A Single-Center, Open-Label Study Investigating the Excretion Balance, Pharmacokinetics, Metabolism, and Absolute Oral Bioavailability of a Single Oral Dose of [14C]-Labeled Idasanutlin and an Intravenous Tracer Dose of [13C]-Labeled Idasanutlin in a Single Cohort of Patients With Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Plasma Elimination Half-Life (t1/2) of Unlabeled Idasanutlin
研究概览
简要总结
The purpose of this single-center, open-label, non-randomized study is to assess the excretion balance, pharmacokinetics, metabolism and absolute oral bioavailability of [14C]-labeled idasanutlin administered orally and [13C]-labeled idasanutlin administered intravenously in a single cohort of eligible participants. Participants will be screened for participation in this study within 21 days of receiving the first dose of study drug on Day 1. Treatment period will continue up to Day 28 after which participants will enter 28 day follow-up or the optional treatment extension of idasanutlin, depending on safety parameters and as per opinion of the Investigator.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2, at the discretion of the Investigator
- •Histologically or cytologically confirmed advanced malignancy, except leukemia and lymphoma
- •Measureable or evaluable disease by Response evaluation criteria in solid tumors (RECIST) version 1.1, with no more than a single active malignancy in the previous 3 to 5 years prior to the administration of study drug
- •Life expectancy of at least 12 weeks
- •Participants taking opioid analgesics for pain should be on a stable pain and palliative care bowel regimen for one month prior to the first dose of study medication
- •Adequate bone marrow, hepatic, and renal function
- •Agreement to remain abstinent or use contraceptive methods specified in the study
排除标准
- •History of any form of leukemia, except for Stage 0 - 1 chronic lymphocytic leukemia, not requiring treatment in addition to their underlying malignancy
- •Have received hormonal therapy within the two weeks prior to the first dose of study drug
- •Have pre-existing gastrointestinal disorders that may interfere with proper absorption of the drug
- •History of seizure disorders or unstable Central Nervous System metastases (participants with stable CNS metastases allowed)
- •Have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study
- •Receive certain per protocol prohibited medications while on study. These medications must be discontinued 7 days prior to start of study drug
- •Have bone marrow disorders, electrolyte imbalance, infrequent bowel movements (less than once per 48 hours), coagulopathy, platelet disorder or history of non-drug induced thrombocytopenia
- •Positive for human immunodeficiency virus currently receiving combination anti-retroviral therapy
- •Regular work with ionizing radiation or radioactive material or treated with radiotherapy within 3 weeks prior to the first dose of study drug
- •Refuse to potentially receive blood products and/or have a hypersensitivity to blood products
研究组 & 干预措施
Idasanutlin
On Day 1, 300 milligram (mg) idasanutlin tablet orally and 100 mg [14C]-radiolabeled idasanutlin capsule orally (2, 50 mg capsules containing approximately 100 microcurie of radioactivity). After 5 hours and 45 minutes of the oral dose, 100 microgram (mcg) of [13C]-radiolabeled idasanutlin will be administered over a 15-minute intravenous (IV) infusion. On Day 11, idasanutlin matching placebo aqueous dispersion orally and approximately after 1 hour, 400 mg idasanutlin tablet will be administered orally in the form of an aqueous dispersion. On Day 19, 400 mg idasanutlin tablet will be administered orally in the form of an aqueous dispersion. Participants, who are eligible to enter in optional treatment extension phase, will continue treatment with idasanutlin 200 mg tablet orally once daily for 5 days, and no treatment during 23 days of 28-day cycle, until the development of progressive disease, unacceptable toxicity, consent withdrawal or any other criteria for removal.
干预措施: [13C]-radiolabeled Idasanutlin (Drug)
Idasanutlin
On Day 1, 300 milligram (mg) idasanutlin tablet orally and 100 mg [14C]-radiolabeled idasanutlin capsule orally (2, 50 mg capsules containing approximately 100 microcurie of radioactivity). After 5 hours and 45 minutes of the oral dose, 100 microgram (mcg) of [13C]-radiolabeled idasanutlin will be administered over a 15-minute intravenous (IV) infusion. On Day 11, idasanutlin matching placebo aqueous dispersion orally and approximately after 1 hour, 400 mg idasanutlin tablet will be administered orally in the form of an aqueous dispersion. On Day 19, 400 mg idasanutlin tablet will be administered orally in the form of an aqueous dispersion. Participants, who are eligible to enter in optional treatment extension phase, will continue treatment with idasanutlin 200 mg tablet orally once daily for 5 days, and no treatment during 23 days of 28-day cycle, until the development of progressive disease, unacceptable toxicity, consent withdrawal or any other criteria for removal.
干预措施: Idasanutlin (Drug)
Idasanutlin
On Day 1, 300 milligram (mg) idasanutlin tablet orally and 100 mg [14C]-radiolabeled idasanutlin capsule orally (2, 50 mg capsules containing approximately 100 microcurie of radioactivity). After 5 hours and 45 minutes of the oral dose, 100 microgram (mcg) of [13C]-radiolabeled idasanutlin will be administered over a 15-minute intravenous (IV) infusion. On Day 11, idasanutlin matching placebo aqueous dispersion orally and approximately after 1 hour, 400 mg idasanutlin tablet will be administered orally in the form of an aqueous dispersion. On Day 19, 400 mg idasanutlin tablet will be administered orally in the form of an aqueous dispersion. Participants, who are eligible to enter in optional treatment extension phase, will continue treatment with idasanutlin 200 mg tablet orally once daily for 5 days, and no treatment during 23 days of 28-day cycle, until the development of progressive disease, unacceptable toxicity, consent withdrawal or any other criteria for removal.
干预措施: Placebo (Drug)
Idasanutlin
On Day 1, 300 milligram (mg) idasanutlin tablet orally and 100 mg [14C]-radiolabeled idasanutlin capsule orally (2, 50 mg capsules containing approximately 100 microcurie of radioactivity). After 5 hours and 45 minutes of the oral dose, 100 microgram (mcg) of [13C]-radiolabeled idasanutlin will be administered over a 15-minute intravenous (IV) infusion. On Day 11, idasanutlin matching placebo aqueous dispersion orally and approximately after 1 hour, 400 mg idasanutlin tablet will be administered orally in the form of an aqueous dispersion. On Day 19, 400 mg idasanutlin tablet will be administered orally in the form of an aqueous dispersion. Participants, who are eligible to enter in optional treatment extension phase, will continue treatment with idasanutlin 200 mg tablet orally once daily for 5 days, and no treatment during 23 days of 28-day cycle, until the development of progressive disease, unacceptable toxicity, consent withdrawal or any other criteria for removal.
干预措施: [14C]-radiolabeled Idasanutlin (Drug)
结局指标
主要结局
Plasma Elimination Half-Life (t1/2) of Unlabeled Idasanutlin
时间窗: 0 hr predose, 1, 3, 6, 7, 24, 48, 96, 120, 144, 240 hrs postdose
Plasma Apparent Elimination Rate Constant of Unlabeled Idasanutlin
时间窗: 0 hr predose, 1, 3, 6, 7, 24, 48, 96, 120, 144, 240 hrs postdose
Cumulative Amount Excreted in Urine of Unlabeled Idasanutlin
时间窗: 0 hr (within 24 hrs of dosing), pooled sample collected over time interval: 0-6, 6-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144, 144-168, 168-192, 192-216, 216-240, 240-264 hrs postdose
Renal Clearance (CLr) of Unlabeled Idasanutlin
时间窗: 0 hr predose, 1, 3, 6, 7, 24, 48, 96, 120, 144, 240 hrs postdose
Cumulative Amount Excreted in Feces of Unlabeled Idasanutlin
时间窗: 0 hr (within 24 hrs of dosing), pooled sample collected over time interval: 0-6, 6-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144, 144-168, 168-192, 192-216, 216-240, 240-264 hrs postdose
AUC (0-inf) of Idasanutlin Metabolite
时间窗: 0 hr predose, 1, 3, 6, 7, 24, 48, 96, 120, 144, 240 hrs postdose
AUC(0-last) of Idasanutlin Metabolite
时间窗: 0 hr predose, 1, 3, 6, 7, 24, 48, 96, 120, 144, 240 hrs postdose
Tmax of [13C]-Labeled Idasanutlin
时间窗: 0 hr predose, 5hr 55 minutes (min), 6hr, 6hr 5min, 6hr 10min, 6hr 15min, 6hr 30min, 7, 10, 24, 48, 96, 120, 144, 240 hrs postdose
Absolute Oral Bioavailability of [13C]-Labeled Idasanutlin
时间窗: Oral administration: 0 hr predose, 1, 3, 6, 7, 24, 48, 96, 120, 144, 240 hrs postdose; IV administration: 0 hr predose, 5hr 55min, 6hr, 6hr 5min, 6hr 10min, 6hr 15min, 6hr 30min, 7, 10, 24, 48, 96, 120, 144, 240 hrs postdose
Maximum Observed Plasma Concentration (Cmax) of Unlabeled Idasanutlin
时间窗: 0 hr predose, 1, 3, 6, 7, 24, 48, 96, 120, 144, 240 hrs postdose
Area Under the Plasma Concentration Time-Curve From Time Zero to Extrapolated Infinite Time (AUC [0-inf]) of Unlabeled Idasanutlin
时间窗: 0 hr predose, 1, 3, 6, 7, 24, 48, 96, 120, 144, 240 hrs postdose
Area Under the Plasma Concentration Time-Curve From Zero to the Last Measured Concentration (AUC[0-last]) of Unlabeled Idasanutlin
时间窗: 0 hr predose, 1, 3, 6, 7, 24, 48, 96, 120, 144, 240 hrs postdose
Cmax of Idasanutlin Metabolite
时间窗: 0 hr predose, 1, 3, 6, 7, 24, 48, 96, 120, 144, 240 hrs postdose
Plasma t1/2 of Idasanutlin Metabolite
时间窗: 0 hr predose, 1, 3, 6, 7, 24, 48, 96, 120, 144, 240 hrs postdose
CLr of Idasanutlin Metabolite
时间窗: 0 hr predose, 1, 3, 6, 7, 24, 48, 96, 120, 144, 240 hrs postdose
Vz/F of Idasanutlin Metabolite
时间窗: 0 hr predose, 1, 3, 6, 7, 24, 48, 96, 120, 144, 240 hrs postdose
Cumulative Amount Excreted in Urine of Idasanutlin Metabolite
时间窗: 0 hr (within 24 hrs of dosing), pooled sample collected over time interval: 0-6, 6-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144, 144-168, 168-192, 192-216, 216-240, 240-264 hrs postdose
Cmax of [13C]-Labeled Idasanutlin
时间窗: 0 hr predose, 5hr 55 min, 6hr, 6hr 5min, 6hr 10min, 6hr 15min, 6hr 30min, 7, 10, 24, 48, 96, 120, 144, 240 hrs postdose
AUC(0-inf) of [13C]-Labeled Idasanutlin
时间窗: 0 hr predose, 5hr 55 min, 6hr, 6hr 5min, 6hr 10min, 6hr 15min, 6hr 30min, 7, 10, 24, 48, 96, 120, 144, 240 hrs postdose
Plasma t1/2 of [13C]-Labeled Idasanutlin
时间窗: 0 hr predose, 5hr 55min, 6hr, 6hr 5min, 6hr 10min, 6hr 15min, 6hr 30min, 7, 10, 24, 48, 96, 120, 144, 240 hrs postdose
Whole Blood and Plasma Cmax of [14C]-Labeled Idasanutlin
时间窗: 0 hr predose, 1, 3, 6, 7, 24, 48, 96, 120, 144, 240 hrs postdose
Whole Blood and Plasma AUC(0-inf) of [14C]-Labeled Idasanutlin
时间窗: 0 hr predose, 1, 3, 6, 7, 24, 48, 96, 120, 144, 240 hrs postdose0 hr predose, 1, 3, 6, 7, 24, 48, 96, 120, 144, 240 hrs postdose
Whole Blood and Plasma Apparent Elimination Rate Constant of [14C]-Labeled Idasanutlin
时间窗: 0 hr predose, 1, 3, 6, 7, 24, 48, 96, 120, 144, 240 hrs postdose
Cumulative Amount of Radioactivity Excreted in Urine as Percentage of Dosed Radioactivity of [14C]-Labeled Idasanutlin
时间窗: 0 hr (within 24 hrs of dosing), pooled sample collected over time interval: 0-6, 6-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144, 144-168, 168-192, 192-216, 216-240, 240-264 hrs postdose
Vz/F of [13C]-Labeled Idasanutlin
时间窗: 0 hr predose, 5hr 55min, 6hr, 6hr 5min, 6hr 10min, 6hr 15min, 6hr 30min, 7, 10, 24, 48, 96, 120, 144, 240 hrs postdose
Whole Blood and Plasma Tmax of [14C]-Labeled Idasanutlin
时间窗: 0 hr predose, 1, 3, 6, 7, 24, 48, 96, 120, 144, 240 hrs postdose
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Unlabeled Idasanutlin
时间窗: 0 Hour (hr) predose, 1, 3, 6, 7, 24, 48, 96, 120, 144, 240 hrs postdose
Apparent Oral Clearance (CL/F) of Unlabeled Idasanutlin
时间窗: 0 hr predose, 1, 3, 6, 7, 24, 48, 96, 120, 144, 240 hrs postdose
Apparent Volume of Distribution (Vz/F) of Unlabeled Idasanutlin
时间窗: 0 hr predose, 1, 3, 6, 7, 24, 48, 96, 120, 144, 240 hrs postdose
Whole Blood and Plasma AUC(0-last) of [14C]-Labeled Idasanutlin
时间窗: 0 hr predose, 1, 3, 6, 7, 24, 48, 96, 120, 144, 240 hrs postdose
CL/F of [13C]-Labeled Idasanutlin
时间窗: 0 hr predose, 5hr 55min, 6hr, 6hr 5min, 6hr 10min, 6hr 15min, 6hr 30min, 7, 10, 24, 48, 96, 120, 144, 240 hrs postdose
Cumulative Amount of Radioactivity Excreted in Feces on Toilet Tissue as Percentage of Dosed Radioactivity of [14C]-Labeled Idasanutlin
时间窗: 0 hr (within 24 hrs of dosing), pooled sample collected over time interval: 0-6, 6-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144, 144-168, 168-192, 192-216, 216-240, 240-264 hrs postdose
Tmax of Idasanutlin Metabolite
时间窗: 0 hr predose, 1, 3, 6, 7, 24, 48, 96, 120, 144, 240 hrs postdose
Plasma Apparent Elimination Rate Constant of Idasanutlin Metabolite
时间窗: 0 hr predose, 1, 3, 6, 7, 24, 48, 96, 120, 144, 240 hrs postdose
CL/F of Idasanutlin Metabolite
时间窗: 0 hr predose, 1, 3, 6, 7, 24, 48, 96, 120, 144, 240 hrs postdose
Cumulative Amount Excreted in Feces of Idasanutlin Metabolite
时间窗: 0 hr (within 24 hrs of dosing), pooled sample collected over time interval: 0-6, 6-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144, 144-168, 168-192, 192-216, 216-240, 240-264 hrs postdose
AUC(0-last) of [13C]-Labeled Idasanutlin
时间窗: 0 hr predose, 5hr 55min, 6hr, 6hr 5min, 6hr 10min, 6hr 15min, 6hr 30min, 7, 10, 24, 48, 96, 120, 144, 240 hrs postdose
Cumulative Amount of Radioactivity Excreted in Feces as Percentage of Dosed Radioactivity of [14C]-Labeled Idasanutlin
时间窗: 0 hr (within 24 hrs of dosing), pooled sample collected over time interval: 0-6, 6-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144, 144-168, 168-192, 192-216, 216-240, 240-264 hrs postdose
次要结局
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(Baseline through 28 days after the last dose of study drug (maximum up to approximately 76 days))
- Palatability Assessment Questionnaire Score for Aqueous Dispersion of Idasanutlin(0 hr (pre-Day 11-dose), 0.5 hr, 1 hr, 1.5 hr, 2 hr, and 3 hr post-Day 11-dose)
- Aftertaste Survey Questionnaire Score for Aqueous Dispersion of Idasanutlin(0 hr (pre-Day 11-dose), 0.5 hr, 1 hr, 1.5 hr, 2 hr, and 3 hr post-Day 11-dose)