glycine has been researched along with Nausea in 22 studies
Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses.
| Excerpt | Relevance | Reference |
|---|---|---|
| "On August 25, 2021, the FDA approved ivosidenib for the treatment of adult patients with unresectable locally advanced or metastatic hepatocellular isocitrate dehydrogenase 1 (IDH1) mutated cholangiocarcinoma (CCA) as detected by an FDA-approved test with disease progression after 1 to 2 prior lines of systemic therapy for advanced disease." | 9.51 | FDA Approval Summary: Ivosidenib for the Treatment of Patients with Advanced Unresectable or Metastatic, Chemotherapy Refractory Cholangiocarcinoma with an IDH1 Mutation. ( Beaver, JA; Casak, SJ; Charlab, R; Chow, ECY; Fashoyin-Aje, LA; Fesenko, N; Kluetz, PG; Lemery, SJ; Liu, J; Pazdur, R; Pierce, WF; Pradhan, S; Ren, Y; Shen, YL; Xiong, Y; Xu, Y; Zirklelbach, JF, 2022) |
| "The oral proteasome inhibitor ixazomib is approved in the United States, European Union and other countries, in combination with oral lenalidomide and dexamethasone (Rd), for the treatment of patients with multiple myeloma who have received at least one prior therapy." | 9.24 | Management of adverse events associated with ixazomib plus lenalidomide/dexamethasone in relapsed/refractory multiple myeloma. ( Avivi, I; Berg, D; Einsele, H; Esseltine, DL; Gupta, N; Hájek, R; Hari, P; Kumar, S; Liberati, AM; Lin, J; Lonial, S; Ludwig, H; Masszi, T; Mateos, MV; Minnema, MC; Moreau, P; Richardson, PG; Romeril, K; Shustik, C; Spencer, A, 2017) |
| "The fatty acid amide oleoyl glycine (OlGly) and its more stable methylated form oleoyl alanine (OlAla) reduce naloxone-precipitated morphine withdrawal (MWD)-induced conditioned gaping (nausea) responses in rats." | 8.12 | Effect of oleoyl glycine and oleoyl alanine on lithium chloride induced nausea in rats and vomiting in shrews. ( Limebeer, CL; Mechoulam, R; Parker, LA; Rock, EM; Smoum, R, 2022) |
| "Here, we report that following two exposures to morphine (20 mg/kg, sc) each followed by naloxone (1 mg/kg, sc) 24 h later, rats display nausea-like somatic reactions of lying flattened on belly, abdominal contractions and diarrhea, and display increased mouthing movements and loss of body weight." | 7.96 | Acute naloxone-precipitated morphine withdrawal elicits nausea-like somatic behaviors in rats in a manner suppressed by N-oleoylglycine. ( Ayoub, SM; DeVuono, MV; Di Marzo, V; Gene, A; Lichtman, AH; Limebeer, CL; Mechoulam, R; Parker, LA; Rock, EM; Smoum, R; Wills, KL, 2020) |
| "From May 1989 to October 1991, 101 consecutive patients were operated on for menometrorrhagia with transcervical resection of endometrium and submucous fibroids using glycine 1." | 7.68 | Changes in serum electrolytes after transcervical resection of endometrium and submucous fibroids with use of glycine 1.5% for uterine irrigation. ( Forman, A; Istre, O; Schjoensby, AP; Skajaa, K, 1992) |
| "gov identifier NCT01454076) assessed the relative bioavailability of capsule B in reference to capsule A in adult patients with advanced solid tumors or lymphoma." | 6.87 | A Phase 1 Study to Assess the Relative Bioavailability of Two Capsule Formulations of Ixazomib, an Oral Proteasome Inhibitor, in Patients With Advanced Solid Tumors or Lymphoma. ( Bessudo, A; Gupta, N; Hanley, MJ; Nemunaitis, J; O'Neil, BH; Sharma, S; van de Velde, H; Venkatakrishnan, K; Wang, B, 2018) |
| "Ixazomib is an investigational, orally bioavailable 20S proteasome inhibitor." | 6.79 | Phase 1 study of weekly dosing with the investigational oral proteasome inhibitor ixazomib in relapsed/refractory multiple myeloma. ( Bensinger, WI; Berenson, JR; Berg, D; Di Bacco, A; Gupta, N; Hui, AM; Kumar, SK; Niesvizky, R; Reeder, CB; Shou, Y; Yu, J; Zimmerman, TM, 2014) |
| "On August 25, 2021, the FDA approved ivosidenib for the treatment of adult patients with unresectable locally advanced or metastatic hepatocellular isocitrate dehydrogenase 1 (IDH1) mutated cholangiocarcinoma (CCA) as detected by an FDA-approved test with disease progression after 1 to 2 prior lines of systemic therapy for advanced disease." | 5.51 | FDA Approval Summary: Ivosidenib for the Treatment of Patients with Advanced Unresectable or Metastatic, Chemotherapy Refractory Cholangiocarcinoma with an IDH1 Mutation. ( Beaver, JA; Casak, SJ; Charlab, R; Chow, ECY; Fashoyin-Aje, LA; Fesenko, N; Kluetz, PG; Lemery, SJ; Liu, J; Pazdur, R; Pierce, WF; Pradhan, S; Ren, Y; Shen, YL; Xiong, Y; Xu, Y; Zirklelbach, JF, 2022) |
| "Fluvoxamine was administered for 6 weeks with a specific dosage plan (50-200 mg/day) in 66 Japanese major depressive patients." | 5.32 | Monoamine oxidase A gene polymorphism, 5-HT 2A receptor gene polymorphism and incidence of nausea induced by fluvoxamine. ( Higuchi, H; Inoue, K; Ito, K; Itoh, K; Kamata, M; Naito, S; Ohkubo, T; Sato, K; Shimizu, T; Suzuki, T; Takahashi, H; Yoshida, K, 2003) |
| "Glycine solution was used as the irrigant and ethanol served as a tracer for fluid absorption." | 5.29 | Symptoms of the transurethral resection syndrome using glycine as the irrigant. ( Hahn, RG; Nilsson, A; Olsson, J, 1995) |
| "The oral proteasome inhibitor ixazomib is approved in the United States, European Union and other countries, in combination with oral lenalidomide and dexamethasone (Rd), for the treatment of patients with multiple myeloma who have received at least one prior therapy." | 5.24 | Management of adverse events associated with ixazomib plus lenalidomide/dexamethasone in relapsed/refractory multiple myeloma. ( Avivi, I; Berg, D; Einsele, H; Esseltine, DL; Gupta, N; Hájek, R; Hari, P; Kumar, S; Liberati, AM; Lin, J; Lonial, S; Ludwig, H; Masszi, T; Mateos, MV; Minnema, MC; Moreau, P; Richardson, PG; Romeril, K; Shustik, C; Spencer, A, 2017) |
| "5% glycine for irrigation may be partly explained by toxic effects of glycine and its secondary metabolites in addition to the effects of water intoxication and hyponatremia." | 5.08 | Changes in amino acids, ammonium, and coagulation factors after transcervical resection of the endometrium with a glycine solution used for uterine irrigation. ( Forman, A; Istre, O; Jellum, E; Skajaa, K, 1995) |
| "The fatty acid amide oleoyl glycine (OlGly) and its more stable methylated form oleoyl alanine (OlAla) reduce naloxone-precipitated morphine withdrawal (MWD)-induced conditioned gaping (nausea) responses in rats." | 4.12 | Effect of oleoyl glycine and oleoyl alanine on lithium chloride induced nausea in rats and vomiting in shrews. ( Limebeer, CL; Mechoulam, R; Parker, LA; Rock, EM; Smoum, R, 2022) |
| "Here, we report that following two exposures to morphine (20 mg/kg, sc) each followed by naloxone (1 mg/kg, sc) 24 h later, rats display nausea-like somatic reactions of lying flattened on belly, abdominal contractions and diarrhea, and display increased mouthing movements and loss of body weight." | 3.96 | Acute naloxone-precipitated morphine withdrawal elicits nausea-like somatic behaviors in rats in a manner suppressed by N-oleoylglycine. ( Ayoub, SM; DeVuono, MV; Di Marzo, V; Gene, A; Lichtman, AH; Limebeer, CL; Mechoulam, R; Parker, LA; Rock, EM; Smoum, R; Wills, KL, 2020) |
| "Glyphosate potassium poisoning causes hyperkalemia." | 3.91 | Serial measurement of glyphosate blood concentration in a glyphosate potassium herbicide-intoxicated patient: A case report. ( Ahn, H; Cho, S; Cho, Y; Choi, H; Jeong, W; Kim, S; Min, J; Oh, S; Park, J; You, Y, 2019) |
| "From May 1989 to October 1991, 101 consecutive patients were operated on for menometrorrhagia with transcervical resection of endometrium and submucous fibroids using glycine 1." | 3.68 | Changes in serum electrolytes after transcervical resection of endometrium and submucous fibroids with use of glycine 1.5% for uterine irrigation. ( Forman, A; Istre, O; Schjoensby, AP; Skajaa, K, 1992) |
| "gov identifier NCT01454076) assessed the relative bioavailability of capsule B in reference to capsule A in adult patients with advanced solid tumors or lymphoma." | 2.87 | A Phase 1 Study to Assess the Relative Bioavailability of Two Capsule Formulations of Ixazomib, an Oral Proteasome Inhibitor, in Patients With Advanced Solid Tumors or Lymphoma. ( Bessudo, A; Gupta, N; Hanley, MJ; Nemunaitis, J; O'Neil, BH; Sharma, S; van de Velde, H; Venkatakrishnan, K; Wang, B, 2018) |
| "Ixazomib is an investigational, orally bioavailable 20S proteasome inhibitor." | 2.79 | Phase 1 study of weekly dosing with the investigational oral proteasome inhibitor ixazomib in relapsed/refractory multiple myeloma. ( Bensinger, WI; Berenson, JR; Berg, D; Di Bacco, A; Gupta, N; Hui, AM; Kumar, SK; Niesvizky, R; Reeder, CB; Shou, Y; Yu, J; Zimmerman, TM, 2014) |
| "Fluvoxamine was administered for 6 weeks with a specific dosage plan (50-200 mg/day) in 66 Japanese major depressive patients." | 1.32 | Monoamine oxidase A gene polymorphism, 5-HT 2A receptor gene polymorphism and incidence of nausea induced by fluvoxamine. ( Higuchi, H; Inoue, K; Ito, K; Itoh, K; Kamata, M; Naito, S; Ohkubo, T; Sato, K; Shimizu, T; Suzuki, T; Takahashi, H; Yoshida, K, 2003) |
| "Glycine solution was used as the irrigant and ethanol served as a tracer for fluid absorption." | 1.29 | Symptoms of the transurethral resection syndrome using glycine as the irrigant. ( Hahn, RG; Nilsson, A; Olsson, J, 1995) |
| "This post-resection syndrome is caused by resorption of a large amount of the hypotonic solution used during the surgical procedure and containing 1." | 1.28 | [Resorption of the lavage fluid during transurethral resection of the prostate. Apropos of 13 cases]. ( Clément, P; Paulet, C, 1990) |
| Timeframe | Studies, this research(%) | All Research% |
|---|---|---|
| pre-1990 | 4 (18.18) | 18.7374 |
| 1990's | 7 (31.82) | 18.2507 |
| 2000's | 1 (4.55) | 29.6817 |
| 2010's | 7 (31.82) | 24.3611 |
| 2020's | 3 (13.64) | 2.80 |
| Authors | Studies |
|---|---|
| Rock, EM | 2 |
| Limebeer, CL | 2 |
| Smoum, R | 2 |
| Mechoulam, R | 2 |
| Parker, LA | 2 |
| Casak, SJ | 1 |
| Pradhan, S | 1 |
| Fashoyin-Aje, LA | 1 |
| Ren, Y | 1 |
| Shen, YL | 1 |
| Xu, Y | 1 |
| Chow, ECY | 1 |
| Xiong, Y | 1 |
| Zirklelbach, JF | 1 |
| Liu, J | 1 |
| Charlab, R | 1 |
| Pierce, WF | 1 |
| Fesenko, N | 1 |
| Beaver, JA | 1 |
| Pazdur, R | 1 |
| Kluetz, PG | 1 |
| Lemery, SJ | 1 |
| Ayoub, SM | 1 |
| Gene, A | 1 |
| Wills, KL | 1 |
| DeVuono, MV | 1 |
| Di Marzo, V | 1 |
| Lichtman, AH | 1 |
| Kumar, S | 1 |
| Moreau, P | 1 |
| Hari, P | 1 |
| Mateos, MV | 1 |
| Ludwig, H | 1 |
| Shustik, C | 1 |
| Masszi, T | 1 |
| Spencer, A | 1 |
| Hájek, R | 1 |
| Romeril, K | 1 |
| Avivi, I | 1 |
| Liberati, AM | 1 |
| Minnema, MC | 1 |
| Einsele, H | 1 |
| Lonial, S | 2 |
| Berg, D | 3 |
| Lin, J | 1 |
| Gupta, N | 4 |
| Esseltine, DL | 1 |
| Richardson, PG | 2 |
| Hanley, MJ | 1 |
| Venkatakrishnan, K | 1 |
| Bessudo, A | 1 |
| Sharma, S | 1 |
| O'Neil, BH | 1 |
| Wang, B | 1 |
| van de Velde, H | 1 |
| Nemunaitis, J | 1 |
| Hall, KH | 1 |
| Cho, Y | 1 |
| Jeong, W | 1 |
| Kim, S | 1 |
| Choi, H | 1 |
| You, Y | 1 |
| Cho, S | 1 |
| Oh, S | 1 |
| Ahn, H | 1 |
| Park, J | 1 |
| Min, J | 1 |
| Kumar, SK | 1 |
| Bensinger, WI | 1 |
| Zimmerman, TM | 1 |
| Reeder, CB | 1 |
| Berenson, JR | 1 |
| Hui, AM | 2 |
| Di Bacco, A | 2 |
| Yu, J | 2 |
| Shou, Y | 1 |
| Niesvizky, R | 1 |
| Baz, R | 1 |
| Wang, M | 1 |
| Jakubowiak, AJ | 1 |
| Laubach, JP | 1 |
| Harvey, RD | 1 |
| Talpaz, M | 1 |
| Liu, G | 1 |
| Zouaoui, K | 1 |
| Dulaurent, S | 1 |
| Gaulier, JM | 1 |
| Moesch, C | 1 |
| Lachâtre, G | 1 |
| Yoshida, K | 1 |
| Naito, S | 1 |
| Takahashi, H | 1 |
| Sato, K | 1 |
| Ito, K | 1 |
| Kamata, M | 1 |
| Higuchi, H | 1 |
| Shimizu, T | 1 |
| Itoh, K | 1 |
| Inoue, K | 1 |
| Suzuki, T | 1 |
| Ohkubo, T | 1 |
| Olsson, J | 1 |
| Nilsson, A | 1 |
| Hahn, RG | 3 |
| Istre, O | 3 |
| Jellum, E | 1 |
| Skajaa, K | 2 |
| Forman, A | 3 |
| Bjoennes, J | 1 |
| Naess, R | 1 |
| Hornbaek, K | 1 |
| Sandfeldt, L | 1 |
| Nyman, CR | 1 |
| Aronsen, KF | 1 |
| Wetterlin, S | 1 |
| Emas, S | 1 |
| Vojtsek, V | 1 |
| Mulder, JL | 1 |
| Cort, JH | 1 |
| Schjoensby, AP | 1 |
| Clément, P | 1 |
| Paulet, C | 1 |
| Cameron, PF | 1 |
| Vinnars, E | 1 |
| Fürst, P | 1 |
| Hallgren, B | 1 |
| Hermansson, IL | 1 |
| Josephson, B | 1 |
| Trial | Phase | Enrollment | Study Type | Start Date | Status | ||
|---|---|---|---|---|---|---|---|
| A Phase 1 Study of Oral IXAZOMIB (MLN9708) to Assess Relative Bioavailability, Food Effect, Drug-Drug Interaction With Ketoconazole, Clarithromycin or Rifampin; and Safety and Tolerability in Patients With Advanced Nonhematologic Malignancies or Lymphoma[NCT01454076] | Phase 1 | 112 participants (Actual) | Interventional | 2011-11-10 | Completed | ||
| An Open-Label, Dose-Escalation, Phase 1 Study Evaluating the Safety and Tolerability of Weekly Dosing of the Oral Form of MLN9708, a Second-Generation Proteasome Inhibitor, in Adult Patients With Relapsed and Refractory Multiple Myeloma[NCT00963820] | Phase 1 | 60 participants (Actual) | Interventional | 2009-10-31 | Completed | ||
| An Open-Label, Dose-Escalation, Phase 1 Study of the Oral Form of Ixazomib (MLN9708), a Second-Generation Proteasome Inhibitor, in Adult Patients With Relapsed and/or Refractory Multiple Myeloma[NCT00932698] | Phase 1 | 60 participants (Actual) | Interventional | 2009-10-12 | Completed | ||
| [information is prepared from clinicaltrials.gov, extracted Sep-2024] | |||||||
(NCT01454076)
Timeframe: Arm 1:Days 1, 15 and Arm 5:Day 6 pre-dose and at multiple time points(up to 264 hrs)post-dose;Arm 2, 3:Days 1,15 pre-dose and at multiple time points(up to 216 hrs)post-dose;Arm 4:Day 8 pre-dose and at multiple time points(up to 168 hrs)post-dose
| Intervention | nanogram*hour per milliliter (ng*hr/mL)] (Geometric Mean) |
|---|---|
| Arm 1: Ixazomib 2.5 mg | 551.985 |
| Arm 1: Ixazomib 2.5 mg + Ketoconazole 400 mg | 1148.778 |
| Arm 2: Ixazomib 4 mg Capsule A | 1284.079 |
| Arm 2: Ixazomib 4 mg Capsule B | 1334.659 |
| Arm 3: Ixazomib 4 mg Fasted | 1465.979 |
| Arm 3: Ixazomib 4 mg Fed | 998.698 |
| Arm 4: Ixazomib 4 mg + Rifampin 600 mg | 231.527 |
| Arm 5: Ixazomib 2.5 mg + Clarithromycin 500 mg | 613.112 |
(NCT01454076)
Timeframe: Arm 1:Days 1, 15 and Arm 5:Day 6 pre-dose and at multiple time points(up to 264 hours[hrs])post-dose;Arm 2, 3:Days 1,15 pre-dose and at multiple time points(up to 216 hrs)post-dose;Arm 4:Day 8 pre-dose and at multiple time points(up to 168 hrs)post-dose
| Intervention | nanogram per milliliter (ng/mL) (Geometric Mean) |
|---|---|
| Arm 1: Ixazomib 2.5 mg | 38.975 |
| Arm 1: Ixazomib 2.5 mg + Ketoconazole 400 mg | 39.250 |
| Arm 2: Ixazomib 4 mg Capsule A | 61.866 |
| Arm 2: Ixazomib 4 mg Capsule B | 71.949 |
| Arm 3: Ixazomib 4 mg Fasted | 77.001 |
| Arm 3: Ixazomib 4 mg Fed | 22.752 |
| Arm 4: Ixazomib 4 mg + Rifampin 600 mg | 25.706 |
| Arm 5: Ixazomib 2.5 mg + Clarithromycin 500 mg | 37.245 |
(NCT01454076)
Timeframe: Cycle 1 Day 1 up to 30 days after last dose of study drug (Arm 1 and 5: Cycle 19 Day 45; Arm 2: Cycle 7 Day 45; Arm 3: Cycle 22 Day 45; Arm 4: Cycle 25 Day 45
| Intervention | participants (Number) |
|---|---|
| Arm 1: Ixazomib 2.5 mg + Ketoconazole 400 mg | 0 |
| Arm 2: Ixazomib 4 mg Capsule A or B | 0 |
| Arm 3: Ixazomib 4 mg Fasted or Fed | 0 |
| Arm 4: Ixazomib 4 mg + Rifampin 600 mg | 0 |
| Arm 5: Ixazomib 2.5 mg + Clarithromycin 500 mg | 0 |
(NCT01454076)
Timeframe: Arm 1:Days 1, 15 and Arm 5:Day 6 pre-dose and at multiple time points(up to 264 hrs)post-dose;Arm 2, 3:Days 1,15 pre-dose and at multiple time points(up to 216 hrs)post-dose;Arm 4:Day 8 pre-dose and at multiple time points(up to 168 hrs)post-dose
| Intervention | hours (Median) |
|---|---|
| Arm 1: Ixazomib 2.5 mg | 1.090 |
| Arm 1: Ixazomib 2.5 mg + Ketoconazole 400 mg | 1.500 |
| Arm 2: Ixazomib 4 mg Capsule A | 1.290 |
| Arm 2: Ixazomib 4 mg Capsule B | 1.250 |
| Arm 3: Ixazomib 4 mg Fasted | 1.020 |
| Arm 3: Ixazomib 4 mg Fed | 4.000 |
| Arm 4: Ixazomib 4 mg + Rifampin 600 mg | 1.450 |
| Arm 5: Ixazomib 2.5 mg + Clarithromycin 500 mg | 1 |
(NCT01454076)
Timeframe: Cycle 1 Day 1 up to 30 days after last dose of study drug (Arm 1 and 5: Cycle 19 Day 45; Arm 2: Cycle 7 Day 45; Arm 3: Cycle 22 Day 45; Arm 4: Cycle 25 Day 45)
| Intervention | participants (Number) | |
|---|---|---|
| TEAEs | SAEs | |
| Arm 1: Ixazomib 2.5 mg + Ketoconazole 400 mg | 29 | 12 |
| Arm 2: Ixazomib 4 mg Capsule A or B | 20 | 5 |
| Arm 3: Ixazomib 4 mg Fasted or Fed | 24 | 12 |
| Arm 4: Ixazomib 4 mg + Rifampin 600 mg | 18 | 3 |
| Arm 5: Ixazomib 2.5 mg + Clarithromycin 500 mg | 21 | 10 |
(NCT01454076)
Timeframe: Cycle 1 Day 1 up to 30 days after last dose of study drug (Arm 1 and 5: Cycle 19 Day 45; Arm 2: Cycle 7 Day 45; Arm 3: Cycle 22 Day 45; Arm 4: Cycle 25 Day 45
| Intervention | participants (Number) | ||
|---|---|---|---|
| Blood and lymphatic system disorders | Investigations | Metabolism and nutrition disorders | |
| Arm 1: Ixazomib 2.5 mg + Ketoconazole 400 mg | 11 | 10 | 22 |
| Arm 2: Ixazomib 4 mg Capsule A or B | 7 | 5 | 12 |
| Arm 3: Ixazomib 4 mg Fasted or Fed | 9 | 11 | 13 |
| Arm 4: Ixazomib 4 mg + Rifampin 600 mg | 2 | 4 | 6 |
| Arm 5: Ixazomib 2.5 mg + Clarithromycin 500 mg | 1 | 5 | 6 |
Best overall response for a participant is best observed post-baseline disease response as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1: Complete response (CR) was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis less than (<) 10 millimeter [mm]). No new lesions. Partial response (PR) was defined as greater than or equal to (>=) 30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. Stable disease (SD) was defined as not qualifying for CR, PR, Progressive Disease (PD). An increase of >=20% from the nadir (or baseline, if it represents the point at which the sum of target disease was lowest) represents PD. (NCT01454076)
Timeframe: Baseline up to end of treatment (approximately 1.9 years)
| Intervention | percentage of participants (Number) | |||
|---|---|---|---|---|
| CR | PR | SD | PD | |
| Arm 1: Ixazomib 2.5 mg + Ketoconazole 400 mg | 0 | 0 | 63 | 38 |
| Arm 2: Ixazomib 4 mg Capsule A or B | 0 | 0 | 50 | 50 |
| Arm 3: Ixazomib 4 mg Fasted or Fed | 0 | 6 | 35 | 59 |
| Arm 4: Ixazomib 4 mg + Rifampin 600 mg | 0 | 0 | 53 | 47 |
| Arm 5: Ixazomib 2.5 mg + Clarithromycin 500 mg | 0 | 1 | 53 | 47 |
MLN2238 is the complete hydrolysis product of the study drug ixazomib citrate (MLN9708). (NCT00963820)
Timeframe: Day 15 of Cycle 1
| Intervention | unitless (Mean) |
|---|---|
| 1.68 mg/m^2 | 2.64 |
| 2.23 mg/m^2 | 1.45 |
| 2.97 mg/m^2 | 2.25 |
| 3.95 mg/m^2 | 1.19 |
| Relapsed and Refractory (RR) | 2.25 |
| VELCADE-relapsed (VR) | 2.19 |
| PI naïve | 1.97 |
| Carfilzomib | 2.37 |
A Whole Blood 20S Proteasome Inhibition Parameter. There were no subjects in the Pharmacodynamic (PD) Analysis Set for the 2.23 mg/m^2 cohort, so PD tables do not include that arm. (NCT00963820)
Timeframe: Days 1 and 15 of Cycle 1
| Intervention | Percentage of inhibition (Mean) |
|---|---|
| 0.24 mg/m^2 | NA |
| 0.48 mg/m^2 | NA |
| 0.80 mg/m^2 | NA |
| 1.20 mg/m^2 | NA |
| 1.68 mg/m^2 | NA |
| 2.23 mg/m^2 | NA |
| 2.97 mg/m^2 | NA |
| 3.95 mg/m^2 | NA |
| Relapsed and Refractory (RR) | NA |
| VELCADE-relapsed (VR) | NA |
| PI naïve | NA |
| Carfilzomib | NA |
"An Adverse Event is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.~A Serious Adverse Event (SAE) was any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant." (NCT00963820)
Timeframe: From the first dose through 30 days after last dose of ixazomib citrate or until the start of subsequent antineoplastic therapy (Up to 354 days)
| Intervention | participants (Number) |
|---|---|
| 0.24 mg/m^2 | 3 |
| 0.48 mg/m^2 | 3 |
| 0.80 mg/m^2 | 2 |
| 1.20 mg/m^2 | 3 |
| 1.68 mg/m^2 | 4 |
| 2.23 mg/m^2 | 3 |
| 2.97 mg/m^2 | 8 |
| 3.95 mg/m^2 | 5 |
| Relapsed and Refractory (RR) | 11 |
| VELCADE-relapsed (VR) | 10 |
| PI naïve | 6 |
| Carfilzomib | 4 |
(NCT00963820)
Timeframe: Days 1 and 15 of Cycle 1
| Intervention | Hours (Mean) |
|---|---|
| 0.24 mg/m^2 | NA |
| 0.48 mg/m^2 | NA |
| 0.80 mg/m^2 | NA |
| 1.20 mg/m^2 | NA |
| 1.68 mg/m^2 | NA |
| 2.23 mg/m^2 | NA |
| 2.97 mg/m^2 | NA |
| 3.95 mg/m^2 | NA |
| Relapsed and Refractory (RR) | NA |
| VELCADE-relapsed (VR) | NA |
| PI naïve | NA |
| Carfilzomib | NA |
Terminal elimination rate constant (λz) is the rate at which drugs are eliminated from the body and the values were used for calculation of T1/2. MLN2238 is the complete hydrolysis product of the study drug ixazomib citrate (MLN9708). (NCT00963820)
Timeframe: Day 15 of Cycle 1
| Intervention | 1/hour (Mean) |
|---|---|
| 0.80 mg/m^2 | 0.000 |
| 1.20 mg/m^2 | 0.000 |
| 1.68 mg/m^2 | 0.000 |
| 2.23 mg/m^2 | 0.00 |
| 2.97 mg/m^2 | 0.00 |
| 3.95 mg/m^2 | 0.00 |
| Relapsed and Refractory (RR) | 0.00 |
| VELCADE-relapsed (VR) | 0.00 |
| PI naïve | 0.01 |
| Carfilzomib | 0.01 |
Terminal phase elimination half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma. MLN2238 is the complete hydrolysis product of the study drug ixazomib citrate (MLN9708). (NCT00963820)
Timeframe: Day 15 of Cycle 1
| Intervention | hour (Mean) |
|---|---|
| 0.80 mg/m^2 | 271.00 |
| 1.20 mg/m^2 | 190.50 |
| 1.68 mg/m^2 | 189.00 |
| 2.23 mg/m^2 | 175.00 |
| 2.97 mg/m^2 | 246.00 |
| 3.95 mg/m^2 | 165.00 |
| Relapsed and Refractory (RR) | 186.00 |
| VELCADE-relapsed (VR) | 202.33 |
| PI naïve | 123.90 |
| Carfilzomib | 108.00 |
AUC(0-168) is a measure of the area under the plasma concentration-time curve over the dosing interval (tau) (AUC[0-tau]), where tau is the length of the dosing interval - 168 hours in this study). MLN2238 is the complete hydrolysis product of the study drug ixazomib citrate (MLN9708). (NCT00963820)
Timeframe: Days 1 and 15 of Cycle 1
| Intervention | hr*ng/mL (Mean) | |
|---|---|---|
| Cycle 1 Day 1 (n=0,0,0,0,2,1,3,4,3,5,4,3) | Cycle 1 Day 15 (n=0,0,2,0,2,1,2,1,1,4,3,2) | |
| 0.24 mg/m^2 | NA | NA |
| 0.48 mg/m^2 | NA | NA |
| 0.80 mg/m^2 | NA | 398.50 |
| 1.20 mg/m^2 | NA | NA |
| 1.68 mg/m^2 | 258.00 | 663.00 |
| 2.23 mg/m^2 | 598.00 | 868.00 |
| 2.97 mg/m^2 | 1269.67 | 3100.00 |
| 3.95 mg/m^2 | 1371.25 | 1460.00 |
| Carfilzomib | 813.67 | 2075.00 |
| PI naïve | 750.25 | 1549.00 |
| Relapsed and Refractory (RR) | 1793.33 | 3690.00 |
| VELCADE-relapsed (VR) | 854.20 | 1777.75 |
Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve. MLN2238 is the complete hydrolysis product of the study drug ixazomib citrate (MLN9708). (NCT00963820)
Timeframe: Days 1 and 15 of Cycle 1
| Intervention | ng/mL (Mean) | |
|---|---|---|
| Cycle 1 Day 1 (n=1,1,2,1,3,2,5,4,5,8,5,3) | Cycle 1 Day 15 (n=3,1,3,2,2,1,2,1,5,5,4,3) | |
| 0.24 mg/m^2 | 3.010 | 3.64 |
| 0.48 mg/m^2 | 2.91 | 4.64 |
| 0.80 mg/m^2 | 5.75 | 6.89 |
| 1.20 mg/m^2 | 15.10 | 17.90 |
| 1.68 mg/m^2 | 13.83 | 17.63 |
| 2.23 mg/m^2 | 29.05 | 9.24 |
| 2.97 mg/m^2 | 65.46 | 100.55 |
| 3.95 mg/m^2 | 123.95 | 134.00 |
| Carfilzomib | 83.73 | 55.10 |
| PI naïve | 77.70 | 118.05 |
| Relapsed and Refractory (RR) | 75.92 | 50.46 |
| VELCADE-relapsed (VR) | 110.43 | 93.68 |
Neurotoxicity is graded using participant responses to 11 functional questions on a 5-point scale, where 0=Not at all and 4=Very much, using the Functional Assessment of Cancer Therapy/Gynecology Oncology Group - Neurotoxicity Questionnaire, Version 4.0(14). Neurotoxicity subscale is a sum of 11 reversed item scores where each original score is transformed as (4 - score). The highest possible score is 44, and a higher score indicates more neurotoxicity. (NCT00963820)
Timeframe: Cycle 1 Day 1 and End of Study (Up to 354 days)
| Intervention | score on a scale (Mean) | |
|---|---|---|
| Cycle 1 Day 1 (n=2,3,3,3,4,3,7,4,9,8,6,4) | End of Study (n=3,3,2,1,1,3,4,3,8,5,4,3) | |
| 0.24 mg/m^2 | 36.00 | 25.00 |
| 0.48 mg/m^2 | 40.33 | 40.67 |
| 0.80 mg/m^2 | 42.00 | 38.50 |
| 1.20 mg/m^2 | 36.00 | 35.00 |
| 1.68 mg/m^2 | 39.50 | 42.00 |
| 2.23 mg/m^2 | 36.80 | 36.00 |
| 2.97 mg/m^2 | 33.14 | 36.00 |
| 3.95 mg/m^2 | 38.50 | 33.33 |
| Carfilzomib | 32.00 | 27.33 |
| PI naïve | 38.00 | 37.00 |
| Relapsed and Refractory (RR) | 38.44 | 33.88 |
| VELCADE-relapsed (VR) | 33.73 | 27.24 |
"Responses were based on International Myeloma Working Group Uniform Criteria. Complete Response (CR)=Negative immunofixation on serum and urine and disappearance of any soft tissue plasmacytomas and <5% plasma cells in bone marrow.~Partial Response (PR)= reduction in M-Protein ≥50% in serum and ≥90% in 24-hour urine. If M-protein unmeasurable, ≥50% decrease in difference of involved and uninvolved Free Light Chain (FLC). If M-protein and FLC unmeasurable, ≥50% reduction in plasma cells is required, if baseline bone marrow plasma cell ≥30%. And ≥50% reduction in the size of soft tissue plasmacytomas.~Minimal Response (MR)= 25-49% reduction in serum paraprotein for 6 weeks. 50-89% reduction in 24 hour urinary light chain excretion for 6 weeks. For Non-secretory myeloma patients, 25-49 % reduction in plasma cells in bone marrow and trephine biopsy for a 6 weeks. 25-49% reduction in the size of soft tissue plasmacytomas. No increase in the size or number of lytic bone lesions." (NCT00963820)
Timeframe: Up to 354 days
| Intervention | percentage of participants (Number) | |
|---|---|---|
| CR + PR | CR + PR + MR | |
| 0.24 mg/m^2 | 0 | 0 |
| 0.48 mg/m^2 | 0 | 0 |
| 0.80 mg/m^2 | 0 | 0 |
| 1.20 mg/m^2 | 0 | 0 |
| 1.68 mg/m^2 | 0 | 0 |
| 2.23 mg/m^2 | 0 | 0 |
| 2.97 mg/m^2 | 25 | 25 |
| 3.95 mg/m^2 | 25 | 25 |
| Carfilzomib | 25 | 25 |
| PI naïve | 17 | 17 |
| Relapsed and Refractory (RR) | 9 | 18 |
| VELCADE-relapsed (VR) | 22 | 33 |
Tmax: Time to reach the maximum observed plasma concentration (Cmax), equal to time to Cmax. MLN2238 is the complete hydrolysis product of the study drug ixazomib citrate (MLN9708). (NCT00963820)
Timeframe: Days 1 and 15 of Cycle 1
| Intervention | hours (Median) | |
|---|---|---|
| Cycle 1 Day 1 (n=1,1,2,1,3,2,5,4,5,8,5,3) | Cycle 1 Day 15 (n=3,1,3,2,2,1,2,1,5,5,4,3) | |
| 0.24 mg/m^2 | 1.50 | 1.07 |
| 0.48 mg/m^2 | 1.53 | 0.50 |
| 0.80 mg/m^2 | 1.52 | 1.83 |
| 1.20 mg/m^2 | 1.00 | 1.00 |
| 1.68 mg/m^2 | 1.52 | 1.27 |
| 2.23 mg/m^2 | 1.25 | 8.00 |
| 2.97 mg/m^2 | 1.00 | 1.25 |
| 3.95 mg/m^2 | 1.00 | 1.03 |
| Carfilzomib | 1.42 | 1.03 |
| PI naïve | 1.00 | 1.00 |
| Relapsed and Refractory (RR) | 2.00 | 1.50 |
| VELCADE-relapsed (VR) | 0.50 | 1.00 |
MTD was highest dose of Ixazomib, at which <=1 of 6 participants experienced dose-limiting toxicity (DLT) during Cycle 1 of Phase 1. DLT was defined as any of following considered possibly related to therapy: Grade 4 neutropenia (absolute neutrophil count [ANC] <500 cell per cubic millimeter [cells/mm^3]) for >7 days;Grade 3 neutropenia with fever or infection; Grade 4 thrombocytopenia (platelets < 25,000/mm^3) for >7 days;Grade 3 thrombocytopenia with clinically significant bleeding; platelet count <10,000/mm^3; Grade 2 peripheral neuropathy with pain or >=Grade 3 peripheral neuropathy; >=Grade 3 nausea/emesis, diarrhea controlled by supportive therapy; Grade 3 QTc prolongation (QTc >500 millisecond [msec]);any >=Grade 3 nonhematologic toxicity except Grade 3 arthralgia/myalgia; or <1 week Grade 3 fatigue; delay in initiation of the subsequent therapy cycle by >2 weeks; other >=Grade 2 study drug-related nonhematologic toxicities requiring therapy discontinuation. (NCT00932698)
Timeframe: Cycle 1 (21 days)
| Intervention | mg/m^2 (Number) |
|---|---|
| Ixazomib (All Groups) | 2 |
The number of participants with any clinically significant changes in vital signs collected throughout the study that were reported as TEAEs. Measurement of vital signs, included oral temperature, blood pressure, and heart rate. (NCT00932698)
Timeframe: From first dose of the study drug through 30 days after the last dose of study drug or start of subsequent antineoplastic therapy (Up to 81.1 months)
| Intervention | Participants (Count of Participants) |
|---|---|
| Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^2 | 0 |
| Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^2 | 0 |
| Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^2 | 0 |
| Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^2 | 0 |
| Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^2 | 0 |
| Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^2 | 0 |
| Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^2 | 1 |
| Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^2 | 0 |
| Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^2 | 0 |
| Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^2 | 0 |
| Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^2 | 0 |
The RP2D of Ixazomib was determined in Part 1 (dose escalation) on the basis of the totality of safety, tolerability, pharmacokinetics (PK) and pharmacodynamic data observed in Cycle 1 and beyond. (NCT00932698)
Timeframe: Cycle 1 through Cycle 39 (Up to 28.3 months)
| Intervention | mg/m^2 (Number) |
|---|---|
| Ixazomib (All Groups) | 2 |
(NCT00932698)
Timeframe: Cycle 1, Day 11: predose and at multiple time points (up to 264 hours) postdose
| Intervention | hr (Mean) |
|---|---|
| Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^2 | 135.00 |
| Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^2 | 126.50 |
| Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^2 | 129.33 |
| Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^2 | 105.88 |
| Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^2 | 92.70 |
| Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^2 | 115.85 |
| Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^2 | 123.06 |
| Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^2 | 124.93 |
| Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^2 | 134.00 |
(NCT00932698)
Timeframe: Cycle 1, Day 11: predose and at multiple time points (Up to 264 hours) postdose
| Intervention | 1/hr (Mean) |
|---|---|
| Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^2 | 0.005 |
| Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^2 | 0.005 |
| Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^2 | 0.006 |
| Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^2 | 0.007 |
| Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^2 | 0.008 |
| Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^2 | 0.006 |
| Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^2 | 0.006 |
| Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^2 | 0.006 |
| Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^2 | 0.005 |
(NCT00932698)
Timeframe: Cycle 1, Days 1 and 11: Predose and at multiple time points (Up to 72 hours) postdose
| Intervention | hr*ng/mL (Mean) |
|---|---|
| Day 11 | |
| Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^2 | 56.53 |
| Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^2 | 177.67 |
(NCT00932698)
Timeframe: Cycle 1, Days 1 and 11: Predose and at multiple time points (Up to 72 hours) postdose
| Intervention | hr*ng/mL (Mean) | |
|---|---|---|
| Day 1 | Day 11 | |
| Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^2 | 509.00 | 1010.00 |
| Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^2 | 109.00 | 458.00 |
| Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^2 | 159.05 | 605.00 |
| Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^2 | 251.00 | 808.50 |
| Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^2 | 449.00 | 1435.60 |
| Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^2 | 416.50 | 1915.00 |
| Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^2 | 410.00 | 2297.20 |
| Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^2 | 451.64 | 903.85 |
| Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^2 | 351.00 | 937.86 |
(NCT00932698)
Timeframe: Cycle 1, Days 1 and 11: Predose and at multiple time points (Up to 264 hours) postdose
| Intervention | hr*ng/mL (Mean) | |
|---|---|---|
| Day 1 | Day 11 | |
| Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^2 | 509.000 | 1010.000 |
| Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^2 | 3.383 | 56.533 |
| Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^2 | 20.700 | 177.667 |
| Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^2 | 109.000 | 458.000 |
| Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^2 | 159.050 | 605.000 |
| Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^2 | 251.000 | 808.500 |
| Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^2 | 449.000 | 1435.600 |
| Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^2 | 416.500 | 1915.000 |
| Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^2 | 410.000 | 2297.200 |
| Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^2 | 418.175 | 903.846 |
| Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^2 | 351.000 | 937.857 |
(NCT00932698)
Timeframe: Cycle 1, Days 1 and 11: Predose and at multiple time points (up to 264 hours) postdose
| Intervention | ng/mL (Mean) | |
|---|---|---|
| Day 1 | Day 11 | |
| Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^2 | 26.600 | 27.200 |
| Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^2 | 2.120 | 2.837 |
| Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^2 | 10.190 | 8.857 |
| Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^2 | 22.200 | 31.650 |
| Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^2 | 29.000 | 56.500 |
| Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^2 | 21.100 | 101.100 |
| Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^2 | 68.167 | 85.420 |
| Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^2 | 117.933 | 105.450 |
| Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^2 | 85.600 | 109.660 |
| Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^2 | 58.900 | 59.871 |
| Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^2 | 59.343 | 61.800 |
Neurotoxicity was assessed as the number of participants with the TEAE of peripheral neuropathy. (NCT00932698)
Timeframe: From first dose of the study drug through 30 days after the last dose of study drug or start of subsequent antineoplastic therapy (Up to 81.1 months)
| Intervention | Participants (Count of Participants) | |
|---|---|---|
| Neuropathy Peripheral | Peripheral Sensory Neuropathy | |
| Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^2 | 0 | 0 |
| Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^2 | 0 | 0 |
| Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^2 | 1 | 0 |
| Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^2 | 1 | 0 |
| Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^2 | 0 | 0 |
| Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^2 | 0 | 1 |
| Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^2 | 1 | 0 |
| Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^2 | 0 | 0 |
| Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^2 | 1 | 0 |
| Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^2 | 3 | 0 |
| Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^2 | 3 | 0 |
The number of participants with any clinically significant abnormal standard safety laboratory values collected throughout the study reported as TEAEs. Parameters assessed were hematology, serum chemistry and urinalysis. (NCT00932698)
Timeframe: From first dose of the study drug through 30 days after the last dose of study drug or start of subsequent antineoplastic therapy (Up to 81.1 months)
| Intervention | Participants (Count of Participants) | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Blood Creatinine Increased | Blood Urea Increased | White Blood Cell Count Decreased | Neutrophil Count Decreased | Alanine Aminotransferase Increased | Liver Function Test Increased | Blood Calcium Increased | Platelet Count Decreased | Haematocrit Decreased | Haemoglobin Decreased | |
| Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^2 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^2 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^2 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^2 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^2 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^2 | 1 | 0 | 1 | 1 | 0 | 0 | 0 | 1 | 0 | 0 |
| Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^2 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^2 | 2 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 |
| Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^2 | 2 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 1 |
An AE is any untoward medical occurrence in a participant administered a medicinal investigational drug. The untoward medical occurrence does not necessarily have to have a causal relationship with treatment. An SAE is any untoward medical occurrence that results in death;is life-threatening;requires inpatient hospitalization or prolongation of present hospitalization;results in persistent or significant disability/incapacity;is a congenital anomaly/birth defect;or is a medically important event that may not be immediately life-threatening or result in death or hospitalization, but may jeopardize the participant or may require intervention to prevent one of other outcomes listed in definition above, or involves suspected transmission via a medicinal product of an infectious agent. A TEAE is defined as an AE that occurs after administration of first dose of study drug and through 30 days after last dose of study drug or until start of subsequent antineoplastic therapy. (NCT00932698)
Timeframe: From first dose of the study drug through 30 days after the last dose of study drug or start of subsequent antineoplastic therapy (Up to 81.1 months)
| Intervention | Participants (Count of Participants) | |
|---|---|---|
| AEs | SAEs | |
| Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^2 | 2 | 2 |
| Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^2 | 3 | 0 |
| Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^2 | 3 | 0 |
| Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^2 | 3 | 2 |
| Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^2 | 3 | 2 |
| Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^2 | 3 | 0 |
| Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^2 | 7 | 5 |
| Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^2 | 4 | 3 |
| Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^2 | 6 | 3 |
| Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^2 | 20 | 14 |
| Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^2 | 12 | 6 |
ORR is defined as percentage of participants with complete response (CR) or partial response (PR) or minimal response (MR) as assessed by the investigator using International Myeloma Working Group Uniform Response criteria. CR=Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and <5% plasma cells in bone marrow. PR=≥50% reduction of serum M-protein and reduction in 24-h urinary M-protein by ≥90% or to <200 mg /24 h. MR=25-49% reduction in the serum monoclonal paraprotein maintained for a minimum of 6 weeks; 50-89% reduction in 24-h urinary light chain excretion, which still exceeds 200 mg/24 h, maintained for a minimum of 6 weeks; for participants with non-secretory myeloma only, 25-49% reduction in plasma cells in a bone marrow aspirate and on trephine biopsy, if biopsy is performed, maintained for a minimum of 6 weeks; 25-49% reduction in the size of soft tissue plasmacytomas; no increase in the size or number of lytic bone lesions. (NCT00932698)
Timeframe: Cycle 1 through Cycle 115 (Up to 80.1 months)
| Intervention | percentage of participants (Number) | |
|---|---|---|
| CR+PR | CR+PR+MR | |
| Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^2 | 0 | 0 |
| Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^2 | 0 | 0 |
| Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^2 | 0 | 0 |
| Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^2 | 0 | 0 |
| Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^2 | 33 | 33 |
| Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^2 | 0 | 0 |
| Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^2 | 0 | 0 |
| Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^2 | 50 | 50 |
| Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^2 | 33 | 33 |
| Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^2 | 5 | 10 |
| Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^2 | 9 | 18 |
(NCT00932698)
Timeframe: Cycle 1, Days 1 and 11: Predose and at multiple time points (Up to 264 hours) postdose
| Intervention | hours (Median) | |
|---|---|---|
| Day 1 | Day 11 | |
| Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^2 | 1.000 | 1.500 |
| Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^2 | 1.000 | 1.100 |
| Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^2 | 1.000 | 1.000 |
| Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^2 | 0.775 | 1.275 |
| Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^2 | 0.775 | 0.500 |
| Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^2 | 1.000 | 1.000 |
| Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^2 | 1.000 | 0.667 |
| Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^2 | 1.000 | 0.832 |
| Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^2 | 0.525 | 1.500 |
| Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^2 | 1.000 | 1.010 |
| Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^2 | 0.617 | 0.583 |
1 review available for glycine and Nausea
| Article | Year |
|---|---|
Too much of a good thing.
Topics: Amino Acids; Animals; Blood Pressure; Central Nervous System; Eye Diseases; Food Additives; Glutamat | 1971 |
8 trials available for glycine and Nausea
| Article | Year |
|---|---|
FDA Approval Summary: Ivosidenib for the Treatment of Patients with Advanced Unresectable or Metastatic, Chemotherapy Refractory Cholangiocarcinoma with an IDH1 Mutation.
Topics: Abdominal Pain; Adult; Asthenia; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Cholangiocarcinoma; | 2022 |
Management of adverse events associated with ixazomib plus lenalidomide/dexamethasone in relapsed/refractory multiple myeloma.
Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols | 2017 |
A Phase 1 Study to Assess the Relative Bioavailability of Two Capsule Formulations of Ixazomib, an Oral Proteasome Inhibitor, in Patients With Advanced Solid Tumors or Lymphoma.
Topics: Administration, Oral; Adult; Aged; Antineoplastic Agents; Biological Availability; Boron Compounds; | 2018 |
Management of Gastrointestinal Toxicities From Ixazomib: Tips to Curb Nausea, Vomiting, Diarrhea, and Constipation.
Topics: Antineoplastic Agents; Boron Compounds; Constipation; Diarrhea; Glycine; Humans; Multiple Myeloma; N | 2019 |
Phase 1 study of weekly dosing with the investigational oral proteasome inhibitor ixazomib in relapsed/refractory multiple myeloma.
Topics: Administration, Oral; Adult; Aged; Area Under Curve; Boron Compounds; Diarrhea; Dose-Response Relati | 2014 |
Phase 1 study of twice-weekly ixazomib, an oral proteasome inhibitor, in relapsed/refractory multiple myeloma patients.
Topics: Administration, Oral; Aged; Aged, 80 and over; Area Under Curve; Boron Compounds; Dose-Response Rela | 2014 |
Changes in amino acids, ammonium, and coagulation factors after transcervical resection of the endometrium with a glycine solution used for uterine irrigation.
Topics: Adult; Amino Acids; Blood Coagulation Factors; Endometrium; Female; Glycine; Humans; Hypotonic Solut | 1995 |
Double-blind randomized study of symptoms associated with absorption of glycine 1.5% or mannitol 3% during transurethral resection of the prostate.
Topics: Absorption; Affect; Aged; Aged, 80 and over; Blood Loss, Surgical; Bradycardia; Confidence Intervals | 1998 |
13 other studies available for glycine and Nausea
| Article | Year |
|---|---|
Effect of oleoyl glycine and oleoyl alanine on lithium chloride induced nausea in rats and vomiting in shrews.
Topics: Alanine; Animals; Glycine; Lithium Chloride; Nausea; Rats; Rats, Sprague-Dawley; Shrews; Vomiting | 2022 |
Acute naloxone-precipitated morphine withdrawal elicits nausea-like somatic behaviors in rats in a manner suppressed by N-oleoylglycine.
Topics: Animals; Female; Glycine; Male; Medically Unexplained Symptoms; Morphine; Morphine Dependence; Nalox | 2020 |
Serial measurement of glyphosate blood concentration in a glyphosate potassium herbicide-intoxicated patient: A case report.
Topics: Aged; Arrhythmias, Cardiac; Glycine; Glyphosate; Herbicides; Humans; Hyperkalemia; Male; Nausea; Pot | 2019 |
Determination of glyphosate and AMPA in blood and urine from humans: about 13 cases of acute intoxication.
Topics: Accidents; Acidosis; Adult; Aged; Arrhythmias, Cardiac; Chemical and Drug Induced Liver Injury; Chro | 2013 |
Monoamine oxidase A gene polymorphism, 5-HT 2A receptor gene polymorphism and incidence of nausea induced by fluvoxamine.
Topics: Adult; Aged; Alanine; Analysis of Variance; Drug Administration Schedule; Female; Fluvoxamine; Gene | 2003 |
Symptoms of the transurethral resection syndrome using glycine as the irrigant.
Topics: Absorption; Aged; Aged, 80 and over; Bradycardia; Chest Pain; Confusion; Ethanol; Extravasation of D | 1995 |
Transurethral resection syndrome after transurethral resection of bladder tumours.
Topics: Abdominal Pain; Absorption; Aged; Aged, 80 and over; Ethanol; Extravasation of Diagnostic and Therap | 1995 |
Postoperative cerebral oedema after transcervical endometrial resection and uterine irrigation with 1.5% glycine.
Topics: Absorption; Adult; Brain Edema; Endometrium; Female; Follow-Up Studies; Glycine; Humans; Hyponatremi | 1994 |
[The action of triglycylvasopressin on control subjects and patients with upper gastrointestinal bleeding (author's transl)].
Topics: Adolescent; Adult; Aged; Animals; Colic; Defecation; Dogs; Esophageal and Gastric Varices; Female; G | 1975 |
Changes in serum electrolytes after transcervical resection of endometrium and submucous fibroids with use of glycine 1.5% for uterine irrigation.
Topics: Absorption; Adult; Chlorides; Electrolytes; Endometrium; Female; Glycine; Humans; Leiomyoma; Menorrh | 1992 |
[Resorption of the lavage fluid during transurethral resection of the prostate. Apropos of 13 cases].
Topics: Absorption; Diplopia; Glycine; Humans; Hypotonic Solutions; Male; Nausea; Osmolar Concentration; Pro | 1990 |
An assessment of a rapid release, once daily, iron and folic acid supplement in pregnancy.
Topics: Anemia, Hypochromic; Blood Volume; Capsules; Drug Combinations; Fatigue; Female; Folic Acid; Gestati | 1974 |
The nutritive effect in man of non-essential amino acids infused intravenously (together with the essential ones). I. Individual non-essential amino acids.
Topics: Adult; Alanine; Amino Acids; Ammonia; Arginine; Creatinine; Female; Glutamates; Glycine; Histidine; | 1970 |