A Phase 1, Open-label, Parallel-group, Fixed-sequence Study to Investigate the Effect of the CYP3A Inducer Rifampin and the CYP3A Inhibitor Itraconazole on the Pharmacokinetics of Pamiparib (BGB-290) in Cancer Patients
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 25
- 试验地点
- 4
- 主要终点
- AUC From Time Zero to Time of Last Quantifiable Concentration Post-dose (AUC0-tlast) in Plasma for Part B
研究概览
简要总结
The study was an open-label, parallel-group, fixed-sequence study in male and female cancer patients. The study consists of 2 phases: the Core Phase, which is divided into Part A and Part B, and the Extension Phase. Part A investigated the effect of CYP3A induction by rifampin on the single dose pharmacokinetics (PK) of pamiparib, and Part B investigated the effect of CYP3A inhibition by itraconazole on the single dose PK of pamiparib. Participants were offered participation in the Extension Phase, in which they received pamiparib until progression of disease, unacceptable toxicity, withdrawal of consent, or any other reason for discontinuation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 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
- •Age ≥ 18 years
- •Histologically or cytologically confirmed advanced or metastatic solid tumors that are refractory or resistant to standard therapy or for which no suitable effective standard therapy exists.
- •Disease that is evaluable per RECIST Version 1.1 or Prostate Cancer Working Group-3 (PCWG-3)
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
- •Life expectancy ≥ 12 weeks
- •Adequate hematologic and end-organ function
排除标准
- •History of hypersensitivity to rifampin, any rifamycin or any of the components of the rifampin capsule (Part A).
- •History of hypersensitivity to itraconazole or any of the components of the itraconazole capsule (Part B).
- •Prior treatment with a poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor at therapeutic doses is allowed, provided that such treatment was not the most recent therapy (PARP inhibitor must have been discontinued ≥ 3 months prior to the first dose of pamiparib):
- •Participants who experienced prior severe toxicity to PARP inhibitors that in the opinion of the investigator precludes further treatment with PARP inhibitors should be excluded
- •Diagnosis of Myelodysplastic syndrome (MDS)
- •Active infection requiring systemic treatment
- •Any of the following cardiovascular criteria:
- •Cardiac chest pain, defined as moderate pain that limits instrumental activities of daily living, ≤ 28 days before Day 1 of pamiparib administration
- •Symptomatic pulmonary embolism ≤ 28 days before Day 1 of pamiparib administration
- •Any history of acute myocardial infarction ≤ 6 months before Day 1 of pamiparib administration
- •Any history of heart failure meeting New York Heart Association Classification III or IV ≤ 6 months before Day 1 of pamiparib
- •Participants with congestive heart failure or history of heart failure should be excluded from Part B (itraconazole)
- •Any event of ventricular arrhythmia ≥ Grade 2 in severity ≤ 6 months before Day 1 of pamiparib administration
- •Any history of cerebral vascular accident ≤ 6 months before Day 1 of pamiparib administration
- •Previous complete gastric resection or lap-band surgery, chronic diarrhea, active inflammatory gastrointestinal disease, known diverticular disease or any other disease-causing malabsorption syndrome
- •Gastroesophageal reflux disease under treatment with proton pump inhibitors is allowed
- •Active bleeding disorder, including gastrointestinal bleeding, as evidenced by hematemesis, significant hemoptysis, or melena ≤ 6 months before Day 1 of pamiparib administration
- •Use or anticipated need for food or drugs known to be strong or moderate CYP3A inhibitors or strong CYP3A inducers ≤ 14 days (or ≤ 5 half-lives if half-life is known) prior to Day 1 of pamiparib administration
- •Known history of intolerance to the excipients of the pamiparib capsule
- •Have known hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption
- •NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Part A (core phase)
60 mg pamiparib administered orally on Days 1 and 10 fasting 8 hours pre-dose 600 mg rifampin once a day from days 3 to 11 in the fasted state (at least 2 hours predose)
干预措施: pamiparib 60 mg (Drug)
Part A (core phase)
60 mg pamiparib administered orally on Days 1 and 10 fasting 8 hours pre-dose 600 mg rifampin once a day from days 3 to 11 in the fasted state (at least 2 hours predose)
干预措施: rifampin (Drug)
Part B (core phase)
Single dose of 20 mg pamiparib orally in the fasted state (at least 8 hours predose) on days 1 and 7 200 mg itraconazole once a day approximately 30 minutes after completing a meal Day 3 to day 8
干预措施: pamiparib 20 mg (Drug)
Part B (core phase)
Single dose of 20 mg pamiparib orally in the fasted state (at least 8 hours predose) on days 1 and 7 200 mg itraconazole once a day approximately 30 minutes after completing a meal Day 3 to day 8
干预措施: itraconazole (Drug)
Extension phase
60 mg pamiparib orally twice a day in 28-day cycles until progression of disease
干预措施: pamiparib (Drug)
结局指标
主要结局
AUC From Time Zero to Time of Last Quantifiable Concentration Post-dose (AUC0-tlast) in Plasma for Part B
时间窗: Part B: from Day -1 (admission) to Day 9 (discharge) 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, 12, 24, and 48 hours post-dose
AUC From Zero to Infinity (AUC0-inf) of Pamiparib in Plasma for Part A
时间窗: Part A: from Day -1 (admission) to Day 12 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, 12, 24, and 48 hours post-dose
Apparent Volume of Distribution (Vz/F) of Pamiparib in Plasma for Part A
时间窗: Part A: from Day -1 (admission) to Day 12 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, 12 hours post-dose
AUC From Time Zero to Time of Last Quantifiable Concentration Post-dose (AUC0-tlast) in Plasma for Part A
时间窗: Part A: from Day -1 (admission) to Day 12 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, 12, 24, and 48 hours post-dose
AUC From Zero to 9 Hours (AUC0-9) of Pamiparib in Plasma for Part A
时间窗: Part A: from Day -1 (admission) to Day 12 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, and 9 hours post-dose
Apparent Terminal Elimination Half-life (t1/2) of Pamiparib in Plasma for Part A
时间窗: Part A: from Day -1 (admission) to Day 12 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, 12 hours post-dose
Apparent Volume of Distribution (Vz/F) of Pamiparib in Plasma for Part B
时间窗: Part B: from Day -1 (admission) to Day 9 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, 12 hours post-dose
AUC From Zero to 9 Hours (AUC0-9) of Pamiparib in Plasma for Part B
时间窗: Part B: from Day -1 (admission) to Day 9 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, and 9 hours post-dose
Maximum Observed Concentration (Cmax) of Pamiparib in Plasma for Part A
时间窗: Part A: from Day -1 (admission) to Day 12 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, 12, 24, and 48 hours post-dose
Maximum Observed Concentration (Cmax) of Pamiparib in Plasma for Part B
时间窗: Part B: from Day -1 (admission) to Day 9 (discharge; ) 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, 12, 24, and 48 hours post-dose
AUC From Zero to Infinity (AUC0-inf) of Pamiparib in Plasma for Part B
时间窗: Part B: from Day -1 (admission) to Day 9 (discharge) 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, 12, 24, and 48 hours post-dose
Time of the Maximum Observed Concentration (Tmax) of Pamiparib for Part A
时间窗: Part A: from Day -1 (admission) to Day 12 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, 12 hours post-dose
Apparent Terminal Elimination Half-life (t1/2) of Pamiparib in Plasma for Part B
时间窗: Part B: from Day -1 (admission) to Day 9 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, 12 hours post-dose
Apparent Oral Clearance (CL/F) of Pamiparib in Plasma for Part A
时间窗: Part A: from Day -1 (admission) to Day 12 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, 12 hours post-dose
AUC From Zero to 12 Hours (AUC0-12) of Pamiparib in Plasma for Part A
时间窗: Part A: from Day -1 (admission) to Day 12 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, and 12 hours post-dose
AUC From Zero to 12 Hours (AUC0-12) of Pamiparib in Plasma for Part B
时间窗: Part B: from Day -1 (admission) to Day 9 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, and 12 hours post-dose
Time of the Maximum Observed Concentration (Tmax) of Pamiparib for Part B
时间窗: Part B: from Day -1 (admission) to Day 9 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, 12 hours post-dose
Apparent Oral Clearance (CL/F) of Pamiparib in Plasma for Part B
时间窗: Part B: from Day -1 (admission) to Day 9 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, 12 hours post-dose
次要结局
- Number of Participants With Clinically Significant Abnormalities in Laboratory Assessments, Vital Signs, ECG Parameters and Physical Examinations(Up to approximately 26 months)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)(From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months))