + PR 24/48 | 74.7 |
| Placebo 24 Wks + PR48 | 5.2 |
The Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12)
The table below shows the percentage of participants who achieved undetectable plasma Hepatitis C virus ribonucleic acid levels at the end of treatment (EOT) and 12 Weeks after the EOT. (NCT00882908)
Timeframe: Up to Week 36 or 52
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 75 mg 12 Wks + PR 24/48 | 83.3 |
| TMC435 75 mg 24 Wks + PR 24/48 | 76.0 |
| TMC435 150 mg 12 Wks + PR 24/48 | 80.5 |
| TMC435 150 mg 24 Wks + PR 24/48 | 86.1 |
| Placebo 24 Wks + PR48 | 66.2 |
The Percentage of Participants Achieving a Sustained Virologic Response at Week 72 (SVRW72)
The table below shows the percentage of participants in each treatment group who achieved a SVRW72, defined as the percentage of participants with undetectable plasma Hepatitis C virus ribonucleic acid levels at end of treatment (EOT) and at Week 72. (NCT00882908)
Timeframe: Week 72
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 75 mg 12 Wks + PR 24/48 | 80.8 |
| TMC435 75 mg 24 Wks + PR 24/48 | 70.7 |
| TMC435 150 mg 12 Wks + PR 24/48 | 77.9 |
| TMC435 150 mg 24 Wks + PR 24/48 | 84.8 |
| Placebo 24 Wks + PR48 | 64.9 |
The Percentage of Participants Achieving an Early Virologic Response (EVR)
The table below shows the percentage of participants who achieved an EVR, defined as having a change from baseline in plasma Hepatitis C virus ribonucleic acid of 2 log10 at Week 12. (NCT00882908)
Timeframe: Baseline (Day 1) and Week 12
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 75 mg 12 Wks + PR 24/48 | 97.4 |
| TMC435 75 mg 24 Wks + PR 24/48 | 96.0 |
| TMC435 150 mg 12 Wks + PR 24/48 | 96.1 |
| TMC435 150 mg 24 Wks + PR 24/48 | 96.2 |
| Placebo 24 Wks + PR48 | 89.6 |
The Percentage of Participants Who Achieved a Sustained Virologic Response 24 Weeks After the Planned End of Treatment (SVR24)
The table below shows the percentage of participants in each treatment group who achieved a SVR24, defined as having undetectable plasma Hepatitis C virus ribonucleic acid levels at the end of treatment (EOT) and 24 weeks after the EOT. (NCT00882908)
Timeframe: Week 48 or 72
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 75 mg 12 Wks + PR 24/48 | 82.1 |
| TMC435 75 mg 24 Wks + PR 24/48 | 74.7 |
| TMC435 150 mg 12 Wks + PR 24/48 | 80.5 |
| TMC435 150 mg 24 Wks + PR 24/48 | 86.1 |
| Placebo 24 Wks + PR48 | 64.9 |
Plasma Concentrations of TMC435
The table below shows median (range) predose plasma concentration (C0h) values and median (range) average steady-state plasma concentration (Css,av) values for participants in each of the 4 TMC435 treatment groups. (NCT00882908)
Timeframe: Two random blood samples taken at least 2 hours apart at Weeks 2, 4, 8, 12, 16, and 24
| Intervention | ng/mL (Median) |
|---|
| Coh | Css, av |
|---|
| TMC435 150 mg 12 Wks + PR 24/48 | 1123.3 | 1661.8 |
,| TMC435 150 mg 24 Wks + PR 24/48 | 1176.7 | 1501.6 |
,| TMC435 75 mg 12 Wks + PR 24/48 | 240.9 | 413.6 |
,| TMC435 75 mg 24 Wks + PR 24/48 | 213.6 | 374.0 |
The Percentage of Participants Achieving Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels of Greater Than or Equal to 2 log10 Drop During Treatment
The table below shows the percentage of participants in each treatment group who achieved plasma levels of HCV RNA greater than or equal to 2 log10 drop from Baseline at selected time points during treatment. (NCT00882908)
Timeframe: Baseline (Day 1) and Weeks, 2, 4, 8, and 12
| Intervention | Percentage of participants (Number) |
|---|
| Week 2 | Week 4 | Week 8 | Week 12 |
|---|
| Placebo 24 Wks + PR48 | 40.3 | 71.4 | 84.4 | 89.6 |
,| TMC435 150 mg 12 Wks + PR 24/48 | 97.4 | 97.4 | 97.4 | 96.1 |
,| TMC435 150 mg 24 Wks + PR 24/48 | 98.7 | 93.7 | 94.9 | 96.2 |
,| TMC435 75 mg 12 Wks + PR 24/48 | 93.6 | 94.9 | 97.4 | 97.4 |
,| TMC435 75 mg 24 Wks + PR 24/48 | 98.7 | 98.7 | 97.3 | 96.0 |
The Percentage of Participants Achieving Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels of Less Than 25 IU/mL Undetectable During Treatment and Follow-up
The table below shows the percentage of participants in each treatment group who achieved plasma HCV RNA levels of less than 25 IU/mL undetectable at selected time points during treatment, follow-up, and at end of treatment (EOT). (NCT00882908)
Timeframe: Weeks, 2, 4, 8, 12, 24, 36, 48, 60, 72, and at EOT (up to Week 24 or 48)
| Intervention | Percentage of participants (Number) |
|---|
| Week 2 | Week 4 | Week 8 | Week 12 | Week 24 | Week 36 | Week 48 | Week 60 | Week 72 | EOT (up to Week 24 or 48) |
|---|
| Placebo 24 Wks + PR48 | 2.6 | 5.2 | 26.0 | 55.8 | 77.9 | 76.6 | 74.0 | 63.6 | 64.9 | 79.2 |
,| TMC435 150 mg 12 Wks + PR 24/48 | 23.4 | 75.3 | 92.2 | 93.5 | 84.4 | 81.8 | 79.2 | 75.3 | 77.9 | 92.2 |
,| TMC435 150 mg 24 Wks + PR 24/48 | 39.2 | 74.7 | 93.7 | 94.9 | 87.3 | 84.8 | 82.3 | 83.5 | 82.3 | 93.7 |
,| TMC435 75 mg 12 Wks + PR 24/48 | 39.7 | 75.6 | 87.2 | 91.0 | 92.3 | 85.9 | 79.5 | 79.5 | 79.5 | 92.3 |
,| TMC435 75 mg 24 Wks + PR 24/48 | 30.7 | 68.0 | 90.7 | 93.3 | 93.3 | 81.3 | 77.3 | 68.0 | 70.7 | 97.3 |
The Percentage of Participants Who Achieved Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels of Less Than 25 IU/mL Detectable or Undetectable During Treatment and Follow-up
The table below shows the percentage of participants in each treatment group who achieved plasma levels of HCV RNA less than 25 IU/mL detectable or undetectable at selected time points during treatment, follow-up, and at end of treatment (EOT). (NCT00882908)
Timeframe: Weeks 2, 4, 8, 12, 24, 36, 48, 60, 72, and at EOT (up to Week 24 or 48)
| Intervention | Percentage of participants (Number) |
|---|
| Week 2 | Week 4 | Week 8 | Week 12 | Week 24 | Week 36 | Week 48 | Week 60 | Week 72 | EOT (up to Week 24 or 48) |
|---|
| Placebo 24 Wks + PR48 | 5.2 | 15.6 | 49.4 | 66.2 | 80.5 | 79.2 | 75.3 | 64.9 | 64.9 | 83.1 |
,| TMC435 150 mg 12 Wks + PR 24/48 | 75.3 | 90.9 | 93.5 | 96.1 | 84.4 | 81.8 | 79.2 | 75.3 | 77.9 | 92.2 |
,| TMC435 150 mg 24 Wks + PR 24/48 | 78.5 | 91.1 | 93.7 | 94.9 | 89.9 | 84.8 | 82.3 | 83.5 | 83.5 | 96.2 |
,| TMC435 75 mg 12 Wks + PR 24/48 | 65.4 | 85.9 | 93.6 | 93.6 | 92.3 | 85.9 | 79.5 | 79.5 | 79.5 | 93.6 |
,| TMC435 75 mg 24 Wks + PR 24/48 | 66.7 | 88.0 | 94.7 | 94.7 | 93.3 | 81.3 | 77.3 | 68.0 | 70.7 | 97.3 |
Number of Participants With Viral Breakthrough
The table below shows the number of participants in each treatment group who experienced viral breakthrough during the TMC435 treatment period of the study, defined as a confirmed increase of more than 1 log10 IU/mL in plasma Hepatitis C virus (HCV) ribonucleic acid (RNA) level from the lowest level reached or a confirmed value of plasma HCV RNA more than 100 IU/mL in participants whose plasma HCV RNA level had previously been below the limit of quantification (less than 25 IU/mL detectable or undetectable). (NCT00882908)
Timeframe: Week 24 or 48
| Intervention | Participants (Number) |
|---|
| TMC435 75 mg 12 Wks + PR 24/48 | 5 |
| TMC435 75 mg 24 Wks + PR 24/48 | 2 |
| TMC435 150 mg 12 Wks + PR 24/48 | 6 |
| TMC435 150 mg 24 Wks + PR 24/48 | 2 |
| Placebo 24 Wks + PR48 | 4 |
The Percentage of Participants Achieving a Complete Early Virologic Response (cEVR)
The table below shows the percentage of participants in each treatment group who had a cEVR, defined as having undetectable plasma levels of Hepatitis C virus ribonucleic acid at Week 12. (NCT00980330)
Timeframe: Week 12
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 100mg 12 Wks + PR48 | 81.8 |
| TMC435 100mg 24 Wks + PR48 | 73.8 |
| TMC435 100mg 48 Wks + PR48 | 72.7 |
| TMC435 150mg 12 Wks + PR48 | 80.3 |
| TMC435 150mg 24 Wks + PR48 | 85.3 |
| TMC435 150mg 48 Wks + PR48 | 83.1 |
| Placebo 48Wks + PR48 | 19.7 |
The Percentage of Participants Achieving a Rapid Virologic Response (RVR)
The table below shows the percentage of participants in each treatment group who achieved a RVR, defined as having an undetectable plasma Hepatitis C virus ribonucleic acid level after receiving 4 weeks of treatment. (NCT00980330)
Timeframe: Week 4
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 100mg 12 Wks + PR48 | 66.7 |
| TMC435 100mg 24 Wks + PR48 | 58.5 |
| TMC435 100mg 48 Wks + PR48 | 53.0 |
| TMC435 150mg 12 Wks + PR48 | 62.1 |
| TMC435 150mg 24 Wks + PR48 | 67.6 |
| TMC435 150mg 48 Wks + PR48 | 66.2 |
| Placebo 48Wks + PR48 | 1.5 |
The Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12)
The table below shows the percentage of participants in the overall population who achieved undetectable plasma Hepatitis C virus ribonucleic acid levels at the end of treatment (EOT) and 12 Weeks after the planned EOT. (NCT00980330)
Timeframe: Week 60
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 100mg 12 Wks + PR48 | 69.7 |
| TMC435 100mg 24 Wks + PR48 | 67.7 |
| TMC435 100mg 48 Wks + PR48 | 60.6 |
| TMC435 150mg 12 Wks + PR48 | 66.7 |
| TMC435 150mg 24 Wks + PR48 | 72.1 |
| TMC435 150mg 48 Wks + PR48 | 80.0 |
| Placebo 48Wks + PR48 | 22.7 |
The Percentage of Participants Achieving Plasma Levels of Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Undetectable During Treatment and Follow-up
The table below shows the percentage of participants in each treatment who achieved plasma HCV RNA levels of <25 IU/mL undetectable at selected time points during treatment and follow-up and at the end of treatment (EOT). (NCT00980330)
Timeframe: Weeks, 2, 4, 8, 12, 24, 36, 48, 60, 72 and EOT (up to Week 48)
| Intervention | Percentage of participants (Number) |
|---|
| Week 2 | Week 4 | Week 8 | Week 12 | Week 24 | Week 36 | Week 48 | Week 60 | Week 72 | EOT (up to Week 48) |
|---|
| Placebo 48Wks + PR48 | 0.0 | 1.5 | 7.6 | 19.7 | 42.4 | 39.4 | 37.9 | 22.7 | 22.7 | 40.9 |
,| TMC435 100mg 12 Wks + PR48 | 22.7 | 66.7 | 77.3 | 81.8 | 81.8 | 78.8 | 81.8 | 69.7 | 69.7 | 80.3 |
,| TMC435 100mg 24 Wks + PR48 | 18.5 | 58.5 | 75.4 | 73.8 | 75.4 | 73.8 | 73.8 | 67.7 | 66.2 | 78.5 |
,| TMC435 100mg 48 Wks + PR48 | 15.2 | 53.0 | 77.3 | 72.7 | 78.8 | 78.8 | 74.2 | 59.1 | 60.6 | 80.3 |
,| TMC435 150mg 12 Wks + PR48 | 24.2 | 62.1 | 84.8 | 80.3 | 83.3 | 80.3 | 75.8 | 66.7 | 66.7 | 80.3 |
,| TMC435 150mg 24 Wks + PR48 | 32.4 | 67.6 | 83.8 | 85.3 | 86.8 | 83.8 | 80.9 | 72.1 | 73.5 | 83.8 |
,| TMC435 150mg 48 Wks + PR48 | 27.7 | 66.2 | 83.1 | 83.1 | 86.2 | 81.5 | 81.5 | 76.9 | 80.0 | 86.2 |
The Percentage of Participants Achieving a Sustained Virologic Response at the End of Treatment (EOT) and 24 Weeks After the EOT (SVR24)
The table below shows the percentage of participants in the overall population with an SVR24, defined as having plasma levels of Hepatitis C Virus ribonucleic acid less than 25 IU/mL undetectable at the EOT and 24 weeks after the EOT. (NCT00980330)
Timeframe: Week 72
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 100mg 12 Wks + PR48 | 69.7 |
| TMC435 100mg 24 Wks + PR48 | 66.2 |
| TMC435 100mg 48 Wks + PR48 | 60.6 |
| TMC435 150mg 12 Wks + PR48 | 66.7 |
| TMC435 150mg 24 Wks + PR48 | 72.1 |
| TMC435 150mg 48 Wks + PR48 | 80.0 |
| Placebo 48Wks + PR48 | 22.7 |
The Percentage of Participants Achieving an Early Virologic Response (EVR)
The table below shows the percentage of participants who achieved an EVR, defined as having a greater than or equal to 2 log10 reduction in plasma Hepatitis C virus ribonucleic acid from baseline at Week 12. (NCT00980330)
Timeframe: Week 12
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 100mg 12 Wks + PR48 | 90.9 |
| TMC435 100mg 24 Wks + PR48 | 87.7 |
| TMC435 100mg 48 Wks + PR48 | 84.8 |
| TMC435 150mg 12 Wks + PR48 | 92.4 |
| TMC435 150mg 24 Wks + PR48 | 91.2 |
| TMC435 150mg 48 Wks + PR48 | 92.3 |
| Placebo 48Wks + PR48 | 60.6 |
The Percentage of Participants With Viral Breakthrough
The table below shows the percentage of participants in the overall population in each treatment group during the treatment period who experienced viral breakthrough, defined as a confirmed increase of greater than 1 log10 IU/mL in Hepatitis C virus (HCV) ribonucleic acid (RNA) from the lowest level reached or a confirmed HCV RNA of > 100 IU/mL in participants whose HCV RNA had previously been below the lower limit of quantification (i.e., less than 25 IU/mL detectable or undetectable). (NCT00980330)
Timeframe: EOT (up to Week 48)
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 100mg 12 Wks + PR48 | 10.6 |
| TMC435 100mg 24 Wks + PR48 | 13.8 |
| TMC435 100mg 48 Wks + PR48 | 13.6 |
| TMC435 150mg 12 Wks + PR48 | 9.1 |
| TMC435 150mg 24 Wks + PR48 | 10.3 |
| TMC435 150mg 48 Wks + PR48 | 7.7 |
| Placebo 48Wks + PR48 | 1.5 |
The Percentage of Participants With Viral Relapse
The table below shows the percentage of participants in the overall population who had viral relapse, defined as confirmed detectable Hepatitis C virus (HCV) ribonucleic acid (RNA) during the follow-up period in participants with HCV RNA less than 25 IU/mL undetectable at end of treatment. (NCT00980330)
Timeframe: Up to Week 72
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 100mg 12 Wks + PR48 | 9.3 |
| TMC435 100mg 24 Wks + PR48 | 13.7 |
| TMC435 100mg 48 Wks + PR48 | 18.0 |
| TMC435 150mg 12 Wks + PR48 | 11.8 |
| TMC435 150mg 24 Wks + PR48 | 14.0 |
| TMC435 150mg 48 Wks + PR48 | 5.5 |
| Placebo 48Wks + PR48 | 44.4 |
Plasma Concentrations of TMC435
The table below shows median (range) predose plasma concentration (C0h) values and median (range) average steady-state plasma concentration (Css,av) values for TMC435 for participants in each of the 6 TMC435 treatment groups. (NCT00980330)
Timeframe: 0 (predose, baseline) and 4, 8, 12, and 24 hours post-dose at Weeks 2, 4, 8, 12, 16, 24, and 48
| Intervention | ng/mL (Median) |
|---|
| C0h | Css,av |
|---|
| TMC435 100mg 12 Wks + PR48 | 380.5 | 691.1 |
,| TMC435 100mg 24 Wks + PR48 | 411.3 | 770.5 |
,| TMC435 100mg 48 Wks + PR48 | 529.8 | 892.0 |
,| TMC435 150mg 12 Wks + PR48 | 1323.5 | 1960.9 |
,| TMC435 150mg 24 Wks + PR48 | 1074.0 | 1792.3 |
,| TMC435 150mg 48 Wks + PR48 | 886.1 | 1606.9 |
The Percentage of Participants Achieving Plasma Levels of Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Detectable or Undetectable During Treatment and Follow-up
The table below shows the percentage of participants in each treatment group who achieved plasma HCV RNA levels below the limit of quantification defined as less than 25 IU/mL (detectable or undetectable) at selected time points during treatment, follow-up, and at the end of treatment (EOT). (NCT00980330)
Timeframe: Weeks, 2, 4, 8, 12, 24, 36, 48, 60, 72, and EOT (up to Week 48)
| Intervention | Percentage of Participants (Number) |
|---|
| Week 2 | Week 4 | Week 8 | Week 12 | Week 24 | Week 36 | Week 48 | Week 60 | Week 72 | EOT (up to Week 48) |
|---|
| Placebo 48Wks + PR48 | 3.0 | 3.0 | 12.1 | 34.8 | 50.0 | 43.9 | 40.9 | 22.7 | 22.7 | 47.0 |
,| TMC435 100mg 12 Wks + PR48 | 60.6 | 78.8 | 87.9 | 87.9 | 84.8 | 81.8 | 83.3 | 71.2 | 69.7 | 86.4 |
,| TMC435 100mg 24 Wks + PR48 | 55.4 | 72.3 | 81.5 | 81.5 | 78.5 | 73.8 | 73.8 | 67.7 | 66.2 | 81.5 |
,| TMC435 100mg 48 Wks + PR48 | 54.5 | 81.8 | 84.8 | 83.3 | 80.3 | 78.8 | 74.2 | 60.6 | 60.6 | 81.8 |
,| TMC435 150mg 12 Wks + PR48 | 63.6 | 86.4 | 87.9 | 89.4 | 86.4 | 81.8 | 78.8 | 66.7 | 66.7 | 89.4 |
,| TMC435 150mg 24 Wks + PR48 | 60.3 | 82.4 | 89.7 | 88.2 | 86.8 | 86.8 | 82.4 | 72.1 | 73.5 | 89.7 |
,| TMC435 150mg 48 Wks + PR48 | 66.2 | 86.2 | 87.7 | 89.2 | 89.2 | 84.6 | 81.5 | 78.5 | 80.0 | 89.2 |
The Percentage of Participants With a Greater Than 2 log10 Drop in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels at Time Points During Treatment
The table below shows the percentage of participants in each treatment group who achieved a greater than 2 log10 drop in plasma levels of HCV RNA at selected time points during treatment. (NCT00980330)
Timeframe: Weeks, 2, 4, 8, and 12
| Intervention | Percentage of participants (Number) |
|---|
| Week 2 | Week 4 | Week 8 | Week 12 |
|---|
| Placebo 48Wks + PR48 | 24.2 | 36.4 | 57.6 | 60.6 |
,| TMC435 100mg 12 Wks + PR48 | 97.0 | 92.4 | 92.4 | 90.9 |
,| TMC435 100mg 24 Wks + PR48 | 93.8 | 93.8 | 89.2 | 87.7 |
,| TMC435 100mg 48 Wks + PR48 | 97.0 | 92.4 | 89.4 | 84.8 |
,| TMC435 150mg 12 Wks + PR48 | 100.0 | 97.0 | 93.9 | 92.4 |
,| TMC435 150mg 24 Wks + PR48 | 95.6 | 91.2 | 91.2 | 91.2 |
,| TMC435 150mg 48 Wks + PR48 | 96.9 | 96.9 | 95.4 | 92.3 |
Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24h) for TMC435
The table below shows the median (range) AUC24h values for TMC435 for participants in each TMC435 treatment group. (NCT00980330)
Timeframe: 0 (predose, baseline) and 4, 8, 12, and 24 hours post-dose at Weeks 2, 4, 8, 12, 16, 24, and 48
| Intervention | ng.h/mL (Median) |
|---|
| TMC435 100mg 12 Wks + PR48 | 16587.0 |
| TMC435 100mg 24 Wks + PR48 | 18492.5 |
| TMC435 100mg 48 Wks + PR48 | 21409.0 |
| TMC435 150mg 12 Wks + PR48 | 47061.8 |
| TMC435 150mg 24 Wks + PR48 | 43015.0 |
| TMC435 150mg 48 Wks + PR48 | 38564.5 |
The Number of Participants Who Achieved Normalized Alanine Aminotransferase (ALT) Levels at the End of Treatment (EOT)
The table below shows the number of participants with abnormal ALT levels at Baseline who achieved the normal ALT levels at the EOT (up to Week 48). (NCT00980330)
Timeframe: EOT (up to Week 48)
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 100mg 12 Wks + PR48 | 26 |
| TMC435 100mg 24 Wks + PR48 | 37 |
| TMC435 100mg 48 Wks + PR48 | 31 |
| TMC435 150mg 12 Wks + PR48 | 23 |
| TMC435 150mg 24 Wks + PR48 | 31 |
| TMC435 150mg 48 Wks + PR48 | 33 |
| All TMC435 | 181 |
Time to Reach the Maximum Plasma Concentration (Tmax) of TMC435
"The table below shows the median time in hours to reach the maximum plasma concentration (tmax) of TMC435 for participants in the 2 TMC435 50 mg treatment groups combined (TMC12/PR24 50 mg and TMC24/PR24 50 mg) and for participants in the 2 TMC435 100 mg treatment groups combined (TMC12/PR24 100 mg and TMC24/PR24 100 mg) who had intensive blood samples collected at Weeks 4 to 6. NOTE: All outcome measures reported in this study are Exploratory; not Primary as indicated (refer to Limits and Caveats)." (NCT00996476)
Timeframe: within 15 minutes and at 1, 2, 4, 6, 8, 12, and 24 hours post-dose between Week 4 and Week 6 after the initiation of treatment
| Intervention | Hours (Median) |
|---|
| TMC435 50 mg | 5.97 |
| TMC435 100 mg | 6.00 |
Actual Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Values up to Week 24 in the Post-treatment Follow-up Period
"The table below shows the mean (standard deviation) of the actual HCV RNA values by treatment group at Baseline and Weeks 4, 12, 24, 48, end of treatment (EOT, up to Weeks 24 or 48), Weeks 60 and 72 (Week 24 in the post-treatment follow-up period). The number of participants analyzed is listed at each time point in order of the treatment groups from left to right in the table (ie, Week x, n=x, x, x, x, and x) if different from the Number of Participants Analyzed. NOTE: All outcome measures reported in this study are Exploratory; not Primary as indicated (refer to Limits and Caveats)." (NCT00996476)
Timeframe: Baseline, Week 4, 12, 24, 48, EOT (up to Week 24 or 48), and Weeks 60 and 72
| Intervention | log10 IU/mL (Mean) |
|---|
| Baseline | Week 4 (n=27, 24, 12, 13, and 11) | Week 12 (n=27, 22, 12, 13, and 11) | Week 24 (n=26, 21, 11, 13, and 11) | Week 48 (n=25, 20, 12, 13, and 10) | Week 60 (n=0, 0, 0 ,0, and 9) | Week 72 (n=0, 0, 0 ,0, and 8) | EOT (up to Week 24 or 48) |
|---|
| PR48 Control | 6.10 | 3.38 | 1.84 | 1.42 | 1.11 | 2.90 | 2.70 | 1.28 |
,| TMC12/PR24 100 mg | 6.16 | 0.95 | 0.95 | 0.95 | 1.22 | NA | NA | 0.95 |
,| TMC12/PR24 50 mg | 6.19 | 0.98 | 0.95 | 1.12 | 1.97 | NA | NA | 1.12 |
,| TMC24/PR24 100 mg | 6.43 | 0.97 | 0.95 | 0.95 | 1.29 | NA | NA | 0.95 |
,| TMC24/PR24 50 mg | 6.16 | 0.98 | 0.95 | 0.95 | 1.42 | NA | NA | 1.17 |
Predose Plasma Concentrations (C0h) of TMC435 (Sparse Blood Sampling)
"The table below shows the mean (standard deviation) predose plasma concentration (C0h) for participants in each treatment group at Weeks 4, 12, and 24. The number of participants analyzed is listed at each time point in order of the treatment groups from left to right in the table (ie, Week x, n=x, x, x, x, and x) if different from the Number of Participants Analyzed. NOTE: All outcome measures reported in this study are Exploratory; not Primary as indicated (refer to Limits and Caveats)." (NCT00996476)
Timeframe: Weeks 4, 12, and 24
| Intervention | ng/mL (Mean) |
|---|
| Week 4 (n=20, 22, 10, and 9) | Week 12 (n=26, 20, 12, and 12) | Week 24 (n=0, 0, 10, 10) |
|---|
| TMC12/PR24 100 mg | 1229 | 1483 | NA |
,| TMC12/PR24 50 mg | 238 | 261 | NA |
,| TMC24/PR24 100 mg | 1816 | 2546 | 2204 |
,| TMC24/PR24 50 mg | 194 | 221 | 310 |
The Number of Participants With Alanine Aminotransaminase (ALT) Values Within the Normal Range at the End-of-treatment (EOT)
"The table below shows the number of participants whose ALT results were within the normal range on Day 1 (initial day of treatment), Week 24, 48, and EOT (up to Weeks 24 or 48).The number of participants analyzed is listed at each time point in order of the treatment groups from left to right in the table (ie, Week x, n=x, x, x, x, and x) if different from the Number of Participants Analyzed. NOTE: All outcome measures reported in this study are Exploratory; not Primary as indicated (refer to Limits and Caveats)." (NCT00996476)
Timeframe: Day 1, Weeks 24, 48, and EOT (up to Weeks 24 or 48)
| Intervention | Participants (Number) |
|---|
| Day 1 (n=27, 24, 13, 13, 77, and 11) | Week 24 (n=26, 21, 11, 13, 71, and 11) | Week 48 (n=25, 20, 12, 13, 70, and 10) | EOT (Weeks 24 or 48) |
|---|
| All TMC435 | 44 | 64 | 68 | 71 |
,| PR48 Control | 7 | 8 | 8 | 9 |
,| TMC12/PR24 100 mg | 15 | 18 | 20 | 24 |
,| TMC12/PR24 50 mg | 15 | 24 | 24 | 23 |
,| TMC24/PR24 100 mg | 7 | 11 | 12 | 11 |
,| TMC24/PR24 50 mg | 7 | 11 | 12 | 13 |
The Percentage of Participants With a Decrease of Greater Than or Equal to 2 log10 IU/mL From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Through the Post-treatment Follow-up Period
"The table below shows the percentage of participants in each treatment group with a decrease of greater than (>) or equal (=) to 2 log10 IU/mL from baseline in plasma HCV RNA levels at time points during the treatment period and post treatment follow-up period. The number of participants analyzed is listed at each time point in order of the treatment groups from left to right in the table (ie, Week x, n=x, x, x, x, and x) if different from the Number of Participants Analyzed. NOTE: All outcome measures reported in this study are Exploratory; not Primary as indicated (refer to Limits and Caveats)." (NCT00996476)
Timeframe: Days 1 (4 hr), 1 (8 hr), 3, Weeks 1, 2, 3, 4, 6, 8, 12, 16, 20, 24,28, 36, 42, 48, 52, 60, 72, and EOT (up to Week 24 or 48)
| Intervention | Percentage of participants (Number) |
|---|
| Day 1 (4hr) | Day 1 (8hr) | Day 3 | Week 1 | Week 2 (n=27, 24, 12, 13, and 11) | Week 3 (n=27, 24, 12, 13, and 11) | Week 4 (n=27, 24, 12, 13, and 11) | Week 6 (n=27, 23, 12, 13, and 11) | Week 8 (n=27, 22, 12, 13, and 11) | Week 12 (n=27, 22, 12, 13, and 11) | Week 16 (n=26, 22, 12, 13, and 11) | Week 20 (n=26, 22, 12, 13, and 11) | Week 24 (n=26, 21, 11, 13, and 11) | Week 28 (n=26, 21, 11, 13, and 11) | Week 36 (n=26, 21, 12, 13, and 11) | Week 42 (0, 0, 0, 0, and 10) | Week 48 (25, 20, 12, 13, and 10) | EOT (n=27, 24, 13, 13, and 11) | Week 52 ((n=0, 0, 0, 0, and 9) | Week 60 (0, 0, 0, 0, and 9) | Week 72 (0, 0, 0, 0, and 8) |
|---|
| PR48 Control | NA | NA | 18.2 | 27.3 | 54.5 | 54.5 | 54.5 | 72.7 | 81.8 | 81.8 | 90.9 | 90.9 | 90.9 | 90.9 | 90.9 | 90.0 | 100.0 | 90.9 | 88.9 | 55.6 | 62.5 |
,| TMC12/PR24 100 mg | NA | NA | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 95.5 | 95.5 | 100.0 | 95.2 | 95.2 | NA | 95.0 | 100.0 | NA | NA | NA |
,| TMC12/PR24 50 mg | NA | NA | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 96.2 | 92.3 | 88.5 | NA | 80.0 | 96.3 | NA | NA | NA |
,| TMC24/PR24 100 mg | NA | NA | 92.3 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 92.3 | NA | 92.3 | 100.0 | NA | NA | NA |
,| TMC24/PR24 50 mg | NA | NA | 92.3 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 91.7 | NA | 91.7 | 100.0 | NA | NA | NA |
The Percentage of Participants With Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels Undetectable or Below the Limit of Quantification (<1.2 log10 IU/mL Detectable) During Treatment and During Post Treatment Follow-up
"The table below shows the percentage of participants in each treatment group with plasma HCV RNA levels undetectable or below the limit of quantification (<1.2 log10 IU/mL detectable ) at time points during treatment and post treatment follow-up.The number of participants analyzed is listed at each time point in order of the treatment groups from left to right in the table (ie, Week x, n=x, x, x, x, and x) if different from the Number of Participants Analyzed. NOTE: All outcome measures reported in this study are Exploratory; not Primary as indicated (refer to Limits and Caveats)." (NCT00996476)
Timeframe: Week 4, 12, 24, 36, 48, EOT (up to Week 24 or 48), and Week 60 and 72
| Intervention | Percentage of participants (Number) |
|---|
| Week 4 (n=27, 24,12,13, and 11) | Week 12 (n=27, 22, 12, 13, and 7) | Week 24 (n=26, 21, 11, 13, and 11) | Week 36 (n=26, 21, 11, 12, and 11) | Week 48 (n=25, 20, 12, 13, and 10) | EOT (up to Week 24 or 48) | Week 60 (n=0,0,0,0, and 9) | Week 72 (n=0,0,0,0, and 8) |
|---|
| PR48 Control | 18.2 | 81.8 | 81.8 | 90.9 | 90.0 | 90.9 | 55.6 | 62.5 |
,| TMC12/PR24 100 mg | 100.0 | 100.0 | 100.0 | 90.5 | 95.0 | 100.0 | NA | NA |
,| TMC12/PR24 50 mg | 100.0 | 100.0 | 96.2 | 88.5 | 80.0 | 96.3 | NA | NA |
,| TMC24/PR24 100 mg | 100.0 | 100.0 | 100.0 | 92.3 | 92.3 | 100.0 | NA | NA |
,| TMC24/PR24 50 mg | 100.0 | 100.0 | 100.0 | 91.7 | 83.3 | 100.0 | NA | NA |
The Percentage of Participants With Sustained Virologic Response (SVR)
"The table below shows the percentage of participants with a SVR4, SVR12, and SVR24 defined as undetectable plasma hepatitis C virus (HCV) ribonucleic acid (RNA) at the end of treatment (EOT) (up to Weeks 24 or 48) and at 4, 12, and 24 weeks, respectively, after the last dose of treatment. NOTE: All outcome measures reported in this study are Exploratory; not Primary as indicated (refer to Limits and Caveats)." (NCT00996476)
Timeframe: SVR4 (up to Week 28 or Week 52), SVR12 (up to Weeks 36 or 60), and SVR24 (up to Weeks 48 or 72)
| Intervention | Percentage of participants (Number) |
|---|
| SVR4 (up to Week 28 or 52) | SVR12 (up to Week 36 or 60) | SVR24 (up to Week 48 or 72) |
|---|
| PR48 Control | 63.6 | 45.5 | 45.5 |
,| TMC12/PR24 100 mg | 95.8 | 79.2 | 79.2 |
,| TMC12/PR24 50 mg | 88.9 | 85.2 | 77.8 |
,| TMC24/PR24 100 mg | 92.3 | 92.3 | 92.3 |
,| TMC24/PR24 50 mg | 92.3 | 84.6 | 76.9 |
The Percentage of Participants With Undetectable Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels During the Study
"The table below shows the percentage of participants in each treatment group with undetectable plasma HCV RNA levels at Weeks 4, 12, 24, 48, and end of treatment (EOT, up to Week 24 or 48). The number of participants analyzed is listed at each time point in order of the treatment groups from left to right in the table (ie, Week x, n=x, x, x, x, and x) if different from the Number of Participants Analyzed.NOTE: All outcome measures reported in this study are Exploratory; not Primary as indicated (refer to Limits and Caveats)." (NCT00996476)
Timeframe: Weeks 4, 12, 24 or 48, and EOT (up to Week 24 or 48)
| Intervention | Percentage of participants (Number) |
|---|
| Week 4 (n=27, 24, 12, 13, and 11) | Week 12 (n=27, 22, 12, 13, and 11) | Week 24 (n=26, 21, 11, 13, and 11) | Week 48 (n=25, 20, 12, 13, and 10) | EOT (up to Week 24 or 48) |
|---|
| PR48 Control | 9.1 | 54.45 | 81.8 | 90.0 | 90.9 |
,| TMC12/PR24 100 mg | 100.0 | 100.0 | 100.0 | 95.0 | 100.0 |
,| TMC12/PR24 50 mg | 85.2 | 100.00 | 96.2 | 80.0 | 96.3 |
,| TMC24/PR24 100 mg | 92.3 | 100.0 | 100.0 | 92.3 | 100.0 |
,| TMC24/PR24 50 mg | 83.3 | 100.0 | 100.0 | 83.3 | 92.3 |
The Number of Participants With Viral Breakthrough
"The table below shows the number of participants in each treatment group who experienced viral breakthrough during the 48 week treatment period with at least one study medication (TMC435 or PegIFNα-2a and ribavirin). Viral breakthrough is defined as a confirmed increase of greater than (>) 1 log10 IU/mL in plasma hepatitis C virus (HCV) ribonucleic acid (RNA) level from the lowest level reached or a confirmed value of plasma HCV RNA of > 2.0 log10 IU/mL in participants whose plasma HCV RNA level had previously been reported below 1.2 log10 IU/mL detectable or undetectable during the treatment period. The number of participants analyzed is listed at each time point in order of the treatment groups from left to right in the table (ie, Week x, n=x, x, x, x, and x) if different from the Number of Participants Analyzed. NOTE: All outcome measures reported in this study are Exploratory; not Primary as indicated (refer to Limits and Caveats)." (NCT00996476)
Timeframe: Up to EOT (up to Week 24 or 48)
| Intervention | Participants (Number) |
|---|
| TMC12/PR24 50 mg | 0 |
| TMC12/PR24 100 mg | 0 |
| TMC24/PR24 50 mg | 0 |
| TMC24/PR24 100 mg | 0 |
| PR48 Control | 0 |
The Percentage of Participants With Viral Relapse
"The table below shows the percentage of participants in each treatment group who experienced viral relapse within 12 weeks (ie, at Week 36 or 60) after actual end of treatment (EOT) (up to Week 24 or 48). Viral relapse was defined as confirmed detectable plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels during the post treatment follow-up period at Weeks 36 or 60 in participants with undetectable plasma HCV RNA at EOT. The statistical analysis shows the difference in treatments (ie, each TMC435 group minus PR48 control) in viral relapse. NOTE: All outcome measures reported in this study are Exploratory; not Primary as indicated (refer to Limits and Caveats)." (NCT00996476)
Timeframe: Week 36 or 60
| Intervention | Participants (Number) |
|---|
| TMC12/PR24 50 mg | 15.4 |
| TMC12/PR24 100 mg | 12.5 |
| TMC24/PR24 50 mg | 16.7 |
| TMC24/PR24 100 mg | 7.7 |
| PR48 Control | 40.0 |
The Number of Participants Who Met Virologic Stopping/Continuation Rules and Completed All Study Medications
"The table below shows the number of participants who met response-guided treatment (RGT) stopping criteria in the TMC435 treatment groups. Participants who achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels less than 1.4 log10 IU/mL at Week 4 and had undetectable plasma HCV RNA at Weeks 12, 16 and 20 were to stop all study medication (TMC435, PegIFNα-2a, and ribavirin) at Week 24. All other participants continued PegIFNα-2a and ribavirin until Week 48. NOTE: All outcome measures reported in this study are Exploratory; not Primary as indicated (refer to Limits and Caveats)." (NCT00996476)
Timeframe: Week 24
| Intervention | Participants (Number) |
|---|
| TMC12/PR24 50 mg | 25 |
| TMC12/PR24 100 mg | 22 |
| TMC24/PR24 50 mg | 10 |
| TMC24/PR24 100 mg | 12 |
| PR48 Control | 0 |
The Area Under the Plasma Concentration-time Curve From the Time of Administration up to 24 Hours After Dosing (AUC24) for TMC435
"The table below shows the mean AUC24 of TMC435 for participants in the 2 TMC435 50 mg treatment groups combined (TMC12/PR24 50 mg and TMC24/PR24 50 mg) and for participants in the 2 TMC435 100 mg treatment groups combined (TMC12/PR24 100 mg and TMC24/PR24 100 mg) who had intensive blood samples collected at Weeks 4 to 6. NOTE: All outcome measures reported in this study are Exploratory; not Primary as indicated (refer to Limits and Caveats)." (NCT00996476)
Timeframe: within 15 minutes and at 1, 2, 4, 6, 8, 12, and 24 hours post-dose between Week 4 and Week 6 after the initiation of treatment
| Intervention | ng∙h/mL (Mean) |
|---|
| TMC435 50 mg | 11182 |
| TMC435 100 mg | 60197 |
Predose Plasma Concentrations (C0h) of TMC435 (Intensive Blood Sampling)
"The table below shows the mean predose plasma concentration (C0h) for participants in the 2 TMC435 50 mg treatment groups combined and for participants in the 2 TMC435 100 mg treatment groups combined who had intensive blood samples collected at Weeks 4 to 6. NOTE: All outcome measures reported in this study are Exploratory; not Primary as indicated (refer to Limits and Caveats)." (NCT00996476)
Timeframe: Weeks 4 to 6
| Intervention | ng/mL (Mean) |
|---|
| TMC435 50 mg | 192 |
| TMC435 100 mg | 1732 |
Change in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels From Baseline to Week 4
"The table below shows the least-squares (LS) mean change and 95% confidence intervals (CI) change from baseline at Week 4 in HCV RNA levels for participants in the 2 TMC435 50 mg treatment groups combined (TMC12/PR24 50 mg and TMC24/PR24 50 mg) and for participants in the 2 TMC435 100 mg treatment groups combined (TMC12/PR24 100 mg and TMC24/PR24 100 mg). The statistical analyses show the difference in LS mean change from baseline from the PR48 control group and the 95% CI for each dose group (ie, each TMC435 dose group minus PR48 control). NOTE: All outcome measures reported in this study are Exploratory; not Primary as indicated (refer to Limits and Caveats)." (NCT00996476)
Timeframe: Day 1 (Baseline) and Week 4
| Intervention | log10 IU/mL (Least Squares Mean) |
|---|
| TMC435 50 mg | -5.23 |
| TMC435 100 mg | -5.24 |
| PR48 Control | -2.83 |
The Percentage of Participants Achieving a Rapid Virologic Response (RVR)
The table below shows the percentage of participants in each treatment group who achieved a RVR, defined as having undetectable plasma Hepatitis C virus ribonucleic acid levels after receiving 4 weeks of treatment. (NCT01281839)
Timeframe: Week 4
| Intervention | Percentage of Participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 77.2 |
| PBO 12Wks PR48 | 3.1 |
The Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12)
The table below shows the percentage of participants in each treatment group who achieved a SVR12, defined as the percentage of participants with undetectable plasma Hepatitis C virus ribonucleic acid 12 weeks after planned end of treatment. (NCT01281839)
Timeframe: Week 36 or Week 60
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 79.2 |
| PBO 12Wks PR48 | 36.1 |
The Percentage of Participants Achieving a Sustained Virologic Response at Week 72 (SVRW72)
The table below shows the percentage of participants in each treatment group who achieved a SVRW72, defined as the percentage of participants with undetectable plasma Hepatitis C virus ribonucleic acid levels at end of treatment (EOT) and at Week 72. (NCT01281839)
Timeframe: Week 72
| Intervention | Percentage of Participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 76.5 |
| PBO 12Wks PR48 | 33.8 |
The Percentage of Participants Who Achieved a Sustained Virologic Response 24 Weeks After the Planned End of Treatment (SVR24)
The table below shows the percentage of participants in each treatment group who achieved a SVR24, defined as the percentage of participants with undetectable plasma Hepatitis C virus ribonucleic acid levels 24 weeks after planned end of treatment. (NCT01281839)
Timeframe: Week 48 or Week 72
| Intervention | Percentage of Participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 77.3 |
| PBO 12Wks PR48 | 33.8 |
The Percentage of Participants Who Achieved a Sustained Virologic Response 4 Weeks After the Planned End of Treatment (SVR4)
The table below shows the percentage of participants in each treatment group who achieved a SVR4, defined as the percentage of participants with undetectable plasma Hepatitis C virus ribonucleic acid levels 4 weeks after planned end of treatment. (NCT01281839)
Timeframe: Week 28 or Week 52
| Intervention | Percentage of Participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 88.5 |
| PBO 12Wks PR48 | 48.1 |
The Percentage of Participants Who Completed All Study Treatment at Week 24 Because of the Treatment Duration Rule
The table below shows the percentage of participants in the TMC435 treatment group who met the treatment duration rule (ie, having hepatitis C virus [HCV] ribonucleic acid [RNA] levels <25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA levels at Week 12) and completed treatment with PegIFNα-2a and RBV for 24 weeks. Participants in the TMC435 treatment group not meeting RGT criteria and participants in the placebo group were treated with PegIFNα-2a and RBV treatment for 48 weeks. (NCT01281839)
Timeframe: Week 24
| Intervention | Percentage of Participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 90.0 |
| PBO 12Wks PR48 | 0 |
The Percentage of Participants With <1 log10 Decrease in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) From Baseline at Week 4
The table below shows the percentage of participants in each treatment group with <1 log10 HCV RNA decrease at Week 4. (NCT01281839)
Timeframe: Week 4
| Intervention | Percentage of Participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 0.8 |
| PBO 12Wks PR48 | 9.3 |
The Percentage of Participants With Normalization of Alanine Aminotransferase (ALT)
The percentage of participants analyzed were those with baseline ALT values out of the normal range (ie, 156 of 260 participants in the TMC435 treatment group and 84 of 133 participants in the Placebo group had ALT values at baseline that were out of the normal range.). Normalization of ALT values means that ALT values out of the normal range returned to within the normal range. (NCT01281839)
Timeframe: Up to Week 48
| Intervention | Percentage of Participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 69.9 |
| PBO 12Wks PR48 | 69.0 |
The Percentage of Participants With Null Response
The table below shows the percentage of participants with null response, defined as <2 log10 reduction in Hepatitis C virus ribonucleic acid at Week 12 compared to baseline. (NCT01281839)
Timeframe: Week 12
| Intervention | Percentage of Participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 1.2 |
| PBO 12Wks PR48 | 4.8 |
The Percentage of Participants With On-treatment Failure
The table below shows percentage of participants with on-treatment failure defined as confirmed detectable Hepatitis C virus ribonucleic acid levels at actual end of treatment. (NCT01281839)
Timeframe: Week 48
| Intervention | Percentage of Participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 3.1 |
| PBO 12Wks PR48 | 27.1 |
The Percentage of Participants With Partial Response
The table below shows the percentage of participants with partial response, defined as =>2 log10 reduction in Hepatitis C virus (HCV) ribonucleic acid (RNA) at Week 12 compared to baseline, but not achieving undetectable HCV RNA while on treatment. (NCT01281839)
Timeframe: Week 12
| Intervention | Percentage of Participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 10.5 |
| PBO 12Wks PR48 | 0 |
The Percentage of Participants With Viral Breakthrough
The table below shows the percentage of participants with viral breakthrough, defined as a confirmed increase of greater than 1 log10 IU/mL in plasma Hepatitis C virus (HCV) ribonucleic acid (RNA) level from the lowest level reached (ie, lowest value measured in between baseline and current value), or a confirmed plasma HCV RNA level of greater than 100 IU/mL in participants whose plasma HCV RNA had previously been below the limit of quantification (25 IU/mL detectable) or undetectable (<25 IU/mL undetectable). (NCT01281839)
Timeframe: Up to Week 48
| Intervention | Percentage of Participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 0.0 |
| PBO 12Wks PR48 | 2.3 |
The Percentage of Participants With Viral Relapse
The table below shows the percentage of participants with viral relapse, defined as having confirmed detectable plasma level of Hepatitis C virus (HCV) ribonucleic acid (RNA) during the follow-up period in participants with undetectable plasma HCV RNA (less than 25 IU/mL undetectable) at the end of treatment. (NCT01281839)
Timeframe: Up to Week 72
| Intervention | Percentage of Participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 18.9 |
| PBO 12Wks PR48 | 50.5 |
Time From End-of-treatment to Viral Relapse
The table below shows the mean number of days to viral relapse, defined as participants having confirmed detectable plasma level of Hepatitis C Virus (HCV) ribonucleic acid (RNA) during the follow-up period in participants with undetectable plasma HCV RNA (<25 IU/mL undetectable) at the end of treatment. (NCT01281839)
Timeframe: Up to Week 72
| Intervention | Days (Mean) |
|---|
| TMC435 150mg 12Wks PR24/48 | 284.09 |
| PBO 12Wks PR48 | 115.22 |
Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <100 IU/mL
The table below shows mean time in days to reach HCV RNA levels <100 IU/mL. (NCT01281839)
Timeframe: Up to Week 48
| Intervention | Days (Median) |
|---|
| TMC435 150mg 12Wks PR24/48 | 8 |
| PBO 12Wks PR48 | 85 |
Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <1000 IU/mL
The table below shows mean time in days to reach HCV RNA levels <1000 IU/mL. (NCT01281839)
Timeframe: Up to Week 48
| Intervention | Days (Median) |
|---|
| TMC435 150mg 12Wks PR24/48 | 4 |
| PBO 12Wks PR48 | 57 |
Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Undetectable
The table below shows mean time in days to reach HCV RNA levels <25 IU/mL undetectable or detectable. (NCT01281839)
Timeframe: Up to Week 48
| Intervention | Days (Median) |
|---|
| TMC435 150mg 12Wks PR24/48 | 28 |
| PBO 12Wks PR48 | 141 |
Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Undetectable or Detectable
The table below shows mean time in days to reach HCV RNA levels <25 IU/mL undetectable or detectable. (NCT01281839)
Timeframe: Up to Week 48
| Intervention | Days (Median) |
|---|
| TMC435 150mg 12Wks PR24/48 | 14 |
| PBO 12Wks PR48 | 110 |
Actual Values of log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
The table below shows actual values of log10 HCV RNA levels. From Week 4 onwards, most participants in TMC 435 150mg 12Wks PR24/48 group had plasma HCV RNA levels below the limit of detection of the HCV RNA assay. (NCT01281839)
Timeframe: Day 3, Week 1, Week 4, Week 12, Week 24, and Week 48
| Intervention | log10 IU/mL (Mean) |
|---|
| Day 3 | Week 1 | Week 4 | Week 12 | Week 24 | Week 48 |
|---|
| PBO 12Wks PR48 | 5.445 | 5.376 | 3.838 | 2.005 | 1.108 | 0.995 |
,| TMC435 150mg 12Wks PR24/48 | 2.884 | 1.889 | 1.128 | 1.018 | 0.956 | 0.954 |
Change From Baseline in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
The table below shows change from baseline in log10 HCV RNA levels. (NCT01281839)
Timeframe: Day 3, Week 1, Week 4, Week 12, Week 24, and Week 48
| Intervention | log10 IU/mL (Mean) |
|---|
| Day 3 | Week 1 | Week 4 | Week 12 | Week 24 | Week 48 |
|---|
| PBO 12Wks PR48 | -1.039 | -1.099 | -2.638 | -4.476 | -5.373 | -5.473 |
,| TMC435 150mg 12Wks PR24/48 | -3.537 | -4.535 | -5.295 | -5.404 | -5.449 | -5.635 |
The Percentage of Participants With On-treatment Virologic Response at All Time Points
The table below shows the percentage of participants with HCV ribonucleic acid (RNA plasma levels below the limit of detection (ie, <25 IU/mL undetectable), the percentage of participants with a HCV RNA plasma level below the limit of quantification (ie, less than [<] 25 IU/mL detectable or undetectable), the percentage of participants with plasma levels of HCV RNA <100 IU/mL, the percentage of participants with virologic responses of a greater than or equal to 2 log10 change from baseline in plasma levels of HCV RNA. (NCT01281839)
Timeframe: Day 3, Week 1, Week 2, Week 8, Week 16, Week 20, Week 28, Week 36, and Week 42
| Intervention | Percentage of Participants (Number) |
|---|
| Day 3:<25 IU/mL undetectable | Week 1:<25 IU/mL undetectable | Week 2:<25 IU/mL undetectable | Week 8:<25 IU/mL undetectable | Week 16:<25 IU/mL | Week 20:<25 IU/mL | Week 28:<25 IU/mL | Week 36:<25 IU/mL | Week 42:<25 IU/mL | Day 3:<25 IU/mL undetectable/detectable | Week 1:<25 IU/mL undetectable/detectable | Week 2:<25 IU/mL undetectable/detectable | Week 8:<25 IU/mL undetectable/detectable | Week 16:<25 IU/mL undetectable/detectable | Week 20:<25 IU/mL undetectable/detectable | Week 28:<25 IU/mL undetectable/detectable | Week 36:<25 IU/mL undetectable/detectable | Week 42:<25 IU/mL undetectable/detectable | Day 3:<100 IU/mL | Week 1:<100 IU/mL | Week 2:<100 IU/mL | Week 8:<100 IU/mL | Week 16:<100 IU/mL | Week 20:<100 IU/mL | Week 28:<100 IU/mL | Week 36:<100 IU/mL | Week 42:<100 IU/mL | Day 3:> or = 2 log10 change from baseline | Week 1:> or = 2 log10 change from baseline | Week 2:> or = 2 log10 change from baseline | Week 8:> or = 2 log10 change from baseline | Week 16:> or = 2 log10 change from baseline | Week 20:> or = 2 log10 change from baseline | Week 28:> or = 2 log10 change from baseline | Week 36:> or = 2 log10 change from baseline | Week 42:> or = 2 log10 change from baseline |
|---|
| PBO 12Wks PR48 | 0.8 | 0 | 0.8 | 15.0 | 47.4 | 65.5 | 84.5 | 91.9 | 91.7 | 0.8 | 0.8 | 1.5 | 27.6 | 77.6 | 89.4 | 100.0 | 99.0 | 97.9 | 0.8 | 0.8 | 2.3 | 37.0 | 84.5 | 93.8 | 100.0 | 100.0 | 100.0 | 14.1 | 13.7 | 35.4 | 87.4 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 |
,| TMC435 150mg 12Wks PR24/48 | 0 | 3.9 | 28.3 | 95.7 | 98.4 | 99.6 | 88.9 | 90.0 | 100.0 | 3.1 | 35.9 | 82.6 | 98.0 | 100.0 | 99.6 | 100.0 | 90.0 | 100.0 | 9.1 | 62.2 | 92.2 | 98.0 | 100.0 | 99.6 | 100.0 | 90.0 | 100.0 | 97.6 | 99.6 | 99.6 | 98.4 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 |
The Percentage of Participants With Viral Breakthrough at Different Time Points
The table below shows the percentage of participants at different time points with viral breakthrough, defined as a confirmed increase of greater than 1 log10 IU/mL in plasma HCV ribonucleic acid (RNA) level from the lowest level reached (ie, lowest value measured in between baseline and current value), or a confirmed plasma HCV RNA level of greater than 100 IU/mL in participants whose plasma HCV RNA had previously been below the limit of quantification (25 IU/mL detectable) or undetectable (<25 IU/mL undetectable). (NCT01281839)
Timeframe: Up to Week 48
| Intervention | Percentage of Participants (Number) |
|---|
| =<12 weeks | >12-=<24 weeks | >24 weeks |
|---|
| PBO 12Wks PR48 | 0.0 | 0.0 | 0.0 |
,| TMC435 150mg 12Wks PR24/48 | 1.9 | 0.0 | 10.0 |
Percentage of Participants With in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels >1000 IU/mL at Week 4
The table below shows the percentage of participants in each treatment group with HCV RNA levels >1000 IU/mL at Week 4. (NCT01281839)
Timeframe: Week 4
| Intervention | Percentage of Participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 1.9 |
| PBO 12Wks PR48 | 69.9 |
Plasma Concentration of TMC435: Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h)
The table below shows mean (standard deviation) values of the area under the plasma concentration-time curve from time of administration to 24 hours (AUC 24hr) after dosing for TMC435. To calculate the mean AUC 24 for the study, AUC 24 hr values were derived for each participant at each visit and then the median of AUC value across visits for each participant was used to calculate the mean AUC 24 hr for the study. (NCT01281839)
Timeframe: From the time of administration up to 24 hours after dosing through Week 12
| Intervention | ng*h/mL (Mean) |
|---|
| TMC435 150mg 12Wks PR24/48 | 60987 |
Plasma Concentration of TMC435: Predose Plasma Concentration (C0h)
The table below shows mean (standard deviation) of C0h values of TMC435. To calculate the mean C0h for the study, C0h values were derived for each participant at each visit and then the median of C0h values across visits for each participant was used to calculate the mean C0h for the study. (NCT01281839)
Timeframe: Before administration of TMC435 through Week 12
| Intervention | ng/mL (Mean) |
|---|
| TMC435 150mg 12Wks PR24/48 | 2081 |
Plasma Concentration of TMC435: Systemic Clearance (CL)
The table below shows mean (standard deviation) of CL values of TMC435. To calculate the mean CL for the study, CL values were derived for each participant at each visit and then the median of CL values across visits for each participant was used to calculate the mean CL for the study. (NCT01281839)
Timeframe: From the time of administration through Week 12
| Intervention | L/h (Mean) |
|---|
| TMC435 150mg 12Wks PR24/48 | 4.92 |
The Percentage of Participants Achieving a Complete Early Virologic Response (cEVR)
The table below shows the percentage of participants in each treatment group who had a cEVR, defined as having undetectable plasma Hepatitis C Virus ribonucleic acid levels at Week 12. (NCT01281839)
Timeframe: Week 12
| Intervention | Percentage of Participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 98.0 |
| PBO 12Wks PR48 | 27.4 |
The Percentage of Participants Achieving a Early Virologic Response (EVR)
The table below shows the percentage of participants who achieved an EVR, defined as having a change from baseline in plasma Hepatitis C virus ribonucleic acid of greater than or equal to 2 log10 at Week 12. (NCT01281839)
Timeframe: Week 12
| Intervention | Percentage of Participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 98.8 |
| PBO 12Wks PR48 | 95.2 |
The Percentage of Participants Achieving a Extended Rapid Virologic Response (eRVR)
The table below shows the percentage of participants in each treatment group who had a eRVR, defined as having undetectable plasma Hepatitis C Virus ribonucleic acid levels at Week 4 and 12. (NCT01281839)
Timeframe: Week 4 and Week 12
| Intervention | Percentage of Participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 77.6 |
| PBO 12Wks PR48 | 1.6 |
The Percentage of Participants With Undetectable Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels During Treatment for Participants Who Did Not Achieve Undetectable Plasma HCV RNA Levels at Week 12
"The table below shows the percentage of participants with undetectable HCV RNA at Weeks 24, 48, end of treatment (EOT), at the time of assessment for a sustained virologic response (SVR) 12 weeks after the last planned dose (SVR12) (Week 36 or 60), and SVR24 (Week 48 or 72) who did not achieve undetectable HCV RNA levels at Week 12. The number of participants analyzed is listed at each time point in order of the treatment groups from left to right in the table (ie, Week x, n=x, x) if different from the Number of Participants Analyzed. Results are not available for Weeks 24, 48, and EOT because there were no participants who met the criteria for a SVR at those time points." (NCT01288209)
Timeframe: Weeks 24, 48, EOT (Weeks 24 or 48), SVR12 (Weeks 36 or 60), and SVR24 (Weeks 48 or 72)
| Intervention | Percentage of participants (Number) |
|---|
| SVR12 (Weeks 36 or 60) (n=6; n=8) | SVR24 (Weeks 48 or 72) (n=6; n=8) | Week 24 | Week 48 | EOT |
|---|
| TMC435 100 mg 12 Wks + PR24/48 | 0.0 | 0.0 | NA | NA | NA |
,| TMC435 100 mg 24 Wks + PR24/48 | 0.0 | 0.0 | NA | NA | NA |
The Percentage of Participants With Undetectable Plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) During Treatment and at the End of Treatment (EOT)
The table below shows the percentage of participants with undetectable HCV RNA (<1.2 log10 IU/mL) during treatment at Weeks 4, 12, 24, 36, 48, 60, 72, and at EOT (Week 24 or 48). (NCT01288209)
Timeframe: Weeks 4, 12, 24, 36, 48, 60, 72, and at EOT
| Intervention | Percentage of participants (Number) |
|---|
| Week 4 | Week 12 | Week 24 | Week 36 | Week 48 | Week 60 | Week 72 | EOT |
|---|
| TMC435 100 mg 12 Wks + PR24/48 | 58.5 | 84.9 | 79.2 | 52.8 | 50.9 | 50.9 | 50.9 | 83.0 |
,| TMC435 100 mg 24 Wks + PR24/48 | 50.9 | 79.2 | 71.7 | 35.8 | 35.8 | 35.8 | 35.8 | 84.9 |
The Number of Participants Demonstrating Viral Relapse During the Study
The table below shows the number of participants in each treatment group who demonstrated viral relapse during the study. Viral relapse is defined as undetectable plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels at EOT and detectable HCV RNA during follow-up or detectable HCV RNA at the time points for a sustained viral response (SVR) assessment. The incidence of viral relapse was only calculated for participants with undetectable HCV RNA levels at EOT and with at least one follow-up HCV RNA measurement. (NCT01288209)
Timeframe: Up to 72 weeks
| Intervention | Participants (Number) |
|---|
| TMC435 100 mg 12 Wks + PR24/48 | 17 |
| TMC435 100 mg 24 Wks + PR24/48 | 23 |
The Number of Participants With Viral Breakthrough During the Study
The table below shows the number of all participants in each treatment group who experienced viral breakthrough during the treatment period in the study (Baseline to end of treatment [EOT], ie, Week 24 or 48). Viral breakthrough is defined as a confirmed increase of greater than (>) 1 log10 IU/mL in plasma hepatitis C virus (HCV) ribonucleic acid (RNA) level from the lowest level reached or a confirmed value of plasma HCV RNA of > 2.0 log10 IU/mL in all participants whose plasma HCV RNA level had previously been below 1.2 log10 IU/mL detectable or undetectable. (NCT01288209)
Timeframe: Up to EOT (Week 24 or 48)
| Intervention | Participants (Number) |
|---|
| TMC435 100 mg 12 Wks + PR24/48 | 7 |
| TMC435 100 mg 24 Wks + PR24/48 | 6 |
The Number Participants With Abnormal Alanine Aminotransferase (ALT) Levels at Baseline Who Achieved Normal ALT Levels at the End of Treatment (EOT)
The table below shows the number of participants in each treatment group with abnormal ALT levels at baseline (Day 1) who achieved normalization of ALT levels defined as having an ALT value less than or equal to the Upper Limit of Normality (ie, 40 IU/mL) at the EOT. At Baseline, 34/53 participants in the TMC435 100 mg 12 Wks PR 24/48 treatment group and 35/53 participants in the TMC435 100 mg 24 Wks PR 24/48 treatment group had abnormal ALT levels. (NCT01288209)
Timeframe: EOT (Week 24 or 48)
| Intervention | Participants (Number) |
|---|
| TMC435 100 mg 12 Wks + PR24/48 | 20 |
| TMC435 100 mg 24 Wks + PR24/48 | 28 |
The Percentage of Participants Who Met Response Guided Treatment (RGT) Criteria and Completed Treatment With Peginterferon Alpha-2a (PegIFNα-2a) and Ribavirin (RBV) at Week 24
The table below shows the percentage of participants in each treatment group who met RGT criteria (ie, who had plasma levels of hepatitis C virus ribonucleic acid [HCV RNA] <1.2 log10 IU/mL detectable/undetectable at Week 4 and <1.2 log 10 IU/mL undetectable at Week 12) and completed treatment with PegIFNα-2a and RBV at Week 24. Participants in the TMC435 treatment groups not meeting RGT criteria continued treatment with PegIFNα-2a and RBV to Week 48. (NCT01288209)
Timeframe: Week 24
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 100 mg 12 Wks + PR24/48 | 81.1 |
| TMC435 100 mg 24 Wks + PR24/48 | 73.6 |
The Percentage of Participants With a Sustained Virologic Response 24 Weeks After the End of Treatment (EOT) and 24 Weeks After the Last Dose of Treatment (SVR24)
The table below shows the observed percentage of participants in each treatment group with a SVR24 defined as undetectable plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels at the EOT (Week 24 or 48) and at 24 weeks after the last dose of treatment (Week 48 or 72). (NCT01288209)
Timeframe: EOT (Week 24 or 48) and Week 48 or 72
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 100 mg 12 Wks + PR24/48 | 50.9 |
| TMC435 100 mg 24 Wks + PR24/48 | 35.8 |
The Percentage of Participants With a Sustained Virologic Response at the End of Treatment (EOT) and 12 Weeks After the Last Dose of Treatment (SVR12)
The table below shows the observed percentage of participants in each treatment group with a SVR12 defined as undetectable plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels at the EOT (Week 24 or 48) and at 12 weeks after the last dose of treatment (Week 36 or 60). (NCT01288209)
Timeframe: EOT (Week 24 or 48) and Week 36 or 60
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 100 mg 12 Wks + PR24/48 | 52.8 |
| TMC435 100 mg 24 Wks + PR24/48 | 35.8 |
Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24h) for TMC435
"The table below shows the median (range) AUC24h values for participants in each treatment group at Week 12, Week 24, and Overall (Weeks 4, 12, and 24). The time frame of Overall represents the median exposure estimate using all available data collected at Weeks 4, 12, and 24 for each participant in the study. The number of participants analyzed is listed at each time point in order of the treatment groups from left to right in the table (ie, Week x, n=x, x) if different from the Number of Participants Analyzed." (NCT01288209)
Timeframe: Week 12, Week 24, and Overall (Weeks 4, 12, and 24)
| Intervention | ng.h/mL (Median) |
|---|
| AUC24h (Week 12) (n=47; n=44) | AUC24h (Week 24) (n=0; n=40) | Overall (n=53; n=53) |
|---|
| TMC435 100 mg 12 Wks + PR24/48 | 62993 | NA | 62313 |
,| TMC435 100 mg 24 Wks + PR24/48 | 39867 | 38931 | 40014 |
Plasma Concentrations of TMC435
"The table below shows median (range) TMC435 predose plasma concentration (C0h) values and TMC435 maximum plasma concentration (Cmax) values for participants in each treatment group at Week 12, Week 24, and Overall (Weeks 4, 12, and 24). The time frame of Overall representes the median exposure estimate using all available data collected at Weeks 4, 12, and 24 for each participant in the study. The number of participants analyzed is listed at each time point in order of the treatment groups from left to right in the table (ie, Week x, n=x, x) if different from the Number of Participants Analyzed." (NCT01288209)
Timeframe: Week 12, Week 24, and Overall (Weeks 4, 12, and 24)
| Intervention | ng/mL (Median) |
|---|
| C0h (Week 12) (n=47; n=44) | C0h (Week 24) (n=0; n=40) | C0h (Overall) (n=53; n=53) | Cmax (Week 12) (n=47; n=44) | Cmax (Week 24) (n=0; n=40) | Cmax (Overall) (n=53; n=53) |
|---|
| TMC435 100 mg 12 Wks + PR24/48 | 1844 | NA | 1784 | 3408 | NA | 3401 |
,| TMC435 100 mg 24 Wks + PR24/48 | 910 | 866 | 906 | 2476 | 2443 | 2488 |
The Percentage of Participants Who Achieved a Greater Than or Equal to 2 log10 IU/mL Drop From Baseline in Plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) at Each Time Point During Treatment and Follow-up
The table below shows the percentage of participants in each treatment group with a greater than (>) or equal to (=) 2 log10 IU/mL drop from baseline in HCV RNA at each time point during treatment and post-treatment follow-up. (NCT01288209)
Timeframe: Day 3, Day 7, and Weeks 2, 3, 4, 8, 12, 16, 20, 24, 28, 36, 48, 60, 72, EOT, and Follow-up (FU) Weeks 4, 12, and 24
| Intervention | Percentage of participants (Number) |
|---|
| Day 3 | Day 7 | Week 2 | Week 3 | Week 4 | Week 8 | Week 12 | Week 16 | Week 20 | Week 24 | Week 28 | week 36 | Week 48 | Week 60 | Week 72 | EOT | FU Week 4 | FU Week 12 | FU Week 24 |
|---|
| TMC435 100 mg 12 Wks + PR24/48 | 96.2 | 100 | 100 | 100 | 100 | 88.7 | 88.7 | 84.9 | 84.9 | 84.9 | 75.5 | 52.8 | 50.9 | 50.9 | 50.9 | 88.7 | 77.4 | 52.8 | 50.9 |
,| TMC435 100 mg 24 Wks + PR24/48 | 96.2 | 100 | 96.2 | 94.3 | 90.6 | 90.6 | 86.8 | 83.0 | 79.2 | 75.5 | 69.8 | 41.5 | 37.7 | 35.8 | 35.8 | 90.6 | 81.1 | 39.6 | 35.8 |
The Percentage of Participants With <1 log10 Decrease in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) From Baseline at Week 4
The table below shows the percentage of participants in each treatment group with <1 log10 HCV RNA decrease at Week 4. (NCT01289782)
Timeframe: Week 4
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 0 |
| PBO 12Wks PR48 | 15.7 |
Percentage of Participants With On-treatment Virologic Response at All Time Points
The table below shows the percentage of participants with Hepatitis C virus (HCV) ribonucleic acid (RNA) plasma levels below the limit of detection (ie, <25 IU/mL undetectable), the percentage of participants with a HCV RNA plasma level below the limit of quantification (ie, < 25 IU/mL detectable or undetectable), the percentage of participants with plasma levels of HCV RNA <100 IU/mL, the percentage of participants with virologic responses of a greater than or equal to 2 log10 change from baseline in plasma levels of HCV RNA. (NCT01289782)
Timeframe: Day 3, Week 1, Week 2, Week 8, Week 16, Week 20, Week 28, Week 36, and Week 42
| Intervention | Percentage of participants (Number) |
|---|
| Day 3:<25 IU/mL undetectable | Week 1:<25 IU/mL undetectable | Week 2:<25 IU/mL undetectable | Week 8:<25 IU/mL undetectable | Week 16:<25 IU/mL undetectable | Week 20:<25 IU/mL undetectable | Week 28:<25 IU/mL undetectable | Week 36:<25 IU/mL undetectable | Week 42:<25 IU/mL undetectable | Day 3:<25 IU/mL undetectable/detectable | Week 1:<25 IU/mL undetectable/detectable | Week 2:<25 IU/mL undetectable/detectable | Week 8:<25 IU/mL undetectable/detectable | Week 16:<25 IU/mL undetectable/detectable | Week 20:<25 IU/mL undetectable/detectable | Week 28:<25 IU/mL undetectable/detectable | Week 36:<25 IU/mL undetectable/detectable | Week 42:<25 IU/mL undetectable/detectable | Day 3:<100 IU/mL | Week 1:<100 IU/mL | Week 2:<100 IU/mL | Week 8:<100 IU/mL | Week 16:<100 IU/mL | Week 20:<100 IU/mL | Week 28:<100 IU/mL | Week 36:<100 IU/mL | Week 42:<100 IU/mL | Day 3:> or = 2 log10 change from baseline | Week 1:> or = 2 log10 change from baseline | Week 2:> or = 2 log10 change from baseline | Week 8:> or = 2 log10 change from baseline | Week 16:> or = 2 log10 change from baseline | Week 20:> or = 2 log10 change from baseline | Week 28:> or = 2 log10 change from baseline | Week 36:> or = 2 log10 change from baseline | Week 42:> or = 2 log10 change from baseline |
|---|
| PBO 12Wks PR48 | 0.8 | 0.8 | 2.3 | 26.2 | 69.2 | 78.2 | 96.3 | 100.0 | 98.7 | 0.8 | 2.3 | 6.3 | 40.5 | 82.7 | 84.2 | 98.8 | 100.0 | 100.0 | 1.6 | 3.1 | 7.8 | 46.0 | 84.6 | 86.1 | 98.8 | 100.0 | 100.0 | 13.3 | 20.2 | 35.2 | 80.2 | 99.0 | 97.0 | 97.5 | 98.7 | 98.7 |
,| TMC435 150mg 12Wks PR24/48 | 0.4 | 6.6 | 35.8 | 90.0 | 93.8 | 93.4 | 90.9 | 90.9 | 90.9 | 2.4 | 36.8 | 76.7 | 94.0 | 95.4 | 95.0 | 100.0 | 100.0 | 100.0 | 11.4 | 62.8 | 85.2 | 94.8 | 96.7 | 96.7 | 100.0 | 100.0 | 100.0 | 95.3 | 98.1 | 98.8 | 98.4 | 100.0 | 98.3 | 100.0 | 100.0 | 100.0 |
The Percentage of Participants With Viral Breakthrough at Different Time Points
The table below shows the percentage of participants at different time points with viral breakthrough, defined as a confirmed increase of greater than 1 log10 IU/mL in plasma HCV ribonucleic acid (RNA) level from the lowest level reached (ie, lowest value measured in between baseline and current value), or a confirmed plasma HCV RNA level of greater than 100 IU/mL in participants whose plasma HCV RNA had previously been below the limit of quantification (25 IU/mL detectable) or undetectable (<25 IU/mL undetectable). (NCT01289782)
Timeframe: Up to Week 48
| Intervention | Percentage of participants (Number) |
|---|
| < 12 Weeks | Week 12 - Week 24 | > Week 24 |
|---|
| PBO 12Wks PR48 | 1.5 | 6.8 | 1.2 |
,| TMC435 150mg 12Wks PR24/48 | 2.7 | 2.5 | 0 |
Percentage of Participants Who Completed All Study Treatment at Week 24 Because of the Treatment Duration Rule
The table below shows the percentage of participants in the TMC435 treatment group who met the treatment duration rule (ie, having hepatitis C virus [HCV] ribonucleic acid [RNA] levels <25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA levels at Week 12) and completed treatment with PegIFNα-2a and RBV for 24 weeks. Participants in the TMC435 treatment group not meeting RGT criteria and participants in the placebo group were treated with PegIFNα-2a and RBV treatment for 48 weeks. (NCT01289782)
Timeframe: Week 24
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 83 |
| PBO 12Wks PR48 | NA |
Percentage of Participants With in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels >1000 IU/mL at Week 4
The table below shows the percentage of participants in each treatment group with HCV RNA levels >1000 IU/mL at Week 4. (NCT01289782)
Timeframe: Week 4
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 4.5 |
| PBO 12Wks PR48 | 63.8 |
Percentage of Participants With Null Response
The table below shows the percentage of participants with null response, defined as <2 log10 reduction in Hepatitis C virus ribonucleic acid at Week 12 compared to baseline. (NCT01289782)
Timeframe: Week 12
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 0.8 |
| PBO 12Wks PR48 | 14.8 |
Percentage of Participants With On-treatment Failure
The table below shows percentage of participants with on-treatment failure defined as confirmed detectable Hepatitis C virus ribonucleic acid levels at actual end of treatment. (NCT01289782)
Timeframe: Week 48
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 9.1 |
| PBO 12Wks PR48 | 33.8 |
Percentage of Participants With Partial Response
The table below shows the percentage of participants with partial response, defined as greater than or equal to 2 log10 reduction in Hepatitis C virus ribonucleic acid at Week 12 compared to baseline, but not achieving undetectable HCV RNA while on treatment. (NCT01289782)
Timeframe: Week 12
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 3.2 |
| PBO 12Wks PR48 | 13.1 |
Percentage of Participants With Viral Breakthrough
The table below shows the percentage of participants with viral breakthrough, defined as a confirmed increase of greater than 1 log10 IU/mL in plasma Hepatitis C virus (HCV) ribonucleic acid (RNA) level from the lowest level reached (ie, lowest value measured in between baseline and current value), or a confirmed plasma HCV RNA level of greater than 100 IU/mL in participants whose plasma HCV RNA had previously been below the limit of quantification (25 IU/mL detectable) or undetectable (<25 IU/mL undetectable). (NCT01289782)
Timeframe: Up to Week 48
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 4.9 |
| PBO 12Wks PR48 | 7.7 |
Percentage of Participants With Viral Relapse
The table below shows the percentage of participants with viral relapse, defined as having confirmed detectable plasma level of Hepatitis C virus (HCV) ribonucleic acid (RNA) during the follow-up period in participants with undetectable plasma HCV RNA (less than 25 IU/mL undetectable) at the end of treatment. (NCT01289782)
Timeframe: Up to Week 72
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 9.0 |
| PBO 12Wks PR48 | 22.6 |
Plasma Concentration of TMC435: Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h)
The table below shows mean (standard deviation) values of the area under the plasma concentration-time curve from time of administration to 24 hours after dosing for TMC435 for all participants. To calculate the mean AUC 24 for the study, AUC 24 hr values were derived for each participant at each visit and then a median AUC value calcuated across all visits for each participant. The median AUC value across all visits for each participant was used to calculate the mean AUC 24 hr all participants in the study. (NCT01289782)
Timeframe: Fom the time of administration up to 24 hours after dosing at Weeks 2, 4, 8, and 12
| Intervention | ng*h/mL (Mean) |
|---|
| TMC435 150mg 12Wks PR24/48 | 54795 |
Plasma Concentration of TMC435: Predose Plasma Concentration (C0h)
The table below shows the mean (standard deviation) values for the C0h of TMC435.To calculate the mean C0h for the study, C0h values were derived for each participant at each visit and then a median C0H value calculated across visits for each participant. The median COh value for each participant across all visits was used to calculate the mean C0h for the study. (NCT01289782)
Timeframe: Before administration of TMC435 at Weeks 2, 4, 8, and 12
| Intervention | ng/mL (Mean) |
|---|
| TMC435 150mg 12Wks PR24/48 | 1825 |
Plasma Concentration of TMC435: Systemic Clearance (CL)
The table below shows the mean (standard deviation) values for the CL of TMC435.To calculate the mean CL for all participants in the study, CL values were first derived for each participant at each visit and then a median CL value calculated across visits for each participant. The median CL value for each participant was used to calculate the mean CL for all participants in the study. (NCT01289782)
Timeframe: Across Weeks 2, 4, 8, and 12
| Intervention | L/h (Mean) |
|---|
| TMC435 150mg 12Wks PR24/48 | 5.05 |
The Percentage of Participants Achieving a Complete Early Virologic Response (cEVR)
The table below shows the percentage of participants in each treatment group who had a cEVR, defined as having undetectable plasma Hepatitis C Virus ribonucleic acid levels at Week 12. (NCT01289782)
Timeframe: Week 12
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 92.8 |
| PBO 12Wks PR48 | 50.8 |
The Percentage of Participants Achieving a Early Virologic Response (EVR)
The table below shows the percentage of participants who achieved an EVR, defined as having a change from baseline in plasma Hepatitis C virus ribonucleic acid of greater than or equal to 2 log10 at Week 12. (NCT01289782)
Timeframe: Week 12
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 99.2 |
| PBO 12Wks PR48 | 85.2 |
The Percentage of Participants Achieving a Extended Rapid Virologic Response (eRVR)
The table below shows the percentage of participants in each treatment group who had a eRVR, defined as having undetectable plasma Hepatitis C Virus ribonucleic acid levels at Week 4 and 12. (NCT01289782)
Timeframe: Week 4 and 12
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 78.9 |
| PBO 12Wks PR48 | 11.7 |
The Percentage of Participants Achieving a Rapid Virologic Response (RVR)
The table below shows the percentage of participants in each treatment group who achieved a RVR, defined as having undetectable plasma Hepatitis C virus ribonucleic acid levels after receiving 4 weeks of treatment. (NCT01289782)
Timeframe: Week 4
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 79.5 |
| PBO 12Wks PR48 | 11.8 |
The Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12)
The table below shows the percentage of participants in each treatment group who achieved a SVR12, defined as the percentage of participants with undetectable plasma Hepatitis C virus ribonucleic acid 12 weeks after planned end of treatment. (NCT01289782)
Timeframe: Week 36 or Week 60
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 79.5 |
| PBO 12Wks PR48 | 50 |
The Percentage of Participants Achieving a Sustained Virologic Response at Week 72 (SVRW72)
The table below shows the percentage of participants in each treatment group who achieved a SVRW72, defined as the percentage of participants with undetectable plasma Hepatitis C virus ribonucleic acid levels at end of treatment (EOT) and at Week 72. (NCT01289782)
Timeframe: Week 72
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 78.4 |
| PBO 12Wks PR48 | 49.2 |
The Percentage of Participants Who Achieved a Sustained Virologic Response 24 Weeks After the Planned End of Treatment (SVR24)
The table below shows the percentage of participants in each treatment group who achieved a SVR24, defined as the percentage of participants with undetectable plasma Hepatitis C virus ribonucleic acid levels 24 weeks after planned end of treatment. (NCT01289782)
Timeframe: Week 48 or Week 72
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 79.5 |
| PBO 12Wks PR48 | 49.2 |
The Percentage of Participants Who Achieved a Sustained Virologic Response 4 Weeks After the Planned End of Treatment (SVR4)
The table below shows the percentage of participants in each treatment group who achieved a SVR4, defined as the percentage of participants with undetectable plasma Hepatitis C virus ribonucleic acid levels 4 weeks after planned end of treatment. (NCT01289782)
Timeframe: Week 28 or Week 52
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 82.2 |
| PBO 12Wks PR48 | 56.2 |
The Percentage of Participants With Normalization of Alanine Aminotransferase (ALT)
The percentage of participants analyzed were those with baseline ALT values out of the normal range (ie, 158 of 264 participants in the TMC435 treatment group and 89 of 130 participants in the Placebo group had ALT values at baseline that were out of the normal range.). Normalization of ALT values means that ALT values out of the normal range returned to within the normal range. (NCT01289782)
Timeframe: Up to Week 48
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 81.0 |
| PBO 12Wks PR48 | 77.5 |
Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <100 IU/mL
The table below shows median time in days to reach HCV RNA levels <100 IU/mL. (NCT01289782)
Timeframe: Up to Week 48
| Intervention | Days (Median) |
|---|
| TMC435 150mg 12Wks PR24/48 | 28 |
| PBO 12Wks PR48 | 84 |
Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <1000 IU/mL
The table below shows median time in days to reach HCV RNA levels <1000 IU/mL. (NCT01289782)
Timeframe: Up to Week 48
| Intervention | Days (Median) |
|---|
| TMC435 150mg 12Wks PR24/48 | 4 |
| PBO 12Wks PR48 | 56.5 |
Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Undetectable
The table below shows median time in days to reach HCV RNA levels <25 IU/mL undetectable. (NCT01289782)
Timeframe: Up to Week 48
| Intervention | Days (Median) |
|---|
| TMC435 150mg 12Wks PR24/48 | 28 |
| PBO 12Wks PR48 | 111 |
Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Undetectable or Detectable
The table below shows median time in days to reach HCV RNA levels <25 IU/mL undetectable or detectable. (NCT01289782)
Timeframe: Up to Week 48
| Intervention | Days (Median) |
|---|
| TMC435 150mg 12Wks PR24/48 | 14 |
| PBO 12Wks PR48 | 85 |
Actual Values of log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
The table below shows actual values of log10 HCV RNA levels. (NCT01289782)
Timeframe: Day 3, Week 1, Week 4, Week 12, Week 24, and Week 48
| Intervention | log10 IU/mL (Mean) |
|---|
| Day 3 | Week 1 | Week 4 | Week 12 | Week 24 | Week 48 |
|---|
| PBO 12Wks PR48 | 5.351 | 5.202 | 3.723 | 2.111 | 1.334 | 0.961 |
,| TMC435 150mg 12Wks PR24/48 | 2.914 | 1.973 | 1.223 | 1.090 | 1.113 | 0.993 |
Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) for Impairment in Daily Activity Scores Due to Hepatitis C Virus (HCV) Infection and Its Treatment
Impairment in daily activity was measured using the Work Productivity and Activity Impairment (WPAI): Hepatitis C questionnaire, Question 6. Scores ranged from 0 (no effect on activities) to 10 (completely prevented me from doing my daily activities). An area under the curve (AUC) analysis compared the impairment in daily activity scores in each treatment group from Baseline to Week 72. The null hypothesis was that there would be no difference between the treatment arms in impairment in daily activity scores from Baseline to Week 72. The Table below shows the lease squares (LS) mean estimates of AUC at Week 72 (as well as at Week 60) in the impairment in daily activity scores and the statistical comparison between treatment groups. (NCT01289782)
Timeframe: Baseline to Week 60 and Week 72
| Intervention | scores on a scale*weeks (Least Squares Mean) |
|---|
| Week 60 | Week 72 |
|---|
| PBO 12Wks PR48 | 1792.460 | 1975.457 |
,| TMC435 150mg 12Wks PR24/48 | 1514.400 | 1667.735 |
Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) for the Fatigue Severity Scale (FSS) Total Scores
Study participants completed FSS questionnaires during study visits before treatment began and throughout treatment and follow-up to rate the severity and impact of fatigue they experienced in the preceding 2 weeks on their daily lives. FSS total scores are the average of nine questions with a range from 1 [no fatigue] to 7 [worst possible fatigue]. An area under the curve (AUC) analysis compared the overall severity of fatigue in each treatment group from baseline to Week 72. The null hypothesis was that there would be no difference between the treatment arms in the amount of fatigue participants experienced throughout the study resulting in equal AUC from baseline to Week 72 (AUC72) for FSS total scores. The Table below shows the lease squares (LS) mean estimates of AUC at Week 72 (as well as at Week 60) and the statistical comparison between treatment groups. (NCT01289782)
Timeframe: Baseline to Week 60 and Week 72
| Intervention | scores on a scale*weeks (Least Squares Mean) |
|---|
| Week 60 | Week 72 |
|---|
| PBO 12Wks PR48 | 235.586 | 274.322 |
,| TMC435 150mg 12Wks PR24/48 | 214.907 | 250.522 |
Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) in Work Productivity and Activity (WPAI) Absenteeism Scores Due to Hepatitis C Virus (HCV) Infection and Its Treatment
Time missed from work in hours because of HCV infection or its treatment was assessed by measuring the change from baseline in the Work Productivity and Activity Impairment (WPAI): Hepatitis C questionnaire Absenteeism score (time missed from work, question #2). The number of hours missed from work because of HCV was divided by the total number of hours supposed to work, and expressed as a percentage. An area under the curve (AUC) analysis compared the WPAI absenteeism scores in each treatment group from Baseline to Week 72. The null hypothesis was that there would be no difference between the treatment arms WPAI absenteeism scores from Baseline to Week 72. The Table below shows the lease squares (LS) mean estimates of AUC at Week 72 (as well as at Week 60) in WPAI absenteeism scores and the statistical comparison between treatment groups. (NCT01289782)
Timeframe: Baseline to Week 60 and Week 72
| Intervention | scores on a scale*weeks (Least Squares Mean) |
|---|
| Week 60 | Week 72 |
|---|
| PBO 12Wks PR48 | 400.771 | 430.285 |
,| TMC435 150mg 12Wks PR24/48 | 447.170 | 487.449 |
Change From Baseline in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
The table below shows the change from baseline in log10 HCV RNA levels. (NCT01289782)
Timeframe: Day 3, Week 1, Week 4, Week 12, Week 24, and Week 48
| Intervention | log10 IU/mL (Mean) |
|---|
| Day 3 | Week 1 | Week 4 | Week 12 | Week 24 | Week 48 |
|---|
| PBO 12Wks PR48 | -0.93 | -1.08 | -2.56 | -4.18 | -4.89 | -5.23 |
,| TMC435 150mg 12Wks PR24/48 | -3.52 | -4.47 | -5.22 | -5.34 | -5.32 | -5.33 |
Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) for Impairment in Overall Work Productivity Scores Due to Hepatitis C Virus (HCV) Infection and Its Treatment
Impairment in overall work productivity was measured using the Work Productivity and Activity Impairment (WPAI): Hepatitis C questionnaire completed by participants during study visits throughout the study. WPAI Overall Productivity Scores ranged from 0% to 100% (higher WPAI scores indicated greater impairment in productivity). An area under the curve (AUC) analysis compared the overall WPAI Overall Work Productivity Scores in each treatment group from Baseline to Week 72. The null hypothesis was that there would be no difference between the treatment arms in the WPAI Overall Work Productivity Scores from Baseline to Week 72. The Table below shows the lease squares (LS) mean estimates of AUC at Week 72 (as well as at Week 60) in WPAI Work Productivity Scores and the statistical comparison between treatment groups. (NCT01289782)
Timeframe: Baseline to Week 60 and Week 72
| Intervention | scores on a scale*weeks (Least Squares Mean) |
|---|
| Week 60 | Week 72 |
|---|
| PBO 12Wks PR48 | 1785.668 | 1966.449 |
,| TMC435 150mg 12Wks PR24/48 | 1555.204 | 1718.241 |
Time From End-of-treatment to Viral Relapse
The table below shows the mean number of days to viral relapse, defined as participants having confirmed detectable plasma level of Hepatitis C Virus (HCV) ribonucleic acid (RNA) during the follow-up period in participants with undetectable plasma HCV RNA (<25 IU/mL undetectable) at the end of treatment. (NCT01289782)
Timeframe: Up to Week 72
| Intervention | Days (Mean) |
|---|
| TMC435 150mg 12Wks PR24/48 | 100.96 |
| PBO 12Wks PR48 | 146.04 |
Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Undetectable or Detectable
The table below shows the median time in days to reach HCV RNA levels <25 IU/mL undetectable or detectable. (NCT01290679)
Timeframe: Up to Week 48
| Intervention | Days (Median) |
|---|
| TMC435 150mg 12Wks PR24/48 | 14 |
| PBO 12Wks PR48 | 85 |
Actual Values of log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
The table below shows actual values of log10 HCV RNA levels. (NCT01290679)
Timeframe: Day 3, Week 1, Week 4, Week 12, Week 24, and Week 48
| Intervention | log10 IU/mL (Mean) |
|---|
| Day 3 | Week 1 | Week 4 | Week 12 | Week 24 | Week 48 |
|---|
| PBO 12Wks PR48 | 5.165 | 5.171 | 3.657 | 2.157 | 1.388 | 0.960 |
,| TMC435 150mg 12Wks PR24/48 | 2.777 | 1.852 | 1.093 | 1.027 | 1.094 | 1.015 |
Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) for Impairment in Daily Activities Due to Hepatitis C Virus (HCV) Infection and Its Treatment
Impairment in daily activity was measured using the Work Productivity and Activity Impairment (WPAI): Hepatitis C questionnaire, Question 6. The possible impairment in WPAI daily activity score range from baseline to Week 60 was 0-6000 and to Week 72 was 0-7200, with the higher scores indicating more impairment in daily activities. The average WPAI impairment in daily activity score from baseline to Week 72 was calculated for each participant and then the average of those values were calculated to show the average WPAI impairment in daily activity score for each treatment group. The null hypothesis was there is no statistically significant difference between the treatment arms in the AUC for the change from baseline to Week 72 (AUC72) in WPAI impairment in daily activity scores. The Table below shows the WPAI Impairment in daily activity scores at Week 72 (as well as at Week 60) and the statistical analysis between treatment groups. (NCT01290679)
Timeframe: Baseline to Week 60 and Week 72
| Intervention | Scores on a scale*weeks (Least Squares Mean) |
|---|
| Week 60 | Week 72 |
|---|
| PBO 12Wks PR48 | 1863.071 | 2056.283 |
,| TMC435 150mg 12Wks PR24/48 | 1580.635 | 1727.079 |
Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) for Impairment in Overall Work Productivity Due to Hepatitis C Virus (HCV) Infection and Its Treatment
Impairment in overall work productivity was measured using the Work Productivity and Activity Impairment (WPAI): Hepatitis C questionnaire completed by participants throughout the study. WPAI Overall Productivity Scores ranged from 0% to 100% (higher WPAI scores indicated greater impairment in productivity). The average WPAI score from baseline to Week 72 was calculated for each participant and then the average of those values were calculated to show the average WPAI score for each treatment group. The null hypothesis was there is no statistically significant difference between the treatment groups in the AUC for the change from baseline to Week 72 (AUC72) in WPAI Productivity Scores. The Table below shows WPAI Productivity Scores at Week 72 (as well as at Week 60) from the model used to calculate the AUC and the statistical comparison between treatment groups. (NCT01290679)
Timeframe: Baseline to Week 60 and Week 72
| Intervention | Scores on a scale*weeks (Least Squares Mean) |
|---|
| Week 60 | Week 72 |
|---|
| PBO 12Wks PR48 | 1910.235 | 2106.131 |
,| TMC435 150mg 12Wks PR24/48 | 1628.075 | 1781.768 |
Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) for the Fatigue Severity Scale (FSS) Total Scores
Study participants completed FSS questionnaires during study visits before treatment and throughout follow-up to rate the severity and impact of fatigue experienced in the preceding 2 weeks. FSS total scores are the average of nine questions with a range from 1 [no fatigue] to 7 [worst fatigue]; the possible score range from baseline to Week 60 would be 60-420 and to Week 72 would be 72-504. The average FSS total score from baseline to Week 60 and to Week 72 was calculated for each participant and then the average of those values were calculated to show the average FSS total score for each treatment group. The null hypothesis was that there would be no difference between the treatment arms in the FSS total score. The Table below shows the lease squares (LS) mean estimates of the area under the curve (AUC) at Week 72 (as well as at Week 60) and the statistical comparison between treatment groups. (NCT01290679)
Timeframe: Baseline to Week 60 and Week 72
| Intervention | Scores on a scale*weeks (Least Squares Mean) |
|---|
| Week 60 | Week 72 |
|---|
| PBO 12Wks PR48 | 225.194 | 259.532 |
,| TMC435 150mg 12Wks PR24/48 | 208.418 | 240.695 |
Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) for Time Missed From Work Due to Hepatitis C Virus (HCV) Infection and Its Treatment
Hours missed from work because of HCV infection or its treatment was assessed by measuring the change from baseline in the Work Productivity and Activity Impairment (WPAI): Hepatitis C questionnaire Absenteeism score (time missed from work). The possible WPAI WPAI absenteeism score range from baseline to Week 60 was 0-6000 and to Week 72 was 0-7200, with the higher scores indicating more impairment in WPAI absenteeism. The average WPAI absenteeism score from baseline to Week 60/72 was calculated for each participant and then the average of those values calculated for each treatment group. The area under the curve (AUC60/AUC72) over time from baseline to Week 60/72 was derived from a piecewise-linear model allowing the slopes to change at Week 4, 12, 24, 36, 48 and 60. The null hypothesis was there is no statistically significant difference between the treatment arms in the area under the curve (AUC) from baseline to Week 72 (AUC72) in WPAI absenteeism score. (NCT01290679)
Timeframe: Baseline to Week 60 and Week 72
| Intervention | Scores on a scale*weeks (Least Squares Mean) |
|---|
| Week 60 | Week 72 |
|---|
| PBO 12Wks PR48 | 840.495 | 886.425 |
,| TMC435 150mg 12Wks PR24/48 | 653.642 | 698.223 |
Change From Baseline in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
The table below shows changes from baseline in log10 HCV RNA. (NCT01290679)
Timeframe: Day 3, Week 1, Week 4, Week 12, Week 24, and Week 48
| Intervention | log10 IU/mL (Mean) |
|---|
| Day 3 | Week 1 | Week 4 | Week 12 | Week 24 | Week 48 |
|---|
| PBO 12Wks PR48 | -1.22 | -1.21 | -2.72 | -4.21 | -4.93 | -5.28 |
,| TMC435 150mg 12Wks PR24/48 | -3.60 | -4.52 | -5.28 | -5.34 | -5.27 | -5.83 |
Percentage of Participants With On-treatment Virologic Response at All Time Points
The table below shows the percentage of participants with Hepatitis C Virus (HCV) ribonucleic acid (RNA) plasma levels below the limit of detection (ie, <25 IU/mL undetectable), the percentage of participants with a HCV RNA plasma level below the limit of quantification (ie, less than [<] 25 IU/mL detectable or undetectable), the percentage of participants with plasma levels of HCV RNA <100 IU/mL, the percentage of HCV-Infected participants with virologic responses of a greater than or equal to 2 log10 change from baseline in plasma levels of HCV RNA. (NCT01290679)
Timeframe: Day 3, Week 1, Week 2, Week 8, Week 16, Week 20, Week 28, Week 36, and Week 42
| Intervention | Percentage of participants (Number) |
|---|
| Day 3:<25 IU/mL undetectable | Week 1:<25 IU/mL undetectable | Week 2:<25 IU/mL undetectable | Week 8:<25 IU/mL undetectable | Week 16:<25 IU/mL undetectable | Week 20:<25 IU/mL undetectable | Week 28:<25 IU/mL undetectable | Week 36:<25 IU/mL undetectable | Week 42:<25 IU/mL undetectable | Day 3:<25 IU/mL detectable or undetectable | Week 1:<25 IU/mL detectable or undetectable | Week 2:<25 IU/mL detectable or undetectable | Week 8:<25 IU/mL detectable or undetectable | Week 16:<25 IU/mL detectable or undetectable | Week 20:<25 IU/mL detectable or undetectable | Week 28:<25 IU/mL detectable or undetectable | Week 36:<25 IU/mL detectable or undetectable | Week 42:<25 IU/mL detectable or undetectable | Day 3:<100 IU/mL | Week 1:<100 IU/mL | Week 2:<100 IU/mL | Week 8:<100 IU/mL | Week 16:<100 IU/mL | Week 20:<100 IU/mL | Week 28:<100 IU/mL | Week 36:<100 IU/mL | Week 42:<100 IU/mL | Day 3:> or = 2 log 10 change from baseline | Week 1:> or =2 log 10 change from baseline | Week 2:> or =2 log 10 change from baseline | Week 8:> or =2 log 10 change from baseline | Week 16:> or =2 log 10 change from baseline | Week 20:> or =2 log 10 change from baseline | Week 28:> or =2 log 10 change from baseline | Week 36:> or =2 log 10 change from baseline | Week 42:> or =2 log 10 change from baseline |
|---|
| PBO 12Wks PR48 | 0 | 1.5 | 3.8 | 31.3 | 65.5 | 68.2 | 88.0 | 95.3 | 95.0 | 0 | 2.3 | 12.0 | 45.0 | 73.5 | 79.1 | 97.8 | 98.8 | 100.0 | 1.5 | 6.0 | 14.3 | 50.4 | 77.0 | 83.6 | 97.8 | 98.8 | 100.0 | 20.8 | 24.1 | 39.8 | 80.2 | 97.3 | 93.6 | 100.0 | 98.8 | 100.0 |
,| TMC435 150mg 12Wks PR24/48 | 0.4 | 6.3 | 31.7 | 93.7 | 96.3 | 95.9 | 66.7 | 100.0 | 100.0 | 4.7 | 37.0 | 80.7 | 98.0 | 98.0 | 97.1 | 77.8 | 100.0 | 100.0 | 15.3 | 65.7 | 92.0 | 98.8 | 98.8 | 98.0 | 77.8 | 100.0 | 100.0 | 96.9 | 99.6 | 99.6 | 99.6 | 99.2 | 98.8 | 88.9 | 100.0 | 100.0 |
The Percentage of Participants With Viral Breakthrough at Different Time Points
The table below shows the percentage of participants at different time points with viral breakthrough, defined as a confirmed increase of greater than 1 log10 IU/mL in plasma HCV ribonucleic acid (RNA) level from the lowest level reached (ie, lowest value measured in between baseline and current value), or a confirmed plasma HCV RNA level of greater than 100 IU/mL in participants whose plasma HCV RNA had previously been below the limit of quantification (25 IU/mL detectable) or undetectable (<25 IU/mL undetectable). (NCT01290679)
Timeframe: Up to Week 48
| Intervention | Percentage of participants (Number) |
|---|
| < 12 Weeks | Week 12 - Week 24 | > Week 24 |
|---|
| PBO 12Wks PR48 | 3.7 | 6.4 | 2.1 |
,| TMC435 150mg 12Wks PR24/48 | 1.2 | 3.3 | 12.5 |
Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <1000 IU/mL
The table below shows the median time in days to reach HCV RNA levels <1000 IU/mL. (NCT01290679)
Timeframe: Up to Week 48
| Intervention | Days (Median) |
|---|
| TMC435 150mg 12Wks PR24/48 | 4 |
| PBO 12Wks PR48 | 57 |
Time From End-of-treatment to Viral Relapse
The table below shows the mean number of days to viral relapse, defined as participants having confirmed detectable plasma level of Hepatitis C Virus (HCV) ribonucleic acid (RNA) during the follow-up period in participants with undetectable plasma HCV RNA (<25 IU/mL undetectable) at the end of treatment. (NCT01290679)
Timeframe: Up to Week 72
| Intervention | Days (Mean) |
|---|
| TMC435 150mg 12Wks PR24/48 | 229.77 |
| PBO 12Wks PR48 | 77.74 |
The Percentage of Participants With Normalization of Alanine Aminotransferase (ALT)
The percentage of participants analyzed were those with baseline ALT values out of the normal range (ie, 164 of 257 participants in the TMC435 treatment group and 79 of 134 participants in the Placebo group had ALT values at baseline that were out of the normal range.). Normalization of ALT values means that ALT values out of the normal range returned to within the normal range. (NCT01290679)
Timeframe: Up to Week 48
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 79.9 |
| PBO 12Wks PR48 | 81.0 |
The Percentage of Participants With <1 log10 Decrease in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) From Baseline at Week 4
The table below shows the percentage of participants in each treatment group with <1 log10 HCV RNA decrease at Week 4. (NCT01290679)
Timeframe: Week 4
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 0.4 |
| PBO 12Wks PR48 | 17.3 |
The Percentage of Participants Who Achieved a Sustained Virologic Response 4 Weeks After the Planned End of Treatment (SVR4)
The table below shows the percentage of participants in each treatment group who achieved a SVR4, defined as the percentage of participants with undetectable plasma Hepatitis C virus ribonucleic acid levels 4 weeks after planned end of treatment. (NCT01290679)
Timeframe: Week 28 or Week 52
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 84.8 |
| PBO 12Wks PR48 | 53.0 |
The Percentage of Participants Who Achieved a Sustained Virologic Response 24 Weeks After the Planned End of Treatment (SVR24)
The table below shows the percentage of participants in each treatment group who achieved a SVR24, defined as the percentage of participants with undetectable plasma Hepatitis C virus ribonucleic acid levels 24 weeks after planned end of treatment. (NCT01290679)
Timeframe: Week 48 or Week 72
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 80.5 |
| PBO 12Wks PR48 | 50.0 |
The Percentage of Participants Achieving a Sustained Virologic Response at Week 72 (SVRW72)
The table below shows the percentage of participants in each treatment group who achieved a SVRW72, defined as the percentage of participants with undetectable plasma Hepatitis C virus ribonucleic acid levels at end of treatment (EOT) and at Week 72. (NCT01290679)
Timeframe: Week 72
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 78.6 |
| PBO 12Wks PR48 | 50.0 |
The Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12)
The table below shows the percentage of participants in each treatment group who achieved a SVR12, defined as the percentage of participants with undetectable plasma Hepatitis C virus ribonucleic acid 12 weeks after planned end of treatment. (NCT01290679)
Timeframe: Week 36 or Week 60
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 81.3 |
| PBO 12Wks PR48 | 50.0 |
The Percentage of Participants Achieving a Rapid Virologic Response (RVR)
The table below shows the percentage of participants in each treatment group who achieved a RVR, defined as having undetectable plasma Hepatitis C virus ribonucleic acid levels after receiving 4 weeks of treatment. (NCT01290679)
Timeframe: Week 4
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 79.2 |
| PBO 12Wks PR48 | 12.8 |
The Percentage of Participants Achieving a Extended Rapid Virologic Response (eRVR)
The table below shows the percentage of participants in each treatment group who had a eRVR, defined as having undetectable plasma Hepatitis C Virus ribonucleic acid levels at Week 4 and 12. (NCT01290679)
Timeframe: Weeks 4 and 12
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 78.3 |
| PBO 12Wks PR48 | 13.4 |
The Percentage of Participants Achieving a Early Virologic Response (EVR)
The table below shows the percentage of participants who achieved an EVR, defined as having a change from baseline in plasma Hepatitis C virus ribonucleic acid of 2 log10 at Week 12. (NCT01290679)
Timeframe: Week 12
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 98.8 |
| PBO 12Wks PR48 | 89.8 |
The Percentage of Participants Achieving a Complete Early Virologic Response (cEVR)
The table below shows the percentage of participants in each treatment group who had a cEVR, defined as having undetectable plasma Hepatitis C Virus ribonucleic acid levels at Week 12. (NCT01290679)
Timeframe: Week 12
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 96.8 |
| PBO 12Wks PR48 | 44.9 |
Percentage of Participants With Viral Relapse
The table below shows the percentage of participants with viral relapse, defined as having confirmed detectable plasma level of Hepatitis C virus (HCV) ribonucleic acid (RNA) during the follow-up period in participants with undetectable plasma HCV RNA (<25 IU/mL undetectable) at the end of treatment. (NCT01290679)
Timeframe: Up to Week 72
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 12.3 |
| PBO 12Wks PR48 | 23.9 |
Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <100 IU/mL
The table below shows the median time in days to reach HCV RNA levels <100 IU/mL. (NCT01290679)
Timeframe: Up to Week 48
| Intervention | Days (Median) |
|---|
| TMC435 150mg 12Wks PR24/48 | 8 |
| PBO 12Wks PR48 | 71 |
Percentage of Participants Who Completed All Study Treatment at Week 24 Because of the Treatment Duration Rule
The table below shows the percentage of participants in the TMC435 treatment group who met the treatment duration rule (ie, having hepatitis C virus [HCV] ribonucleic acid [RNA] levels <25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA levels at Week 12) and completed treatment with PegIFNα-2a and RBV for 24 weeks. Participants in the TMC435 treatment group not meeting RGT criteria and participants in the placebo group were treated with PegIFNα-2a and RBV treatment for 48 weeks. (NCT01290679)
Timeframe: Week 24
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 89.5 |
| PBO 12Wks PR48 | NA |
Percentage of Participants With in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels >1000 IU/mL at Week 4
The table below shows the percentage of participants in each treatment group with HCV RNA levels >1000 IU/mL at Week 4. (NCT01290679)
Timeframe: Week 4
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 1.2 |
| PBO 12Wks PR48 | 61.2 |
Percentage of Participants With Null Response
The table below shows the percentage of participants with null response, defined as <2 log10 reduction in Hepatitis C virus ribonucleic acid at Week 12 compared to baseline. (NCT01290679)
Timeframe: Week 12
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 1.2 |
| PBO 12Wks PR48 | 10.2 |
Percentage of Participants With On-treatment Failure
The table below shows percentage of participants with on-treatment failure defined as confirmed detectable Hepatitis C virus ribonucleic acid levels at actual end of treatment. (NCT01290679)
Timeframe: Week 48
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 7.0 |
| PBO 12Wks PR48 | 32.1 |
Percentage of Participants With Partial Response
The table below shows the percentage of participants with partial response, defined as =>2 log10 reduction in Hepatitis C virus (HCV) ribonucleic acid (RNA) at Week 12 compared to baseline, but not achieving undetectable HCV RNA while on treatment. (NCT01290679)
Timeframe: Week 12
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 0.4 |
| PBO 12Wks PR48 | 17.3 |
Percentage of Participants With Viral Breakthrough
The table below shows the percentage of participants with viral breakthrough, defined as a confirmed increase of greater than 1 log10 IU/mL in plasma Hepatitis C virus (HCV) ribonucleic acid (RNA) level from the lowest level reached (ie, lowest value measured in between baseline and current value), or a confirmed plasma HCV RNA level of greater than 100 IU/mL in participants whose plasma HCV RNA had previously been below the limit of quantification (25 IU/mL detectable) or undetectable (<25 IU/mL undetectable). (NCT01290679)
Timeframe: Up to Week 48
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 4.7 |
| PBO 12Wks PR48 | 10.4 |
Plasma Concentration of TMC435: Systemic Clearance (CL)
The table below shows the mean (standard deviation) of CL values of TMC435. NOTE: the pre-dose CL values taken at Weeks, 2, 4, 8, and 12 were averaged and then the mean values from all participants were averaged to provide the final value reported below. (NCT01290679)
Timeframe: At protocol-specified time points at Weeks 2, 4, 8, and 12
| Intervention | L/h (Mean) |
|---|
| TMC435 150mg 12Wks PR24/48 | 5.23 |
Plasma Concentration of TMC435: Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h)
The table below shows the mean (standard deviation) values of the area under the plasma concentration-time curve from time of administration to 24 hours after dosing for TMC435. (NCT01290679)
Timeframe: At protocol-specified time points from the time of administration up to 24 hours after dosing at Weeks 2, 4, 8, and 12
| Intervention | ng*h/mL (Mean) |
|---|
| TMC435 150mg 12Wks PR24/48 | 56611 |
Plasma Concentration of TMC435: Predose Plasma Concentration (C0h)
The table below shows the mean (standard deviation) of C0h values of TMC435. NOTE: the timing of collection of blood samples post-dose for analysis at Week 2, 4, 8, and 12 was not specifed; only the interval was between blood samples was specified (ie, 2 samples collected 2 hours apart at Week 2, 4, 8, and 12). (NCT01290679)
Timeframe: Blood samples tested were taken before administration of TMC435 and at 2 random time points after dosing (taken atleast 2 hours apart from each other) at Week 2, 4, 8, and 12
| Intervention | ng/mL (Mean) |
|---|
| TMC435 150mg 12Wks PR24/48 | 1902 |
Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Undetectable
The table below shows the median time in days to reach HCV RNA levels <25 IU/mL undetectable. (NCT01290679)
Timeframe: Up to Week 48
| Intervention | Days (Median) |
|---|
| TMC435 150mg 12Wks PR24/48 | 29 |
| PBO 12Wks PR48 | 113 |
The Number of Participants With Viral Breakthrough
Viral breakthrough was defined as a confirmed increase of greater than 1 log10 IU/mL in plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels from the lowest level reached or a confirmed value of plasma HCV RNA of > 2.0 log10 IU/mL in particpants whose plasma HCV RNA level had previously been below 1.2 log10 IU/mL detectable or undetectable during the treatment period. The table below shows that no viral breakthrough was noted in any participants during the treatment period of the study. (NCT01290731)
Timeframe: Day 1 until end of treatment (EOT [Week 24 or 48])
| Intervention | Participants (Number) |
|---|
| TMC435 100 mg 12 Wks + PR24/48 | 0 |
The Percentage of Participants With a Sustained Virologic Response 12 Weeks After the Actual End of Treatment (SVR12)
The table below shows the percentage of participants with an SVR12 defined as participants with undetectable plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) at the end of treatment (Week 24 or 48) who also had undetectable plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) 12 weeks after the last dose of treatment (Week 36 or 60). (NCT01290731)
Timeframe: Week 36 or 60
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 100 mg 12 Wks + PR24/48 | 95.9 |
The Percentage of Participants With a Sustained Virologic Response 24 Weeks After the Actual End of Treatment (SVR24)
The table below shows the percentage of participants with a SVR24 defined as participants with undetectable plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) at the end of treatment (Week 24 or 48) and at 24 weeks after the last dose of treatment (Week 48 or 72). (NCT01290731)
Timeframe: Week 48 or 60
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 100 mg 12 Wks + PR24/48 | 89.8 |
Plasma Concentrations of TMC435
"The table below shows median (range) TMC435 predose plasma concentration (C0h) values and the TMC435 maximum plasma concentration (Cmax) values for all participants who received TMC435 for up to 12 weeks. Overall is the median exposure estimate using all available data for each participant in the study.Sparse blood samples were collected during the study (blood sampling times were 3 and 5 hours post- dose at Week 2 and Week 8 and pre-dose and 2 hours post-dose at Week 4 and Week 12)." (NCT01290731)
Timeframe: Overall (blood sampling times were 3 and 5 hours post- dose at Week 2 and Week 8 and pre-dose and 2 hours post-dose at Week 4 and Week 12)
| Intervention | ng/mL (Median) |
|---|
| C0h | Cmax |
|---|
| TMC435 100 mg 12 Wks + PR24/48 | 1822 | 3440 |
The Percentage of Participants Who Achieved a Greater Than or Equal to 2 log10 IU/mL Drop From Baseline in Plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) at Each Time Point During Treatment and Follow-up
The table below shows the percentage of participants with greater than or equal to 2 log10 IU/mL drop from baseline in plasma HCV RNA at each time point during treatment, at the end of treatment (Week 24 or 48), and post-treatment follow-up. (NCT01290731)
Timeframe: Days 3 and 7, Weeks 2, 3, 4, 8, 12, 16, 20, 24, 28, 36, 48, 60, 72, EOT, and follow-up (FU) Weeks 4, 12, and 24
| Intervention | Percentage of participants (Number) |
|---|
| Day 3 | Day 7 | Week 2 | Week 3 | Week 4 | Week 8 | Week 12 | Week 16 | Week 20 | Week 24 | Week 28 | Week 36 | Week 48 | Week 60 | Week 72 | EOT | FU Week 4 | FU Week 12 | FU Week 24 |
|---|
| TMC435 100 mg 12 Wks + PR24/48 | 93.9 | 100.0 | 100.0 | 98.0 | 100.0 | 100.0 | 100.0 | 98.0 | 100.0 | 95.9 | 100.0 | 93.9 | 89.8 | 89.8 | 89.8 | 100 | 100 | 95.9 | 91.8 |
The Percentage of Participants With Undetectable Plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) During Treatment and at the End of Treatment (EOT)
The table below shows the percentage of participants with undetectable HCV RNA (defined as less than 1.2 log10 IU/mL during treatment at Weeks 4, 12, 24, 36, 48, 60, 72, and at EOT [Week 24 or 48]). (NCT01290731)
Timeframe: Weeks 4, 12, 24, 36, 48, 60, 72, and at EOT
| Intervention | Percentage of participants (Number) |
|---|
| Week 4 | Week 12 | Week 24 | Week 36 | Week 48 | Week 60 | Week 72 | EOT |
|---|
| TMC435 100 mg 12 Wks + PR24/48 | 81.6 | 100.0 | 95.9 | 91.8 | 89.8 | 89.8 | 89.8 | 100.0 |
Area Under the Plasma Concentration-time Curve From 0 to 24 Hrs (AUC24h) for TMC435
"The table below shows the median (range) AUC24h values for TMC435 for all participants who received TMC435 for up to 12 weeks. Overall is the median exposure estimate using all available data for each participant in the study. Sparse blood samples were collected during the study (blood sampling times were 3 and 5 hours post- dose at Week 2 and Week 8 and pre-dose and 2 hours post-dose at Week 4 and Week 12)." (NCT01290731)
Timeframe: Overall (blood sampling times were 3 and 5 hours post- dose at Week 2 and Week 8 and pre-dose and 2 hours post-dose at Week 4 and Week 12)
| Intervention | ng.h/mL (Median) |
|---|
| TMC435 100 mg 12 Wks + PR24/48 | 63261 |
The Number of Participants Demonstrating Viral Relapse
The table below shows the number of participants who demonstrated viral relapse, defined as undetectable Hepatitis C Virus Ribonucleic Acid (HCV RNA) at end of treatment (EOT) and detectable HCV RNA during follow-up or detectable HCV RNA at the time points of sustained virologic response (SVR) assessment . The incidence of viral relapse was calculated for participants with undetectable HCV RNA levels at EOT and with at least one follow-up HCV RNA measurement. (NCT01290731)
Timeframe: Up to 72 weeks
| Intervention | Participants (Number) |
|---|
| TMC435 100 mg 12 Wks + PR24/48 | 4 |
The Number of Participants With Abnormal Alanine Aminotransferase (ALT) Levels at Baseline Who Achieved Normal ALT Levels at the End of Treatment (EOT)
The table below shows the number of participants with abnormal ALT levels at baseline (Day 1) who achieved normalization of ALT levels (defined as an ALT value less than or equal to the Upper Limit of Normality [ie, 40 IU/mL] at EOT). At baseline, 15/49 participants had abnormal ALT levels. (NCT01290731)
Timeframe: EOT (Week 24 or 48)
| Intervention | Participants (Number) |
|---|
| TMC435 100 mg 12 Wks + PR24/48 | 11 |
The Number of Participants With Viral Breakthrough
Viral breakthrough was defined as a confirmed increase of > 1 log10 IU/mL in plasma levels of hepatitis C virus (HCV) ribonucleic acid (RNA)l from the lowest level reached or a confirmed value of plasma HCV RNA of > 2.0 log10 IU/mL in participants whose plasma HCV RNA level had previously been below 1.2 log10 IU/mL detectable or undetectable during the treatment period (up to the end of treatment [EOT]). (NCT01292239)
Timeframe: Up to EOT (up to Week 24 or 48)
| Intervention | Participants (Number) |
|---|
| TMC435 100 mg 12 Wks + PR 24/48 | 1 |
| PBO 12 Wks + PR 48 | 2 |
The Percentage of Participants in the TMC435 Treatment Group Who Met Response Guided Treatment (RGT) Criteria and Completed Treatment With Peginterferon Alpha-2a (PegIFN Alpha-2a) and Ribavirin (RBV) at Week 24
The table below shows the percentage of participants in the TMC435 treatment group who met RGT criteria (ie, who had plasma levels of hepatitis C virus ribonucleic acid [HCV RNA] <1.2 log10 IU/mL detectable/undetectable at Week 4 and <1.2 log 10 IU/mL undetectable at Week 12) and completed treatment with pegIFN alpha 2a and RBV at Week 24. Participants in the TMC435 treatment group not meeting RGT criteria and participants in the placebo group continued treatment with PegIFN alpha 2a and RBV to Week 48. (NCT01292239)
Timeframe: Week 24
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 100 mg 12 Wks + PR 24/48 | 91.9 |
The Percentage of Participants With a Sustained Virologic Response at the End of Treatment (EOT) and 12 Weeks After the Last Dose of Treatment (SVR12)
The table below shows the observed percentage of participants with a SVR12 defined as undetectable plasma hepatitis C virus (HCV) ribonucleic acid (RNA) at EOT (Week 24 or 48) and at 12 weeks after the last dose of treatment (Week 36 or 60). (NCT01292239)
Timeframe: EOT (up to Week 24 or 48) and 12 weeks after the EOT (up to Week 36 or 60)
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 100 mg 12 Wks + PR 24/48 | 88.6 |
| PBO 12 Wks + PR 48 | 61.7 |
The Percentage of Participants With a Sustained Virologic Response at the End of Treatment (EOT) and 24 Weeks After the Last Dose of Treatment (SVR24)
The table below shows the observed percentage of participants with a SVR24 defined as undetectable plasma hepatitis C virus (HCV) ribonucleic acid (RNA) at the end of treatment (EOT, defined as up to Week 24 or 48) and at 24 weeks after the last dose of treatment (up to Week 48 or 72). (NCT01292239)
Timeframe: EOT (up to Week 24 or 48) and 24 weeks after the after the last dose of treatment (up to Week 48 or 72)
| Intervention | Percentage of participants (Number) |
|---|
| TMC435 100 mg 12 Wks + PR 24/48 | 88.6 |
| PBO 12 Wks + PR 48 | 56.7 |
Plasma Concentrations of TMC435
"The table below shows median (range) predose plasma concentration (C0h) values and median (range) maximum plasma concentration (Cmax) values for TMC435 for all participants in the TMC435 treatment group. The time frame of Overall (up to Week 12) represents the median exposure estimate using all available data for each participant in the study." (NCT01292239)
Timeframe: Overall (ie, Up to Week 12)
| Intervention | ng/mL (Median) |
|---|
| C0h | Cmax |
|---|
| TMC435 100 mg 12 Wks + PR 24/48 | 1005 | 2601 |
The Percentage of Participants Who Achieved a Greater Than or Equal to 2 log10 IU/mL Drop From Baseline in Plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) at Each Time Point During Treatment and Follow-up
The table below shows the percentage of participants with greater than (>) or equal to (=) 2 log10 IU/mL drop from baseline in plasma levels of HCV RNA at each time point during treatment and post-treatment follow-up (FU). (NCT01292239)
Timeframe: Day 3, Day 7 and Weeks 2, 3, 4, 8, 12, 16, 20, 24, 28, 36, 42, 48, 52, 60, 72, EOT (up to Week 24 or 48), FU Week 4, 12, and 24
| Intervention | Percentage of participants (Number) |
|---|
| Day 3 | Day 7 | Week 2 | Week 3 | Week 4 | Week 8 | Week 12 | Week 16 | Week 20 | Week 24 | Week 28 | Week 36 | Week 42 | Week 48 | Week 52 | Week 60 | Week 72 | EOT (up to Week 24 or 48) | FU Week 4 | FU Week 12 | FU Week 24 |
|---|
| PBO 12 Wks + PR 48 | 26.7 | 46.7 | 58.3 | 71.7 | 76.7 | 88.3 | 88.3 | 88.3 | 86.7 | 83.3 | 80.0 | 80.0 | 76.7 | 75.0 | 71.7 | 65.0 | 58.3 | 96.7 | 83.3 | 65.0 | 58.3 |
,| TMC435 100 mg 12 Wks + PR 24/48 | 98.4 | 99.2 | 100.0 | 100.0 | 99.2 | 100.0 | 97.6 | 95.1 | 95.9 | 92.7 | 94.3 | 87.8 | 2.4 | 86.2 | 0.0 | 88.6 | 88.6 | 99.2 | 96.7 | 89.4 | 88.6 |
The Percentage of Participants With Undetectable Plasma Levels of Hepatitis C Virus Ribonucleic Acid (HCV RNA) During Treatment and at the End of Treatment (EOT)
The table below shows the percentage of participants with undetectable plasma levels of HCV RNA <1.2 log10 IU/mL during treatment at Weeks 4, 12, 24, 36, 48, 60, 72, and at the EOT (up to Week 24 or 48). (NCT01292239)
Timeframe: Weeks 4, 12, 24, 36, 48, 60, 72, and at EOT (up to Week 24 or 48)
| Intervention | Percentage of participants (Number) |
|---|
| Week 4 | Week 12 | Week 24 | Week 36 | Week 48 | Week 60 | Week 72 | EOT (up to Week 24 or 48) |
|---|
| PBO 12 Wks + PR 48 | 13.3 | 63.3 | 73.3 | 71.7 | 75.0 | 61.7 | 56.7 | 88.3 |
,| TMC435 100 mg 12 Wks + PR 24/48 | 83.7 | 96.7 | 91.9 | 87.0 | 86.2 | 88.6 | 88.6 | 99.2 |
The Number of Participants Demonstrating Viral Relapse
The table below shows the number of participants who demonstrated viral relapse, defined as undetectable plasma levels of hepatitis C virus (HCV) ribonucleic acid (RNA) at the End of Treatment (EOT) (up to Week 24 or 48) and detectable HCV RNA during follow-up or detectable plasma levels of HCV RNA at the time points of sustained virologic response (SVR) assessment. The incidence of viral relapse was only calculated for participants with undetectable plasma levels of HCV RNA at the EOT and with at least one follow-up HCV RNA. measurement. (NCT01292239)
Timeframe: Up to Week 72
| Intervention | Participants (Number) |
|---|
| TMC435 100 mg 12 Wks + PR 24/48 | 9 |
| PBO 12 Wks + PR 48 | 15 |
Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24h) for TMC435
"The table below shows the median (range) AUC24h values for TMC435 for all participants in the TMC435 treatment group who received TMC435 for up to 12 weeks. The time frame of Overall (up to Week 12) represents the median exposure estimate using all available data for each participant in the study." (NCT01292239)
Timeframe: Overall (Up to Week 12)
| Intervention | ng.h/mL (Median) |
|---|
| TMC435 100 mg 12 Wks + PR 24/48 | 42721 |
The Number of Participants With Abnormal Alanine Aminotransferase (ALT) Levels at Baseline Who Achieved Normal ALT Levels at the End of Treatment (EOT)
The table below shows the number of participants with abnormal ALT levels at Baseline (Day 1) who achieved normal ALT levels at the EOT (up to Week 24 or 48). At Baseline, 61/123 participants in the TMC435 treatment group and 25/60 participants in the Placebo treatment group had abnormal ALT levels. At the EOT, 47 (77.0%) participants in the TMC435 treatment group and 18 (72.0%) participants in the Placebo treatment group had ALT levels that returned to normal (or normalization of ALT levels defined as an ALT value less than or equal to the Upper Limit of Normality [ie, 40 IU/mL] at EOT.). (NCT01292239)
Timeframe: Baseline (Day 1) to EOT (up to Week 24 or 48)
| Intervention | Participants (Number) |
|---|
| TMC435 100 mg 12 Wks + PR 24/48 | 47 |
| PBO 12 Wks + PR 48 | 18 |
The Percentage of Participants Who Met Response Guided Treatment (RGT) Criteria and Completed Treatment With Peginterferon Alpha-2b (PegIFNα-2b) and Ribavirin (RBV) at Week 24
"The table below shows the percentage of participants in each treatment group who met RGT criteria (ie, who had plasma levels of hepatitis C virus ribonucleic acid [HCV RNA] <1.2 log10 IU/mL detectable/undetectable at Week 4 and <1.2 log 10 IU/mL undetectable at Week 12) and completed treatment with PegIFNα-2b and RBV at Week 24. Participants in the TMC435 Treatment-Naïve and TMC435 Prior Relapser treatment groups not meeting RGT criteria continued treatment with PegIFNα-2a and RBV to Week 48 (does not apply to the TMC435 Non-responder treatment group because the specified treatment duration was 48 weeks and RGT criteria was not assessed at Week 24). NOTE: All outcome measures reported in this study are Exploratory; not Primary as indicated (refer to Limits and Caveats)." (NCT01366638)
Timeframe: Week 24 or 48
| Intervention | Percentage of participants (Number) |
|---|
| Treatment-Naive: TMC435 100 mg 12 Wks+PR 24/48 | 91.7 |
| Prior Relapser: TMC435 100 mg 12 Wks+PR 24/48 | 96.6 |
The Number of Participants With Abnormal Alanine Aminotransferase (ALT) Levels at Baseline Who Achieved Normal Limit of ALT at the End of Treatment (EOT)
"The table below shows the number of participants in each treatment group with abnormal ALT levels at Baseline who achieved normalization of ALT levels defined as having an ALT value less than or equal to the Upper Limit of Normality (ie, 40 IU/mL) at EOT. At Baseline, 15 treatment-naïve participants, 13 prior relapsers, and 13 prior non-responders had abnormal ALT levels at Baseline. NOTE: All outcome measures reported in this study are Exploratory; not Primary as indicated (refer to Limits and Caveats)." (NCT01366638)
Timeframe: Up to Week 48
| Intervention | Percentage of participants (Number) |
|---|
| Treatment-Naive: TMC435 100 mg 12 Wks+PR 24/48 | 13 |
| Prior Relapser: TMC435 100 mg 12 Wks+PR 24/48 | 8 |
| Prior Non-Responder: TMC435 100 mg 12 Wks+PR 48 | 8 |
The Percentage of Participants With a Sustained Virologic Response 12 Weeks After the Actual End of Treatment (SVR12)
"The table below shows the percentage of participants in each treatment group with an SVR12 defined as participants with undetectable plasma Hepatitis C virus (HCV) ribonucleic acid (RNA) at the end of treatment (Week 24 or 48) who also had undetectable plasma HCV RNA 12 weeks after the last dose of treatment (Week 36 or 60). NOTE: All outcome measures reported in this study are Exploratory; not Primary as indicated (refer to Limits and Caveats)." (NCT01366638)
Timeframe: Week 36 or 60
| Intervention | Percentage of Participants (Number) |
|---|
| Treatment-Naive: TMC435 100 mg 12 Wks+PR 24/48 | 91.7 |
| Prior Relapser: TMC435 100 mg 12 Wks+PR 24/48 | 100.0 |
| Prior Non-Responder: TMC435 100 mg 12 Wks+PR 48 | 38.5 |
The Percentage of Participants With Undetectable Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) During Treatment and at the End of Treatment
"The table below shows the percentage of participants in each treatment group with undetectable HCV RNA less than 1.2 log10 IU/mL during treatment and at end of treatment (EOT). NOTE: All outcome measures reported in this study are Exploratory; not Primary as indicated (refer to Limits and Caveats)." (NCT01366638)
Timeframe: Weeks 4, 12, 24, 36, 48, 60, 72, and EOT (up to Week 48)
| Intervention | Percentage of participants (Number) |
|---|
| Week 4 | Week 12 | Week 24 | Week 36 | Week 48 | Week 60 | Week 72 | EOT |
|---|
| Prior Non-Responder: TMC435 100 mg 12 Wks+PR 48 | 57.7 | 76.9 | 65.4 | 57.7 | 53.8 | 38.5 | 38.5 | 57.7 |
,| Prior Relapser: TMC435 100 mg 12 Wks+PR 24/48 | 86.2 | 100 | 96.6 | 96.6 | 96.6 | 96.6 | 96.6 | 100 |
,| Treatment-Naive: TMC435 100 mg 12 Wks+PR 24/48 | 79.2 | 100 | 100 | 87.5 | 83.3 | 91.7 | 91.7 | 100 |
The Percentage of Participants Who Achieved a Greater Than or Equal to 2 log10 IU/mL Drop From Baseline in Plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) at Each Time Point During Treatment and Follow-up
"The table below shows the percentage of participants in each treatment group with greater than or equal to 2 log10 IU/mL drop from baseline in plasma hepatitis C virus (HCV) ribonucleic acid (RNA) at each time point during treatment and post-treatment follow-up. NOTE: All outcome measures reported in this study are Exploratory; not Primary as indicated (refer to Limits and Caveats)." (NCT01366638)
Timeframe: Day 3, Day 7 and Weeks 2, 3, 4, 8, 12, 16, 20, 24, 28, 36, 48, 60, 72, EOT (up to Week 24 or 48), follow-up (FU) Week 4, 12, and 24
| Intervention | Percentage of participants (Number) |
|---|
| Day 3 | Day 7 | Week 2 | Week 3 | Week 4 | Week 8 | Week 12 | Week 16 | Week 20 | Week 24 | Week 28 | Week 36 | Week 48 | Week 60 | Week 72 | EOT | FU Week 4 | FU Week 12 | FU Week 24 |
|---|
| Prior Non-Responder: TMC435 100 mg 12 Wks+PR 48 | 88.5 | 100 | 100 | 96.2 | 96.2 | 92.3 | 84.6 | 76.9 | 76.9 | 73.1 | 69.2 | 65.4 | 61.5 | 42.3 | 38.5 | 80.8 | 46.2 | 42.3 | 38.5 |
,| Prior Relapser: TMC435 100 mg 12 Wks+PR 24/48 | 100 | 100 | 100 | 100 | 100 | 100 | 100 | 96.6 | 100 | 96.6 | 96.6 | 96.6 | 96.6 | 96.6 | 96.6 | 100 | 100 | 100 | 96.6 |
,| Treatment-Naive: TMC435 100 mg 12 Wks+PR 24/48 | 100 | 100 | 100 | 100 | 100 | 100 | 100 | 100 | 95.8 | 100 | 91.7 | 87.5 | 83.3 | 91.7 | 91.7 | 100 | 95.8 | 91.7 | 91.7 |
Plasma Concentrations of TMC435
"The table below shows the median (range) TMC435 predose plasma concentrations (C0h) and maximum concentration (Cmax) values for participants in each treatment group. Overall is the median exposure estimate using all available data for each participant in the study. NOTE: All outcome measures reported in this study are Exploratory; not Primary as indicated (refer to Limits and Caveats)." (NCT01366638)
Timeframe: Overall (Up to Week 12)
| Intervention | ng/mL (Median) |
|---|
| Cmax | C0h |
|---|
| Prior Non-Responder: TMC435 100 mg 12 Wks+PR 48 | 2521 | 921 |
,| Prior Relapser: TMC435 100 mg 12 Wks+PR 24/48 | 3643 | 2015 |
,| Treatment-Naive: TMC435 100 mg 12 Wks+PR 24/48 | 2304 | 735 |
The Percentage of Participants With a Sustained Virologic Response 24 Weeks After the Actual End of Treatment (SVR24)
"The table below shows the percentage of participants in each treatment group with a SVR24 defined as participants with undetectable plasma hepatitis C virus (HCV) ribonucleic acid (RNA) at the end of treatment and at 24 weeks after the last dose of treatment (Week 48 or 72). NOTE: All outcome measures reported in this study are Exploratory; not Primary as indicated (refer to Limits and Caveats)." (NCT01366638)
Timeframe: 24 weeks after the last dose of treatment (Week 48 or 72)
| Intervention | Percentage of participants (Number) |
|---|
| Treatment-Naive: TMC435 100 mg 12 Wks+PR 24/48 | 91.7 |
| Prior Relapser: TMC435 100 mg 12 Wks+PR 24/48 | 96.6 |
| Prior Non-Responder: TMC435 100 mg 12 Wks+PR 48 | 38.5 |
The Number of Participants With Viral Breakthrough
"The table below shows the number of participants in each treatment group who experienced viral breakthrough during the TMC435 treatment period. Viral breakthrough is defined as a confirmed increase of greater than 1 log10 IU/mL in plasma hepatitis C virus (HCV) ribonucleic acid (RNA) level from the lowest level reached or a confirmed value of plasma HCV RNA of greater than 2.0 log10 IU/mL in participants whose plasma HCV RNA level had previously been reported below 1.2 log10 IU/mL detectable or undetectable. NOTE: All outcome measures reported in this study are Exploratory; not Primary as indicated (refer to Limits and Caveats)." (NCT01366638)
Timeframe: Up to 48 Weeks
| Intervention | Participants (Number) |
|---|
| Treatment-Naive: TMC435 100 mg 12 Wks+PR 24/48 | 0 |
| Prior Relapser: TMC435 100 mg 12 Wks+PR 24/48 | 0 |
| Prior Non-Responder: TMC435 100 mg 12 Wks+PR 48 | 2 |
The Number of Participants Demonstrating Viral Relapse
"The table below shows the number of participants in each treatment group who demonstrated viral relapse, defined as having undetectable plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels at end of treatment (EOT [Week 24 or 48]) and detectable HCV RNA during follow-up or detectable HCV RNA at the time points of an assessment of sustained virologic response (SVR). The number of participants analyzed in each treatment group below are those with undetectable HCV RNA levels at EOT and with at least one follow-up HCV RNA measurement. NOTE: All outcome measures reported in this study are Exploratory; not Primary as indicated (refer to Limits and Caveats)." (NCT01366638)
Timeframe: Up to 72 weeks
| Intervention | Participants (Number) |
|---|
| Treatment-Naive: TMC435 100 mg 12 Wks+PR 24/48 | 2 |
| Prior Relapser: TMC435 100 mg 12 Wks+PR 24/48 | 1 |
| Prior Non-Responder: TMC435 100 mg 12 Wks+PR 48 | 4 |
The Area Under the Plasma Concentration-Time Curve (From 0 to 24 Hours) (AUC24h)
"The table below shows the median (range) AUC24h values for TMC435 for all participants in each TMC435 treatment group who received TMC435 for up to 12 weeks. Overall is the median exposure estimate using all available data for each participant in the study. NOTE: All outcome measures reported in this study are Exploratory; not Primary as indicated (refer to Limits and Caveats)." (NCT01366638)
Timeframe: Overall (Up to Week 12)
| Intervention | ng·h/mL (Median) |
|---|
| Treatment-Naive: TMC435 100 mg 12 Wks+PR 24/48 | 35448 |
| Prior Relapser: TMC435 100 mg 12 Wks+PR 24/48 | 68130 |
| Prior Non-Responder: TMC435 100 mg 12 Wks+PR 48 | 40645 |
Number of Participants With a Sustained Virologic Response (SVR) 4 Weeks After the Planned End of Treatment (EOT)
Participants with hepatitis C virus (HCV) ribonucleic acid (RNA) undetectable at end of treatment and HCV RNA less than (<) 25 international unit per milliliter (IU/mL) (detectable or undetectable) at 4 weeks after the planned end of treatment. (NCT01466790)
Timeframe: Week 12 and 16 (for the arms treated for 12 weeks) or Week 24 and 28 (for the arms treated for 24 weeks)
| Intervention | Participants (Number) |
|---|
| Cohort 1: TMC435, PSI-7977 and Ribavirin for 24 Weeks | 20 |
| Cohort 1: TMC435 and PSI-7977 for 24 Weeks | 14 |
| Cohort 1: TMC435, PSI-7977 and Ribavirin for 12 Weeks | 26 |
| Cohort 1: TMC435 and PSI-7977 for 12 Weeks | 13 |
| Cohort 2: TMC435, PSI-7977 and Ribavirin for 24 Weeks | 28 |
| Cohort 2: TMC435 and PSI-7977 for 24 Weeks | 16 |
| Cohort 2: TMC435, PSI-7977 and Ribavirin for 12 Weeks | 26 |
| Cohort 2: TMC435 and PSI-7977 for 12 Weeks | 14 |
Number of Participants With a Sustained Virologic Response (SVR) at Week 48
Participants with HCV RNA undetectable at end of treatment and HCV RNA less than (<) 25 IU/mL (detectable or undetectable) at week 48. (NCT01466790)
Timeframe: Week 48
| Intervention | Participants (Number) |
|---|
| Cohort 1: TMC435, PSI-7977 and Ribavirin for 24 Weeks | 19 |
| Cohort 1: TMC435 and PSI-7977 for 24 Weeks | 14 |
| Cohort 1: TMC435, PSI-7977 and Ribavirin for 12 Weeks | 26 |
| Cohort 1: TMC435 and PSI-7977 for 12 Weeks | 13 |
| Cohort 2: TMC435, PSI-7977 and Ribavirin for 24 Weeks | 27 |
| Cohort 2: TMC435 and PSI-7977 for 24 Weeks | 16 |
| Cohort 2: TMC435, PSI-7977 and Ribavirin for 12 Weeks | 24 |
| Cohort 2: TMC435 and PSI-7977 for 12 Weeks | 13 |
Number of Participants With a Sustained Virologic Response (SVR) 24 Weeks After the Planned End of Treatment (EOT)
Participants with HCV RNA undetectable at end of treatment and HCV RNA less than (<) 25 IU/mL (detectable or undetectable) at 24 weeks after the planned end of treatment. (NCT01466790)
Timeframe: Week 12 and 36 (for the arms treated for 12 weeks) or Week 24 and 48 (for the arms treated for 24 weeks)
| Intervention | Participants (Number) |
|---|
| Cohort 1: TMC435, PSI-7977 and Ribavirin for 24 Weeks | 19 |
| Cohort 1: TMC435 and PSI-7977 for 24 Weeks | 14 |
| Cohort 1: TMC435, PSI-7977 and Ribavirin for 12 Weeks | 26 |
| Cohort 1: TMC435 and PSI-7977 for 12 Weeks | 13 |
| Cohort 2: TMC435, PSI-7977 and Ribavirin for 24 Weeks | 28 |
| Cohort 2: TMC435 and PSI-7977 for 24 Weeks | 16 |
| Cohort 2: TMC435, PSI-7977 and Ribavirin for 12 Weeks | 25 |
| Cohort 2: TMC435 and PSI-7977 for 12 Weeks | 13 |
Number of Participants With a Sustained Virologic Response (SVR) 12 Weeks After the Planned End of Treatment (EOT)
Participants with hepatitis C virus (HCV) ribonucleic acid (RNA) undetectable at end of treatment and HCV RNA less than (<) 25 international unit per milliliter (IU/mL) (detectable or undetectable) at 12 weeks after the planned end of treatment. (NCT01466790)
Timeframe: Week 12 and 24 (for the arms treated for 12 weeks) or Week 24 and 36 (for the arms treated for 24 weeks)
| Intervention | Participants (Number) |
|---|
| Cohort 1: TMC435, PSI-7977 and Ribavirin for 24 Weeks | 19 |
| Cohort 1: TMC435 and PSI-7977 for 24 Weeks | 14 |
| Cohort 1: TMC435, PSI-7977 and Ribavirin for 12 Weeks | 26 |
| Cohort 1: TMC435 and PSI-7977 for 12 Weeks | 13 |
| Cohort 2: TMC435, PSI-7977 and Ribavirin for 24 Weeks | 28 |
| Cohort 2: TMC435 and PSI-7977 for 24 Weeks | 16 |
| Cohort 2: TMC435, PSI-7977 and Ribavirin for 12 Weeks | 25 |
| Cohort 2: TMC435 and PSI-7977 for 12 Weeks | 13 |
Number of Participants With Inadequate Virologic Response
Inadequate Virologic Response was defined as confirmed detectable HCV RNA at or after Week 8 and not meeting the viral breakthrough definition. (NCT01466790)
Timeframe: Week 8 and End of Treatment [Week 12 (for the arms treated for 12 weeks) or Week 24 (for the arms treated for 24 weeks)]
| Intervention | Participants (Number) |
|---|
| Cohort 1: TMC435, PSI-7977 and Ribavirin for 24 Weeks | 0 |
| Cohort 1: TMC435 and PSI-7977 for 24 Weeks | 0 |
| Cohort 1: TMC435, PSI-7977 and Ribavirin for 12 Weeks | 0 |
| Cohort 1: TMC435 and PSI-7977 for 12 Weeks | 0 |
| Cohort 2: TMC435, PSI-7977 and Ribavirin for 24 Weeks | 0 |
| Cohort 2: TMC435 and PSI-7977 for 24 Weeks | 0 |
| Cohort 2: TMC435, PSI-7977 and Ribavirin for 12 Weeks | 0 |
| Cohort 2: TMC435 and PSI-7977 for 12 Weeks | 0 |
Number of Participants With Viral Breakthrough
Viral breakthrough was defined as confirmed quantifiable HCV RNA after becoming less than (<) lower limit of quantification (LLOQ) or confirmed greater than (>) 1 log10 HCV RNA increase from the lowest level reached on 2 consecutive occasions. (NCT01466790)
Timeframe: Up to End of Treatment [Week 12 (for the arms treated for 12 weeks) or Week 24 (for the arms treated for 24 weeks)]
| Intervention | Participants (Number) |
|---|
| Cohort 1: TMC435, PSI-7977 and Ribavirin for 24 Weeks | 0 |
| Cohort 1: TMC435 and PSI-7977 for 24 Weeks | 0 |
| Cohort 1: TMC435, PSI-7977 and Ribavirin for 12 Weeks | 0 |
| Cohort 1: TMC435 and PSI-7977 for 12 Weeks | 0 |
| Cohort 2: TMC435, PSI-7977 and Ribavirin for 24 Weeks | 0 |
| Cohort 2: TMC435 and PSI-7977 for 24 Weeks | 0 |
| Cohort 2: TMC435, PSI-7977 and Ribavirin for 12 Weeks | 0 |
| Cohort 2: TMC435 and PSI-7977 for 12 Weeks | 0 |
Number of Participants With Viral Relapse
Viral relapse was defined as undetectable HCV RNA at the actual EOT and confirmed quantifiable HCV RNA (>= 25 IU/mL) during follow-up period. (NCT01466790)
Timeframe: During the Follow-up [Week 36 (for the arms treated for 12 weeks) or Week 24 (for the arms treated for 24 weeks)]
| Intervention | Participants (Number) |
|---|
| Cohort 1: TMC435, PSI-7977 and Ribavirin for 24 Weeks | 1 |
| Cohort 1: TMC435 and PSI-7977 for 24 Weeks | 0 |
| Cohort 1: TMC435, PSI-7977 and Ribavirin for 12 Weeks | 1 |
| Cohort 1: TMC435 and PSI-7977 for 12 Weeks | 1 |
| Cohort 2: TMC435, PSI-7977 and Ribavirin for 24 Weeks | 0 |
| Cohort 2: TMC435 and PSI-7977 for 24 Weeks | 0 |
| Cohort 2: TMC435, PSI-7977 and Ribavirin for 12 Weeks | 2 |
| Cohort 2: TMC435 and PSI-7977 for 12 Weeks | 1 |
Percentage of Participants With Viral Relapse
Participants were considered to have a viral relapse when, at actual end of treatment, HCV RNA levels were less than 25 IU per mL undetectable; and during the follow-up period, HCV RNA levels were more than or equal to 25 IU per mL. (NCT01479868)
Timeframe: Week 1 to 72
| Intervention | percentage of participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 10.3 |
Percentage of Participants With Viral Breakthrough
Confirmed increase of more than 1 log10 IU per mL in HCV RNA level from the lowest level reached, or a confirmed HCV RNA level of more than 100 IU per mL in participants whose HCV RNA levels had previously been below the limit of quantification (less than 25 IU per mL detectable) or undetectable (less than 25 IU per mL undetectable), while on study therapy. (NCT01479868)
Timeframe: Week 1 to 48
| Intervention | percentage of participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 11.4 |
Percentage of Participants With Sustained Virologic Response at Week 12 (SVR 12)
The SVR 12 was defined as hepatitis C virus (HCV) ribonucleic acid (RNA) levels less than (<) 25 international unit per milliliter (IU/mL) undetectable at the actual end of treatment (EOT), and HCV RNA levels <25 IU/mL undetectable or HCV RNA levels <25 IU/mL detectable at 12 Weeks after end of treatment. (NCT01479868)
Timeframe: 12 weeks after end of treatment (Week 24 or 48)
| Intervention | percentage of participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 73.6 |
Percentage of Participants With On-treatment Failure
Participants were considered as an on-treatment failure if, at actual end of treatment (EOT), there was confirmed detectable HCV RNA levels. (NCT01479868)
Timeframe: Week 1 to 48
| Intervention | percentage of participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 17 |
Percentage of Participants With Normalized Alanine Aminotransferase Levels
Participants with normalized alanine aminotransferase levels observed whose alanine aminotransferase levels were out of range at Baseline. (NCT01479868)
Timeframe: Baseline up to Week 72
| Intervention | percentage of participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 81.5 |
Percentage of Human Immunodeficiency Virus (HIV) Participants With Virologic Failure
Participants had confirmed HIV virologic failure if HIV viral load values were greater than or equal to 50 or 200 copies/mL among those who previously had less than 50 copies/mL. (NCT01479868)
Timeframe: Baseline to Week 72.
| Intervention | percentage of participants (Number) |
|---|
| Greater than or equal to 50 copies/mL | Greater than or equal to 200 copies/mL |
|---|
| TMC435 150mg 12Wks PR24/48 | 5.4 | 2.2 |
Percentage of Participants With Sustained Virologic Response at Week 24 (SVR 24)
The SVR 24 was defined as hepatitis C virus (HCV) ribonucleic acid (RNA) levels less than (<) 25 international unit per milliliter (IU/mL) undetectable at the actual end of treatment (EOT), and HCV RNA levels <25 IU/mL undetectable or HCV RNA levels <25 IU/mL detectable at 24 weeks after end of treatment. (NCT01479868)
Timeframe: 24 weeks after end of treatment (Week 24 or 48)
| Intervention | percentage of participants (Number) |
|---|
| TMC435 150mg 12Wks PR24/48 | 72.6 |
Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between administration of study drug and up to Day 126 that were absent before treatment or that worsened relative to pre-treatment state. (NCT01479868)
Timeframe: Week 1 to Week 72
| Intervention | participants (Number) |
|---|
| TEAEs | TESAEs |
|---|
| TMC435 150mg 12Wks PR24/48 | 102 | 6 |
Mean Change From Baseline in Log10 Plasma Human Immunodeficiency Virus (HIV) Viral Load
(NCT01479868)
Timeframe: Baseline (Day 1), Week 2, 4, 8, 12, 16, 20, 24, 28, 36, 42, 48, 52, 60 and 72
| Intervention | copies per milliliter (Mean) |
|---|
| Baseline (n=93) | Change at Week 2 (n=91) | Change at Week 4 (n=93) | Change at Week 8 (n=92) | Change at Week 12 (n=90) | Change at Week 16 (n=88) | Change at Week 20 (n=86) | Change at Week 24 (n=88) | Change at Week 28 (n=82) | Change at Week 36 (n=85) | Change at Week 42 (n=35) | Change at Week 48 (n=79) | Change at Week 52 (n=36) | Change at Week 60 (n=40) | Change at Week 72 (n=38) | Change at End of study (n=93) |
|---|
| TMC435 150mg 12Wks PR24/48 | 1.3726 | -0.0724 | -0.0704 | -0.0442 | -0.0655 | -0.0829 | -0.0847 | -0.0689 | -0.0564 | 0.0004 | -0.0623 | -0.0041 | 0.0011 | -0.0184 | -0.0265 | 0.0099 |
Mean Change From Baseline in CD4+ Cell Count
(NCT01479868)
Timeframe: Baseline (Day 1), Week 2, 4, 8, 12, 16, 20, 24, 28, 36, 42, 48, 52, 60 and 72
| Intervention | cell counts per microliter (Mean) |
|---|
| Baseline (n=93) | Change at Week 2 (n=89) | Change at Week 4 (n=91) | Change at Week 8 (n=92) | Change at Week 12 (n=91) | Change at Week 16 (n=88) | Change at Week 20 (n=84) | Change at Week 24 (n=89) | Change at Week 28 (n=82) | Change at Week 36 (n=83) | Change at Week 42 (n=33) | Change at Week 48 (n=77) | Change at Week 52 (n=35) | Change at Week 60 (n=40) | Change at Week 72 (n=38) | Change at End of Study (n=93) |
|---|
| TMC435 150mg 12Wks PR24/48 | 640.3 | -95.0 | -171.5 | -244.2 | -271.7 | -275.5 | -283.5 | -288.8 | -252.3 | -198.7 | -336.8 | -166.6 | -202.7 | -90.6 | -62.9 | -51.1 |
Change From Baseline in CD4+ Cell Count in Percentage
(NCT01479868)
Timeframe: Baseline (Day 1), Week 2, 4, 8, 12, 16, 20, 24, 28, 36, 42, 48, 52, 60 and 72
| Intervention | percentage of lymphocyte (Mean) |
|---|
| Baseline (n=93) | Change at Week 2 (n=89) | Change at Week 4 (n=91) | Change at Week 8 (n=92) | Change at Week 12 (n=91) | Change at Week 16 (n=88) | Change at Week 20 (n=84) | Change at Week 24 (n=89) | Change at Week 28 (n=82) | Change at Week 36 (n=83) | Change at Week 42 (n=33) | Change at Week 48 (n=77) | Change at Week 52 (n=35) | Change at Week 60 (n=40) | Change at Week 72 (n=38) | Change at End of study (n=93) |
|---|
| TMC435 150mg 12Wks PR24/48 | 31.65 | 0.42 | 2.50 | 3.85 | 3.93 | 5.47 | 5.27 | 5.50 | 3.79 | 2.75 | 6.41 | 2.09 | 3.26 | 0.25 | 0.70 | 0.13 |
Percentage of Participants With Hepatitis C Virus Ribonucleic Acid (HCV-RNA) Less Than (<) 25 International Units (IU/mL) Undetectable or Detectable/Undetectable
Percentage of participants with HCV RNA less than (<) 25 IU/mL undetectable (undet.) or detectable (det.)/undetectable at specific time points were observed. (NCT01479868)
Timeframe: Week 4, 12, 24, 36, and 48
| Intervention | percentage of participants (Number) |
|---|
| Week 4: < 25 IU/mL HCV-RNA undet. (n=105) | Week 4:< 25 IU/mL HCV-RNA det./undet. (n=105) | Week 12:< 25 IU/mL HCV-RNA undet. (n=97) | Week 12:< 25 IU/mL HCV-RNA det./undet. (n=97) | Week 24:< 25 IU/mL HCV-RNA undet. (n=90) | Week 24:< 25 IU/mL HCV-RNA det./undet. (n=90) | Week 48:< 25 IU/mL HCV-RNA undet. (n=20) | Week 48:< 25 IU/mL HCV-RNA det./undet. (n=20) |
|---|
| TMC435 150mg 12Wks PR24/48 | 65.7 | 88.6 | 94.8 | 97.9 | 90.0 | 93.3 | 100 | 100 |
Percentage of Participants With Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12)
Participants are considered to have reached SVR12 if both conditions below are met: 1) HCV RNA levels less than (<) 25 International unit per milliliter (IU/mL) undetectable; 2) HCV RNA levels <25 IU/mL undetectable or HCV RNA levels <25 IU/mL detectable. (NCT01485991)
Timeframe: 12 Weeks After the Planned End of Treatment (EOT: Week 48)
| Intervention | percentage of participants (Number) |
|---|
| Simeprevir+Placebo+Peginterferon Alfa-2a+Ribavirin | 53.6 |
| Telaprevir+Placebo+Peginterferon Alfa-2a+Ribavirin | 54.7 |
Percentage of Participants With Viral Relapse
Participants are considered to have a viral relapse if both conditions as specified are met: 1) <25 IU/mL undetectable HCV RNA at the actual end of study drug treatment; 2) confirmed HCV RNA greater than or equal to (>=) 25 IU/mL during follow-up. (NCT01485991)
Timeframe: End of Treatment (Week 48) up to Follow-up Period (until Week 72)
| Intervention | percentage of participants (Number) |
|---|
| Simeprevir+Placebo+Peginterferon Alfa-2a+Ribavirin | 17.9 |
| Telaprevir+Placebo+Peginterferon Alfa-2a+Ribavirin | 16.4 |
Percentage of Participants With Sustained Virologic Response 24 Weeks After the Planned End of Treatment (SVR24)
Participants are considered to have reached SVR24 if both conditions below are met: 1) HCV RNA levels less than <25 International unit per milliliter (IU/mL) undetectable (at the actual end of treatment);2) HCV RNA levels <25 IU/mL undetectable or HCV RNA levels <25 IU/mL detectable (24 weeks after the planned EOT). (NCT01485991)
Timeframe: 24 Weeks After the Planned EOT (Week 48)
| Intervention | percentage of participants (Number) |
|---|
| Simeprevir+Placebo+Peginterferon Alfa-2a+Ribavirin | 53.3 |
| Telaprevir+Placebo+Peginterferon Alfa-2a+Ribavirin | 55.2 |
Percentage of Participants With Rapid Virologic Response (RVR) at Week 4
RVR was defined as hepatitis C virus (HCV) RNA levels to be NCT01628692)
Timeframe: Week 4
| Intervention | Percentage of participants (Number) |
|---|
| Genotype 1b: Daclatasvir + Simeprevir (Naive) | 79.2 |
| Genotype 1b: Daclatasvir + Simeprevir (Null) | 69.6 |
| Genotype 1b: Daclatasvir + Simeprevir + Ribavirin (Naive) | 68.6 |
| Genotype 1b: Daclatasvir + Simeprevir + Ribavirin (Null) | 85 |
| Genotype 1a: Daclatasvir + Simeprevir + Ribavirin (Naive) | 75 |
| Genotype 1a: Daclatasvir + Simeprevir + Ribavirin (Null) | 33.3 |
Percentage of Participants With Sustained Virologic Response at Week 12 (SVR12) by rs12979860 Single Nucleotide Polymorphisms in the IL-28B Gene Categories
Participants were categorized into 3 genotypes based on single nucleotide polymorphisms in the IL28B gene. SVR12 was defined as hepatitis C virus (HCV) RNA levels below lower limit of quantitation, target detected or target not detected at follow-up Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. (NCT01628692)
Timeframe: Baseline, post-treatment Week 12 (Follow-up period)
| Intervention | Percentage of participants (Number) |
|---|
| IL28B Genotype CC type (n= 16,1,13,1,3,0) | IL28B Genotype CT type (n= 22,15, 28,10,9,8) | IL28B Genotype TT type (n= 12,6,10,7,0,1) |
|---|
| Genotype 1a: Daclatasvir + Simeprevir + Ribavirin (Naive) | 66.7 | 66.7 | NA |
,| Genotype 1a: Daclatasvir + Simeprevir + Ribavirin (Null) | NA | 0 | 0 |
,| Genotype 1b: Daclatasvir + Simeprevir (Naive) | 87.5 | 95.5 | 66.7 |
,| Genotype 1b: Daclatasvir + Simeprevir (Null) | 100 | 60 | 83.3 |
,| Genotype 1b: Daclatasvir + Simeprevir + Ribavirin (Naive) | 84.6 | 82.1 | 40 |
,| Genotype 1b: Daclatasvir + Simeprevir + Ribavirin (Null) | 100 | 90 | 100 |
Percentage of Participants With Sustained Virologic Response Rate at Post-treatment Week 12 (SVR12)
SVR12 rate was defined as hepatitis C virus (HCV) RNA levels to be NCT01628692)
Timeframe: Post Treatment Week 12 (Follow-up period)
| Intervention | Percentage of participants (Number) |
|---|
| Genotype 1b: Daclatasvir + Simeprevir (Naive) | 84.9 |
| Genotype 1b: Daclatasvir + Simeprevir (Null) | 69.6 |
| Genotype 1b: Daclatasvir + Simeprevir + Ribavirin (Naive) | 74.5 |
| Genotype 1b: Daclatasvir + Simeprevir + Ribavirin (Null) | 95 |
| Genotype 1a: Daclatasvir + Simeprevir + Ribavirin (Naive) | 66.7 |
| Genotype 1a: Daclatasvir + Simeprevir + Ribavirin (Null) | 0 |
Percentage of Participants With Extended Rapid Virologic Response (eRVR)
eRVR were defined as hepatitis C virus (HCV) RNA levels to be NCT01628692)
Timeframe: Week 4 and Week 12
| Intervention | Percentage of participants (Number) |
|---|
| Genotype 1b: Daclatasvir + Simeprevir (Naive) | 71.7 |
| Genotype 1b: Daclatasvir + Simeprevir (Null) | 60.9 |
| Genotype 1b: Daclatasvir + Simeprevir + Ribavirin (Naive) | 62.7 |
| Genotype 1b: Daclatasvir + Simeprevir + Ribavirin (Null) | 75 |
| Genotype 1a: Daclatasvir + Simeprevir + Ribavirin (Naive) | 58.3 |
| Genotype 1a: Daclatasvir + Simeprevir + Ribavirin (Null) | 11.1 |
Percentage of Participants With Complete Early Virologic Response (cEVR)
cEVR was defined as hepatitis C virus (HCV) RNA levels to be NCT01628692)
Timeframe: Week 12
| Intervention | Percentage of participants (Number) |
|---|
| Genotype 1b: Daclatasvir + Simeprevir (Naive) | 84.9 |
| Genotype 1b: Daclatasvir + Simeprevir (Null) | 73.9 |
| Genotype 1b: Daclatasvir + Simeprevir + Ribavirin (Naive) | 82.4 |
| Genotype 1b: Daclatasvir + Simeprevir + Ribavirin (Null) | 90 |
| Genotype 1a: Daclatasvir + Simeprevir + Ribavirin (Naive) | 66.7 |
| Genotype 1a: Daclatasvir + Simeprevir + Ribavirin (Null) | 11.1 |
Percentage of Participants With End of Treatment Response (EOTR)
EOTR were defined as hepatitis C virus (HCV) RNA levels NCT01628692)
Timeframe: End of treatment (Week 24)
| Intervention | Percentage of participants (Number) |
|---|
| Genotype 1b: Daclatasvir + Simeprevir (Naive) | 88.7 |
| Genotype 1b: Daclatasvir + Simeprevir (Null) | 78.3 |
| Genotype 1b: Daclatasvir + Simeprevir + Ribavirin (Naive) | 78.4 |
| Genotype 1b: Daclatasvir + Simeprevir + Ribavirin (Null) | 95 |
| Genotype 1a: Daclatasvir + Simeprevir + Ribavirin (Naive) | 66.7 |
| Genotype 1a: Daclatasvir + Simeprevir + Ribavirin (Null) | 0 |
Number of Participants With Serious Adverse Events (SAEs) and Discontinuations Due to Adverse Events (AEs) and Who Died
AE was defined as any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. SAE was defined as a medical event that at any dose resulted in death, persistent or significant disability/incapacity, or drug dependency/abuse; was life-threatening, an important medical event, or a congenital anomaly/birth defect; or required or prolonged hospitalization. Based on the severity, AEs were categorized as Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death. (NCT01628692)
Timeframe: From start of treatment (Day 1) up to 7 days post last dose of study treatment (Week 24)
| Intervention | Participants (Number) |
|---|
| SAEs | AEs Leading to Discontinuation | Death |
|---|
| Genotype 1b: Daclatasvir + Simeprevir (Naive + Null) | 7 | 2 | 1 |
,| Genotype1a: Daclatasvir +Simeprevir + Ribavirin(Naive + Null) | 1 | 0 | 0 |
,| Genotype1b: Daclatasvir +Simeprevir + Ribavirin (Naive + Null) | 3 | 2 | 0 |
Percentage of Participants With On-treatment Failure
A participant with on-treatment failure refers to a participant with confirmed detectable HCV RNA at the end of treatment. (NCT01725529)
Timeframe: End of Treatment (EOT: Week 24 or 48)
| Intervention | percentage of participants (Number) |
|---|
| Placebo | 12.5 |
| Simeprevir (TMC435) 100mg | 3.3 |
| Simeprevir (TMC435) 150mg | 3.3 |
Percentage of Participants With Viral Breakthrough
The number of patients who experience viral breakthrough will be determined by measuring Hepatitis C virus (HCV) ribonucleic acid (RNA) levels in plasma. Viral breakthrough was defined as a confirmed increase of >1 log10 IU/mL in HCV RNA level from the lowest level reached, or a confirmed HCV RNA level of >100 IU/mL in subjects whose HCV RNA levels had previously been below the limit of quantification (<25 IU/mL detectable) or undetectable (<25 IU/mL undetectable) while on study treatment. (NCT01725529)
Timeframe: Week 24 or 48 (End of Treatment)
| Intervention | percentage of participants (Number) |
|---|
| Placebo | 2.0 |
| Simeprevir (TMC435) 100mg | 2.6 |
| Simeprevir (TMC435) 150mg | 2.6 |
Percentage of Participants With Sustained Virologic Response at Week 72 (SVRW72)
(NCT01725529)
Timeframe: Week 72
| Intervention | percentage of participants (Number) |
|---|
| Placebo | 75.0 |
| Simeprevir (TMC435) 100mg | 87.6 |
| Simeprevir (TMC435) 150mg | 90.1 |
Percentage of Participants With Sustained Virologic Response 24 Weeks After End of Study Drug Treatment (SVR24)
Participants considered to have achieved SVR24 if both conditions are met: 1). the hepatitis C virus ribonucleic acid (HCV RNA) is less than (<) lower limit of quantification (LLOQ;25 IU/mL) undetectable at end of treatment and, 2). the HCV RNA is < LLOQ detectable or undetectable at 24 weeks after the planned end of study drug treatment. (NCT01725529)
Timeframe: 24 weeks after the end of treatment (EOT: Week 24 or 48)
| Intervention | percentage of participants (Number) |
|---|
| Placebo | 75.0 |
| Simeprevir (TMC435) 100mg | 88.9 |
| Simeprevir (TMC435) 150mg | 90.8 |
Percentage of Participants With Sustained Virologic Response 12 Weeks After End of Study Drug Treatment (SVR12)
Participants considered to have achieved SVR12 if both conditions are met: 1). the hepatitis C virus ribonucleic acid (HCV RNA) is less than (<) lower limit of quantification (LLOQ; 25 international unit per milliliter [IU/mL]) undetectable at end of treatment and, 2). the HCV RNA is < LLOQ detectable or undetectable at 12 weeks after the planned end of study drug treatment. (NCT01725529)
Timeframe: 12 weeks after the end of treatment (EOT: Week 24 or 48)
| Intervention | Percentage of participants (Number) |
|---|
| Placebo | 75.7 |
| Simeprevir (TMC435) 100mg | 88.9 |
| Simeprevir (TMC435) 150mg | 90.8 |
Percentage of Participants With On-treatment Normalization of Alanine Aminotransferase Level
Percentage of participants with on-treatment normalization of alanine aminotransferase level were assessed. (NCT01725529)
Timeframe: 72 weeks after the EOT (Week 24 or 48)
| Intervention | percentage of participants (Number) |
|---|
| Placebo | 85.7 |
| Simeprevir (TMC435) 100mg | 86.1 |
| Simeprevir (TMC435) 150mg | 89.9 |
Percentage of Participants With Viral Relapse
Viral relapse was defined as undetectable HCV RNA at the actual end of treatment and last HCV RNA measurement during follow-up ≥25 IU/mL. (NCT01725529)
Timeframe: 72 weeks after the EOT (Week 24 or 48)
| Intervention | percentage of participants (Number) |
|---|
| Placebo | 11.5 |
| Simeprevir (TMC435) 100mg | 1.4 |
| Simeprevir (TMC435) 150mg | 2.8 |
Percentage of Participants With HCV RNA (< 25 IU/mL Undetectable) and HCV RNA < 25 IU/mL Detectable
Percentage of participants with detectable and undetectable HCV RNA (<) 25 IU/mL during treatment at Weeks 2,4, 12, and 24 were reported. (NCT01938625)
Timeframe: Weeks 2, 4, 12, and 24
| Intervention | percentage of participants (Number) |
|---|
| Week 2: <25 IU/mL detectable | Week 2: <25 IU/mL undetectable | Week 4: <25 IU/mL detectable | Week 4: <25 IU/mL undetectable | Week 12: <25 IU/mL detectable | Week 12: <25 IU/mL undetectable | Week 24: <25 IU/mL detectable | Week 24: <25 IU/mL undetectable |
|---|
| Cyclosporine | 30 | 10 | 30 | 70 | 0 | 100 | 0 | 100 |
,| Tacrolimus | 36 | 12 | 24 | 68 | 0 | 96 | 0 | 100 |
Percentage of Participants With Sustained Virologic Response 4 Weeks After the End of Treatment (SVR 4)
Participants were considered to have achieved SVR4 if HCV RNA levels were (<) 25 IU/mL detectable or undetectable at 4 weeks after the end of treatment. (NCT01938625)
Timeframe: Week 28
| Intervention | percentage of participants (Number) |
|---|
| Cyclosporine | 100 |
| Tacrolimus | 88 |
Number of Participants With On-Treatment Failure
On-treatment failure is defined as participants who did not achieve SVR12 and with confirmed detectable HCV RNA at the actual end of treatment. This was to include participants with: 1) Viral breakthrough, defined as a confirmed increase of greater than (>)1 log10 in HCV RNA from nadir, or confirmed HCV RNA of >100 IU/mL in participants whose HCV RNA had previously been NCT01938625)
Timeframe: Up to Week 24 after actual EOT (week 24)
| Intervention | participants (Number) |
|---|
| Cyclosporine | 0 |
| Tacrolimus | 3 |
Number of Participants With Viral Breakthrough
Viral breakthrough is defined as a confirmed increase of >1 log10 IU/mL in HCV RNA level from the lowest level reached, or a confirmed HCV RNA level of >100 IU/mL in participants whose HCV RNA levels had previously been below the limit of quantification (<25 IU/mL detectable) or undetectable (<25 IU/mL undetectable) while on study treatment. (NCT01938625)
Timeframe: Up to week 24
| Intervention | participants (Number) |
|---|
| Cyclosporine | 0 |
| Tacrolimus | 3 |
Number of Participants With Viral Relapse
Participants who did not achieve SVR12, with undetectable HCV RNA at the actual end of study drug treatment and confirmed HCV RNA greater than or equal to (>=) LLOQ during follow-up. (NCT01938625)
Timeframe: Up to Week 24 after actual EOT (week 24)
| Intervention | participants (Number) |
|---|
| Cyclosporine | 0 |
| Tacrolimus | 0 |
Percentage of Participants With Sustained Virologic Response 12 Weeks After the End of Treatment (SVR 12)
Participants were considered to have achieved SVR12 if hepatitis C virus ribonucleic acid (HCV RNA) levels were less than (<) 25 international unit per milliliter (IU/mL) detectable or undetectable at 12 weeks after the end of treatment. (NCT01938625)
Timeframe: Week 36
| Intervention | percentage of participants (Number) |
|---|
| Cyclosporine | 100 |
| Tacrolimus | 88 |
Percentage of Participants With Sustained Virologic Response 24 Weeks After the End of Treatment (SVR 24)
Participants were considered to have achieved SVR 24 if hepatitis C virus ribonucleic acid (HCV RNA) levels were (<) 25 IU/mL detectable or undetectable at 24 weeks after the end of treatment. (NCT01938625)
Timeframe: Week 48
| Intervention | percentage of participants (Number) |
|---|
| Cyclosporine | 100 |
| Tacrolimus | 88 |
Percentage of Participants With HCV RNA (<) 100 IU/mL at Week 4
Percentage of participants with HCV RNA (<) 100 IU/mL at week 4 were reported. (NCT01938625)
Timeframe: Week 4
| Intervention | percentage of participants (Number) |
|---|
| Cyclosporine | 100 |
| Tacrolimus | 100 |
Percentage of Participants With Depression by Using Center for Epidemiologic Studies Depression Scale (CES-D)
The CES-D Scale assessed how often during the past week participants experienced 20 symptoms commonly associated with major depression. The CES-D scores range from 0 (no symptoms) to 60 (all 20 symptoms most or all of the time during the past 5 to 7 days). The CES-D scores between 16 and 23 points indicate mild to moderate depressive illness while CES-D scores >=23 indicate probable major depressive illness. (NCT02114151)
Timeframe: Baseline, Week 12, Follow-up Week 12 and 24
| Intervention | Percentage of Participants (Number) |
|---|
| Baseline: No Depression (n=96) | Baseline: Mild to Moderate Depression (n=96) | Baseline: Severe Depression (n=96) | Week 12: No Depression (n=88) | Week 12: Mild to Moderate Depression (n=88) | Week 12: Severe Depression (n=88) | Follow-up Week 12: No Depression (n=94) | Follow-up Week12:Mild to Moderate Depression(n=94) | Follow-up Week 12: Severe Depression (n=94) | Follow-up Week 24: No Depression (n=88) | Follow-up Week24:Mild to Moderate Depression(n=88) | Follow-up Week 24: Severe Depression (n=88) |
|---|
| Simeprevir Plus Sofosbuvir | 67.7 | 16.7 | 15.6 | 77.3 | 15.9 | 6.8 | 79.8 | 6.4 | 13.8 | 79.5 | 10.2 | 10.2 |
Number of Participants Not Achieving SVR Showing Emerging Mutation at Time of Failure in HCV NS3/4A Sequence and NS5B up to Follow-up Week 24
Sequencing of the HCV nonstructural protein 3/4A (NS3/4A) and nonstructural protein 5B (NS5B) genes was done to identify pre-existing sequence polymorphisms and characterize emerging HCV viral variants in participants not achieving SVR. Sequencing data is available for 16 participants. (NCT02114151)
Timeframe: Baseline, Day 3, Week 1, 2, 3, 4, 8, 12, Follow-up Week 4, 12 and 24
| Intervention | Participants (Number) |
|---|
| HCV NS3 | NS5B |
|---|
| Simeprevir Plus Sofosbuvir | 13 | 0 |
Change From Baseline in Hepatitis C Symptom and Impact Questionnaire Version 4 (HCV-SIQv4) Overall Body System Score (OBSS) up to Follow-up Week 12
The HCV-SIQv4 OBSS was a self-administered questionnaire that contained 33 items: 29 questions developed to assess severity or frequency of symptoms associated with HCV or its treatment, 3 questions regarding the impact of symptoms on work/school attendance, and 1 question regarding the impact of symptoms on daily activities. A symptom severity score (the mean of responses to the 29 symptom items); each symptom score was transformed to have a range from 0 to 100 (most severe). Higher HCV SIQv4 scores indicates worse symptom severity, more time missed from work/school, and more impairment in daily activities, respectively. (NCT02114151)
Timeframe: Baseline, Week 4, Week 12 and Follow-Up Week 12
| Intervention | Units on a Scale (Mean) |
|---|
| Baseline (n=98) | Change at Week 4 (n=96) | Change at Week 12 (n=89) | Change at Follow-up Week 12 (n=94) |
|---|
| Simeprevir Plus Sofosbuvir | 17.4 | -4.9 | -4.7 | -5.8 |
Change From Baseline in Fatigue Severity Score (FSS) up to Follow-up Week 24
The FSS was a self-administered questionnaire with 9 items developed to assess disabling fatigue that has been used extensively in studies of chronic HCV infection. Item responses were measured on a 7-point Likert scale ranging from strongly disagree (1 point) to strongly agree (7 points). The 9 items were averaged to produce a total score; a lower total score indicates less severe fatigue. FSS scores have a range from 1 to 7 where higher scores indicate more severe fatigue. (NCT02114151)
Timeframe: Baseline, Week 12, Follow-up Week 12 and 24
| Intervention | Units on a Scale (Mean) |
|---|
| Baseline (n=96) | Change at Week 12 (n=86) | Change at Follow-up Week 12 (n=92) | Change at Follow-up Week 24 (n=86) |
|---|
| Simeprevir Plus Sofosbuvir | 3.4 | -0.4 | -0.6 | -0.8 |
Change From Baseline in EuroQol 5 Dimension Questionnaire (EQ-5D) up to Follow-up Week 24
"The EQ-5D questionnaire was a brief, generic health-related quality of life (HRQOL) assessment that could also be used to incorporate participant preferences into health economic evaluations. The EQ-5D questionnaire assessed HRQOL in terms of degree of limitation on 5 health dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) and as overall health using a thermometer visual analog scale with response options ranging from 0 (worst imaginable health) to 100 (best imaginable health)." (NCT02114151)
Timeframe: Baseline, Follow-up Week 12 and 24
| Intervention | Units on a Scale (Mean) |
|---|
| Baseline (n=96) | Change at Follow-up Week 12 (n=92) | Change at Follow-up Week 24 (n=86) |
|---|
| Simeprevir Plus Sofosbuvir | 70.1 | 9.8 | 9.5 |
Percentage of Participants With a Sustained Virologic Response (SVR) 24 Weeks After the Actual End of Treatment (EOT)
Participants with hepatitis C virus (HCV) ribonucleic acid (RNA) less than (<) 25 international unit per milliliter (IU/mL) (detectable or undetectable) at 24 weeks after the actual end of treatment. (NCT02114151)
Timeframe: Week 36
| Intervention | Percentage of Participants (Number) |
|---|
| Simeprevir Plus Sofosbuvir | 82.5 |
Percentage of Participants With a Sustained Virologic Response (SVR) 4 Weeks After the Actual End of Treatment (EOT)
Participants with hepatitis C virus (HCV) ribonucleic acid (RNA) less than (<) 25 international unit per milliliter (IU/mL) (detectable or undetectable) at 4 weeks after the actual end of treatment. (NCT02114151)
Timeframe: Week 16
| Intervention | Percentage of Participants (Number) |
|---|
| Simeprevir Plus Sofosbuvir | 86.4 |
Percentage of Participants With On-treatment Failure
On-treatment failure is defined as participants who do not achieve SVR12 and with confirmed detectable HCV RNA at the actual end of study drug treatment. (NCT02114151)
Timeframe: Week 12
| Intervention | Percentage of Participants (Number) |
|---|
| Simeprevir Plus Sofosbuvir | 2.9 |
Percentage of Participants With Viral Breakthrough
Viral breakthrough was defined as confirmed greater than (>) 1 log10 increase in HCV RNA from nadir or confirmed HCV RNA >100 IU/mL in participants who had previously achieved HCV RNA < LLOQ (25 IU/mL). (NCT02114151)
Timeframe: Up to End of Treatment (Week 12)
| Intervention | Percentage of Participants (Number) |
|---|
| Simeprevir Plus Sofosbuvir | 1.9 |
Percentage of Participants With Viral Relapse
Viral relapse was defined as participants who did not achieve SVR12 and had HCV RNA < LLOQ (25 IU/mL) undetectable at EOT and had HCV RNA >= LLOQ (25 IU/mL) during the follow-up period. (NCT02114151)
Timeframe: During the Follow-up (Week 24)
| Intervention | Percentage of Participants (Number) |
|---|
| Simeprevir Plus Sofosbuvir | 13.1 |
Percentage of Participants With a Sustained Virologic Response (SVR) 12 Weeks After the Actual End of Treatment (EOT)
Participants with hepatitis C virus (HCV) ribonucleic acid (RNA) less than (<) 25 international unit per milliliter (IU/mL) (detectable or undetectable) at 12 weeks after the actual end of treatment. (NCT02114151)
Timeframe: Week 24
| Intervention | Percentage of Participants (Number) |
|---|
| Simeprevir Plus Sofosbuvir | 83.5 |
Percentage of Participants With On-treatment Virologic Response
On-treatment virologic response was determined by HCV RNA results satisfying a specified threshold. NCT02114151)
Timeframe: Week 2, 4 and End of Treatment (Week 12)
| Intervention | Percentage of Participants (Number) |
|---|
| Week 2: < 100 IU/mL (n=102) | Week 2: < 25 IU/mL (n=102) | Week 2: < 25 IU/mL Detectable (n=102) | Week 2: < 25 IU/mL Undetectable (n=102) | Week 4: < 100 IU/mL (n=102) | Week 4: < 25 IU/mL (n=102) | Week 4: < 25 IU/mL Detectable (n=102) | Week 4: < 25 IU/mL Undetectable (n=102) | EOT (Week 12): < 100 IU/mL (n=103) | EOT (Week 12): < 25 IU/mL (n=103) | EOT (Week 12): < 25 IU/mL Detectable (n=103) | EOT (Week 12): < 25 IU/mL Undetectable (n=103) |
|---|
| Simeprevir Plus Sofosbuvir | 90.2 | 68.6 | 44.1 | 24.5 | 99.0 | 99.0 | 15.7 | 83.3 | 97.1 | 97.1 | 0 | 97.1 |
Percentage of Participants Achieving a Sustained Virologic Response 24 Weeks After the Actual End of Treatment (SVR24)
Participants considered to have achieved SVR24, if the hepatitis C virus ribonucleic acid (HCV RNA) is less than (<) lower limit of quantification (LLOQ; 25 international unit per milliliter [IU/mL]) detectable or undetectable at 24 weeks after the Actual end of study drug treatment. (NCT02114177)
Timeframe: 24 weeks after the end of treatment (EOT) (Week 32 or Week 36)
| Intervention | Percentage of participants (Number) |
|---|
| Simeprevir and Sofosbuvir for 8 Weeks | 82.6 |
| Simeprevir and Sofosbuvir for 12 Weeks | 96.8 |
Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Actual End of Treatment (SVR12)
Participants considered to have achieved SVR12, if the hepatitis C virus ribonucleic acid (HCV RNA) is less than (<) lower limit of quantification (LLOQ; 25 international unit per milliliter [IU/mL]) detectable or undetectable at 12 weeks after the actual end of study drug treatment. (NCT02114177)
Timeframe: 12 weeks after the end of treatment (EOT) (Week 20 or Week 24)
| Intervention | Percentage of participants (Number) |
|---|
| Simeprevir and Sofosbuvir for 8 Weeks | 82.6 |
| Simeprevir and Sofosbuvir for 12 Weeks | 96.8 |
Percentage of Participants Achieving a On-treatment Virologic Response
Ontreatment virologic response was determined by HCV RNA results satisfying a specified threshold. NCT02114177)
Timeframe: Day 14, Day 28, End of treatment (Week 8 or Week 12)
| Intervention | Percentage of participants (Number) |
|---|
| Day 14: < 100 IU/mL (n=154, 152) | Day 14: < 25 IU/mL (n=154, 152) | Day 14: < 25 IU/mL detectable (n=154, 152) | Day 14: < 25 IU/mL undetectable (n=154, 152) | Day 28: < 100 IU/mL (n=154, 153) | Day 28: < 25 IU/mL (n=154, 153) | Day 28: < 25 IU/mL detectable (n=154, 153) | Day 28: < 25 IU/mL undetectable (n=154, 153) | EOT: < 100 IU/mL (n=155, 155) | EOT: < 25 IU/mL (n=155, 155) | EOT: < 25 IU/mL undetectable (n=155, 155) |
|---|
| Simeprevir and Sofosbuvir for 12 Weeks | 93.4 | 79.6 | 45.4 | 34.2 | 100 | 98.7 | 11.1 | 87.6 | 100 | 100 | 100 |
,| Simeprevir and Sofosbuvir for 8 Weeks | 90.9 | 77.92 | 40.26 | 37.66 | 100 | 98.7 | 16.2 | 82.5 | 100 | 100 | 100 |
Percentage of Participants Achieving a Sustained Virologic Response 4 Weeks After the Actual End of Treatment (SVR4)
Participants considered to have achieved SVR4, if the hepatitis C virus ribonucleic acid (HCV RNA) is less than (<) lower limit of quantification (LLOQ; 25 international unit per milliliter [IU/mL]) detectable or undetectable at 4 weeks after the actual end of study drug treatment. (NCT02114177)
Timeframe: 4 weeks after the end of treatment (EOT) (Week 12 or Week 16)
| Intervention | Percentage of Participants (Number) |
|---|
| Simeprevir and Sofosbuvir for 8 Weeks | 83.9 |
| Simeprevir and Sofosbuvir for 12 Weeks | 96.8 |
Percentage of Participants With Viral Breakthrough
Percentage of participants with greater than 1 log10 IU/mL increase in plasma Hepatitis C virus ribonucleic acid level from the lowest level reached (ie, lowest value measured in between baseline and current value), or a confirmed plasma HCV RNA level of greater than 100 IU/mL in participants whose plasma HCV RNA had previously been less than 25 IU/mL. (NCT02114177)
Timeframe: Up to Week 24
| Intervention | Percentage of participants (Number) |
|---|
| Simeprevir and Sofosbuvir for 8 Weeks | 0 |
| Simeprevir and Sofosbuvir for 12 Weeks | 0 |
Percentage of Participants With Viral Relapse
Percentage of participants who did not achieve sustained virologic response 12, have less than 25 IU/mL undetectable plasma HCV RNA at end of treatment, and greater than or equal to 25 IU/mL plasma HCV RNA during the follow-up phase. (NCT02114177)
Timeframe: Up to Week 24
| Intervention | Percentage of participants (Number) |
|---|
| Simeprevir and Sofosbuvir for 8 Weeks | 17.4 |
| Simeprevir and Sofosbuvir for 12 Weeks | 2.6 |
Change From Baseline in Center for Epidemiologic Studies Depression Scale (CES-D) Scores
The CES-D scale assesses how often during the past week participants experienced 20 symptoms commonly associated with major depression. CES-D scores range from 0 (no symptoms) to 60 (all 20 symptoms most or all of the time during the past 5-7 days). The CES-D scores between 16 and 23 points indicate mild to moderate depressive illness while CES-D scores greater than or equal to 23 indicate probable major depressive illness. (NCT02114177)
Timeframe: Baseline (Day 1), Week 4, Week 8, Week 12, Follow-up Week 4, Follow-up Week 12 and Follow-up Week 24
| Intervention | units on a scale (Mean) |
|---|
| Baseline (n=144, 149) | Change at Week 4 (n=139, 140) | Change at Week 8 (n=141, 144) | Change at Week 12 (n=141, 144) | Change at Follow-up Week 4 (n=141, 148) | Change at Follow-up Week 12 (n=140, 145) | Change at Follow-up Week 24 (n=131, 143) |
|---|
| Simeprevir and Sofosbuvir for 12 Weeks | 10.2 | -0.8 | -0.3 | 1.0 | -0.6 | -0.1 | -1.0 |
,| Simeprevir and Sofosbuvir for 8 Weeks | 8.8 | -0.6 | -0.6 | NA | -2.6 | -1.5 | -2.8 |
Change From Baseline in EuroQol 5 Dimension (EQ-5D) Visual Analogue Scale
"The EQ-5D questionnaire is a brief, generic health-related quality of life assessment (HRQOL) that can also be used to incorporate participant preferences into health economic evaluations. The EQ-5D questionnaire assesses HRQOL in terms of degree of limitation on 5 health dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) and as overall health using a thermometer visual analog scale with response options ranging from 0 (worst imaginable health) to 100 (best imaginable health). Lower scores indicate worsening." (NCT02114177)
Timeframe: Baseline (Day 1), Week 4, Week 8, Week 12, Follow-up Week 4, Follow-up Week 12 and Follow-up Week 24
| Intervention | units on a scale (Mean) |
|---|
| Baseline (N=144, 149) | Change at Week 4 (n=142, 141) | Change at Week 8 (n=142, 144) | Change at Week 12 (n=0, 140) | Change at Follow-up Week 4 (n=141, 148) | Change at Follow-up Week 12 (n=138, 145) | Change at Follow-up Week 24 (n=131, 143) |
|---|
| Simeprevir and Sofosbuvir for 12 Weeks | 76.7 | 2.4 | 2.7 | 2.5 | 4.4 | 3.9 | 5.3 |
,| Simeprevir and Sofosbuvir for 8 Weeks | 79.3 | 4.6 | 4.0 | NA | 6.9 | 5.5 | 6.2 |
Change From Baseline in Fatigue Severity Scale (FSS) Score up to Follow-up Week 24
The FSS was a self-administered questionnaire with 9 items developed to assess disabling fatigue that has been used extensively in studies of chronic HCV infection. Item responses were measured on a 7point Likert scale ranging from strongly disagree (1 point) to strongly agree (7 points). The 9 items were averaged to produce a total score; a lower total score indicates less severe fatigue. FSS scores have a range from 1 to 7 where higher scores indicate more severe fatigue. (NCT02114177)
Timeframe: Baseline (Day 1), Week 4, Week 8, Week 12, Follow-up Week 4, Follow-up Week 12 and Follow-up Week 24
| Intervention | units on a scale (Mean) |
|---|
| Baseline (n=144, 149) | Change at Week 4 (n=142, 142) | Change at Week 8 (n=142, 144) | Change at Week 12 (n=0, 140) | Change at Follow-up Week 4 (n=141, 148) | Change at Follow-up Week 12 (n=140, 145) | Change at Follow-up Week 24 (n=132, 143) |
|---|
| Simeprevir and Sofosbuvir for 12 Weeks | 3.2 | -0.1 | -0.2 | -0.1 | -0.4 | -0.4 | -0.5 |
,| Simeprevir and Sofosbuvir for 8 Weeks | 2.9 | -0.1 | -0.1 | NA | -0.4 | -0.5 | -0.6 |
Change From Baseline in Hepatitis C Symptom and Impact Questionnaire 4 (HCV-SIQv4) Overall Body System Score (OBSS)
HCVSIQv4 OBSS was a self-administered questionnaire that contained 33 items: 29 questions developed to assess severity or frequency of symptoms associated with HCV or its treatment, 3 questions regarding the impact of symptoms on work/school attendance, and 1 question regarding the impact of symptoms on daily activities. A symptom severity score (the mean of responses to the 29 symptom items); each symptom score was transformed to have a range from 0 to 100 (most severe). Higher HCV SIQv4 scores indicates worse symptom severity, more time missed from work/school, and more impairment in daily activities, respectively. (NCT02114177)
Timeframe: Baseline (Day 1), Week 4, Week 8, Week 12, Follow-up Week 4, Follow-up Week 12 and Follow-up Week 24
| Intervention | units on a scale (Mean) |
|---|
| Baseline (n=145, 149) | Change at Week 4 (n=145, 146) | Change at Week 8 (n=144, 146) | Change at Week 12 (n=0, 141) | Change at Follow-up Week 4 (n=142, 148) | Change at Follow-up Week 12 (n=141, 145) | Change at Follow-up Week 24 (n=133, 143) |
|---|
| Simeprevir and Sofosbuvir for 12 Weeks | 13.3 | -0.9 | -0.4 | 0.1 | -3.0 | -3.5 | -4.4 |
,| Simeprevir and Sofosbuvir for 8 Weeks | 10.8 | -0.4 | -0.2 | NA | -3.5 | -2.0 | -3.6 |
Number of Participants With Treatment Discontinuation
Treatment discontinuation is reported by sub-categories of reasons for treatment discontinuation. Futility rule is defined as HCV RNA drop <3 log10 at Week 8, HCV RNA >/=100 IU/mL at Week 12, or HCV RNA >/=15 IU/mL at Week 24. (NCT02118597)
Timeframe: Up to Week 48
| Intervention | participants (Number) |
|---|
| Sponsor's decision | Adverse event | Futility rule |
|---|
| Triple Combination Therapy | 7 | 4 | 2 |
Number of Participants With Adverse Events
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. (NCT02118597)
Timeframe: Up to 72 weeks
| Intervention | participants (Number) |
|---|
| Triple Combination Therapy | 17 |
Number of Participants With Treatment Discontinuation Due to Futility
Treatment discontinuation due to futility is defined as HCV RNA drop <3 log10 at Week 8, HCV RNA >/=100 IU/mL at Week 12, or HCV RNA >/=15 IU/mL at Week 24. (NCT02118597)
Timeframe: Up to Week 48
| Intervention | participants (Number) |
|---|
| Triple Combination Therapy | 2 |
Number of Participants With Virological Breakthrough
Virological breakthrough is defined as either HCV RNA >=15 IU/mL in participants with prior virological response or as an increase in HCV RNA >/=1 log10 above nadir. (NCT02118597)
Timeframe: Up to Week 48
| Intervention | participants (Number) |
|---|
| Triple Combination Therapy | 1 |
Number of Participants With Virological Relapse
Virological response is defined as HCV RNA >/=15 IU/mL during the treatment free follow-up period in participants with virological response at the end of treatment. (NCT02118597)
Timeframe: Week 49 up to Week 72
| Intervention | participants (Number) |
|---|
| Triple Combination Therapy | 1 |
Sustained Virological Response 24 (SVR24) Rate
The SVR 24 rate is defined as percentage of participants with Hepatitis C virus (HCV) Ribonucleic Acid (RNA) less than 15 international unit/milliliter (IU/mL) after the 24-weeks follow-up. (NCT02118597)
Timeframe: 24 weeks after end of treatment (EOT) at Week 72
| Intervention | percentage of participants (Number) |
|---|
| Triple Combination Therapy | 0 |
Percentage of Participants With Virological Response
Virological response is defined as HCV RNA <15 IU/mL. (NCT02118597)
Timeframe: Weeks 4, 8, 12, and 24
| Intervention | percentage of participants (Number) |
|---|
| Week 4 (n=3) | Week 8 (n=18) | Week 12 (n=17) | Week 24 (n=16) |
|---|
| Triple Combination Therapy | 0.0 | 73.7 | 73.7 | 78.9 |
Proportion of Participants With Sustained Virologic Response 12 (SVR-12)
Undetectable virus (sensitive nucleic acid test) in Serum at 3 months post-therapy (NCT02168361)
Timeframe: 12 weeks post-therapy
| Intervention | participants (Number) |
|---|
| All Oral Therapy | 54 |
| Interferon-containing Arm | 18 |
Serum HCV RNA Level
(NCT02168361)
Timeframe: 4 and 12 weeks into therapy
| Intervention | IU/ml (Median) |
|---|
| Serum HCV RNA level at 4 weeks | Serum HCV RNA level at 8 weeks |
|---|
| All Oral Therapy | 154 | 31 |
,| Interferon-containing Arm | 880 | 740 |
Sustained Viral Response
Comparison of sustained virologic response at 12 weeks post-treatment (SVR12) in 2 arms of IFN-II patients: one receiving 12 weeks of simeprevir (SMV) (150mg QD)+ sofosbuvir (SOF) (400mg QD) and the second receiving to SMV (150mg QD)+SOF (400mg QD)+weight-based ribavirin (RBV) 1000-1200 mg/day. SVR12 is defined as a patient having undetectable hepatitis C virus (HCV) ribonucleic acid (RNA) levels 12 weeks post-treatment. Achieving SVR12 is generally indicative of hepatitis C infection being cured. (NCT02214420)
Timeframe: 12 weeks
| Intervention | Participants (Count of Participants) |
|---|
| SMV+SOF | 13 |
| SMV+SOF+RBV | 8 |
Percentage of Participants With Sustained Virologic Response 24 Weeks After End of Therapy (SVR24)
Participants were considered to have reached SVR24, if at the time point of SVR24 (that is [i.e.], 24 weeks after the end of treatment [EOT]) the following condition has been met: HCV RNA < lower limit of quantification (LLOQ), i.e., 15 IU/mL, detectable or undetectable. (NCT02250807)
Timeframe: At 24 weeks after EOT
| Intervention | percentage of participants (Number) |
|---|
| SMV+SOF 12 Weeks | 100 |
Percentage of Participants With On-Treatment Failure
Participants were considered on-treatment failures if they have at EOT (confirmed) detectable HCV RNA, i.e., =LLOQ. (NCT02250807)
Timeframe: through 12 weeks (EOT)
| Intervention | percentage of participants (Number) |
|---|
| SMV+SOF 12 Weeks | 0 |
Percentage of Participants With Sustained Virologic Response 12 Weeks After End of Treatment (EOT) (SVR12)
SVR12 is defined as the percentage of participants with hepatitis C virus ribonucleic acid (HCV RNA) less than (<) lower limit of quantification (LLOQ; 15 international unit per milliliter [IU/mL]) detectable or undetectable 12 weeks after actual EOT. (NCT02250807)
Timeframe: 12 weeks after EOT
| Intervention | percentage of participants (Number) |
|---|
| SMV+SOF 12 Weeks | 100 |
Percentage of Participants With On-treatment Virologic Response of Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
Percentage of participants with HCV RNA less than (<) 15 IU/mL undetectable or detectable or detectable /undetectable at specific time points were observed. (NCT02250807)
Timeframe: Week 2, 3, 4, 12 and EOT
| Intervention | percentage of participants (Number) |
|---|
| Week 2: < 100 IU/mL | Week 2: < 15 IU/mL undetectable/detectable | Week 2: < 15 IU/mL undetectable | Week 3: < 100 IU/mL | Week 3: < 15 IU/mL undetectable/detectable | Week 3: < 15 IU/mL undetectable | Week 4: < 100 IU/mL | Week 4: < 15 IU/mL undetectable/detectable | Week 4: < 15 IU/mL undetectable (RVR) | Week 12: < 100 IU/mL | Week 12: < 15 IU/mL undetectable/detectable | Week 12: < 15 IU/mL undetectable | End of Treatment (EOT): < 100 IU/mL | EOT: < 15 IU/mL undetectable/detectable | EOT: < 15 IU/mL undetectable |
|---|
| SMV+SOF 12 Weeks | 87.5 | 40.0 | 17.5 | 100.0 | 82.5 | 40.0 | 100.0 | 87.5 | 65.0 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 |
Percentage of Participants With Viral Breakthrough
Participants with confirmed >1.0 log10 increase in HCV RNA from nadir or confirmed HCV RNA >100 IU/mL in participants who had previously achieved HCV RNA NCT02250807)
Timeframe: Up to follow-up Week 24
| Intervention | percentage of participants (Number) |
|---|
| SMV+SOF 12 Weeks | 0 |
Percentage of Participants With Viral Relapse
Participants were considered to have viral relapse if they did not achieve SVR12 and meet the following conditions: 1) at EOT, HCV RNA less than (<)LLOQ, undetectable, and 2) during the follow-up period, HCV RNA greater than or equal to (>=)LLOQ. (NCT02250807)
Timeframe: Up to follow-up week 24
| Intervention | percentage of participants (Number) |
|---|
| SMV+SOF 12 Weeks | 0 |
Percentage of Participants With Sustained Virologic Response 4 Weeks After End of Therapy (SVR4)
SVR4 is defined as the percentage of participants with hepatitis C virus ribonucleic acid (HCV RNA) less than (<) lower limit of quantification (LLOQ; 15 international unit per milliliter [IU/mL]) detectable or undetectable 4 weeks after actual EOT. (NCT02250807)
Timeframe: 4 weeks after EOT
| Intervention | percentage of participants (Number) |
|---|
| SMV+SOF 12 Weeks | 100 |
Percentage of Participants With On-treatment Failure
On-treatment failure is defined as participants who do not achieve SVR12 and with confirmed detectable HCV RNA at the actual end of study drug treatment. (NCT02262728)
Timeframe: Week 12
| Intervention | Percentage of Participants (Number) |
|---|
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | 0 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | 0 |
Percentage of Participants With Sustained Virologic Response 12 Weeks After End of Study Drug Treatment (SVR12)
Participants were considered to have achieved SVR12 if the hepatitis C virus ribonucleic acid (HCV RNA) was less than (<) lower limit of quantification (LLOQ; 15 international unit per milliliter [IU/mL]) detectable or undetectable at 12 weeks after the end of study drug treatment. (NCT02262728)
Timeframe: Week 24
| Intervention | Percentage of Participants (Number) |
|---|
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | 100 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | 100 |
Percentage of Participants With SVR12 Who Maintained to Have HCV RNA Percentage of participants with SVR12 who maintained to have HCV RNA NCT02262728)
Timeframe: Week 24 post treatment until the end of 3-year follow-up
| Intervention | Percentage of participants (Number) |
|---|
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | 78.9 |
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | 85.7 |
Absolute Values of Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) Levels at Follow-up Week 24 (Week 36)
(NCT02262728)
Timeframe: Follow-up Week 24 (Week 36)
| Intervention | Units per Liter (U/L) (Mean) |
|---|
| Baseline : ALT | Baseline : AST | Follow-Up Week 24 : ALT | Follow-Up Week 24 : AST |
|---|
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | 137.8 | 119.1 | 34.8 | 39.2 |
,| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | 60.9 | 83.5 | 32.3 | 35.0 |
Percentage of Participants With On-Treatment Virologic Response
On-treatment virologic response was determined by HCV RNA results satisfying a specified threshold. The following thresholds were considered at any time point: NCT02262728)
Timeframe: Week 1, 2, 4, 6, 8, 10, 12
| Intervention | Percentage of Participants (Number) |
|---|
| Week 1 : >= 15 IU/mL | Week 1 : < 100 IU/mL | Week 1: < 15 IU/mL undetect/detectable | Week 1 : < 15 IU/mL detectable | Week 1 : < 15 IU/mL Undetectable | Week 2 : >= 15 IU/mL | Week 2 : < 100 IU/mL | Week 2: < 15 IU/mL undetect/detectable | Week 2 : < 15 IU/mL detectable | Week 2: < 15 IU/mL undetectable (vRVR) | Week 4 : >= 15 IU/mL | Week 4 : < 100 IU/mL | Week 4: < 15 IU/mL undetect/detectable | Week 4 : < 15 IU/mL detectable | Week 4 : < 15 IU/mL undetectable (RVR) | Week 6 : >= 15 IU/mL | Week 6 : < 100 IU/mL | Week 6: < 15 IU/mL undetect/detectable | Week 6 : < 15 IU/mL detectable | Week 6 : < 15 IU/mL undetectable | Week 8 : >= 15 IU/mL | Week 8 : < 100 IU/mL | Week 8: < 15 IU/mL undetect/detectable | Week 8 : < 15 IU/mL detectable | Week 8 : < 15 IU/mL undetectable | Week 10 : >= 15 IU/mL | Week 10 : < 100 IU/mL | Week 10: < 15 IU/mL undetect/detectable | Week 10 : < 15 IU/mL detectable | Week 10 : < 15 IU/mL undetectable | Week 12 : >= 15 IU/mL | Week 12 :< 100 IU/mL | Week 12: < 15 IU/mL undetect/detectable | Week 12 : < 15 IU/mL detectable | Week 12 : < 15 IU/mL undetectable |
|---|
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | 72.2 | 61.1 | 27.8 | 11.1 | 16.7 | 10.5 | 94.7 | 89.5 | 36.8 | 52.6 | 0 | 100.0 | 100.0 | 5.6 | 94.4 | 0 | 100.0 | 100.0 | 5.3 | 94.7 | 0 | 100.0 | 100.0 | 0 | 100.0 | 0 | 100.0 | 100.0 | 0 | 100.0 | 0 | 100.0 | 100.0 | 0 | 100.0 |
,| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | 76.2 | 38.1 | 23.8 | 19.0 | 4.8 | 47.6 | 71.4 | 52.4 | 19.0 | 33.3 | 9.5 | 100.0 | 90.5 | 28.6 | 61.9 | 0 | 100.0 | 100.0 | 20.0 | 80.0 | 0 | 100.0 | 100.0 | 4.8 | 95.2 | 0 | 100.0 | 100.0 | 0 | 100.0 | 0 | 100.0 | 100.0 | 0 | 100.0 |
Percentage of Participants With SVR 4 Weeks After End of Study Drug Treatment (SVR4) and SVR 24 Weeks After End of Study Drug Treatment (SVR24)
Participants were considered to have achieved SVR4 and SVR24 if the HCV RNA was NCT02262728)
Timeframe: Week 16 and Week 36
| Intervention | Percentage of Participants (Number) |
|---|
| SVR 4 | SVR 24 |
|---|
| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh A | 100 | 100 |
,| SMV 150mg/DCV 60mg/SOF 400mg - Child-Pugh B | 100 | 100 |
Percentage of Participants With Sustained Virologic Response 12 Weeks After End of Study Drug Treatment (SVR12)
Participants were considered to have reached SVR12, if 12 weeks after the actual end of treatment (EOT), hepatitis C virus (HCV) ribonucleic acid (RNA) was less than lower limit of quantification (NCT02268864)
Timeframe: At 12 weeks after end of treatment
| Intervention | percentage of participants (Number) |
|---|
| 12 Weeks Prior Amendment | 70.6 |
| 12 Weeks Post Amendment | 100 |
| 24 Weeks Extension | 93.8 |
Number of Participants With Viral Breakthrough
Participants were considered to have had viral breakthrough if they had a confirmed greater than (>) 1.0 log10 international units/milliliter (IU/mL) increase in HCV RNA from nadir OR confirmed HCV RNA >100 IU/mL while previously having achieved HCV RNA NCT02268864)
Timeframe: Up to Week 24
| Intervention | participants (Number) |
|---|
| 12 Weeks Prior Amendment | 4 |
| 12 Weeks Post Amendment | 0 |
| 24 Weeks Extension | 3 |
Number of Participants With Viral Relapse
Participants were considered to have had viral relapse if they did not achieve SVR12 and met the following conditions: had HCV RNA =LLOQ during the follow-up period. (NCT02268864)
Timeframe: Up to Week 24 after actual EOT
| Intervention | participants (Number) |
|---|
| 12 Weeks Prior Amendment | 0 |
| 12 Weeks Post Amendment | 0 |
| 24 Weeks Extension | 1 |
Percentage of Participants With On-treatment Failure
Participants were considered on-treatment failures if they did not achieve SVR12 and had (confirmed) detectable HCV RNA, ie, =) LLOQ at EOT. (NCT02268864)
Timeframe: Up to Week 24 after actual EOT
| Intervention | percentage of participants (Number) |
|---|
| 12 Weeks Prior Amendment | 29.4 |
| 12 Weeks Post Amendment | 0.0 |
| 24 Weeks Extension | 4.7 |
Percentage of Participants With Sustained Virologic Response 4 Weeks After End of Study Drug Treatment (SVR4)
Participants were considered to have reached SVR4, if 4 weeks after the actual EOT, HCV RNA was NCT02268864)
Timeframe: At 4 weeks after actual EOT
| Intervention | percentage of participants (Number) |
|---|
| 12 Weeks Prior Amendment | 70.6 |
| 12 Weeks Post Amendment | 100 |
| 24 Weeks Extension | 93.8 |
Percentage of Participants With SVR 24 Weeks After End of Study Drug Treatment (SVR 24)
Participants were considered to have reached SVR24, if 24 weeks after the actual EOT, HCV RNA was NCT02268864)
Timeframe: At 24 weeks after actual EOT
| Intervention | percentage of participants (Number) |
|---|
| 12 Weeks Prior Amendment | 70.6 |
| 12 Weeks Post Amendment | 100 |
| 24 Weeks Extension | 93.8 |
Number of Participants With HCV Nonstructural Protein 3/4A (NS3/4A), NS5A and NS5B Sequence in Participants Not Achieving SVR
Sequencing of the HCV nonstructural protein 3/4A (NS3/4A), nonstructural protein 5A (NS5A) and nonstructural protein 5B (NS5B) genes was done to identify preexisting sequence polymorphisms and characterize emerging HCV viral variants in participants not achieving SVR. (NCT02349048)
Timeframe: Up to Week 30 for Arm A and up to Week 32 for Arm B
| Intervention | Participants (Number) |
|---|
| Arm A: Simeprevir/Daclatasvir/Sofosbuvir - 6 Weeks | 8 |
| Arm B: Simeprevir/Daclatasvir/Sofosbuvir - 8 Weeks | 0 |
Number of Participants With Late Viral Relapse
Late Viral Relapse: Participant who achieved SVR12 and the post treatment HCV RNA measurement fulfilled 1 the following conditions: a) at least 2 consecutive measurements not lesser than (<)15 IU/mL undetectable, of which at least the second measurement was >=15 IU/mL quantifiable or b) the last available measurement was >=15 IU/mL quantifiable. (NCT02349048)
Timeframe: From Week 18 to Week 30 (for Arm A), From Week 20 to Week 32 (for Arm B)
| Intervention | Participants (Number) |
|---|
| Arm A: Simeprevir/Daclatasvir/Sofosbuvir - 6 Weeks | 1 |
| Arm B: Simeprevir/Daclatasvir/Sofosbuvir - 8 Weeks | 0 |
Number of Participants With Viral Relapse
Viral Relapse: Participants who did not achieve SVR12, with undetectable HCV RNA at the actual end of study drug treatment and confirmed HCV RNA greater than or equal to (>=) LLOQ during followup. (NCT02349048)
Timeframe: From Week 6 to Week 18 (for Arm A) and From Week 8 to Week 20 (for Arm B)
| Intervention | Participants (Number) |
|---|
| Arm A: Simeprevir/Daclatasvir/Sofosbuvir - 6 Weeks | 7 |
| Arm B: Simeprevir/Daclatasvir/Sofosbuvir - 8 Weeks | 0 |
Percentage of Participants With On-Treatment Failure
Participants who did not achieve SVR12 and with confirmed detectable HCV RNA at the actual end of treatment. Includes participants with: 1) viral breakthrough, defined as a confirmed increase of greater than (>)1 log10 in HCV RNA from nadir, or confirmed HCV RNA 2) confirmed detectable HCV RNA at the actual end of treatment (example, completed treatment, discontinued due to adverse events, withdrawal of consent) of >100 IU/mL in participants whose HCV RNA had previously been NCT02349048)
Timeframe: Baseline up to End of Treatment (Week 6 for Arm A and Week 8 for Arm B)
| Intervention | Percentage of Participants (Number) |
|---|
| Arm A: Simeprevir/Daclatasvir/Sofosbuvir - 6 Weeks | 1.7 |
| Arm B: Simeprevir/Daclatasvir/Sofosbuvir - 8 Weeks | 0 |
Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After End of Study Drug Treatment (SVR12)
Participants were considered to have achieved SVR12 if the hepatitis C virus ribonucleic acid (HCV RNA) was less than (<) lower limit of quantification (LLOQ; 15 international unit per milliliter [IU/mL]) detectable or undetectable at 12 weeks after the end of study drug treatment. (NCT02349048)
Timeframe: 12 weeks after end of study drug treatment (week 18 for Arm A and week 20 for Arm B)
| Intervention | Percentage of Participants (Number) |
|---|
| Arm A: Simeprevir/Daclatasvir/Sofosbuvir - 6 Weeks | 86.4 |
| Arm B: Simeprevir/Daclatasvir/Sofosbuvir - 8 Weeks | 100 |
Percentage of Participants With On-treatment Virologic Response
"On-treatment virologic response was determined by hepatitis C virus (HCV) ribonucleic acid (RNA) results satisfying a specified threshold.~The following thresholds were considered at any time point: NCT02349048)
Timeframe: Day 2, Day 3, Week 1, 2, 3, 4, 6 (for Arm A) and 8 (for Arm B only)
| Intervention | Percentage of Participants (Number) |
|---|
| Day 2 : >= 15 IU/mL (n = 56, 9) | Day 2 : < 100 IU/mL (n = 56, 9) | Day 2 : < 15 IU/mL undetect/detectable (n = 56, 9) | Day 2 : < 15 IU/mL detectable (n = 56, 9) | Day 2: < 15 IU/mL undetectable (n = 56, 9) | Day 3 : >= 15 IU/mL (n = 58, 9) | Day 3 : < 100 IU/mL (n = 58, 9) | Day 3 : < 15 IU/mL undetect/detectable (n = 58, 9) | Day 3 : < 15 IU/mL detectable (n = 58, 9) | Day 3 : < 15 IU/mL undetectable (n = 58, 9) | Week 1: >= 15 IU/mL (n = 58, 9) | Week 1: < 100 IU/mL (n = 58, 9) | Week 1: < 15 IU/mL undetect/detectable (n = 58, 9) | Week 1 : < 15 IU/mL detectable (n = 58, 9) | Week 1 : < 15 IU/mL undetectable (n = 58, 9) | Week 2 : >= 15 IU/mL (n = 56, 9) | Week 2: < 100 IU/mL (n = 56, 9) | Week 2: < 15 IU/mL undetect/detectable (n = 56, 9) | Week 2 : < 15 IU/mL detectable (n = 56, 9) | Week 2: < 15 IU/mL undetectable (vRVR) (n = 56, 9) | Week 3: >= 15 IU/mL (n = 56, 9) | Week 3: < 100 IU/mL (n = 56, 9) | Week 3: < 15 IU/mL undetect/detectable (n = 56, 9) | Week 3 : < 15 IU/mL detectable (n = 56, 9) | Week 3 : < 15 IU/mL undetectable (n = 56, 9) | Week 4 : >= 15 IU/mL (n = 58, 9) | Week 4: < 100 IU/mL (n = 58, 9) | Week 4: < 15 IU/mL undetect/detectable (n = 58, 9) | Week 4 : < 15 IU/mL detectable ( n = 58, 9) | Week 4 : < 15 IU/mL undetectable (RVR) (n = 58, 9) | Week 6 : >= 15 IU/mL (n = 58, 9) | Week 6: < 100 IU/mL ( n = 58, 9) | Week 6: < 15 IU/mL undetect/detectable (n = 58, 9) | Week 6 : < 15 IU/mL detectable (n = 58, 9) | Week 6 : < 15 IU/mL undetectable (n= 58, 9) | Week 8 : >= 15 IU/ml (n = 0, 9) | Week 8: < 100 IU/mL (n = 0, 9) | Week 8: < 15 IU/mL undetect/detectable (n = 0, 9) | Week 8: < 15 IU/mL detectable (n = 0, 9) | Week 8: < 15 IU/mL undetectable (n = 0, 9) |
|---|
| Arm A: Simeprevir/Daclatasvir/Sofosbuvir - 6 Weeks | 96.4 | 7.1 | 3.6 | 3.6 | 0 | 94.8 | 19.0 | 5.2 | 5.2 | 0 | 58.6 | 75.9 | 41.4 | 36.2 | 5.2 | 19.6 | 94.6 | 80.4 | 41.1 | 39.3 | 7.1 | 100 | 92.9 | 21.4 | 71.4 | 3.4 | 98.3 | 96.6 | 8.6 | 87.9 | 0 | 100 | 100 | 6.9 | 93.1 | NA | NA | NA | NA | NA |
,| Arm B: Simeprevir/Daclatasvir/Sofosbuvir - 8 Weeks | 100 | 0 | 0 | 0 | 0 | 100 | 11.1 | 0 | 0 | 0 | 66.7 | 33.3 | 33.3 | 33.3 | 0 | 66.7 | 77.8 | 33.3 | 0 | 33.3 | 33.3 | 100 | 66.7 | 22.2 | 44.4 | 11.1 | 100 | 88.9 | 33.3 | 55.6 | 0 | 100 | 100 | 0 | 100 | 0 | 100 | 100 | 0 | 100 |
Percentage of Participants With or Without an NS3 Q80K Polymorphism at Baseline Achieving SVR
The Q80K polymorphism, associated with low level SMV in vitro resistance. Percentage of participants who achieved SVR with or without an NS3 Q80K polymorphism at baseline were reported. (NCT02349048)
Timeframe: up to Week 30 for Arm A and Week 32 for Arm B
| Intervention | Percentage of Participants (Number) |
|---|
| With NS3 Q80K polymorphism at baseline (n=25,9) | Without NS3 Q80K polymorphism at baseline (n=23,9) |
|---|
| Arm A: Simeprevir/Daclatasvir/Sofosbuvir - 6 Weeks | 88.0 | 78.3 |
,| Arm B: Simeprevir/Daclatasvir/Sofosbuvir - 8 Weeks | 100 | 100 |
Percentage of Participants With Sustained Virologic Response at 4 Weeks (SVR4) and 24 Weeks (SVR24) After End of Study Drug Treatment
Participants were considered to have achieved SVR4 and SVR24 if the HCV RNA was NCT02349048)
Timeframe: 4 weeks after end of study drug treatment (week 10 for Arm A and 12 for Arm B); 24 weeks after end of study drug treatment (week 30 for Arm A and 32 for Arm B)
| Intervention | Percentage of Participants (Number) |
|---|
| SVR4 | SVR24 |
|---|
| Arm A: Simeprevir/Daclatasvir/Sofosbuvir - 6 Weeks | 93.2 | 84.7 |
,| Arm B: Simeprevir/Daclatasvir/Sofosbuvir - 8 Weeks | 100 | 100 |
Simeprevir AUC Pharmacokinetics
Determine simeprevir area-under-the concentration time curve (AUC) when administered alone and when being co-administered with Dolutegravier. (NCT02404805)
Timeframe: Pre-dose and, 1, 2, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose on day 7
| Intervention | ng*h/mL (Geometric Mean) |
|---|
| Simeprevir Administered Alone | 30946 |
| Simeprevir and Dolutegravier Co-administered | 30333 |
Dolutegravir AUC Pharmacokinetics
Determine Dolutegravir area-under-the concentration time curve (AUC) when administered alone and when co-administered with simeprevir. (NCT02404805)
Timeframe: Pre-dose and, 1, 2, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose on day 7
| Intervention | ng*h/mL (Geometric Mean) |
|---|
| Dolutegravir Administered Alone | 68186 |
| Simeprevir and Dolutegravier Co-administered | 78433 |
Percentage of Participants With Sustained Virologic Response (SVR) 4 Weeks After the Actual EOT (SVR4) and 12 Weeks After the Actual EOT (SVR12)
SVR4 or SVR12 is defined as sustained virologic response 4 or 12 weeks after the actual EOT the participant has HCV RNA NCT02421211)
Timeframe: 4 weeks after EOT (Week 4 of follow-up phase in Panel 1 and Panel 2) and 12 weeks after EOT (Week 12 of follow-up phase in Panel 1 and Panel 2)
| Intervention | percentage of participants (Number) |
|---|
| SVR4 | SVR12 |
|---|
| Panel 1:SMV 150mg(SOF 400mg[2weeks]+LDV 90/SOF 400mg[8 Weeks]) | 100 | 100 |
,| Panel 2: SMV 150mg+LDV 90mg/SOF 400mg (8 Weeks) | 100 | 100 |
Average Plasma Concentration at Steady State (Cavg,ss) of Ledipasvir
The Cavg,ss is calculated as area under the plasma concentration-time curve during a dosing Interval (AUC[tau]) divided by the dosing interval (tau). (NCT02421211)
Timeframe: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
| Intervention | ng/mL (Mean) |
|---|
| Panel 2: LDV 90mg/SOF 400mg (Day 14) | 411 |
| Panel 2: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | 725 |
Trough Plasma Concentration (Ctrough) of Simeprevir
The (Ctrough) is the plasma concentration before dosing or at the end of the dosing interval of any dose other than the first dose in a multiple dosing regimen. (NCT02421211)
Timeframe: Pre-dose on Day 14 and Day 28
| Intervention | nanogram per Milliliters (ng/mL) (Mean) |
|---|
| Panel 1: SMV 150 mg + SOF 400 mg (Day 14) | 3059 |
| Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | 8453 |
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. (NCT02421211)
Timeframe: Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
| Intervention | number of participants (Number) |
|---|
| Adverse events | Serious adverse events |
|---|
| Panel 1:SMV 150mg(SOF 400mg[2weeks]+LDV 90/SOF 400mg[8 Weeks]) | 17 | 2 |
,| Panel 2: SMV 150mg+LDV 90mg/SOF 400mg (8 Weeks) | 15 | 0 |
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Ledipasvir
AUCtau is defined as area under the analyte concentration versus time curve during dosing interval tau, calculated by linear-linear trapezoidal summation. (NCT02421211)
Timeframe: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
| Intervention | ng*h/mL (Mean) |
|---|
| Panel 2: LDV 90mg/SOF 400mg (Day 14) | 9868 |
| Panel 2: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | 17435 |
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Simeprevir
The AUCtau is the measure of the plasma drug concentration from time zero to end of dosing interval. It is used to characterize drug absorption. (NCT02421211)
Timeframe: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
| Intervention | nanogram hour per Milliliters (ng*h/mL) (Mean) |
|---|
| Panel 1: SMV 150 mg + SOF 400 mg (Day 14) | 100492 |
| Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | 243564 |
Percentage of Participants With On-treatment Virologic Response
"On-treatment virologic response was determined by hepatitis C virus (HCV) ribonucleic acid (RNA) results satisfying a specified threshold.~The following thresholds were considered at any time point: less than (<) lower limit of quantification (LLOQ) undetectable, NCT02421211)
Timeframe: Week 1, up to EOT (Week 10 in Panel 1 and Week 8 in Panel 2)
| Intervention | percentage of participants (Number) |
|---|
| Week 1: >= 15 IU/mL | Week 1: < 15 IU/mL undetectable/detectable | Week 1: < 15 IU/mL detectable | Week 1: < 15 IU/mL undetectable | Week 2: >= 15 IU/mL | Week 2: < 15 IU/mL undetectable/detectable | Week 2: < 15 IU/mL detectable | Week 2: < 15 IU/mL undetectable (vRVR) | Week 4: >= 15 IU/mL | Week 4: < 15 IU/mL undetectable/detectable | Week 4: < 15 IU/mL detectable | Week 4: < 15 IU/mL undetectable (RVR) | Week 6: >= 15 IU/mL | Week 6: < 15 IU/mL undetectable/detectable | Week 6: < 15 IU/mL detectable | Week 6: < 15 IU/mL undetectable | Week 8: >= 15 IU/mL | Week 8: < 15 IU/mL undetectable/detectable | Week 8: < 15 IU/mL detectable | Week 8: < 15 IU/mL undetectable | Week 10: >= 15 IU/mL | Week 10: < 15 IU/mL undetectable/detectable | Week 10: < 15 IU/mL detectable | Week 10: < 15 IU/mL undetectable |
|---|
| Panel 1:SMV 150mg(SOF 400mg[2weeks]+LDV 90/SOF 400mg[8 Weeks]) | 65.0 | 35.0 | 15.0 | 20.0 | 25.0 | 75.0 | 30.0 | 45.0 | 0 | 100.0 | 15.0 | 85.0 | 0 | 100.0 | 0 | 100.0 | 0 | 100.0 | 0 | 100.0 | 0 | 100.0 | 0 | 100.0 |
,| Panel 2: SMV 150mg+LDV 90mg/SOF 400mg (8 Weeks) | 60.0 | 40.0 | 35.0 | 5.0 | 35.0 | 65.0 | 30.0 | 35.0 | 5.0 | 95.0 | 5.0 | 90.0 | 0 | 100.0 | 5.0 | 95.0 | 0 | 100.0 | 0 | 100.0 | NA | NA | NA | NA |
Average Plasma Concentration at Steady State (Cavg,ss) of Simeprevir
The Cavg,ss is calculated as area under the plasma concentration-time curve during a dosing Interval (AUC[tau]) divided by the dosing interval (tau). (NCT02421211)
Timeframe: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
| Intervention | ng/mL (Mean) |
|---|
| Panel 1: SMV 150 mg + SOF 400 mg (Day 14) | 4196 |
| Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | 10139 |
Fluctuation Index (FI) of Ledipasvir
Fluctuation index is defined as percentage fluctuation (variation between maximum and minimum concentration at steady state), calculated as: 100*([Cmax Cmin]/Cavg). (NCT02421211)
Timeframe: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
| Intervention | percentage fluctuation (Mean) |
|---|
| Panel 2: LDV 90mg/SOF 400mg (Day 14) | 60.6 |
| Panel 2: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | 51.2 |
Fluctuation Index (FI) of Simeprevir
Fluctuation index is defined as percentage fluctuation (variation between maximum and minimum concentration at steady state), calculated as: 100*([Cmax Cmin]/Cavg). (NCT02421211)
Timeframe: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
| Intervention | percentage fluctuation (Mean) |
|---|
| Panel 1: SMV 150 mg + SOF 400 mg (Day 14) | 144 |
| Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | 84.4 |
Maximum Plasma Concentration (Cmax) of Ledipasvir
The Cmax is the maximum observed plasma concentration. (NCT02421211)
Timeframe: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
| Intervention | ng/mL (Mean) |
|---|
| Panel 2: LDV 90mg/SOF 400mg (Day 14) | 556 |
| Panel 2: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | 930 |
Maximum Plasma Concentration (Cmax) of Simeprevir
The Cmax is the maximum observed plasma concentration. (NCT02421211)
Timeframe: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
| Intervention | ng/mL (Mean) |
|---|
| Panel 1: SMV 150 mg + SOF 400 mg (Day 14) | 6767 |
| Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | 13691 |
Minimum Plasma Concentration (Cmin) of Ledipasvir (LDV)
The Cmin is the minimum observed plasma concentration. (NCT02421211)
Timeframe: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
| Intervention | ng/mL (Mean) |
|---|
| Panel 2: LDV 90mg/SOF 400mg (Day 14) | 319 |
| Panel 2: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | 557 |
Minimum Plasma Concentration (Cmin) of Simeprevir (SMV)
The Cmin is the minimum observed plasma concentration. (NCT02421211)
Timeframe: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
| Intervention | nanogram per Milliliters (ng/mL) (Mean) |
|---|
| Panel 1: SMV 150 mg + SOF 400 mg (Day 14) | 2411 |
| Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | 6701 |
Percentage of Participants With On-treatment Failure
On-treatment failure is defined as participants who did not achieve SVR12 and with confirmed detectable HCV RNA at the actual end of treatment. This was to include participants with: 1) Viral breakthrough, defined as a confirmed increase of greater than (>)1 log10 in HCV RNA from nadir, or confirmed HCV RNA of >100 IU/mL in participants whose HCV RNA had previously been NCT02421211)
Timeframe: Day 70 in Panel 1 and Day 56 in Panel 2
| Intervention | percentage of participants (Number) |
|---|
| Panel 1:SMV 150mg(SOF 400mg[2weeks]+LDV 90/SOF 400mg[8 Weeks]) | 0 |
| Panel 2: SMV 150mg+LDV 90mg/SOF 400mg (8 Weeks) | 0 |
Percentage of Participants With Viral Relapse
Participants who did not achieve SVR12, with undetectable HCV RNA at the actual end of study drug treatment and confirmed HCV RNA greater than or equal to (>=) LLOQ during follow-up. (NCT02421211)
Timeframe: Up to Week 12 follow-up phase after EOT
| Intervention | percentage of participants (Number) |
|---|
| Panel 1:SMV 150mg(SOF 400mg[2weeks]+LDV 90/SOF 400mg[8 Weeks]) | 0 |
| Panel 2: SMV 150mg+LDV 90mg/SOF 400mg (8 Weeks) | 0 |
Time to Reach Maximum Plasma Concentration (Tmax) of Ledipasvir
The Tmax is defined as actual sampling time to reach maximum observed analyte concentration. (NCT02421211)
Timeframe: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
| Intervention | Hour (Median) |
|---|
| Panel 2: LDV 90mg/SOF 400mg (Day 14) | 4.07 |
| Panel 2: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | 6.00 |
Time to Reach Maximum Plasma Concentration (Tmax) of Simeprevir
The Tmax is defined as actual sampling time to reach maximum observed analyte concentration. (NCT02421211)
Timeframe: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
| Intervention | hour (H) (Median) |
|---|
| Panel 1: SMV 150 mg + SOF 400 mg (Day 14) | 6.00 |
| Panel 1: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | 6.00 |
Trough Plasma Concentration (Ctrough) of Ledipasvir
The (Ctrough) is the plasma concentration before dosing or at the end of the dosing interval of any dose other than the first dose in a multiple dosing regimen. (NCT02421211)
Timeframe: Pre-dose on Day 14 and Day 28
| Intervention | ng/mL (Mean) |
|---|
| Panel 2: LDV 90mg/SOF 400mg (Day 14) | 376 |
| Panel 2: SMV 150mg+LDV 90mg/SOF 400mg (Day 28) | 659 |
AUC (0-last) of Odalasvir
AUC(0-last) is the area under the plasma concentration-time curve from time 0 to last measurable plasma concentration of odalasvir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11). (NCT02569710)
Timeframe: Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
| Intervention | ng*h/ml (Mean) |
|---|
| Cohort 1 | 11805.5 |
| Cohort 1b + Cohort 4 | 8635.5 |
| Cohort 2 + Cohort 3 + Cohort 5 | 8648.1 |
| Cohort 6 | 7050.0 |
| Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11 | 8422.2 |
AUC (0-24) of Simeprevir
AUC (0-24) is the area under the plasma concentration-time curve from time 0 to 24 hours of simeprevir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11). (NCT02569710)
Timeframe: Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose
| Intervention | ng*h/ml (Mean) |
|---|
| Cohort 1 | 25018.2 |
| Cohort 2 + Cohort 3 + Cohort 5 | 23061.3 |
| Cohort 6 | 25266.7 |
| Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11 | 27070.7 |
AUC (0-24) for Odalasvir
AUC(0-24) is the area under the plasma concentration-time curve from time zero to time 24 hours for odalasvir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11). (NCT02569710)
Timeframe: Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose
| Intervention | ng*h/mL (Mean) |
|---|
| Cohort 1 | 11805.5 |
| Cohort 1b + Cohort 4 | 5530.0 |
| Cohort 2 + Cohort 3 + Cohort 5 | 5393.8 |
| Cohort 6 | 4048.3 |
| Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11 | 4924.1 |
Cmin of Odalasvir
Cmin is the minimum observed plasma concentration of odalasvir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11). (NCT02569710)
Timeframe: Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
| Intervention | ng/ml (Mean) |
|---|
| Cohort 1 | 322.45 |
| Cohort 1b + Cohort 4 (8 Weeks GT1) | 97.21 |
| Cohort 2 + Cohort 3 + Cohort 5 | 107.90 |
| Cohort 6 | 102.73 |
| Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11 | 131.31 |
Average Plasma Concentration at Steady State (Css,Avg) of Odalasvir
Css,avg is the average plasma concentration at steady state of odalasvir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11). (NCT02569710)
Timeframe: Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
| Intervention | ng/ml (Mean) |
|---|
| Cohort 1 | 491.55 |
| Cohort 1b + Cohort 4 | 181.60 |
| Cohort 2 + Cohort 3 + Cohort 5 | 181.58 |
| Cohort 6 | 147.40 |
| Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11 | 176.86 |
Average Plasma Concentration at Steady State (Css,Avg) of Simeprevir
Css,avg is the average plasma concentration at steady state of simeprevir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11). (NCT02569710)
Timeframe: Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
| Intervention | ng/ml (Mean) |
|---|
| Cohort 1 | 1042.8 |
| Cohort 2 + Cohort 3 + Cohort 5 | 960.5 |
| Cohort 6 | 1053.8 |
| Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11 | 1134.6 |
Body Mass Index (BMI) at End of Treatment
BMI was calculated by dividing the body weight (in kilogram) by the square of height (in meters). BMI at end of treatment was reported. (NCT02569710)
Timeframe: End of treatment (Cohort 3: 6 weeks; Cohort 1, Cohort 1b+ Cohort 4, Cohort 2, Cohort 5a, and Cohort 6, 7, 8: 8 weeks; Cohort 4, Cohort 5b, Cohort 9 and Cohort 11: 12 weeks)
| Intervention | Kilograms per square meter (Kg/m^2) (Mean) |
|---|
| Cohort 1 (8 Weeks Genotype [GT1]) | 25.89 |
| Cohort 1b + Cohort 4 (8 Weeks GT1) | 28.43 |
| Cohort 2 (8 Weeks GT1) | 26.45 |
| Cohort 3 (6 Weeks GT1) | 25.46 |
| Cohort 4 (12 Weeks GT1) | 25.60 |
| Cohort 5a (8 Weeks GT3) | 25.60 |
| Cohort 5b (12 Weeks GT3) | 26.17 |
| Cohort 6,7,8 (8 Weeks GT1 F4) | 27.69 |
| Cohort 9 (12 Weeks GT1 F4) | 27.98 |
| Cohort 11 (12 Weeks GT2 F4) | 23.64 |
Body Weight at End of Treatment
Body weight (measured using a calibrated scale) at end of treatment was reported. (NCT02569710)
Timeframe: End of treatment (Cohort 3: 6 weeks; Cohort 1, Cohort 1b+ Cohort 4, Cohort 2, Cohort 5a, and Cohort 6, 7, 8: 8 weeks; Cohort 4, Cohort 5b, Cohort 9 and Cohort 11: 12 weeks)
| Intervention | Kilograms (kg) (Mean) |
|---|
| Cohort 1 (8 Weeks Genotype [GT1]) | 76.02 |
| Cohort 1b + Cohort 4 (8 Weeks GT1) | 84.58 |
| Cohort 2 (8 Weeks GT1) | 80.19 |
| Cohort 3 (6 Weeks GT1) | 74.07 |
| Cohort 4 (12 Weeks GT1) | 73.09 |
| Cohort 5a (8 Weeks GT3) | 81.30 |
| Cohort 5b (12 Weeks GT3) | 81.83 |
| Cohort 6,7,8 (8 Weeks GT1 F4) | 80.15 |
| Cohort 9 (12 Weeks GT1 F4) | 86.02 |
| Cohort 11 (12 Weeks GT2 F4) | 69.90 |
Clast of Odalasvir
Clast is the last measurable plasma concentration (Clast) of odalasvir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11). (NCT02569710)
Timeframe: Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
| Intervention | ng/ml (Mean) |
|---|
| Cohort 1 | 384.09 |
| Cohort 1b + Cohort 4 | 162.65 |
| Cohort 2 + Cohort 3 + Cohort 5 | 163.54 |
| Cohort 6 | 131.92 |
| Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11 | 152.47 |
Clast of Simeprevir
Clast is the maximum measured plasma concentration of simeprevir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11). (NCT02569710)
Timeframe: Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
| Intervention | ng/ml (Mean) |
|---|
| Cohort 1 | 402.55 |
| Cohort 2 + Cohort 3 + Cohort 5 | 481.76 |
| Cohort 6 | 538.67 |
| Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11 | 602.60 |
Cmax of Odalasvir
Cmax is the maximum observed plasma concentration of odalasvir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11). (NCT02569710)
Timeframe: Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
| Intervention | ng/ml (Mean) |
|---|
| Cohort 1 | 634.27 |
| Cohort 1b + Cohort 4 | 363.36 |
| Cohort 2 + Cohort 3 + Cohort 5 | 322.46 |
| Cohort 6 | 232.85 |
| Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11 | 298.67 |
Cmax of Simeprevir
Cmax is the maximum measured plasma concentration of simeprevir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11). (NCT02569710)
Timeframe: Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
| Intervention | ng/ml (Mean) |
|---|
| Cohort 1 | 1927.7 |
| Cohort 2 + Cohort 3 + Cohort 5 | 1537.6 |
| Cohort 6 | 1769.3 |
| Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11 | 1925.1 |
Percentage of Participants With Maximum Decrease From Baseline in Mean Ejection Fraction
Percentage of participants with maximum decrease from baseline in mean ejection fraction was reported. Percentages are based on the number of participants with available data. (NCT02569710)
Timeframe: Baseline up to End of treatment (up to 43 weeks)
| Intervention | Percentage of participants (Number) |
|---|
| Decline of > 10% | Decline of >5-<=10% | Decline of >0-<=5% |
|---|
| Cohort 1 (8 Weeks Genotype [GT1]) | 0.0 | 0.0 | 65.0 |
,| Cohort 11 (12 Weeks GT2 F4) | 0.0 | 0.0 | 50.0 |
,| Cohort 1b + Cohort 4 (8 Weeks GT1) | 0.0 | 4.0 | 48.0 |
,| Cohort 2 (8 Weeks GT1) | 0.0 | 10.0 | 60.0 |
,| Cohort 3 (6 Weeks GT1) | 0.0 | 10.0 | 50.0 |
,| Cohort 4 (12 Weeks GT1) | 0.0 | 12.5 | 50.0 |
,| Cohort 5a (8 Weeks GT3) | 0.0 | 0.0 | 20.0 |
,| Cohort 5b (12 Weeks GT3) | 0.0 | 21.4 | 64.3 |
,| Cohort 6,7,8 (8 Weeks GT1 F4) | 0.0 | 3.3 | 80.0 |
,| Cohort 9 (12 Weeks GT1 F4) | 0.0 | 6.7 | 46.7 |
Cmin of Simeprevir
Cmin is the minimum measured plasma concentration of simeprevir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11). (NCT02569710)
Timeframe: Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
| Intervention | ng/ml (Mean) |
|---|
| Cohort 1 | 379.75 |
| Cohort 2 + Cohort 3 + Cohort 5 | 452.65 |
| Cohort 6 | 517.00 |
| Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11 | 561.19 |
Ctrough of Odalasvir
Ctrough is the trough plasma concentration of odalasvir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11). (NCT02569710)
Timeframe: Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
| Intervention | ng/ml (Mean) |
|---|
| Cohort 1 | 335.18 |
| Cohort 1b + Cohort 4 | 100.98 |
| Cohort 2 + Cohort 3 + Cohort 5 | 112.44 |
| Cohort 6 | 119.82 |
| Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11 | 141.56 |
Ctrough of Simeprevir
Ctrough is the trough plasma concentration of Simeprevir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11). (NCT02569710)
Timeframe: Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
| Intervention | ng/ml (Mean) |
|---|
| Cohort 1 | 475.42 |
| Cohort 2 + Cohort 3 + Cohort 5 | 570.64 |
| Cohort 6 | 669.00 |
| Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11 | 636.88 |
Number of Participants With HCV Nonstructural Protein NS5A, NS5B, and NS3/4A Sequence in Participants With Virologic Failure
Sequencing of the HCV nonstructural protein 3/4A (NS3/4A), nonstructural protein 5A (NS5A) and nonstructural protein 5B (NS5B) genes was done to identify pre-existing sequence polymorphisms and characterize emerging HCV viral variants in participants with virologic failure. (NCT02569710)
Timeframe: Up to Week 24 (Follow up visit)
| Intervention | Participants (Count of Participants) |
|---|
| Cohort 1b + Cohort 4 (8 Weeks GT1) | 4 |
| Cohort 4 (12 Weeks GT1) | 1 |
| Cohort 5a (8 Weeks GT3) | 0 |
| Cohort 5b (12 Weeks GT3) | 2 |
| Cohort 6,7,8 (8 Weeks GT1 F4) | 1 |
Number of Participants With Treatment Emergent Adverse Event (TEAE)
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent were events between administration of study drug and up to 43 weeks that were absent before treatment or that worsened relative to pre-treatment state. (NCT02569710)
Timeframe: Up to 43 weeks
| Intervention | Participants (Count of Participants) |
|---|
| Cohort 1 (8 Weeks Genotype [GT1]) | 17 |
| Cohort 1b + Cohort 4 (8 Weeks GT1) | 19 |
| Cohort 2 (8 Weeks GT1) | 14 |
| Cohort 3 (6 Weeks GT1) | 13 |
| Cohort 4 (12 Weeks GT1) | 7 |
| Cohort 5a (8 Weeks GT3) | 4 |
| Cohort 5b (12 Weeks GT3) | 13 |
| Cohort 6,7,8 (8 Weeks GT1 F4) | 17 |
| Cohort 9 (12 Weeks GT1 F4) | 10 |
| Cohort 11 (12 Weeks GT2 F4) | 4 |
Percentage of Participants With On-treatment Failure
On-treatment failure was defined by participants who did not achieve SVR12 and with confirmed HCV RNA >= LLOQ at the actual end of study drug treatment. (NCT02569710)
Timeframe: Up to 12 weeks
| Intervention | Percentage of participants (Number) |
|---|
| Cohort 1 (8 Weeks Genotype [GT1]) | 0 |
| Cohort 1b + Cohort 4 (8 Weeks GT1) | 0 |
| Cohort 2 (8 Weeks GT1) | 0 |
| Cohort 3 (6 Weeks GT1) | 0 |
| Cohort 4 (12 Weeks GT1) | 12.5 |
| Cohort 5a (8 Weeks GT3) | 0 |
| Cohort 5b (12 Weeks GT3) | 7.1 |
| Cohort 6,7,8 (8 Weeks GT1 F4) | 0 |
| Cohort 9 (12 Weeks GT1 F4) | 0 |
| Cohort 11 (12 Weeks GT2 F4) | 0 |
Percentage of Participants With Virologic Relapse During the Follow-up Period
Viral relapse is defined as participants SVR12, with HCV RNA =) LLOQ during follow up. (NCT02569710)
Timeframe: Follow up period (Up to Week 12 after end of treatment)
| Intervention | Percentage of participants (Number) |
|---|
| Cohort 1 (8 Weeks Genotype [GT1]) | 0 |
| Cohort 1b + Cohort 4 (8 Weeks GT1) | 16.0 |
| Cohort 2 (8 Weeks GT1) | 0 |
| Cohort 3 (6 Weeks GT1) | 0 |
| Cohort 4 (12 Weeks GT1) | 0 |
| Cohort 5a (8 Weeks GT3) | 100.0 |
| Cohort 5b (12 Weeks GT3) | 14.3 |
| Cohort 6,7,8 (8 Weeks GT1 F4) | 3.3 |
| Cohort 9 (12 Weeks GT1 F4) | 0 |
| Cohort 11 (12 Weeks GT2 F4) | 0 |
Tlast of Odalasvir
Tlast is the time corresponding to last measurable plasma concentration of odalasvir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11). (NCT02569710)
Timeframe: Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
| Intervention | Hours (Median) |
|---|
| Cohort 1 | 24.00 |
| Cohort 1b + Cohort 4 | 47.60 |
| Cohort 2 + Cohort 3 + Cohort 5 | 47.50 |
| Cohort 6 | 47.80 |
| Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11 | 47.50 |
Average Plasma Concentration at Steady State (Css,Avg) of ALS-022227
Css,avg is the average plasma concentration at steady state of ALS-022227. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11). (NCT02569710)
Timeframe: Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
| Intervention | ng/ml (Mean) |
|---|
| Cohort 1 | 121.49 |
| Cohort 1b + Cohort 4 | 135.20 |
| Cohort 2 + Cohort 3 + Cohort 5 | 218.88 |
| Cohort 6 | 217.17 |
| Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11 | 227.37 |
Tlast of Simeprevir
Tlast is the time corresponding to last measurable plasma concentration of simeprevir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11). (NCT02569710)
Timeframe: Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
| Intervention | Hours (Median) |
|---|
| Cohort 1 | 24.00 |
| Cohort 2 + Cohort 3 + Cohort 5 | 24.00 |
| Cohort 6 | 24.00 |
| Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11 | 23.90 |
Tmax of Odalasvir
Tmax is the time to reach the maximum plasma concentration of odalasvir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11). (NCT02569710)
Timeframe: Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
| Intervention | Hours (Median) |
|---|
| Cohort 1 | 6.000 |
| Cohort 1b + Cohort 4 | 6.000 |
| Cohort 2 + Cohort 3 + Cohort 5 | 6.000 |
| Cohort 6 | 4.500 |
| Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11 | 6.000 |
Tmax of Simeprevir
Tmax is the Time to reach the maximum plasma concentration of simeprevir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11). (NCT02569710)
Timeframe: Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
| Intervention | Hours (Median) |
|---|
| Cohort 1 | 6.000 |
| Cohort 2 + Cohort 3 + Cohort 5 | 6.000 |
| Cohort 6 | 6.000 |
| Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11 | 6.000 |
Percentage of Participants by Treatment Emergent Toxicity Grade - Blood Chemistry Parameters
Percentage of participants by treatment emergent toxicity grade (Grade 1,2,3,4,3+4) for Blood Chemistry (Calcium, Phosphate, Potassium, Sodium, Bicarbonate, Alanine aminotransferase, Alkaline phosphatase, Aspartate aminotransferase, Bilirubin, Direct bilirubin, Glucose, Cholesterol, Triglycerides, Urate, Triacylglycerol lipase, Creatinine, Creatinine clearance, Albumin and Creatine kinase) were reported. Toxicity grades were defined as Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe and Grade 4: potentially life-threatening. A toxicity is treatment-emergent if it is worse than the baseline or if baseline is missing. (NCT02569710)
Timeframe: Up to 43 weeks
| Intervention | Percentage of participants (Number) |
|---|
| Calcium: Grade 1 | Calcium: Grade 2 | Calcium: Grade 3 | Calcium: Grade 4 | Calcium: Grade 3+4 | Phosphate: Grade 1 | Phosphate: Grade 2 | Phosphate: Grade 3 | Phosphate: Grade 4 | Phosphate: Grade 3+4 | Potassium: Grade 1 | Potassium: Grade 2 | Potassium: Grade 3 | Potassium: Grade 4 | Potassium: Grade 3+4 | Sodium: Grade 1 | Sodium: Grade 2 | Sodium: Grade 3 | Sodium: Grade 4 | Sodium: Grade 3+4 | Bicarbonate: Grade 1 | Bicarbonate: Grade 2 | Bicarbonate: Grade 3 | Bicarbonate: Grade 4 | Bicarbonate: Grade 3+4 | Alanine aminotransferase: Grade 1 | Alanine aminotransferase: Grade 2 | Alanine aminotransferase: Grade 3 | Alanine aminotransferase: Grade 4 | Alanine aminotransferase: Grade 3+4 | Alkaline phosphatase: Grade 1 | Alkaline phosphatase: Grade 2 | Alkaline phosphatase: Grade 3 | Alkaline phosphatase: Grade 4 | Alkaline phosphatase: Grade 3+4 | Aspartate aminotransferase: Grade: 1 | Aspartate aminotransferase: Grade: 2 | Aspartate aminotransferase: Grade: 3 | Aspartate aminotransferase: Grade: 4 | Aspartate aminotransferase: Grade: 3+4 | Bilirubin: Grade 1 | Bilirubin: Grade 2 | Bilirubin: Grade 3 | Bilirubin: Grade 4 | Bilirubin: Grade 3+4 | Direct bilirubin: Grade 1 | Direct bilirubin: Grade 2 | Direct bilirubin: Grade 3 | Direct bilirubin: Grade 4 | Direct bilirubin: Grade 3+4 | Glucose: Grade 1 | Glucose: Grade 2 | Glucose: Grade 3 | Glucose: Grade 4 | Glucose: Grade 3+4 | Cholesterol: Grade 1 | Cholesterol: Grade 2 | Cholesterol: Grade 3 | Cholesterol: Grade 4 | Cholesterol: Grade 3+4 | Triglycerides: Grade 1 | Triglycerides: Grade 2 | Triglycerides: Grade 3 | Triglycerides: Grade 4 | Triglycerides: Grade 3+4 | Urate: Grade 1 | Urate: Grade 2 | Urate: Grade 3 | Urate: Grade 4 | Urate: Grade 3+4 | Triacylglycerol lipase: Grade 1 | Triacylglycerol lipase: Grade 2 | Triacylglycerol lipase: Grade 3 | Triacylglycerol lipase: Grade 4 | Triacylglycerol lipase: Grade 3+4 | Creatinine: Grade 1 | Creatinine: Grade 2 | Creatinine: Grade 3 | Creatinine: Grade 4 | Creatinine: Grade 3+4 | Creatinine clearance: Grade 1 | Creatinine clearance: Grade 2 | Creatinine clearance: Grade 3 | Creatinine clearance: Grade 4 | Creatinine clearance: Grade 3+4 | Albumin: Grade 1 | Albumin: Grade 2 | Albumin: Grade 3 | Albumin: Grade 4 | Albumin: Grade 3+4 | Creatine kinase: Grade 1 | Creatine kinase: Grade 2 | Creatine kinase: Grade 3 | Creatine kinase: Grade 4 | Creatine kinase: Grade 3+4 |
|---|
| Cohort 1 (8 Weeks Genotype [GT1]) | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 10.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 5.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 15.0 | 0.0 | 0.0 | 0.0 | 0.0 | 20.0 | 15.0 | 0.0 | 0.0 | 0.0 | 5.0 | 0.0 | 0.0 | 0.0 | 0.0 | 5.0 | 0.0 | 0.0 | 0.0 | 0.0 | 5.0 | 15.0 | 5.0 | 0.0 | 5.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 5.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 |
,| Cohort 11 (12 Weeks GT2 F4) | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 25.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 25.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 25.0 | 0.0 | 0.0 | 0.0 | 50.0 | 0.0 | 0.0 | 0.0 | 0.0 | 25.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 |
,| Cohort 1b + Cohort 4 (8 Weeks GT1) | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 20.0 | 0.0 | 0.0 | 0.0 | 4.0 | 0.0 | 0.0 | 0.0 | 0.0 | 8.0 | 0.0 | 0.0 | 0.0 | 0.0 | 16.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 4.0 | 4.0 | 0.0 | 0.0 | 0.0 | 24.0 | 8.0 | 0.0 | 0.0 | 0.0 | 16.0 | 0.0 | 0.0 | 0.0 | 0.0 | 12.0 | 4.0 | 0.0 | 0.0 | 0.0 | 12.0 | 4.0 | 8.0 | 0.0 | 8.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 4.0 | 8.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 |
,| Cohort 2 (8 Weeks GT1) | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 25.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 5.0 | 0.0 | 0.0 | 0.0 | 0.0 | 15.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 10.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 10.0 | 5.0 | 0.0 | 0.0 | 0.0 | 30.0 | 5.0 | 5.0 | 0.0 | 5.0 | 10.0 | 0.0 | 0.0 | 0.0 | 0.0 | 5.0 | 0.0 | 0.0 | 0.0 | 0.0 | 5.0 | 10.0 | 0.0 | 5.0 | 5.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 |
,| Cohort 3 (6 Weeks GT1) | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 15.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 5.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 10.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 5.0 | 0.0 | 0.0 | 0.0 | 0.0 | 35.0 | 5.0 | 0.0 | 0.0 | 0.0 | 15.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 5.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 5.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 |
,| Cohort 4 (12 Weeks GT1) | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 12.5 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 12.5 | 0.0 | 0.0 | 0.0 | 0.0 | 12.5 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 25.0 | 12.5 | 0.0 | 0.0 | 0.0 | 12.5 | 37.5 | 0.0 | 0.0 | 0.0 | 50.0 | 0.0 | 0.0 | 0.0 | 0.0 | 12.5 | 0.0 | 0.0 | 0.0 | 0.0 | 12.5 | 12.5 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 12.5 | 0.0 | 12.5 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 25.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 |
,| Cohort 5a (8 Weeks GT3) | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 20.0 | 0.0 | 0.0 | 0.0 | 0.0 | 20.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 20.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 20.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 |
,| Cohort 5b (12 Weeks GT3) | 3.3 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 14.3 | 21.4 | 0.0 | 21.4 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 7.1 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 35.7 | 14.3 | 0.0 | 0.0 | 0.0 | 42.9 | 0.0 | 0.0 | 0.0 | 0.0 | 28.6 | 14.3 | 0.0 | 0.0 | 0.0 | 28.6 | 0.0 | 0.0 | 0.0 | 0.0 | 7.1 | 7.1 | 0.0 | 0.0 | 0.0 | 0.0 | 7.1 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 7.1 | 0.0 | 0.0 | 0.0 | 0.0 |
,| Cohort 6,7,8 (8 Weeks GT1 F4) | 13.3 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 13.3 | 3.3 | 0.0 | 3.3 | 6.7 | 0.0 | 0.0 | 0.0 | 0.0 | 3.3 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 6.7 | 0.0 | 0.0 | 0.0 | 3.3 | 0.0 | 0.0 | 6.7 | 6.7 | 6.7 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 3.3 | 0.0 | 0.0 | 0.0 | 3.3 | 3.3 | 3.3 | 0.0 | 3.3 | 0.0 | 0.0 | 3.3 | 0.0 | 3.3 | 10.0 | 13.3 | 3.3 | 0.0 | 3.3 | 3.3 | 6.7 | 3.3 | 0.0 | 3.3 | 16.7 | 0.0 | 0.0 | 0.0 | 0.0 | 10.0 | 3.3 | 0.0 | 0.0 | 0.0 | 13.3 | 3.3 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 3.3 | 0.0 | 3.3 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 |
,| Cohort 9 (12 Weeks GT1 F4) | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 6.7 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 20.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 6.7 | 0.0 | 6.7 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 6.7 | 0.0 | 6.7 | 13.3 | 13.3 | 0.0 | 0.0 | 0.0 | 20.0 | 6.7 | 0.0 | 0.0 | 0.0 | 33.3 | 0.0 | 0.0 | 0.0 | 0.0 | 26.7 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 20.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 6.7 | 0.0 | 0.0 | 0.0 |
Percentage of Participants by Treatment Emergent Toxicity Grade - Hematology Parameters
Percentage of participants by treatment emergent toxicity grade (1, 2, 3, 4 and 3+4) for Hematology parameters (hemoglobin, lymphocytes, neutrophils, leukocytes, platelets) were reported. Toxicity grades were defined as Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe and Grade 4: potentially life-threatening. A toxicity is treatment-emergent if it is worse than the baseline or if baseline is missing. (NCT02569710)
Timeframe: Up to 43 weeks
| Intervention | Percentage of participants (Number) |
|---|
| Hemoglobin: Grade 1 | Hemoglobin: Grade 2 | Hemoglobin: Grade 3 | Hemoglobin: Grade 4 | Hemoglobin: Grade 3+4 | Lymphocytes: Grade 1 | Lymphocytes: Grade 2 | Lymphocytes: Grade 3 | Lymphocytes: Grade 4 | Lymphocytes: Grade 3+4 | Neutrophils: Grade 1 | Neutrophils: Grade 2 | Neutrophils: Grade 3 | Neutrophils: Grade 4 | Neutrophils: Grade 3+4 | Leukocytes: Grade 1 | Leukocytes: Grade 2 | Leukocytes: Grade 3 | Leukocytes: Grade 4 | Leukocytes: Grade 3+4 | Platelets: Grade 1 | Platelets: Grade 2 | Platelets: Grade 3 | Platelets: Grade 4 | Platelets: Grade 3+4 |
|---|
| Cohort 1 (8 Weeks Genotype [GT1]) | 5.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 5.0 | 0.0 | 0.0 | 0.0 | 0.0 |
,| Cohort 11 (12 Weeks GT2 F4) | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 25.0 | 0.0 | 0.0 | 0.0 | 0.0 |
,| Cohort 1b + Cohort 4 (8 Weeks GT1) | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 |
,| Cohort 2 (8 Weeks GT1) | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 5.0 | 0.0 | 0.0 | 0.0 | 0.0 |
,| Cohort 3 (6 Weeks GT1) | 5.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 5.0 | 0.0 | 0.0 | 0.0 | 0.0 |
,| Cohort 4 (12 Weeks GT1) | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 |
,| Cohort 5a (8 Weeks GT3) | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 |
,| Cohort 5b (12 Weeks GT3) | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 7.1 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 7.1 | 0.0 | 0.0 | 0.0 | 0.0 |
,| Cohort 6,7,8 (8 Weeks GT1 F4) | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 6.7 | 10.0 | 0.0 | 0.0 | 0.0 | 3.3 | 0.0 | 0.0 | 0.0 | 0.0 | 10.0 | 0.0 | 0.0 | 0.0 | 0.0 | 6.7 | 16.7 | 0.0 | 0.0 | 0.0 |
,| Cohort 9 (12 Weeks GT1 F4) | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 13.3 | 0.0 | 0.0 | 0.0 | 0.0 |
Percentage of Participants by Treatment Emergent Toxicity Grade - Prothrombin International Normalized Ratio (INR)
Percentage of participants by treatment emergent toxicity grade for coagulation parameter (Prothrombin International Normalized Ratio) were reported. Toxicity grades were defined as Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe and Grade 4: potentially life-threatening. A toxicity is treatment-emergent if it is worse than the baseline or if baseline is missing. (NCT02569710)
Timeframe: Up to 43 weeks
| Intervention | Percentage of participants (Number) |
|---|
| Prothrombin INR: Grade 1 | Prothrombin INR: Grade 2 | Prothrombin INR: Grade 3 | Prothrombin INR: Grade 4 | Prothrombin INR: Grade 3+4 |
|---|
| Cohort 1 (8 Weeks Genotype [GT1]) | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 |
,| Cohort 11 (12 Weeks GT2 F4) | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 |
,| Cohort 1b + Cohort 4 (8 Weeks GT1) | 0.0 | 0.0 | 0.0 | 4.0 | 4.0 |
,| Cohort 2 (8 Weeks GT1) | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 |
,| Cohort 3 (6 Weeks GT1) | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 |
,| Cohort 4 (12 Weeks GT1) | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 |
,| Cohort 5a (8 Weeks GT3) | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 |
,| Cohort 5b (12 Weeks GT3) | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 |
,| Cohort 6,7,8 (8 Weeks GT1 F4) | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 |
,| Cohort 9 (12 Weeks GT1 F4) | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 |
Percentage of Participants by Treatment Emergent Toxicity Grade - Urinalysis Parameter (Protein)
Percentage of participants by treatment emergent toxicity grade (Grade 1, 2, 3, 4, 3+4) for urinalysis parameter (protein) was reported. Toxicity grades were defined as Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe and Grade 4: potentially life-threatening. A toxicity is treatment-emergent if it is worse than the baseline or if baseline is missing. (NCT02569710)
Timeframe: Up to 43 weeks
| Intervention | Percentage of participants (Number) |
|---|
| Protein: Grade 1 | Protein: Grade 2 | Protein: Grade 3 | Protein: Grade 4 | Protein: Grade 3+4 |
|---|
| Cohort 1 (8 Weeks Genotype [GT1]) | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 |
,| Cohort 11 (12 Weeks GT2 F4) | 50.0 | 0.0 | 25.0 | 0.0 | 25.0 |
,| Cohort 1b + Cohort 4 (8 Weeks GT1) | 4.0 | 0.0 | 0.0 | 0.0 | 0.0 |
,| Cohort 2 (8 Weeks GT1) | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 |
,| Cohort 3 (6 Weeks GT1) | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 |
,| Cohort 4 (12 Weeks GT1) | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 |
,| Cohort 5a (8 Weeks GT3) | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 |
,| Cohort 5b (12 Weeks GT3) | 7.1 | 0.0 | 0.0 | 0.0 | 0.0 |
,| Cohort 6,7,8 (8 Weeks GT1 F4) | 3.3 | 0.0 | 3.3 | 0.0 | 3.3 |
,| Cohort 9 (12 Weeks GT1 F4) | 26.7 | 13.3 | 0.0 | 0.0 | 0.0 |
Percentage of Participants Who Achieved HCV RNA Percentage of participants who achieved HCV RNA NCT02569710)
Timeframe: Day 2, 3, Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 and End of treatment (Cohort 3: 6 weeks; Cohort 1, Cohort 1b+ Cohort 4, Cohort 2, Cohort 5a, and Cohort 6, 7, 8: 8 weeks; Cohort 4, Cohort 5b, Cohort 9 and Cohort 11: 12 weeks)
| Intervention | Percentage of participants (Number) |
|---|
| Day 2 | Day 3 | Week 1 | Week 2 | Week 3 | Week 4 | Week 5 | Week 6 | Week 7 | Week 8 | Week 9 | Week 10 | Week 11 | Week 12 | End of treatment |
|---|
| Cohort 1 (8 Weeks Genotype [GT1]) | 0 | 0 | 0 | 20.0 | 40.0 | 55.0 | 75.0 | 80.0 | 80.0 | 85.0 | NA | NA | NA | NA | 85.0 |
,| Cohort 11 (12 Weeks GT2 F4) | 0 | 0 | 25.0 | 75.0 | 100 | 100 | 100 | 100 | 100 | 100 | 100 | 100 | 100 | 100 | 100 |
,| Cohort 1b + Cohort 4 (8 Weeks GT1) | 0 | 0 | 8.0 | 20.0 | 40.0 | 52.0 | 96.0 | 88.0 | 92.0 | 96.0 | NA | NA | NA | NA | 96.0 |
,| Cohort 2 (8 Weeks GT1) | 0 | 0 | 0 | 15.0 | 45.0 | 60.0 | 85.0 | 85.0 | 95.0 | 100 | NA | NA | NA | NA | 100 |
,| Cohort 3 (6 Weeks GT1) | 0 | 0 | 10.0 | 40.0 | 65.0 | 80.0 | 85.0 | 80.0 | NA | NA | NA | NA | NA | NA | 80.0 |
,| Cohort 4 (12 Weeks GT1) | 0 | 0 | 0 | 0 | 37.5 | 62.5 | 75.0 | 87.5 | 87.5 | 87.5 | 87.5 | 87.5 | 87.5 | 87.5 | 87.5 |
,| Cohort 5a (8 Weeks GT3) | 0 | 0 | 0 | 20.0 | 60.0 | 40.0 | 80.0 | 80.0 | 80.0 | 100 | NA | NA | NA | NA | 100 |
,| Cohort 5b (12 Weeks GT3) | 0 | 0 | 14.3 | 42.9 | 50.0 | 78.6 | 85.7 | 92.9 | 85.7 | 85.7 | 92.9 | 92.9 | 92.9 | 78.6 | 78.6 |
,| Cohort 6,7,8 (8 Weeks GT1 F4) | 0 | 0 | 16.7 | 50.0 | 73.3 | 80.0 | 90.0 | 96.7 | 100 | 100 | NA | NA | NA | NA | 100 |
,| Cohort 9 (12 Weeks GT1 F4) | 0 | 0 | 13.3 | 66.7 | 86.7 | 86.7 | 100 | 100 | 100 | 93.3 | 93.3 | 93.3 | 86.7 | 93.3 | 93.3 |
Percentage of Participants Who Achieved HCV RNA Less Then (<) LLOQ Undetectable
Percentage of participants who achieved HCV RNA less then (<) LLOQ undetectable was reported. (NCT02569710)
Timeframe: Day 2, 3, Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 and End of treatment (Cohort 3: 6 weeks; Cohort 1, Cohort 1b+ Cohort 4, Cohort 2, Cohort 5a, and Cohort 6, 7, 8: 8 weeks; Cohort 4, Cohort 5b, Cohort 9 and Cohort 11: 12 weeks)
| Intervention | Percentage of participants (Number) |
|---|
| Day 2 | Day 3 | Week 1 | Week 2 | Week 3 | Week 4 | Week 5 | Week 6 | Week 7 | Week 8 | Week 9 | Week 10 | Week 11 | Week 12 | End of treatment |
|---|
| Cohort 1 (8 Weeks Genotype [GT1]) | 0 | 0 | 5.0 | 35.0 | 70.0 | 80.0 | 100 | 90.0 | 90.0 | 95.0 | NA | NA | NA | NA | 95.0 |
,| Cohort 11 (12 Weeks GT2 F4) | 0 | 0 | 25.0 | 75.0 | 100 | 100 | 100 | 100 | 100 | 100 | 100 | 100 | 100 | 100 | 100 |
,| Cohort 1b + Cohort 4 (8 Weeks GT1) | 0 | 0 | 20.0 | 44.0 | 76.0 | 92.0 | 96.0 | 100 | 96.0 | 100 | NA | NA | NA | NA | 100 |
,| Cohort 2 (8 Weeks GT1) | 0 | 0 | 0 | 45.0 | 75.0 | 90.0 | 100 | 85.0 | 95.0 | 100 | NA | NA | NA | NA | 100 |
,| Cohort 3 (6 Weeks GT1) | 0 | 5.0 | 30.0 | 70.0 | 80.0 | 85.0 | 90.0 | 90.0 | NA | NA | NA | NA | NA | NA | 90.0 |
,| Cohort 4 (12 Weeks GT1) | 0 | 0 | 12.5 | 25.0 | 62.5 | 87.5 | 100 | 100 | 100 | 87.5 | 87.5 | 87.5 | 87.5 | 87.5 | 87.5 |
,| Cohort 5a (8 Weeks GT3) | 0 | 0 | 20.0 | 40.0 | 60.0 | 60.0 | 80.0 | 100 | 80.0 | 100 | NA | NA | NA | NA | 100 |
,| Cohort 5b (12 Weeks GT3) | 0 | 0 | 35.7 | 64.3 | 85.7 | 92.9 | 92.9 | 92.9 | 85.7 | 85.7 | 92.9 | 92.9 | 92.9 | 85.7 | 85.7 |
,| Cohort 6,7,8 (8 Weeks GT1 F4) | 0 | 0 | 16.7 | 50.0 | 73.3 | 80.0 | 90.0 | 96.7 | 100 | 100 | NA | NA | NA | NA | 100 |
,| Cohort 9 (12 Weeks GT1 F4) | 0 | 6.7 | 13.3 | 66.7 | 86.7 | 86.7 | 100 | 100 | 100 | 93.3 | 93.3 | 93.3 | 86.7 | 93.3 | 93.3 |
Percentage of Participants With Sustained Virologic Response (SVR) at Week 4, 12 and 24 After End of Treatment
Participants were considered to have achieved SVR if the Hepatitis C virus (HCV) Ribonucleic acid (RNA) less than (<) Lower limit of quantification (LLOQ) (<15 international unit per milliliter [IU/mL]) detectable or undetectable at Week 4, 12 and 24 after the actual end of study drug treatment. (NCT02569710)
Timeframe: At Week 4, 12 and Week 24 after end of treatment (Cohort 3: 6 weeks; Cohort 1, Cohort 1b+ Cohort 4, Cohort 2, Cohort 5a, and Cohort 6, 7, 8: 8 weeks; Cohort 4, Cohort 5b, Cohort 9 and Cohort 11: 12 weeks)
| Intervention | Percentage of participants (Number) |
|---|
| 4 weeks after end of treatment | 12 weeks after end of treatment | 24 weeks after end of treatment |
|---|
| Cohort 1 (8 Weeks Genotype [GT1]) | 100 | 100 | 100 |
,| Cohort 11 (12 Weeks GT2 F4) | 100 | 100 | 100 |
,| Cohort 1b + Cohort 4 (8 Weeks GT1) | 96.0 | 84.0 | 84.0 |
,| Cohort 2 (8 Weeks GT1) | 100 | 100 | 100 |
,| Cohort 3 (6 Weeks GT1) | 100 | 100 | 100 |
,| Cohort 4 (12 Weeks GT1) | 87.5 | 87.5 | 87.5 |
,| Cohort 5a (8 Weeks GT3) | 0 | 0 | 0 |
,| Cohort 5b (12 Weeks GT3) | 71.4 | 71.4 | 71.4 |
,| Cohort 6,7,8 (8 Weeks GT1 F4) | 100 | 96.7 | 96.7 |
,| Cohort 9 (12 Weeks GT1 F4) | 93.3 | 93.3 | 93.3 |
Percentage of Participants With Worst Post-Baseline Values of Vital Signs
Percentage of participants with worst post-baseline values of vital signs (Systolic blood pressure [sBP], Diastolic blood pressure [dBP], and Heart rate) were reported. For sBP, abnormally low: less than or equal to [<=] 90 millimeters mercury [mmHg]; Grade 1 or mild: greater than [>] 140 to less than [<] 160 mmHg; Grade 2 or moderate: >=160 to <180 and Grade 3 or severe: >=180 mmHg. For dBP, abnormally low: <=50 mmHg; Grade 1 or mild: >90 to <100 mmHg; Grade 2 or moderate: >=100 to <110 mmHg and Grade 3 or severe: >=110 mmHg. For Heart Rate, abnormally low: <=50 beats per minute [bpm] and abnormally high: >=120 bpm. (NCT02569710)
Timeframe: Up to 43 weeks
| Intervention | Percentage of participants (Number) |
|---|
| sBP: Abnormally low | sBP: Grade 1 or mild | sBP: Grade 2 or moderate | sBP: Grade 3 or severe | dBP: Abnormally low | dBP: Grade 1 or mild | dBP: Grade 2 or moderate | dBP: Grade 3 or severe | Heart Rate: Abnormally low | Heart Rate: Abnormally high |
|---|
| Cohort 1 (8 Weeks Genotype [GT1]) | 0 | 20.0 | 10.0 | 0 | 0 | 5.0 | 5.0 | 0 | 35.0 | 0 |
,| Cohort 11 (12 Weeks GT2 F4) | 0 | 25.0 | 50.0 | 0 | 0 | 0 | 25.0 | 0 | 0 | 0 |
,| Cohort 1b + Cohort 4 (8 Weeks GT1) | 0 | 32.0 | 8.0 | 4.0 | 4.0 | 20.0 | 12.0 | 0 | 32.0 | 0 |
,| Cohort 2 (8 Weeks GT1) | 0 | 35.0 | 0 | 5.0 | 0 | 35.0 | 0 | 0 | 35.0 | 0 |
,| Cohort 3 (6 Weeks GT1) | 0 | 25.0 | 5.0 | 0 | 0 | 20.0 | 0 | 0 | 30.0 | 0 |
,| Cohort 4 (12 Weeks GT1) | 0 | 37.5 | 37.5 | 0 | 12.5 | 0 | 0 | 25.0 | 50.0 | 12.5 |
,| Cohort 5a (8 Weeks GT3) | 0 | 60.0 | 0 | 0 | 0 | 60.0 | 0 | 0 | 20.0 | 0 |
,| Cohort 5b (12 Weeks GT3) | 0 | 57.1 | 7.1 | 0 | 0 | 21.4 | 14.3 | 7.1 | 21.4 | 0 |
,| Cohort 6,7,8 (8 Weeks GT1 F4) | 3.3 | 26.7 | 20.0 | 3.3 | 0 | 10.0 | 13.3 | 3.3 | 13.3 | 0 |
,| Cohort 9 (12 Weeks GT1 F4) | 0 | 46.7 | 13.3 | 13.3 | 0 | 26.7 | 6.7 | 6.7 | 13.3 | 0 |
Percentage of Participants With Worst Treatment Emergent Abnormalities of Electrocardiogram (ECG) Parameters
Percentage of participants with worst treatment emergent abnormalities of ECG parameters (Fridericia Corrected QT interval [QTcF], Bazett Corrected QT interval [QTcB], Heart rate, QRS and PR, was reported. For QTcF abnormality was defined as 30 milliseconds (ms) less than or equal to (<=) QTcF increase from baseline <= 60 ms; for QTcB abnormality was defined as 30 ms <= QTcB increase from baseline <= 60 ms; for heart rate - abnormal low: <= 50 beats per minute (bpm) and abnormal high: >= 120 bpm; for QRS - abnormal high: >120 ms; for PR - abnormally low: PR < 120 ms; abnormally high - 200 ms < PR <= 240 ms and 240 ms < PR <= 300 ms. (NCT02569710)
Timeframe: Up to 43 weeks
| Intervention | Percentage of participants (Number) |
|---|
| QTcF: Abnormal | QTcB: Abnormal | Heart rate: Abnormal low | Heart rate: Abnormal high | QRS: Abnormal high | PR: Abnormally low (PR<120 ms) | PR: Abnormally high (200 ms| PR: Abnormal high (240 ms | |
|---|
| Cohort 1 (8 Weeks Genotype [GT1]) | 5.0 | 5.0 | 25.0 | 0.0 | 0.0 | 0.0 | 5.0 | 10.0 |
,| Cohort 11 (12 Weeks GT2 F4) | 0.0 | 0.0 | 25.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 |
,| Cohort 1b + Cohort 4 (8 Weeks GT1) | 0.0 | 8.0 | 16.0 | 0.0 | 4.0 | 0.0 | 8.0 | 0.0 |
,| Cohort 2 (8 Weeks GT1) | 5.0 | 10.0 | 10.0 | 0.0 | 0.0 | 0.0 | 15.0 | 0.0 |
,| Cohort 3 (6 Weeks GT1) | 0.0 | 0.0 | 15.0 | 0.0 | 0.0 | 0.0 | 10.0 | 0.0 |
,| Cohort 4 (12 Weeks GT1) | 0.0 | 0.0 | 25.0 | 12.5 | 0.0 | 0.0 | 0.0 | 0.0 |
,| Cohort 5a (8 Weeks GT3) | 0.0 | 0.0 | 20.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 |
,| Cohort 5b (12 Weeks GT3) | 7.1 | 28.6 | 14.3 | 0.0 | 0.0 | 7.1 | 0.0 | 7.1 |
,| Cohort 6,7,8 (8 Weeks GT1 F4) | 3.3 | 3.3 | 13.3 | 0.0 | 0.0 | 3.3 | 6.7 | 0.0 |
,| Cohort 9 (12 Weeks GT1 F4) | 0.0 | 6.7 | 0.0 | 0.0 | 0.0 | 0.0 | 13.3 | 0.0 |
AUC (0-last) of Simeprevir
AUC (0-last) is the area under the plasma concentration-time curve from time 0 to last measurable plasma concentration of simeprevir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for participants without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for participants with cirrhosis (Cohort 6; Cohort 7+8+9+11). (NCT02569710)
Timeframe: Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)
| Intervention | ng*h/ml (Mean) |
|---|
| Cohort 1 | 25018.2 |
| Cohort 2 + Cohort 3 + Cohort 5 | 23061.3 |
| Cohort 6 | 25266.7 |
| Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11 | 27070.7 |
Percentage of Participants With Sustained Virologic Response 24 Weeks After End of Treatment (SVR24)
The SVR24 was defined as HCV RNA NCT02765490)
Timeframe: Week 24 (Follow-Up Phase)
| Intervention | Percentage of Participants (Number) |
|---|
| Arm A: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 6 Weeks | 98.9 |
| Arm B: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 8 Weeks | 97.3 |
Percentage of Participants With Sustained Virologic Response 12 Weeks After End of Treatment (EOT) (SVR12)
The SVR 12 was defined as hepatitis C virus ribonucleic acid (HCV RNA) less than (<) lower limit of quantification (LLOQ; 15 international unit per milliliter [IU/mL]) detectable or undetectable 12 weeks after actual EOT. (NCT02765490)
Timeframe: Week 12 (Follow-Up Phase)
| Intervention | Percentage of Participants (Number) |
|---|
| Arm A: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 6 Weeks | 98.9 |
| Arm B: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 8 Weeks | 97.8 |
Percentage of Participants With On-treatment Failure
On-treatment failure: Participants who did not achieve SVR12 and with confirmed HCV RNA>=LLOQ at the End of Treatment (EOT). (NCT02765490)
Timeframe: EOT up to Week 12 (Follow up Phase)
| Intervention | Percentage of Participants (Number) |
|---|
| Arm A: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 6 Weeks | 0 |
| Arm B: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 8 Weeks | 0 |
Percentage of Participants With Sustained Virologic Response 4 Weeks After End of Treatment (EOT)
The SVR 4 was defined as participants were considered to have reached SVR4, if 4 weeks after the actual EOT, HCV RNA was NCT02765490)
Timeframe: Week 4 (Follow-Up Phase)
| Intervention | Percentage of Participants (Number) |
|---|
| Arm A: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 6 Weeks | 99.5 |
| Arm B: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 8 Weeks | 98.4 |
Number of Participants With Late Viral Relapse
Late Viral Relapse: Participants who achieved SVR12 but had confirmed HCV RNA>=LLOQ afterwards during follow-up. (NCT02765490)
Timeframe: Up to Week 24 (Follow-up Phase)
| Intervention | Participants (Number) |
|---|
| Arm A: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 6 Weeks | 0 |
| Arm B: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 8 Weeks | 1 |
Number of Participants With Viral Relapse
Viral Relapse: Participants who did not achieve SVR12, with HCV RNA =) LLOQ during follow-up. (NCT02765490)
Timeframe: End of Treatment up to Week 24 (Follow up phase)
| Intervention | Participants (Number) |
|---|
| Arm A: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 6 Weeks | 1 |
| Arm B: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 8 Weeks | 4 |
Percentage of Participants With Sustained Virologic Response 12 Weeks (SVR12) After Actual End-of-treatment
SVR12 was defined as HCV RNA < LLOQ (15 IU/mL) detected or not detected at 12 weeks after the actual EOT. (NCT02993250)
Timeframe: Week 12 (follow-up phase)
| Intervention | Percentage of participants (Number) |
|---|
| Cohort 1: Chronic Hepatitis C Without Cirrhosis | 100 |
| Cohort 2: Chronic Hepatitis C With Compensated Cirrhosis | 100 |
Percentage of Participants With Sustained Virologic Response 4 Weeks (SVR4) After Actual End-of-Treatment
SVR4 was defined as hepatitis C virus (HCV) ribonucleic acid (RNA) less than (<) lower limit of quantification (LLOQ; 15 international unit per milliliter [IU/mL]) detected or not detected at 4 weeks after the actual End-of-treatment (EOT). (NCT02993250)
Timeframe: Week 4 (follow-up phase)
| Intervention | Percentage of participants (Number) |
|---|
| Cohort 1: Chronic Hepatitis C Without Cirrhosis | 100 |
| Cohort 2: Chronic Hepatitis C With Compensated Cirrhosis | 100 |
Percentage of Participants With Viral Relapse
Viral relapse was defined as participants who did not achieve SVR12, with HCV RNA < LLOQ (15 IU/mL) at the EOT and confirmed HCV RNA greater than or equal to (>=) LLOQ during follow-up. (NCT02993250)
Timeframe: End of treatment up to Week 24 (follow up phase)
| Intervention | Percentage of participants (Number) |
|---|
| Cohort 1: Chronic Hepatitis C Without Cirrhosis | 0 |
| Cohort 2: Chronic Hepatitis C With Compensated Cirrhosis | 0 |
Time to Achieve HCV RNA Not Detected or HCV RNA Time to Achieve HCV RNA not Detected or HCV RNA NCT02993250)
Timeframe: EOT up to Week 24 (follow up phase)
| Intervention | Days (Mean) |
|---|
| Cohort 1: Chronic Hepatitis C Without Cirrhosis | 19.0 |
| Cohort 2: Chronic Hepatitis C With Compensated Cirrhosis | 18.6 |
Percentage of Participants With On-treatment Virologic Response
Percentage of participants with On-treatment Virologic Response with HCV RNA < LLOQ (15 IU/mL), not detected at specified time points during treatment were reported. (NCT02993250)
Timeframe: Day 2, Day 3, Week 1, 2, 3, 4, 6, 8 (for Cohort 1), 10, and 12 (for Cohort 2 only)
| Intervention | Percentage of participants (Number) |
|---|
| Day 2: < 15 IU/mL not detected | Day 3: < 15 IU/mL not detected | Week 1: < 15 IU/mL not detected | Week 2: < 15 IU/mL not detected | Week 3: < 15 IU/mL not detected | week 4: < 15 IU/mL not detected | Week 6: < 15 IU/mL not detected | Week 8: < 15 IU/mL not detected | Week 10: < 15 IU/mL not detected | Week 12: < 15 IU/mL not detected |
|---|
| Cohort 2: Chronic Hepatitis C With Compensated Cirrhosis | 0 | 0 | 18.2 | 45.5 | 63.6 | 72.7 | 100 | 100 | 100 | 100 |
Percentage of Participants With On-treatment Virologic Response
Percentage of participants with On-treatment Virologic Response with HCV RNA < LLOQ (15 IU/mL), not detected at specified time points during treatment were reported. (NCT02993250)
Timeframe: Day 2, Day 3, Week 1, 2, 3, 4, 6, 8 (for Cohort 1), 10, and 12 (for Cohort 2 only)
| Intervention | Percentage of participants (Number) |
|---|
| Day 2: < 15 IU/mL not detected | Day 3: < 15 IU/mL not detected | Week 1: < 15 IU/mL not detected | Week 2: < 15 IU/mL not detected | Week 3: < 15 IU/mL not detected | week 4: < 15 IU/mL not detected | Week 6: < 15 IU/mL not detected | Week 8: < 15 IU/mL not detected |
|---|
| Cohort 1: Chronic Hepatitis C Without Cirrhosis | 4.5 | 4.5 | 4.5 | 22.7 | 54.5 | 72.7 | 90.9 | 100 |
Percentage of Participants With On-treatment Failure
On-treatment failure was defined as participants who did not achieve SVR12, with confirmed HCV RNA >= LLOQ (15 IU/mL) at the actual EOT. (NCT02993250)
Timeframe: EOT up to Week 12 (follow up phase)
| Intervention | Percentage of Participants (Number) |
|---|
| Cohort 1: Chronic Hepatitis C Without Cirrhosis | 0 |
| Cohort 2: Chronic Hepatitis C With Compensated Cirrhosis | 0 |
Number of Participants With Adverse Events (AEs)
An adverse event was any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. (NCT02993250)
Timeframe: Approximately 38 weeks (Cohort 1) and 42 weeks (Cohort 2)
| Intervention | participants (Number) |
|---|
| Cohort 1: Chronic Hepatitis C Without Cirrhosis | 15 |
| Cohort 2: Chronic Hepatitis C With Compensated Cirrhosis | 9 |
Percentage of Participants With Sustained Virologic Response 24 Weeks (SVR24) After Actual End-of-treatment
SVR 24 was defined as HCV RNA < LLOQ (15 IU/mL) detected or not detected at 24 weeks after the actual EOT. (NCT02993250)
Timeframe: Week 24 (follow-up phase)
| Intervention | Percentage of participants (Number) |
|---|
| Cohort 1: Chronic Hepatitis C Without Cirrhosis | 100 |
| Cohort 2: Chronic Hepatitis C With Compensated Cirrhosis | 90.9 |