| Trial | Phase | Enrollment | Study Type | Start Date | Status |
|---|
| A Double-blind, Randomized, Placebo-controlled Trial of Naloxegol for Prevention of Post-operative Constipation in Spinal Surgery Patients [NCT02946580] | Phase 4 | 53 participants (Actual) | Interventional | 2017-01-31 | Terminated(stopped due to Slow recruitment and inability to extend funding.) |
| Real World Observational Study of Naloxegol for Patients With Cancer Pain Diagnosed With Opioid Induced Constipation. [NCT03638440] | | 183 participants (Actual) | Observational | 2018-08-16 | Completed |
| A Randomized, Double-Blind, Placebo-Controlled Pilot Study of an Oral, Selective Peripheral Opioid Receptor Antagonist in Advanced Non-Small Cell Lung Cancer [NCT03087708] | Phase 2 | 50 participants (Actual) | Interventional | 2017-10-13 | Terminated(stopped due to Insufficient accrual) |
| Evaluation of the Quality of Life of Patients With Opioid-induced Constipation Under Treatment With Naloxegol. A One-year Follow-up Study [NCT04173858] | | 126 participants (Actual) | Observational | 2017-09-21 | Completed |
| A Phase I, Open-label, Randomized, Balanced, Single-dose, Two-Part Study to Assess the Relative Bioavailability of NKTR-118 in Three Formulations Under Fasted (3-Way Crossover) and Fed (2-Way Crossover) Conditions in Male and Non-fertile Female Subjects [NCT01365000] | Phase 1 | 21 participants (Actual) | Interventional | 2011-06-30 | Completed |
| A Phase I, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety, Tolerability and Pharmacokinetics of NKTR-118 Following Single and Multiple Ascending Oral Dose Administration in Healthy Young and Elderly Japanese Subjects, and an Open [NCT01318655] | Phase 1 | 50 participants (Actual) | Interventional | 2011-03-31 | Completed |
| Risk of Major Adverse Cardiovascular Events Among Users of Naldemedine Compared With Other Medications Used for Opioid Induced Constipation in Adult Patients With Chronic Non-Cancer Pain in a Healthcare Claims Database [NCT03720613] | | 34,532 participants (Anticipated) | Observational | 2019-01-04 | Recruiting |
| Evaluation of Naloxegol, a Peripherally Acting µ-opioid Receptor Antagonist, in the Prevention of Postoperative Ileus After Cystectomy [NCT04219046] | Phase 2 | 102 participants (Anticipated) | Interventional | 2021-03-31 | Not yet recruiting |
| An Open-Label 52-week Study to Assess the Long-Term Safety of NKTR-118 in Opioid-Induced Constipation (OIC) in Patients With Non-Cancer-Related Pain [NCT01336205] | Phase 3 | 844 participants (Actual) | Interventional | 2011-04-30 | Completed |
| A Multicenter, Observational Prospective Study on Quality of Life (QOL) in Advanced Cancer Patients With Opioid-induced Constipation (OIC) Treated at Home With Naloxegol According to the Clinical Practice [NCT04294550] | | 250 participants (Actual) | Observational | 2018-09-01 | Completed |
| A Phase I, Open-Label, Single-Centre Study to Assess Absorption, Distribution, Metabolism and Excretion (ADME) After [14C]-Labelled Oral Administration of NKTR-118 to Healthy Male Volunteers [NCT01348724] | Phase 1 | 6 participants (Actual) | Interventional | 2011-06-30 | Completed |
| An Open-Label, Parallel-Group, Phase I Study to Compare the Pharmacokinetics of NKTR-118 Following a Single Oral Dose in Subjects With Renal Impairment and Subjects With Normal Renal Function [NCT01372826] | Phase 1 | 32 participants (Actual) | Interventional | 2011-06-30 | Completed |
| A Phase IV, Randomized, Multi-Center, Open-Label, Prospective, Crossover Study to Evaluate Patient Preference of Movantik™ Versus Polyethylene Glycol 3350 for Opioid-Induced Constipation (OIC) Treatment [NCT03060512] | Phase 4 | 276 participants (Actual) | Interventional | 2017-03-02 | Completed |
| Time to Transit Recovery After Treatment With Naloxegol in Cardiac Surgery Intensive Care Trial [NCT04433390] | Phase 3 | 305 participants (Actual) | Interventional | 2020-10-14 | Completed |
| A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of NKTR-118 in Patients With Non-Cancer-Related Pain and Opioid-Induced Constipation (OIC) [NCT01309841] | Phase 3 | 652 participants (Actual) | Interventional | 2011-03-31 | Completed |
| The Effect of Naloxegol on Refractory Constipation in the Intensive Care Unit [NCT02705378] | Phase 3 | 0 participants (Actual) | Interventional | 2017-05-31 | Withdrawn(stopped due to PI left institution. Protocol never submitted to the IRB, no contract executed only Confidentiality Agreement, and study not done.) |
| An Observational Post-Authorisation Safety Study (PASS) of MOVENTIG® (Naloxegol) Among Patients Aged 18 Years and Older Treated With Opioids Chronically [NCT02813369] | | 10,000 participants (Anticipated) | Observational | 2016-07-31 | Recruiting |
| A Phase 2, Double-Blind, Randomized, Placebo-Controlled, Multiple-Dose, Dose Escalation Study to Evaluate the Efficacy, Safety and Tolerability of NKTR-118 in Patients With Opioid-Induced Constipation (OIC) [NCT00600119] | Phase 2 | 207 participants (Actual) | Interventional | 2007-12-31 | Completed |
| An Open-label, Single-center Study to Assess the Pharmacokinetics of NKTR-118 in Patients With Impaired Hepatic Function and Subjects With Normal Hepatic Function Following Administration of a Single Dose of 25mg NKTR-118 [NCT01392807] | Phase 1 | 24 participants (Actual) | Interventional | 2011-07-31 | Completed |
| Ancillary Effects of Oral Naloxegol (Movantik) [NCT03235739] | Phase 4 | 136 participants (Actual) | Interventional | 2017-10-01 | Completed |
| A Phase I Randomized, Double-Blinded, Placebo-Controlled Study of the Effect of Naloxegol on Gastric, Small Bowel, and Colonic Transit in Healthy Subjects [NCT02737059] | Phase 1 | 72 participants (Actual) | Interventional | 2016-07-01 | Completed |
| A Single Center, Randomized, Double-blinded, Placebo-controlled, Open-label, Positive-controlled, Four-way Crossover Study to Assess the Effect of a Single Oral Dose NKTR-118 Administration on QTc Interval Compared to Placebo, Using AVELOX (Moxifloxacin) [NCT01325415] | Phase 1 | 45 participants (Actual) | Interventional | 2011-04-30 | Completed |
| A Study to Assess the Tolerability, Safety, and Feasibility of Naloxegol in Patients With Cancer and Opioid-Induced Constipation [NCT02839889] | Phase 4 | 12 participants (Actual) | Interventional | 2016-09-30 | Terminated(stopped due to The study was stopped due to challenges recruiting eligible patients.) |
| A Phase I, Open-Label, Multicentre Study to Assess the Pharmacokinetics and Safety of Naloxegol in Paediatric Patients Ages ≥ 6 Months to < 18 Years Receiving Treatment With Opioids [NCT02099591] | Phase 1 | 61 participants (Actual) | Interventional | 2014-11-30 | Completed |
| A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of NKTR-118 in Patients With Non-Cancer-Related Pain and Opioid-Induced Constipation (OIC) [NCT01323790] | Phase 3 | 700 participants (Actual) | Interventional | 2011-03-31 | Completed |
| An Open-label, 1-sequence, 3-period, 3-treatment, Crossover Study to Assess the Effects of Ketoconazole on the Pharmacokinetics of NKTR-118 in Healthy Subjects [NCT01520896] | Phase 1 | 22 participants (Actual) | Interventional | 2012-02-29 | Completed |
| An Open-label, Fixed-sequence, 3-period, 3-treatment, Crossover Study to Assess the Effects of Rifampin on Pharmacokinetics of NKTR-118 in Healthy Subjects [NCT01533870] | Phase 1 | 22 participants (Actual) | Interventional | 2012-03-31 | Completed |
| Placebo-controlled Crossover Study of the Ability of Naloxegol to Reverse Opioid Effect on Colonic Motor Patterns in Healthy Volunteers [NCT05770960] | Phase 4 | 15 participants (Actual) | Interventional | 2018-06-27 | Completed |
| A Prospective Randomized, Double-Blind Study to Evaluate the Addition of Naloxegol to the Pre-Op Regimen of the Cardiac Surgery Patient and Its Effect on Opioid-Induced Constipation [NCT03316859] | Phase 2/Phase 3 | 280 participants (Anticipated) | Interventional | 2017-11-06 | Recruiting |
| A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of NKTR-118 in Relieving Opioid-Induced Constipation (OIC) in Patients With Cancer-Related Pain [NCT01384292] | Phase 3 | 14 participants (Actual) | Interventional | 2011-06-30 | Terminated(stopped due to The study was stopped early due to recruitment challenges) |
| A Randomized, Double-Blind, Placebo-Controlled 12-Week Extension Study to Assess the Safety and Tolerability of NKTR-118 in Patients With Non-Cancer-Related Pain and Opioid-Induced Constipation (OIC) [NCT01395524] | Phase 3 | 302 participants (Actual) | Interventional | 2011-07-31 | Completed |
| A Phase I, Randomised, Open-label, 3 Way Cross-over Study in Healthy Volunteers to Demonstrate the Bioequivalence of the Naloxegol 25 mg Commercial and Phase III Formulations and to Assess the Effect of Food Administration on the Pharmacokinetics of the C [NCT01623609] | Phase 1 | 42 participants (Actual) | Interventional | 2012-07-31 | Completed |
| The NIPA Study: A Randomized Double-blind Control Clinical Trial Naloxegol Administration to Prevent Opioids Induced Gastrointestinal Motility Disturbance in Brain Injured PAtients [NCT05008926] | Phase 3 | 370 participants (Anticipated) | Interventional | 2022-03-15 | Recruiting |
| Methylnaltrexone Versus Naloxegol in the Treatment of Opioid-Induced Constipation in the Emergency Department [NCT03523520] | Phase 4 | 15 participants (Actual) | Interventional | 2020-12-23 | Completed |
| United States Post-Marketing Observational Cardiovascular Safety Study in Patients Taking Naloxegol [NCT02813356] | | 8,800 participants (Anticipated) | Observational | 2016-06-24 | Active, not recruiting |
| An Observational Post-Authorization Safety Study (PASS) of MOVENTIG® (Naloxegol) Drug Utilization in Selected European Populations [NCT02813148] | | 17,254 participants (Actual) | Observational | 2015-08-31 | Completed |
| An Open-label, Sequential, 3-period Study to Assess the Effects of Diltiazem on the Pharmacokinetics of Naloxegol in Healthy Subjects [NCT01594619] | Phase 1 | 44 participants (Actual) | Interventional | 2012-05-31 | Completed |
| An Open-Label, Randomized, 4-Period, 4-Treatment, Crossover, Single-Center, Single-Dose Bioavailability Study With Alternate Methods of Administration of Crushed Naloxegol Tablets, 25 mg and of a Naloxegol Solution Formulation, 25 mg, Compared to Whole Na [NCT02446171] | Phase 1 | 44 participants (Actual) | Interventional | 2015-05-31 | Completed |
| A Phase II, Randomized, Single Center, Pilot Feasibility Study to Evaluate Naloxegol for Opioid-Induced Constipation in Cancer Patients [NCT02745353] | Phase 2 | 7 participants (Actual) | Interventional | 2016-05-31 | Terminated(stopped due to Couldn't enough accrue patients) |
| Impact of Naloxegol on Prevention of Lower GI Tract Paralysis in Critically Ill Adults Initiated on Scheduled Intravenous Opioid Therapy: A Randomized, Double-Blind, Placebo-Controlled, Phase II, Single-Center, Proof of Concept Study [NCT02977286] | Phase 4 | 12 participants (Actual) | Interventional | 2017-01-01 | Terminated(stopped due to Poor enrollment) |
| Naloxegol for Opioid-Related Gastroparesis: A Double-Blind Study With an Open Label Extension [NCT03036891] | Phase 2 | 0 participants (Actual) | Interventional | 2016-12-29 | Withdrawn |
| Movantik for Opioid-Related Esophageal Disorders [NCT02998606] | Phase 2 | 2 participants (Actual) | Interventional | 2017-01-31 | Terminated(stopped due to Investigator left Institution) |
| [information is prepared from clinicaltrials.gov, extracted Sep-2024] |
Change From Baseline in Patient Assessment of Constipation-Symptoms (PAC-SYM) Questionnaire
The PAC-SYM questionnaire is a 12-item questionnaire that evaluates the severity of symptoms of constipation in 3 domains (stool, rectal, and abdominal symptoms) on a 5-point Likert scale ranging from 0 (absent) to 4 (very severe) in the 2 weeks (14 days) prior to assessment. Each domain score is the mean of the non-missing items for that domain. The total score is the mean of all non-missing items (ie, symptoms). The range is 0 (response is 'absent' for each item) to 4 (response is 'very severe' for each item). A negative change from baseline indicates improvement. (NCT00600119)
Timeframe: Days 1 through 28
| Intervention | units on a scale (Mean) |
|---|
| Abdominal Symptoms domain | Rectal Symptoms domain | Stool Symptoms domain | Total Score |
|---|
| NKTR-118 25 mg | 1.1 | 0.7 | 1.2 | 1.1 |
,| NKTR-118 5 mg | 1.1 | 0.7 | 1.5 | 1.2 |
,| NKTR-118 50 mg | 1.3 | 0.7 | 1.2 | 1.1 |
,| Placebo 25 mg | 1.4 | 0.8 | 1.7 | 1.4 |
,| Placebo 5 mg | 1.2 | 0.7 | 1.5 | 1.2 |
,| Placebo 50 mg | 1.2 | 1.2 | 1.8 | 1.5 |
Change From Baseline in Patient Assessment of Constipation-Quality of Life (PAC-QOL) Questionnaire
The PAC-QOL scale is a 28-item self-report instrument designed to evaluate the burden of constipation on patients' everyday functioning and well-being in the 2 weeks (14 days) prior to assessment. Each item is rated on a 5-point Likert scale ranging from 0 (not at all) to 4 (extremely).The instrument can be used to generate an overall score, but is also reported to assess 4 specific constipation-related domains including: 1) worries and concerns (11 items), 2) physical discomfort (4 items), 3) psychosocial discomfort (8 items), and 4) satisfaction (5 items). Each domain score is the mean of the non-missing items for that domain. The total score is the mean of all non-missing items. The range is 0 (response is 'not at all' for each item) to 4 (response is 'extremely' for each item). A negative change from baseline indicates improvement. (NCT00600119)
Timeframe: Days 1 through 28
| Intervention | units on a scale (Mean) |
|---|
| Physical Discomfort domain | Worries/Concerms domain | Psychosocial Discomfort domain | Satisfaction domain | Total Score |
|---|
| NKTR-118 25 mg | 1.2 | 1.1 | 0.8 | 2.0 | 1.2 |
,| NKTR-118 5 mg | 1.2 | 1.3 | 0.8 | 2.4 | 1.3 |
,| NKTR-118 50 mg | 1.3 | 1.2 | 0.8 | 2.2 | 1.3 |
,| Placebo 25 mg | 1.7 | 1.6 | 1.1 | 2.8 | 1.7 |
,| Placebo 5 mg | 1.4 | 1.5 | 0.8 | 2.6 | 1.5 |
,| Placebo 50 mg | 1.7 | 1.5 | 1.0 | 2.8 | 1.6 |
Change From Baseline in Spontaneous Bowel Movements (SBMs) Per Week During Week 1
Change from baseline in SBMs/week during Week 1 was defined as SBMs/week during the first week of double-blind study medication (between Visit 4 and Visit 6) minus baseline SBMs/week. Baseline was defined as the average SBMs/week during the 2-week OIC screening period. An SBM was defined as a BM without the use of laxatives in the previous 24 hours as recorded in the e-diary. (NCT00600119)
Timeframe: Days 1 through 7
| Intervention | Number of SBMs/week (Mean) |
|---|
| Placebo 5 mg | 1.8 |
| NKTR-118 5 mg | 2.6 |
| Placebo 25 mg | 1.9 |
| NKTR-118 25 mg | 3.6 |
| Placebo 50 mg | 1.9 |
| NKTR-118 50 mg | 4.4 |
Change From Baseline in SBMs/Week Across the 28-day Double-blind Period
Change from baseline in SBMs/week across the 28-day double-blind period was calculated as SBMs/week during 28-day double-blind study treatment period minus baseline SBMs/week. Baseline was defined as the average SBMs/week during the 2-week OIC screening period. (NCT00600119)
Timeframe: Days 1 through 28
| Intervention | Number of SBMs/week (Mean) |
|---|
| Placebo 5 mg | 1.7 |
| NKTR-118 5 mg | 2.3 |
| Placebo 25 mg | 1.7 |
| NKTR-118 25 mg | 3.2 |
| Placebo 50 mg | 1.2 |
| NKTR-118 50 mg | 4.6 |
Change From Baseline in Mean Spontaneous Bowel Movements/Week
The number of spontaneous bowel movements/week was determined from the patient's eDiary. (NCT01309841)
Timeframe: Baseline (Week 1) to end of treatment (Week 12)
| Intervention | Number of SBMs/week (Least Squares Mean) |
|---|
| NKTR-118 12.5 mg | 2.56 |
| NKTR-118 25 mg | 3.02 |
| Placebo | 2.02 |
Change From Baseline in Degree of Straining
"A single-item straining question was asked via the eDiary: How much did you strain during your bowel movement? Patients responded on a 5 point Likert scale: 1=Not at all; 2=A little bit; 3=A moderate amount; 4=A great deal; 5=An extreme amount. A negative change from baseline indicates improvement." (NCT01309841)
Timeframe: Baseline (Week 1) to end of treatment (Week 12)
| Intervention | units on a scale (Least Squares Mean) |
|---|
| NKTR-118 12.5 mg | -0.64 |
| NKTR-118 25 mg | -0.73 |
| Placebo | -0.54 |
Change From Baseline in Mean Number of Days Per Week With at Least 1 SBM During Weeks 1 to 12
(NCT01309841)
Timeframe: 12 weeks
| Intervention | Number of Days (Least Squares Mean) |
|---|
| NKTR-118 12.5 mg | 2.21 |
| NKTR-118 25 mg | 2.48 |
| Placebo | 1.66 |
Change From Baseline in Patient Assessment of Constipation Quality of Life (PAC-QOL) Satisfaction Domain
The PAC-QOL scale is a 28-item self-report instrument designed to evaluate the burden of constipation on patients' everyday functioning and well-being in the 2 weeks (14 days) prior to assessment. Each item is rated on a 5-point Likert scale ranging from 0 (not at all) to 4 (extremely). The instrument can be used to generate an overall score, but is also reported to assess 4 specific constipation-related domains including: 1) Worries and concerns (11 items), 2) Physical discomfort (4 items), 3) Psychosocial discomfort (8 items), and 4) Satisfaction (5 items). Each domain score is the mean of the non-missing items for that domain. The total score is the mean of all non-missing items. The range of the domain or total score is 0 (response is 'not at all' for each item) to 4 (response is 'extremely' for each item). A negative change from baseline indicates improvement. (NCT01309841)
Timeframe: Baseline (Week 1) to end of treatment (Week 12)
| Intervention | units on a scale (Least Squares Mean) |
|---|
| NKTR-118 12.5 mg | -0.91 |
| NKTR-118 25 mg | -1.06 |
| Placebo | -0.89 |
Change From Baseline in Percent Numbers of Days With a CSBM (Complete Spontaneous Bowel Movement)
"A single-item question on the completeness of evacuation, developed and validated through 1:1 interviews with OIC patients, was asked via the eDiary: Did you feel like your bowels were completely empty after the bowel movement? Patients provided a yes or a no response. A positive change from baseline indicates improvement." (NCT01309841)
Timeframe: Baseline (Week 1) to end of treatment (Week 12)
| Intervention | Percent days/week (Least Squares Mean) |
|---|
| NKTR-118 12.5 mg | 22.31 |
| NKTR-118 25 mg | 27.04 |
| Placebo | 18.45 |
Time (in Hours) to First Post-dose Laxation Without the Use of Rescue Laxatives Within the Previous 24 Hours
(NCT01309841)
Timeframe: 12 weeks
| Intervention | Hours (Median) |
|---|
| NKTR-118 12.5 mg | 20.4 |
| NKTR-118 25 mg | 5.9 |
| Placebo | 35.8 |
Change From Baseline in Patient Assessment of Constipation Symptoms Questionnaire (PAC-SYM)
The PAC-SYM questionnaire is a 12-item questionnaire that evaluates the severity of symptoms of constipation in 3 domains (stool, rectal, and abdominal symptoms) on a 5-point Likert scale ranging from 0 (absent) to 4 (very severe) in the 2 weeks (14 days) prior to assessment. Each domain score is the mean of the non-missing items for that domain. The total score is the mean of all non-missing items (ie, symptoms). The range of the domain or total score is 0 (response is 'absent' for each item) to 4 (response is 'very severe' for each item). A negative change from baseline indicates improvement. (NCT01309841)
Timeframe: Baseline (Week 1) to end of treatment (Week 12)
| Intervention | units on a scale (Least Squares Mean) |
|---|
| Total score | Abdominal symptoms subscore | Rectal symptoms subscore | Stool symptoms subscore |
|---|
| NKTR-118 12.5 mg | -0.76 | -0.61 | -0.66 | -0.96 |
,| NKTR-118 25 mg | -0.81 | -0.65 | -0.73 | -1.00 |
,| Placebo | -0.69 | -0.63 | -0.53 | -0.84 |
Time (in Hours) to First Post-dose Laxation Without the Use of Rescue Laxatives Within the Previous 24 Hours in the Laxative Inadequate Response (LIR) Subgroup
Time to first post-dose laxation without the use of rescue laxatives within the last 24 hours was calculated in hours as: Date/Time of first post-dose laxation without rescue - First dose date/time. (NCT01309841)
Timeframe: Baseline (Week 1) to end of treatment (Week 12)
| Intervention | hours (Median) |
|---|
| NKTR-118 12.5 mg | 20.6 |
| NKTR-118 25 mg | 5.4 |
| Placebo | 43.4 |
Response (Responder/Non-responder) to Study Drug During Weeks 1 to 12
Responder was defined as having at least 3 spontaneous bowel movements (SBMs)/week with at least 1 SBM/week increase over baseline for at least 9 out of the 12 treatment weeks and 3 out of the last 4 treatment weeks during the double-blind treatment period. An SBM is a bowel movement occurring 24 hours or more since the last use of rescue medication. (NCT01309841)
Timeframe: Baseline (Week 1) to end of treatment (Week 12)
| Intervention | Number of patients (Number) |
|---|
| NKTR-118 12.5 mg | 87 |
| NKTR-118 25 mg | 95 |
| Placebo | 63 |
Response (Responder/Non-responder) to Study Drug in the LIR Subgroup During Weeks 1 to 12
Responder is defined as having at least 3 SBMs/week, with at least 1 SBM/week increase over baseline for at least 9 out of 12 weeks and at least 3 out of the last 4 weeks. (NCT01309841)
Timeframe: Baseline (Week 1) to end of treatment (Week 12)
| Intervention | Number of patients (Number) |
|---|
| NKTR-118 12.5 mg | 49 |
| NKTR-118 25 mg | 57 |
| Placebo | 34 |
Change From Baseline in Degree of Straining
"A single-item straining question was asked via the eDiary: How much did you strain during your bowel movement? Patients responded on a 5 point Likert scale: 1=Not at all; 2=A little bit; 3=A moderate amount; 4=A great deal; 5=An extreme amount. A negative change from baseline indicates improvement." (NCT01323790)
Timeframe: Baseline (Week 1) to end of treatment (Week 12)
| Intervention | units on a scale (Least Squares Mean) |
|---|
| NKTR-118 12.5 mg | -0.67 |
| NKTR-118 25 mg | -0.80 |
| Placebo | -0.48 |
Change From Baseline in Patient Assessment of Constipation Symptoms Questionnaire (PAC-SYM)
The PAC-SYM questionnaire is a 12-item questionnaire that evaluates the severity of symptoms of constipation in 3 domains (stool, rectal, and abdominal symptoms) on a 5-point Likert scale ranging from 0 (absent) to 4 (very severe) in the 2 weeks (14 days) prior to assessment. Each domain score is the mean of the non-missing items for that domain. The total score is the mean of all non-missing items (ie, symptoms). The range of the domain or total score is 0 (response is 'absent' for each item) to 4 (response is 'very severe' for each item). A negative change from baseline indicates improvement. (NCT01323790)
Timeframe: Baseline (Week 1) to end of treatment (Week 12)
| Intervention | units on a scale (Least Squares Mean) |
|---|
| Total score | Abdominal symptoms subscore | Rectal symptoms subscore | Stool symptoms subscore |
|---|
| NKTR-118 12.5 mg | -0.75 | -0.67 | -0.59 | -0.93 |
,| NKTR-118 25 mg | -0.81 | -0.62 | -0.71 | -1.04 |
,| Placebo | -0.63 | -0.72 | -0.47 | -0.66 |
Time (in Hours) to First Post-dose Laxation Without the Use of Rescue Laxatives Within the Previous 24 Hours in the Laxative Inadequate Response (LIR) Subgroup
Time to first post-dose laxation without the use of rescue laxatives within the last 24 hours was calculated in hours as: Date/Time of first post-dose laxation without rescue - First dose date/time. (NCT01323790)
Timeframe: Baseline (Week 1) to end of treatment (Week 12)
| Intervention | hours (Median) |
|---|
| NKTR-118 12.5 mg | 12.8 |
| NKTR-118 25 mg | 18.1 |
| Placebo | 38.2 |
Time (in Hours) to First Post-dose Laxation Without the Use of Rescue Laxatives Within the Previous 24 Hours
(NCT01323790)
Timeframe: 12 weeks
| Intervention | Hours (Median) |
|---|
| NKTR-118 12.5 mg | 19.3 |
| NKTR-118 25 mg | 12.0 |
| Placebo | 37.2 |
Response (Responder/Non-responder) to Study Drug in the LIR Subgroup During Weeks 1 to 12
Responder is defined as having at least 3 SBMs/week, with at least 1 SBM/week increase over baseline for at least 9 out of 12 weeks and at least 3 out of the last 4 weeks. (NCT01323790)
Timeframe: Baseline (Week 1) to end of treatment (Week 12)
| Intervention | Number of patients (Number) |
|---|
| NKTR-118 12.5 mg | 53 |
| NKTR-118 25 mg | 58 |
| Placebo | 38 |
Response (Responder/Non-responder) to Study Drug During Weeks 1 to 12
Responder was defined as having at least 3 spontaneous bowel movements (SBMs)/week with at least 1 SBM/week increase over baseline for at least 9 out of the 12 treatment weeks and 3 out of the last 4 treatment weeks during the double-blind treatment period. An SBM is a bowel movement occurring 24 hours or more since the last use of rescue medication. (NCT01323790)
Timeframe: Baseline (Week 1) to end of treatment (Week 12)
| Intervention | Number of patients (Number) |
|---|
| NKTR-118 12.5 mg | 81 |
| NKTR-118 25 mg | 92 |
| Placebo | 68 |
Change From Baseline in Percent Numbers of Days With a CSBM (Complete Spontaneous Bowel Movement)
"A single-item question on the completeness of evacuation, developed and validated through 1:1 interviews with OIC patients, was asked via the eDiary: Did you feel like your bowels were completely empty after the bowel movement? Patients provided a yes or a no response. A positive change from baseline indicates improvement." (NCT01323790)
Timeframe: Baseline (Week 1) to end of treatment (Week 12)
| Intervention | Percent days/week (Least Squares Mean) |
|---|
| NKTR-118 12.5 mg | 23.48 |
| NKTR-118 25 mg | 27.20 |
| Placebo | 16.76 |
Change From Baseline in Patient Assessment of Constipation Quality of Life (PAC-QOL) Satisfaction Domain
The PAC-QOL scale is a 28-item self-report instrument designed to evaluate the burden of constipation on patients' everyday functioning and well-being in the 2 weeks (14 days) prior to assessment. Each item is rated on a 5-point Likert scale ranging from 0 (not at all) to 4 (extremely). The instrument can be used to generate an overall score, but is also reported to assess 4 specific constipation-related domains including: 1) Worries and concerns (11 items), 2) Physical discomfort (4 items), 3) Psychosocial discomfort (8 items), and 4) Satisfaction (5 items). Each domain score is the mean of the non-missing items for that domain. The total score is the mean of all non-missing items. The range of the domain or total score is 0 (response is 'not at all' for each item) to 4 (response is 'extremely' for each item). A negative change from baseline indicates improvement. (NCT01323790)
Timeframe: Baseline (Week 1) to end of treatment (Week 12)
| Intervention | units on a scale (Least Squares Mean) |
|---|
| NKTR-118 12.5 mg | -1.12 |
| NKTR-118 25 mg | -1.30 |
| Placebo | -0.81 |
Change From Baseline in Mean Spontaneous Bowel Movements/Week
The number of spontaneous bowel movements/week was determined from the patient's eDiary. (NCT01323790)
Timeframe: Baseline (Week 1) to end of treatment (Week 12)
| Intervention | Number of SBMs/week (Least Squares Mean) |
|---|
| NKTR-118 12.5 mg | 2.62 |
| NKTR-118 25 mg | 3.14 |
| Placebo | 2.10 |
Change From Baseline in Mean Number of Days Per Week With at Least 1 SBM During Weeks 1 to 12
(NCT01323790)
Timeframe: 12 weeks
| Intervention | Number of Days (Least Squares Mean) |
|---|
| NKTR-118 12.5 mg | 2.12 |
| NKTR-118 25 mg | 2.41 |
| Placebo | 1.73 |
Incidence of Patients Experiencing at Least One Adverse Event (AE)
The incidence of patients experiencing at least one AE during the randomized treatment and follow-up periods was calculated. (NCT01336205)
Timeframe: Baseline (Week 0) to end of the follow-up period
| Intervention | Participants (Number) |
|---|
| NKTR-118 25 mg | 437 |
| Usual Care | 195 |
Incidence of Patients Experiencing Severe Adverse Events (SAEs)
The incidence of patients experiencing SAEs during the randomized treatment and follow-up periods was calculated. (NCT01336205)
Timeframe: Baseline (Week 0) to end of the follow-up period
| Intervention | Participants (Number) |
|---|
| NKTR-118 25 mg | 51 |
| Usual Care | 30 |
Incidence of Patients Experiencing AEs That Resulted in Discontinuation of Investigational Product (IP)
The incidence of patients experiencing AEs that resulted in discontinuation of IP during the randomized treatment or follow-up periods was calculated. (NCT01336205)
Timeframe: Baseline (Week 0) to end of the follow-up period
| Intervention | Participants (Number) |
|---|
| NKTR-118 25 mg | 56 |
| Usual Care | NA |
Response (Responder/Non-responder) to Study Drug
Response (responder/non-responder) to study drug, where a responder was defined as having at least 3 rescue-free bowel movements (RFBMs) per week during the 4-week Part A treatment period, with at least 1 RFBM per week increase over baseline for at least 3 out of 4 weeks. An RFBM was defined as a bowel movement (BM) without rescue laxatives in the previous 24 hours. (NCT01384292)
Timeframe: Baseline to Week 4
| Intervention | Participants (Number) |
|---|
| NKTR-118 12.5 mg | 4 |
| NKTR-118 25 mg | 3 |
| Placebo | 2 |
Incidence of Patients Experiencing AEs That Resulted in Discontinuation of Investigational Product (IP)
The incidence of patients experiencing AEs that resulted in discontinuation of IP during the randomized treatment or follow-up periods was calculated. (NCT01395524)
Timeframe: Baseline (Week 0) to end of the follow-up period (Week 14)
| Intervention | Participants (Number) |
|---|
| NKTR-118 12.5 mg | 4 |
| NKTR-118 25 mg | 4 |
| Placebo | 3 |
Incidence of Patients Experiencing at Least One Adverse Event (AE)
The incidence of patients experiencing at least one AE during the randomized treatment and follow-up periods was calculated. (NCT01395524)
Timeframe: Baseline (Week 0) to end of the follow-up period (Week 14)
| Intervention | Participants (Number) |
|---|
| NKTR-118 12.5 mg | 32 |
| NKTR-118 25 mg | 40 |
| Placebo | 33 |
Incidence of Patients Experiencing Severe Adverse Events (SAEs)
The incidence of patients experiencing SAEs during the randomized treatment and follow-up periods was calculated. (NCT01395524)
Timeframe: Baseline (Week 0) to end of the follow-up period (Week 14)
| Intervention | Participants (Number) |
|---|
| NKTR-118 12.5 mg | 6 |
| NKTR-118 25 mg | 6 |
| Placebo | 5 |
Change From Baseline in Patient Assessment of Constipation Quality of Life (PAC-QOL)
The PAC-QOL scale is a 28-item self-report instrument designed to evaluate the burden of constipation on patients' everyday functioning and well-being in the 2 weeks (14 days) prior to assessment. Each item is rated on a 5-point Likert scale ranging from 0 (not at all) to 4 (extremely). The instrument can be used to generate an overall score, but is also reported to assess 4 specific constipation-related domains including: 1) Worries and concerns (11 items), 2) Physical discomfort (4 items), 3) Psychosocial discomfort (8 items), and 4) Satisfaction (5 items). Each domain score is the mean of the non-missing items for that domain. The total score is the mean of all non-missing items. The range of the domain or total score is 0 (response is 'not at all' for each item) to 4 (response is 'extremely' for each item). A negative change from baseline indicates improvement. (NCT01395524)
Timeframe: Baseline (prior to treatment) to last on-treatment assessment (up to Week 12)
| Intervention | units on a scale (Mean) |
|---|
| Total score | Physical discomfort | Psychosocial discomfort | Worries/concerns | Satisfaction |
|---|
| NKTR-118 12.5 mg | -1.0 | -1.0 | -0.8 | -1.0 | -1.2 |
,| NKTR-118 25 mg | -0.9 | -1.1 | -0.7 | -0.9 | -1.3 |
,| Placebo | -0.8 | -1.0 | -0.6 | -0.7 | -1.1 |
Change From Baseline in Patient Assessment of Constipation Symptoms Questionnaire (PAC-SYM)
The PAC-SYM questionnaire is a 12-item questionnaire that evaluates the severity of symptoms of constipation in 3 domains (stool, rectal, and abdominal symptoms) on a 5-point Likert scale ranging from 0 (absent) to 4 (very severe) in the 2 weeks (14 days) prior to assessment. Each domain score is the mean of the non-missing items for that domain. The total score is the mean of all non-missing items (ie, symptoms). The range of the domain or total score is 0 (response is 'absent' for each item) to 4 (response is 'very severe' for each item). A negative change from baseline indicates improvement. (NCT01395524)
Timeframe: Baseline (prior to treatment) to last on-treatment assessment (up to Week 12)
| Intervention | units on a scale (Mean) |
|---|
| Total score | Abdominal symptoms subscore | Rectal symptoms subscore | Stool symptoms subscore |
|---|
| NKTR-118 12.5 mg | -0.9 | -0.8 | -0.7 | -1.2 |
,| NKTR-118 25 mg | -0.9 | -0.7 | -0.7 | -1.1 |
,| Placebo | -0.8 | -0.7 | -0.6 | -0.9 |
Apparent Total Body Clearance After Extravascular Administration Estimated as Dose Divided by AUC (CL/F).
This was one of the PK parameters to determine the apparent total body clearance after extravascular administration estimated as dose divided by AUC. Blood was collected pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours post-dose to determine naloxegol plasma concentrations. (NCT02446171)
Timeframe: Pre-dose (0 hours [within 30 minutes prior to IMP administration]) and post-dose at 0.25 (15 minutes), 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours in each treatment period.
| Intervention | L/h (Geometric Mean) |
|---|
| Treatment A | 131 |
| Treatment B | 130 |
| Treatment C | 140 |
| Treatment D | 131 |
Apparent Volume of Distribution During the Terminal Phase After Extravascular Administration (Vz/F).
This was one of the PK parameters to determine the apparent volume of distribution during the terminal phase after extravascular administration. (NCT02446171)
Timeframe: Pre-dose (0 hours [within 30 minutes prior to IMP administration]) and post-dose at 0.25 (15 minutes), 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours in each treatment period.
| Intervention | L (Geometric Mean) |
|---|
| Treatment A | 1738 |
| Treatment B | 1513 |
| Treatment C | 1731 |
| Treatment D | 1640 |
Area Under Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-infinity).
Area under plasma concentration-time curve from time zero extrapolated to infinity (AUC) is presented below. Blood was collected pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours post-dose to determine naloxegol plasma concentrations. (NCT02446171)
Timeframe: Pre-dose (0 hours [within 30 minutes prior to administration of the investigational medicinal product (IMP)]) and post-dose at 0.25 (15 minutes), 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours in each treatment period.
| Intervention | h*ng/mL (Geometric Mean) |
|---|
| Treatment A | 191 |
| Treatment B | 192 |
| Treatment C | 179 |
| Treatment D | 191 |
Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC 0-t).
Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration is presented below. Blood was collected pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours post-dose to determine naloxegol plasma concentrations. (NCT02446171)
Timeframe: Pre-dose (0 hours [within 30 minutes prior to IMP administration]) and post-dose at 0.25 (15 minutes), 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours in each treatment period.
| Intervention | h*ng/mL (Geometric Mean) |
|---|
| Treatment A | 188 |
| Treatment B | 190 |
| Treatment C | 178 |
| Treatment D | 188 |
Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t½λz).
This was one of the PK parameters to determine λz of a t½λz. Blood was collected pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours post-dose to determine naloxegol plasma concentrations. (NCT02446171)
Timeframe: Pre-dose (0 hours [within 30 minutes prior to IMP administration]) and post-dose at 0.25 (15 minutes), 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours in each treatment period.
| Intervention | h (Mean) |
|---|
| Treatment A | 9.92 |
| Treatment B | 8.78 |
| Treatment C | 9.28 |
| Treatment D | 9.22 |
Mean Dissolution Time (MDT).
This was one of the PK parameters to determine MDT (whole tablet only) (calculated as MRT Treatment D [Reference] - MRT Treatment C [Test]). Blood was collected pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours post-dose to determine naloxegol plasma concentrations. (NCT02446171)
Timeframe: Pre-dose (0 hours [within 30 minutes prior to IMP administration]) and post-dose at 0.25 (15 minutes), 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours in each treatment period.
| Intervention | h (Mean) |
|---|
| Treatment D | 1.29 |
Mean Residence Time (MRT).
This was one of the PK parameters to determine MRT. Blood was collected pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours post-dose to determine naloxegol plasma concentrations. (NCT02446171)
Timeframe: Pre-dose (0 hours [within 30 minutes prior to IMP administration]) and post-dose at 0.25 (15 minutes), 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours in each treatment period.
| Intervention | h (Mean) |
|---|
| Treatment A | 6.94 |
| Treatment B | 6.54 |
| Treatment C | 6.21 |
| Treatment D | 6.72 |
Observed Maximum Plasma Concentration (Cmax).
Observed maximum plasma concentration (Cmax) is presented below. Blood was collected pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours post-dose to determine naloxegol plasma concentrations. (NCT02446171)
Timeframe: Pre-dose (0 hours [within 30 minutes prior to IMP administration]) and post-dose at 0.25 (15 minutes), 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours in each treatment period.
| Intervention | ng/mL (Geometric Mean) |
|---|
| Treatment A | 39.2 |
| Treatment B | 40.1 |
| Treatment C | 40.2 |
| Treatment D | 39.7 |
Participants With Significant Findings in 12-Lead Electrocardiography (ECG).
A 12-lead ECG was obtained after the participant rested in supine position for at least 10 minutes. The study physician was to judge the overall interpretation as normal or abnormal. If abnormal, it was decided as to whether or not the abnormality was clinically significant and the reason for the abnormality was recorded. (NCT02446171)
Timeframe: At screening, first admission to the clinical unit (Visit 2, Day -1), 1.25 hours after each dose (Visits 2-5, Day 1), as well as at the final follow-up visit (up to 9 weeks).
| Intervention | participants (Number) |
|---|
| Treatment A | 0 |
| Treatment B | 0 |
| Treatment C | 0 |
| Treatment D | 0 |
Participants With Significant Findings in Columbia-Suicide Severity Rating Scale (C-SSRS).
The C-SSRS is a unique, simple and short method of assessing both behavior and ideation that tracks all suicidal events, and provided a summary of suicidality. It assesses the lethality of attempts and other features of ideation (frequency, duration, controllability, reasons for ideation and deterrents), all of which are significantly predictive of completed suicide. The C-SSRS was performed to determine the presence of suicidality. (NCT02446171)
Timeframe: At Baseline and Days 1-4 of each treatment period.
| Intervention | participants (Number) |
|---|
| Treatment A | 0 |
| Treatment B | 0 |
| Treatment C | 0 |
| Treatment D | 0 |
Participants With Significant Findings in Hematology, Clinical Chemistry and Urinalysis.
Participants were assessed through each laboratory variables for any significant abnormalities. Hematology assessments included white blood cell count, red blood cell count, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin and others. Clinical chemistry assessment included testing levels of sodium, potassium, urea, creatinine, albumin, calcium, glucose (fasting) and others. Urinalysis assessment included glucose, protein, blood and microscopy (if positive for blood or protein). (NCT02446171)
Timeframe: At screening and at the final follow-up visit (maximum 9 weeks apart); in addition, for the first and third treatment period at pre-dose.
| Intervention | participants (Number) |
|---|
| Treatment A | 0 |
| Treatment B | 0 |
| Treatment C | 0 |
| Treatment D | 0 |
Participants With Significant Findings in Physical Examination.
A complete physical examination included an assessment of the general appearance, respiratory, cardiovascular, abdomen, skin, head, and neck (including ears, eyes, nose, mouth and throat), lymph nodes, thyroid, musculoskeletal and neurological systems. Physical examination was performed to check for any significant abnormality in participants. (NCT02446171)
Timeframe: A full physical examination at screening and the final follow-up visit (maximum 9 weeks apart). Abbreviated physical examination on admission (on Day -1 of each treatment period) and at 48-hours post-dose to each treatment period (for up to 4 weeks).
| Intervention | participants (Number) |
|---|
| Treatment A | 0 |
| Treatment B | 0 |
| Treatment C | 0 |
| Treatment D | 0 |
Percentage of Participants With Adverse Events (AE).
An AE is the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.The term AE is used generally to include any AE whether serious or non-serious. An serious AE (SAE) is an AE that fulfills one or more of the following criteria: results in death, is immediately life-threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity or substantial disruption of the ability to conduct normal life functions; is a congenital abnormality or birth defect; is an important medical event that may jeopardize the participant or may require medical intervention to prevent one of the outcomes listed above. (NCT02446171)
Timeframe: For up to 9 weeks (starting with screening).
| Intervention | percentage of participants (Number) |
|---|
| Treatment A | 9.5 |
| Treatment B | 7.0 |
| Treatment C | 11.6 |
| Treatment D | 18.6 |
Time to Reach Maximum Plasma Concentration (Tmax).
This was one of the PK parameters to determine the time to reach maximum plasma concentration (tmax). Blood was collected pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours post-dose to determine naloxegol plasma concentrations. (NCT02446171)
Timeframe: Pre-dose (0 hours [within 30 minutes prior to IMP administration]) and post-dose at 0.25 (15 minutes), 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours in each treatment period.
| Intervention | h (Median) |
|---|
| Treatment A | 0.75 |
| Treatment B | 1.50 |
| Treatment C | 0.50 |
| Treatment D | 1.00 |
Mean Change From Baseline for Vital Signs in Supine Pulse Rate.
Pulse rate: the measurement of vital signs for pulse rate is presented in the below outcome table. (NCT02446171)
Timeframe: Day 2 (24h post-dose), Day 3 (48h post-dose) and Day 4 (72h post-dose).
| Intervention | beats per minute (bpm) (Mean) |
|---|
| Day 2/24h Post-dose (N= 42, 43, 43, 43) | Day 3/48h Post-dose (N= 42, 43, 43, 42) | Day 4/72h Post-dose (N= 9, 11, 11, 12) |
|---|
| Treatment A | 1 | 5 | 8 |
,| Treatment B | 0 | 4 | 4 |
,| Treatment C | 1 | 5 | 8 |
,| Treatment D | 2 | 5 | 12 |
Mean Change From Baseline for Vital Signs of Supine Systolic and Diastolic Blood Pressure.
The following variables were collected after the participants had rested in the supine position for at least 5 minutes: Systolic Blood Pressure (SBP) and Diastolic BP. The measurement of vital signs for SBP and DBP are presented in the below outcome table. (NCT02446171)
Timeframe: Day 2 (24h post-dose), Day 3 (48h post-dose) and Day 4 (72h post-dose).
| Intervention | mmHg (Mean) |
|---|
| Day 2/24h Post-dose (SBP) (N= 42, 43, 43, 43) | Day 3/48h Post-dose (SBP) (N= 42, 43, 43, 42) | Day 4/72h Post-dose (SBP) (N= 9, 11, 11, 12) | Day 2/24h Post-dose (DBP) (N= 42, 43, 43, 43) | Day 3/48h Post-dose (DBP) (N= 42, 43, 43, 42) | Day 4/72h Post-dose (DBP) (N= 9, 11, 11, 12) |
|---|
| Treatment A | -2 | 4 | 7 | -2 | 0 | 5 |
,| Treatment B | -4 | -2 | 0 | -4 | -2 | 0 |
,| Treatment C | -1 | 2 | 1 | -1 | 0 | 4 |
,| Treatment D | 0 | 2 | 7 | 0 | 1 | 4 |
Taste Test Assessment.
"A standardized questionnaire was provided to participants and were asked to complete the questionnaire for the liquid formulations tested, i.e., Naloxegol crushed tablet, oral (Treatment A) and Naloxegol oral solution (Treatment C), without assistance or influence from site personnel. For each formulation, the questionnaire was identical and required the participant's opinion. Sweet, salty, sour, bitter, metallic, hot/spicy were rated on a scale of 0 to 10, where 0 means not at all and 10 means extreme. The overall rating of the taste was rated on a scale of 0 to 10, where 0 means I dislike it extremely much and 10 means I like it extremely much. The smell of the medicine was based on a scale of 0 to 10, where 0 means extremely bad and 10 means extremely nice. The question on whether the participants would consider ever taking the medicine again was based on a scale of 0 to 10, where 0 means Never - under no circumstances and 10 means Yes, definitely." (NCT02446171)
Timeframe: Within 1 hour after dosing (Treatments A and C only).
| Intervention | units on a scale (Median) |
|---|
| Sweet | Salty | Sour | Bitter | Metallic | Hot/Spicy | How would you rate the taste of this medicine? | If the medicine smells, how does it smell? | Would you consider taking this medicine again? |
|---|
| Treatment A | 0.0 | 0.0 | 0.0 | 3.0 | 1.0 | 0.0 | 4.0 | 4.0 | 8.0 |
,| Treatment C | 7.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 7.0 | 7.0 | 9.0 |
Number of Participants That Completed Naloxegol 25mg and the Number of Participants That Completed Standard of Care
completion of treatment defined as participants receiving all single daily doses for 2 weeks (NCT02745353)
Timeframe: 4 weeks
| Intervention | Participants (Count of Participants) |
|---|
| Naloxegol | Standard of Care |
|---|
| Arm A (Naloxegol/Standard of Care) | 4 | 1 |
,| Arm B (Standard of Care/ Naloxego) | 3 | 1 |
Electrocardiogram QTC Interval
Changes from Baseline to Visit 3 (approximately Day 15) for Electrocardiogram (ECG) QTC interval data will be derived by subtracting the baseline value from the final assessment data. (NCT02839889)
Timeframe: Change from Baseline at End of Double Blind Phase (Visit 3, approximately day 15)
| Intervention | milliseconds (Mean) |
|---|
| Placebo | -24.8 |
| Naloxegol | -6.9 |
Numerical Rating Scale (NRS) for Pain Change From Baseline
Change from baseline in mean daily NRS (Numerical Rating Scale) values will be calculated as the post-baseline value minus the baseline. Baseline NRS is the mean daily NRS values recorded during the Opioid Induced Constipation (OIC) Confirmation period. Numeric Rating Scale is 0-10. 0 is no pain and 10 is worst possible pain. Lower values are a better outcome and higher values are a worse outcome. Post-baseline values were calculated as the mean of NRS scores during visits 2-4. (NCT02839889)
Timeframe: Assessed from screening/Opioid Induced Constipation (OIC) Confirmation period through study completion, approximately 6 weeks.
| Intervention | score on a scale (Mean) |
|---|
| Placebo | 0.65 |
| Naloxegol | .33 |
Rescue Free Bowel Movements (RFBM) Responder Rate
Daily diary data will be used to identify RFBMs. The weekly RFBM frequency within each time period will be calculated as: (Total number of RFBMs during the time period of interest/number of days) x 7. RFBM rate calculated from post baseline period. (NCT02839889)
Timeframe: Assessed from Baseline through Study Completion, approximately 6 weeks.
| Intervention | RFBMs/days *7 (Mean) |
|---|
| Placebo | 8.14 |
| Naloxegol | 3.82 |
Patient Assessment of Constipation Symptoms (PAC-SYM)
"The PAC-SYM is divided into three subscales. Each item is scored 0-4. Items 1-4 measure abdominal symptoms (total subscale range 0-16), items 5-7 measure rectal symptoms (total subscale score 0-12), and items 8-12 measure stool symptoms (total subscale range 0-20). For each subscale, lower scores are better and higher scores are worse.~The total construct score is generated by summing the scores of the subscales. This total score ranges from 0-48, with lower scores corresponding to better outcomes, and higher scores corresponding to worse outcomes.~Change from baseline in mean values calculated as post-baseline value minus baseline value for each scale, and for total. Post-baseline values defined as the mean of day 15 and day 29." (NCT02839889)
Timeframe: day 1, day 15, day 29
| Intervention | score on a scale (Mean) |
|---|
| Abdominal Symptoms | Rectal Symptoms | Stool Symptoms | Total Score |
|---|
| Naloxegol | .5 | 1.2 | -.2 | 1.5 |
,| Placebo | 1 | 1.25 | .5 | 2.75 |
Patient Assessment of Constipation Quality of Life (PAC-QOL)
"The PAC-QOL is a 28-item questionnaire divided into 4 subscales. Items 1-4 measure physical discomfort (subscale range 0-16), 5-12 measure psychosocial discomfort (range 0-32), 13-23 measure worries/concerns (range 0-44), and 24-28 measure satisfaction (range 0-20). For each subscale, lower scores are better and higher scores are worse.~The total score is generated by summing the scores of the subscales. This total score ranges from 0-112, with lower scores corresponding to better outcomes, and higher scores corresponding to worse outcomes.~Change from baseline in mean values calculated as post-baseline value minus baseline value for each subscale, and for total. Post-baseline values defined as the mean of day 15 and day 29." (NCT02839889)
Timeframe: day 1, day 15, day 29
| Intervention | score on a scale (Mean) |
|---|
| Physical discomfort | Psychosocial Discomfort | Worries/concerns | Satisfaction | Total Score |
|---|
| Naloxegol | 0.17 | 6 | 1.17 | 3.83 | 11.17 |
,| Placebo | -1.25 | -1 | 1.5 | 3.5 | 2.75 |
Time to First Post-dose Rescue Free Laxation
Time (in hours) to first post-dose rescue free bowel movement minus first dose date and time. (NCT02839889)
Timeframe: First dose date to first post-dose rescue free bowel movement
| Intervention | Hours (Mean) |
|---|
| Placebo | 23.3 |
| Naloxegol | 33.5 |
Change From Baseline in Diastolic Blood Pressure
Change from Baseline in diastolic blood pressure at post baseline (visits 2, 3, 4) will be derived as the value at the visit minus the baseline value for the same assessment. The post-baseline values were calculated as a mean of values from visits 2 through 4. (NCT02839889)
Timeframe: Change from Baseline in diastolic blood pressure through study completion, approximately 6 weeks.
| Intervention | mmHg (Mean) |
|---|
| Placebo | -10.5 |
| Naloxegol | -1.8 |
Change From Baseline in Pulse Rate
Change from Baseline in pulse rate at post baseline (visits 2, 3, 4) will be derived as the value at the visit minus the baseline value for the same assessment. The post-baseline values were calculated as a mean of values from visits 2 through 4. (NCT02839889)
Timeframe: Change from Baseline in pulse rate through study completion, approximately 6 weeks.
| Intervention | beats per minute (Mean) |
|---|
| Placebo | 4.5 |
| Naloxegol | 10.3 |
Daily Opioid Use Change From Baseline
Change from baseline in mean daily opioid dose will be calculated as the post-baseline value minus the baseline value. Positive changes from baseline indicate there was a need to increase the opioid dose. Baseline daily opioid dose is the mean daily opioid dose recorded during the Opioid Induced Constipation (OIC) Confirmation period. (NCT02839889)
Timeframe: Assessed from screening through study completion, approximately 6 weeks.
| Intervention | morphine milligram equivalents per day (Mean) |
|---|
| Placebo | 1144 |
| Naloxegol | 20 |
Change From Baseline in Systolic Blood Pressure
Change from Baseline in systolic blood pressure at post baseline (visits 2, 3, 4) will be derived as the value at the visit minus the baseline value for the same assessment. The post-baseline values were calculated as a mean of values from visits 2 through 4. (NCT02839889)
Timeframe: Change from Baseline in systolic blood pressure through study completion, approximately 6 weeks.
| Intervention | mmHg (Mean) |
|---|
| Placebo | -10.3 |
| Naloxegol | -8.8 |
Complete Evacuation Question With Each Bowel Movement
Change from Baseline in mean values calculated as the post baseline value minus the baseline. The post baseline value is the percentage of days from baseline to study completion with at least one complete bowel evacuation. (NCT02839889)
Timeframe: Assessed at baseline through Study Completion with each bowel movement, approximately 6 weeks.
| Intervention | % of days with complete evacuation (Mean) |
|---|
| Placebo | 21.92 |
| Naloxegol | 7.7 |
Degree of Straining Question With Each Bowel Movement
"Degree of straining scale is 1 to 5 with 1 being not at all and 5 being an extreme amount. Lower scores are better and higher scores are worse.~Change from baseline in mean values calculated as the post baseline value minus the baseline. Degree of Straining scale change from baseline mean scores calculated from baseline to study completion." (NCT02839889)
Timeframe: Assessed at baseline through Study Completion with each bowel movement, approximately 6 weeks.
| Intervention | score on a scale (Mean) |
|---|
| Placebo | .6 |
| Naloxegol | -.35 |
Electrocardiogram Heart Rate
Changes from Baseline to Visit 3 (approximately Day 15) for Electrocardiogram (ECG) heart rate data will be derived by subtracting the baseline value from the final assessment data. (NCT02839889)
Timeframe: Change from Baseline at End of Double Blind Phase (Visit 3, approximately day 15)
| Intervention | beats per minute (Mean) |
|---|
| Placebo | 9 |
| Naloxegol | 10 |
Change From Baseline in Respiratory Rate
Change from Baseline in respiratory rate at post baseline (visits 2, 3, 4) will be derived as the value at the visit minus the baseline value for the same assessment. The post-baseline values were calculated as a mean of values from visits 2 through 4. (NCT02839889)
Timeframe: Change from Baseline in respiratory rate through study completion, approximately 6 weeks.
| Intervention | breaths per minute (Mean) |
|---|
| Placebo | 1.7 |
| Naloxegol | 1.2 |
Length of Stay
(NCT02946580)
Timeframe: through study completion, an average of 6 days
| Intervention | hours (Mean) |
|---|
| MOVANTIK™ (Naloxegol) | 106 |
| Sugar Pill | 133 |
Number of Participants That Experienced Diarrhea
(NCT02946580)
Timeframe: through study completion, an average of 6 days
| Intervention | Participants (Count of Participants) |
|---|
| MOVANTIK™ (Naloxegol) | 0 |
| Sugar Pill | 1 |
Patient's Satisfaction With Their Bowels at Discharge Using a 5-point Likert Scale.
"Patients completed a bowel satisfaction questionnaire on day of discharge. 5-point Likert scale, Very dissatisfied to Very satisfied. Higher scores mean a better outcome." (NCT02946580)
Timeframe: upon discharge from hospital, an average of 5 days
| Intervention | score on a scale (Mean) |
|---|
| MOVANTIK™ (Naloxegol) | 3.4 |
| Sugar Pill | 3.3 |
Patient's Satisfaction With Their Bowels by Use of the Bowel Function Index
BFI normal reference range is 0-28.8 (on a scale of 100 for all 3 items summed and divided by 3). Higher scores mean a worse outcome. (NCT02946580)
Timeframe: through study completion, an average of 6 days
| Intervention | score on a scale (Mean) |
|---|
| MOVANTIK™ (Naloxegol) | 14.3 |
| Sugar Pill | 16.9 |
Time to First Post-operative Spontaneous Bowel Movement
The primary endpoint of the study was time to first post-operative bowel movement, as defined by the first spontaneous bowel movement reported by nursing staff after transfer from the surgical suite to the inpatient floor. A bowel movement was defined as the spontaneous passage of one tablespoon or more of liquid or solid stool (excluding flatus), which could be measured and verified by nursing staff. Time was measured in hours post-operatively with the starting time point marked at the end of the surgical procedure. (NCT02946580)
Timeframe: through study completion, an average of 6 days
| Intervention | hours (Mean) |
|---|
| MOVANTIK™ (Naloxegol) | 91 |
| Sugar Pill | 94 |
Time to Rescue Laxative Medication Use During Hospitalization
"The use of a rescue laxative medication is defined as the administration of an additional bowel medication due to a decision by the clinical treatment team that the subject suffered from constipation and required a rescue bowel medication. Of note, this medication did not include the study drug, placebo, or the standing laxative orders used in all patient (docusate and sennosides). By definition, a rescue medication could only be given before a subject's first bowel movement or discharge" (NCT02946580)
Timeframe: upon discharge from hospital, an average of 5 days
| Intervention | hours (Mean) |
|---|
| MOVANTIK™ (Naloxegol) | 70 |
| Sugar Pill | 75 |
Time to First Spontaneous Bowel Movement (SBM) Administration
Time to first spontaneous bowel movement during ICU admission after randomization (NCT02977286)
Timeframe: First occurrence after study randomization during period of ICU admission or a maximum of 10 ICU days
| Intervention | hours (Mean) |
|---|
| Naloxegol Oral Tablet | 41 |
| Placebo Oral Tablet | 33 |
Daily Fluid Balance
Daily fluid balance measured in mL is the 24 hours ins and outs (NCT02977286)
Timeframe: From randomization to ICU discharge or a maximum of 10 ICU days
| Intervention | mL (Mean) |
|---|
| Naloxegol Oral Tablet | -338 |
| Placebo Oral Tablet | -210 |
Daily Difference in the Pre-dose and Post-dose Clinical Opioid Withdrawal Scale (COWS) Score
Patients were evaluated 1 hour before and 2 hours after the administration of each dose of study medication using the Clinical Opioid Withdrawal Scale (COWS). COWS is used to help determine the stage or severity of opiate withdrawal and assess the level of physical dependence on opioids. The COWS score ranges from 0-36+. A score of 0 is no active opioid withdrawal. A score of 5-12 is mild; 13-24 is moderate; 25-36 is moderately severe and more than 36 is severe opioid withdrawal. (NCT02977286)
Timeframe: One hour before the daily study drug administration and 2 hours after the daily study drug administration
| Intervention | Difference of COWS score (Mean) |
|---|
| Naloxegol Oral Tablet | -0.1 |
| Placebo Oral Tablet | 0.2 |
Average Daily Opioid Requirement [in IV Fentanyl Equivalents (mcg Per Day)]
Average daily opioid requirement is converted to IV fentanyl equivalent listed in mcg per day (NCT02977286)
Timeframe: From randomization to ICU discharge or a maximum of 10 ICU days
| Intervention | mcg per day (Mean) |
|---|
| Naloxegol Oral Tablet | 1420 |
| Placebo Oral Tablet | 1600 |
Abdominal Pressure Measurement
On days when the patient had a urinary catheter in place for clinical reasons, a bladder pressure transducer was inserted and abdominal pressure was measured. The average daily maximum pressure score for each group is reported. (NCT02977286)
Timeframe: From randomization to ICU discharge (or removal of foley catheter) or a maximum of 10 ICU days
| Intervention | mmHg (Mean) |
|---|
| Naloxegol Oral Tablet | 10 |
| Placebo Oral Tablet | 13 |
Daily Maximal Pain Scale Score
"Based on the highest daily Visual Analogue Scale-10 or Clinical Pain Observation tool assessment.~VAS-10 is Visual Analogue Scale which uses a nurse-administered 10 point rating scale. A measurement of 0-1 is minimal pain. A measurement of 10 is severe pain." (NCT02977286)
Timeframe: From randomization to ICU discharge or a maximum of 10 ICU days
| Intervention | score on a scale (Mean) |
|---|
| Naloxegol Oral Tablet | 0 |
| Placebo Oral Tablet | 0 |
Daily Maximal Sedation Assessment Scale (SAS) Score
"The Sedation Assessment Scale is rated 1 to 7. Score of 7 is dangerous agitation. Score of 1 is unarousable. Score of 2 is very sedated. The presence of coma is based on the every 4 hour sedation agitation score scale (SAS) assessment. A score of 1 or 2 any time during the day represents that a coma is present. A score of 3-7 represents a subject with no coma present.~Results listed here is days without coma (SAS score of 3-7)" (NCT02977286)
Timeframe: From randomization to ICU discharge or a maximum of 10 ICU days
| Intervention | days (Median) |
|---|
| Naloxegol Oral Tablet | 3 |
| Placebo Oral Tablet | 7 |
Daily Presence of Delirium Using the Intensive Care Delirium Screening Checklist (ICDSC)
Measures as days without delirium with daily presence of delirium assessed using the Intensive Care Delirium Screening Checklist (ICDSC) (NCT02977286)
Timeframe: From randomization to ICU discharge or a maximum of 10 ICU days
| Intervention | days without delirium (Median) |
|---|
| Naloxegol Oral Tablet | 5 |
| Placebo Oral Tablet | 6 |
Days Without Mechanical Ventilation Support for Duration of ICU Stay
Measure is days without mechanical ventilation for duration of ICU stay as expressed as median and inter-Quartile Range (NCT02977286)
Timeframe: From ICU admission to ICU discharge or a maximum of 10 ICU days
| Intervention | days (Median) |
|---|
| Naloxegol Oral Tablet | 0.5 |
| Placebo Oral Tablet | 1 |
ICU Days Without a SBM
Measured ICU days that subjects did not have a SBM (NCT02977286)
Timeframe: During period of ICU admission or a maximum of 10 ICU days
| Intervention | Days (Mean) |
|---|
| Naloxegol Oral Tablet | 2 |
| Placebo Oral Tablet | 2 |
Number of Patients That Required Use of the Study Laxative Protocol
A 4-step laxative protocol was initiated when there was no spontaneous bowel movement greater than or equal to 3 days time. Data collected on study laxative protocol included any use as well as the highest level needed. (NCT02977286)
Timeframe: From randomization to ICU discharge or a maximum of 10 ICU days
| Intervention | participants (Number) |
|---|
| Naloxegol Oral Tablet | 5 |
| Placebo Oral Tablet | 4 |
Occurrence of Lower GI Tract Paralysis (≥3 Days Without a SBM)
Measurement is the number of subjects in each group having this occurrence of lower GI tract paralysis during time frame (NCT02977286)
Timeframe: From randomization to ICU discharge or a maximum of 10 ICU days
| Intervention | Participants (Count of Participants) |
|---|
| Naloxegol Oral Tablet | 2 |
| Placebo Oral Tablet | 3 |
Occurrence of Lower GI Tract Paralysis Requiring GI/Surgical Consultation
Number of patients with GI tract paralysis requiring Gastroenterology service or Surgical service consultation (NCT02977286)
Timeframe: From randomization to ICU discharge or a maximum of 10 ICU days
| Intervention | Participants (Count of Participants) |
|---|
| Naloxegol Oral Tablet | 0 |
| Placebo Oral Tablet | 0 |
Percentage of Daily Goal Reached for Enteral Nutrition Administration
Enteral nutrition is assessed as daily volume in mL and the reported measure is the percentage of daily goal of enteral nutrition met. (NCT02977286)
Timeframe: From randomization to ICU discharge or a maximum of 10 ICU days
| Intervention | percentage of daily goals met (Mean) |
|---|
| Naloxegol Oral Tablet | 54 |
| Placebo Oral Tablet | 51 |
Time to First Episode of Diarrhea
The number of patients in each group with > or equal to 1 episode of diarrhea after initiation of study drug. The time to first episode of diarrhea was measured in hours. (NCT02977286)
Timeframe: Study drug initiation to first episode of diarrhea in hours.
| Intervention | hours (Median) |
|---|
| Naloxegol Oral Tablet | 40 |
| Placebo Oral Tablet | 109 |
Time to First Spontaneous Bowel Movement (SBM)
Time to first spontaneous bowel movement during the ICU admission after opioid initiation (NCT02977286)
Timeframe: First occurrence after initiation of IV opioid therapy during period of ICU admission or a maximum of 10 ICU days
| Intervention | hours (Mean) |
|---|
| Naloxegol Oral Tablet | 52 |
| Placebo Oral Tablet | 49 |
Patient Reported Influence of Each Medication Characteristic Individual Category Results That Contributed to Their Overall Preference for Movantik or PEG 3350
"In order to assess the reason for patient preference of Movantik or PEG 3350, subjects reported on the influence of 5 medication characteristics using a 4-point rating scale. The following were the scale options: efficacy ('worked better to relieve my OIC'), tolerability ('tolerated better'), convenience ('was more convenient'), works quickly ('worked quickly') and works predictably ('worked predictably'). For each characteristic, influence scores were rated as: 0 = No influence, 1 = Mildly influenced, 2 = Moderately influenced or 3 = Strongly influenced. The scale range for each characteristic was from 0 to 3, and the number of subjects in each characteristic category is presented for the overall PP Set according to which treatment was preferred.~The assessment was only completed by subjects who indicated an overall preference." (NCT03060512)
Timeframe: From Visit 2 (Day 1) of Treatment Period 1 to Visit 5 (Day 36) of Treatment Period 2 (end of study).
| Intervention | Participants (Count of Participants) |
|---|
| Efficacy: No Influence | Efficacy: Mildly Influenced | Efficacy: Moderately Influenced | Efficacy: Strongly Influenced | Tolerability: No Influence | Tolerability: Mildly Influenced | Tolerability: Moderately Influenced | Tolerability: Strongly Influenced | Convenience: No Influence | Convenience: Mildly Influenced | Convenience: Moderately Influenced | Convenience: Strongly Influenced | Works Quickly: No Influence | Works Quickly: Mildly Influenced | Works Quickly: Moderately Influenced | Works Quickly: Strongly Influenced | Works Predictably: No Influence | Works Predictably: Mildly Influenced | Works Predictably: Moderately Influenced | Works Predictably: Strongly Influenced |
|---|
| Preferred Movantik | 4 | 18 | 40 | 61 | 14 | 16 | 30 | 63 | 5 | 6 | 26 | 86 | 15 | 25 | 35 | 48 | 11 | 21 | 36 | 55 |
,| Preferred PEG 3350 | 2 | 20 | 43 | 52 | 15 | 11 | 32 | 59 | 39 | 26 | 17 | 35 | 14 | 30 | 41 | 32 | 12 | 15 | 48 | 42 |
Patient Global Impression of Change (PGIC) Questionnaire to Compare the Impact of Movantik and PEG 3350 on OIC Symptoms
"PGIC was measured on a 7-point scale at the end of each two-week treatment period to assess the subject's impression of the effectiveness of the treatment received for OIC. The scoring was as follows: 1 = No change (or condition has gotten worse); 2 = Almost the same, hardly any change at all; 3 = A little better, but no noticeable change; 4 = Somewhat better, but the change has not made any real difference; 5 = Moderately better, and a slight but noticeable change; 6 = Better and a definite improvement that has made a real and worthwhile difference; and 7 = A great deal better and a considerable improvement that has made all the difference. The score range is from 1 to 7, with 1 indicating the least improvement and 7 indicating the greatest improvement in OIC symptoms.~Mean score results are presented for each treatment for Visits 3 and 5." (NCT03060512)
Timeframe: At Visit 3 (Day 15) of Treatment Period 1 and Visit 5 (Day 36) of Treatment Period 2.
| Intervention | Score (Mean) |
|---|
| Movantik FAS | 4.5 |
| PEG 3350 FAS | 4.5 |
Mean Change From Baseline at Visit 3/5 in Bowel Function Index (BFI) Questionnaire Scores to Compare the Impact of Movantik and PEG 3350 on OIC Symptoms
"The BFI is a 3-item questionnaire administered by a study clinician to measure constipation from the subject's perspective (ease of defecation, feeling of complete evacuation, and personal judgment of constipation). For each item the subject was asked to rate their response on a scale from 0 to 100, where 0 indicates the best response (easy/no diffculty) and 100 the worst response (severe difficulty). The total BFI score was calculated as the mean of the 3 item scores.~The mean change from baseline in BFI scores at Visits 3 and/or 5 are presented." (NCT03060512)
Timeframe: From Baseline (Visit 2, Day 1) to Visit 3 (Day 15) and Visit 5 (Day 36).
| Intervention | Score (Mean) |
|---|
| Movantik FAS | -25.0 |
| PEG 3350 FAS | -26.0 |
PGIC Questionnaire Individual Item Results to Compare the Impact of Movantik and PEG 3350 on OIC Symptoms
"PGIC was measured on a 7-point scale at the end of each two-week treatment period to assess the subject's impression of the effectiveness of the treatment received for OIC. The subjects selected one of the following PGIC items as their response: 1 = No change (or condition has gotten worse); 2 = Almost the same, hardly any change at all; 3 = A little better, but no noticeable change; 4 = Somewhat better, but the change has not made any real differences; 5 = Moderately better, and a slight but noticeable change; 6 = Better and a definite improvement that has made a real and worthwhile difference; and 7 = A great deal better and a considerable improvement that has made all the difference. The score range is from 1 to 7, with 1 indicating the least improvement and 7 indicating the greatest improvement in OIC symptoms.~The number of subjects responding to each PGIC item at Visits 3 and/or 5 is presented for each treatment overall." (NCT03060512)
Timeframe: At Visit 3 (Day 15) of Treatment Period 1 and Visit 5 (Day 36) of Treatment Period 2.
| Intervention | Participants (Number) |
|---|
| PGIC Item 1 | PGIC Item 2 | PGIC Item 3 | PGIC Item 4 | PGIC Item 5 | PGIC Item 6 | PGIC Item 7 |
|---|
| Movantik FAS | 23 | 30 | 21 | 38 | 57 | 61 | 32 |
,| PEG 3350 FAS | 27 | 27 | 20 | 33 | 66 | 65 | 28 |
Patient Reported Preference for Movantik or PEG 3350 for Opioid-induced Constipation (OIC) Treatment
The Patient Preference Assessment was conducted at Visit 5 using a 7-point scale in subjects with chronic non-cancer pain. The 3 categories were formed by collapsing the 7-point rating scale to: 1. Prefer Movantik (including Strong preference for Movantik, Moderate preference for Movantik, Slight preference for Movantik), 2. No preference, and 3. Prefer PEG 3350 (including Strong preference for PEG 3350, Moderate preference for PEG 3350, and Slight preference for PEG 3350). The number of subjects in each category is presented for the total number of subjects in the Per-Protocol (PP) Set. (NCT03060512)
Timeframe: From Visit 2 (Day 1) of Treatment Period 1 to Visit 5 (Day 36) of Treatment Period 2 (end of study).
| Intervention | Participants (Count of Participants) |
|---|
| Prefer Movantik | Prefer PEG 3350 | No preference |
|---|
| Total (PP Set) | 124 | 118 | 4 |
Patient Reported Preference for Movantik or PEG 3350 for OIC Treatment by Treatment Sequence
The Patient Preference Assessment was conducted at Visit 5 using a 7-point scale in subjects with chronic non-cancer pain. The following categories were the possible responses: Strong preference for Movantik, Moderate preference for Movantik, Slight preference for Movantik, No preference, Slight preference for PEG 3350, Moderate preference for PEG 3350 and Strong preference for PEG 3350. Prefer Movantik included subjects in the categories Strong preference for Movantik, Moderate preference for Movantik and Slight preference for Movantik. Prefer PEG 3350 included subjects in the categories Strong preference for PEG 3350, Moderate preference for PEG 3350 and Slight preference for PEG 3350. Preference for Period 1 treatment and Preference for Period 2 treatment included subjects who preferred the first and second treatments respectively taken within a given treatment sequence. The number of subjects in each category is presented per treatment sequence for subjects in the PP Set. (NCT03060512)
Timeframe: From Visit 2 (Day 1) of Treatment Period 1 to Visit 5 (Day 36) of Treatment Period 2 (end of study).
| Intervention | Participants (Count of Participants) |
|---|
| Strong preference for Movantik | Moderate preference for Movantik | Slight preference for Movantik | No preference | Slight preference for PEG 3350 | Moderate preference for PEG 3350 | Strong preference for PEG 3350 | Prefer Movantik | Prefer PEG 3350 | Preference for Period 1 treatment | Preference for Period 2 treatment |
|---|
| Movantik, Then PEG 3350 | 37 | 14 | 11 | 2 | 9 | 15 | 37 | 62 | 61 | 62 | 61 |
,| PEG 3350, Then Movantik | 38 | 17 | 7 | 2 | 8 | 23 | 26 | 62 | 57 | 57 | 62 |
Level of Pain
Pain scores will be summarized by arm. Pain scores will be compared between treatment arms vs. placebo using Wilcoxon test. Pain score scale is 0-10, with 10 being worst pain imaginable (NCT03087708)
Timeframe: Baseline to 6 months
| Intervention | units on a scale (Median) |
|---|
| Average Pain Scores at Baseline ( | Average Pain Scores at 6 Months |
|---|
| Group I (Lower Dose Naloxegol, Placebo) | 6.5 | 0.0 |
,| Group II (Placebo, Higher Dose Naloxegol) | 5.0 | 3.7 |
,| Group III (Placebo) | 4.5 | 2.2 |
Analgesic Use
The protocol-defined analysis for this secondary endpoint was not performed due to not specifying analgesic use in the questionnaire. Analgesic use will be summarized by arm. Frequencies of analgesic used will be compared using chi-square test or Fisher's exact test, as appropriate. (NCT03087708)
Timeframe: Up to 2 years
| Intervention | Participants (Count of Participants) |
|---|
| Analgesic use at Baseline?72486357 | Analgesic use at Baseline?72486358 | Analgesic use at Baseline?72486359 | Analgesic Use at 6 Months?72486358 | Analgesic Use at 6 Months?72486359 | Analgesic Use at 6 Months?72486357 |
|---|
| Yes | No | Missing |
|---|
| Group I (Lower Dose Naloxegol, Placebo) | 13 |
| Group II (Placebo, Higher Dose Naloxegol) | 10 |
| Group III (Placebo) | 11 |
| Group I (Lower Dose Naloxegol, Placebo) | 2 |
| Group II (Placebo, Higher Dose Naloxegol) | 3 |
| Group III (Placebo) | 0 |
| Group I (Lower Dose Naloxegol, Placebo) | 3 |
| Group II (Placebo, Higher Dose Naloxegol) | 5 |
| Group I (Lower Dose Naloxegol, Placebo) | 4 |
| Group II (Placebo, Higher Dose Naloxegol) | 2 |
| Group III (Placebo) | 2 |
| Group I (Lower Dose Naloxegol, Placebo) | 0 |
| Group II (Placebo, Higher Dose Naloxegol) | 0 |
| Group III (Placebo) | 1 |
Incidence of Adverse Events as Described and Graded by the National Cancer Institute's Common Terminology Criteria for Adverse Events, Version 4.0
The frequency of adverse events will be summarized by arm and compared between each treatment arm vs the placebo arm using Fisher's exact test. <3 is better and 3+ is worse. (NCT03087708)
Timeframe: Up to 2 years
| Intervention | Participants (Count of Participants) |
|---|
| Hematologic Adverse Events (regardless of attribution) : 3+ | Hematologic Adverse Events (regardless of attribution) : <3 | Non-Hematologic Adverse Events (regardless of attribution) : 3+ | Non-Hematologic Adverse Events (regardless of attribution) : <3 | Hematologic Adverse Events (at least possibly related to study) : 3+ | Hematologic Adverse Events (at least possibly related to study) : <3 | Non-Hematologic Adverse Events (at least possibly related to study) : 3+ | Non-Hematologic Adverse Events (at least possibly related to study) : <3 |
|---|
| Group I (Lower Dose Naloxegol, Placebo) | 4 | 11 | 9 | 6 | 1 | 14 | 1 | 14 |
,| Group II (Placebo, Higher Dose Naloxegol) | 3 | 12 | 9 | 6 | 0 | 15 | 3 | 12 |
,| Group III (Placebo) | 2 | 11 | 6 | 7 | 0 | 13 | 0 | 13 |
Change in Function Subscales
Health-related quality of life scores at each timepoint and changes in scores between 6 months and baseline will be summarized by mean standard deviation, median (inter-quartile range). Scores will be plotted to explore the pattern over time and to examine differences between treatment arms. Differences in health-related quality of life between the treatment arms and the placebo arm will be conducted through linear mixed models and growth curve models to account for repeated assessments. Function subscales score is 0-28 with 0 being the worst and 28 being the best. (NCT03087708)
Timeframe: Baseline to 6 months
| Intervention | units on a scale (Median) |
|---|
| Physical Well Being | Social Function Well Being | Emotional Well Being | Functional Well Being |
|---|
| Group I (Lower Dose Naloxegol, Placebo) | 4.7 | 6.0 | 2.5 | 6.5 |
,| Group II (Placebo, Higher Dose Naloxegol) | 0.0 | 5.0 | 3.0 | 5.0 |
,| Group III (Placebo) | -0.3 | -2 | 0 | 4.0 |
Opioid-induced Constipation Rating Scale
"Opioid-induced constipation rating scale will be summarized by arm. Scores will be compared between treatment arms vs. placebo arm using Wilcoxon test. Question from Bowel Function Diary is In the past 24 hours, how much pain did you feel in your abdomen because of constipation?. Opioid-induced constipation rating scale is from 0-6, with 0 being none and 6 being very severe." (NCT03087708)
Timeframe: Baseline to 6 months
| Intervention | units on a scale (Median) |
|---|
| Group I (Lower Dose Naloxegol, Placebo) | 0 |
| Group II (Placebo, Higher Dose Naloxegol) | 0 |
| Group III (Placebo) | 0 |
Patient-reported Outcome Assessed by a Urinary Retention Linear Analogue Self-Assessment
Linear Analogue Self-Assessment items will be summarized by arm. Linear Analogue Self-Assessment scores will be compared between treatment arms versus placebo arm using Wilcoxon test. Linear Analogue Self-Assessment score is 0-10, with 0 being no trouble with ability to urinate easily and 10 being worst trouble with ability to urinate easily. (NCT03087708)
Timeframe: Baseline to 6 months
| Intervention | units on a scale (Median) |
|---|
| Group I (Lower Dose Naloxegol, Placebo) | 0.0 |
| Group II (Placebo, Higher Dose Naloxegol) | 0.0 |
| Group III (Placebo) | 0.0 |
Observed Accrual Rate Defined as Rate of Accrual Remaining >= 80% of the Expected
Calculated as the total number of patients accrued to the study over two years divided by 184, the total expected accrual of patients evaluable for the primary endpoint. (NCT03087708)
Timeframe: Up to 2 years
| Intervention | proportion of participants (Number) |
|---|
| Expected Accrued Patients | 0.272 |
Change in Trial Outcome Index
Health-related quality of life scores at each timepoint and changes in scores between 6 months and baseline will be summarized by mean standard deviation, median (inter-quartile range). Scores will be plotted to explore the pattern over time and to examine differences between treatment arms. Differences in health-related quality of life between the treatment arms and the placebo arm will be conducted through linear mixed models and growth curve models to account for repeated assessments. Trial outcome index score is 0-92 with 0 being the worst and 92 being the best. (NCT03087708)
Timeframe: Baseline to 6 months
| Intervention | units on a scale (Median) |
|---|
| Group I (Lower Dose Naloxegol, Placebo) | 21.0 |
| Group II (Placebo, Higher Dose Naloxegol) | 14.0 |
| Group III (Placebo) | 9.0 |
Change in Lung Cancer Subscale of the Functional Assessment of Cancer Therapy-Lung
Health-related quality of life scores at each timepoint and changes in scores between 6 months and baseline will be summarized by mean standard deviation, median (inter-quartile range). Scores will be plotted to explore the pattern over time and to examine differences between treatment arms. Differences in health-related quality of life between the treatment arms and the placebo arm will be conducted through linear mixed models and growth curve models to account for repeated assessments. Lung cancer subscale score is 0-36 with 0 being the worst and 36 being the best. (NCT03087708)
Timeframe: Baseline to 6 months
| Intervention | units on a scale (Median) |
|---|
| Group I (Lower Dose Naloxegol, Placebo) | 6.0 |
| Group II (Placebo, Higher Dose Naloxegol) | 1.0 |
| Group III (Placebo) | 1.0 |
Need for Indwelling Urinary Catheterization
Number of patients receiving Naloxegol requiring indwelling urinary catheters (NCT03235739)
Timeframe: Postoperative days 1-2 or until day of discharge whichever occurs first
| Intervention | Participants (Count of Participants) |
|---|
| Treatment-Naloxegol | 19 |
| Placebo Arm | 7 |
Residual Urine Volume
Residual urine volume in the bladder as assessed by bladder scan (NCT03235739)
Timeframe: from Postoperative days 1 to POD 2 or until day of discharge whichever occurs first
| Intervention | ml (Median) |
|---|
| Day 1 AM | Day 1 PM | Day 2 AM | Day 2 PM |
|---|
| Placebo Arm | 114 | 31 | 28 | 28 |
,| Treatment-Naloxegol | 62 | 48 | 32 | 0 |
Quality of Recovery
Quality of recovery is a validated scoring system that quantifies patients' early postoperative health status with range of 0-150 where higher score means better quality of recovery. We used the 15-question version, the QoR-15 (NCT03235739)
Timeframe: Postoperative Days 2 or discharge day whichever was earlier
| Intervention | units on a scale (Median) |
|---|
| Treatment-Naloxegol | 119 |
| Placebo Arm | 123 |