NCT02997163已完成1 期
A PHASE I OPEN-LABEL PHARMACOKINETICS AND SAFETY STUDY OF TALAZOPARIB (MDV3800) IN PATIENTS WITH ADVANCED SOLID TUMORS AND NORMAL OR VARYING DEGREES OF RENAL IMPAIRMENT
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 34
- 试验地点
- 9
- 主要终点
- Multiple Dose: Area Under the Curve From Time 0 to 24 Hours for Unbound (AUC0-24u) Talazoparib
研究概览
简要总结
This trial will investigate the pharmacokinetics (PK) and safety of talazoparib in patients with advanced solid tumors and impaired renal function.
详细描述
At the End of the Study, patients with no clinically significant toxicities, no contraindications to continue treatment with talazoparib, and no disease progression (underlying cancer progression) may be eligible to continue talazoparib treatment in a separate open-label extension study after discussion with the Principal Investigator and obtaining Sponsor permission. Sponsor decision to allow the patient to continue dosing with talazoparib in an open-label extension study will be based on potential overall benefit-risk, patient acceptance and other relevant criteria.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Signed and dated informed consent form (by the patient or a legally acceptable representative as per the local regulations) obtained prior to initiation of any study-specific procedure and treatment.
- •Female or male of at least 18 years of age.
- •Histologically or cytologically confirmed advanced solid tumor with no available standard approved treatment options in the opinion of the Investigator
- •Eastern Cooperative Oncology Group (ECOG) Performance status (PS) ≤
- •Expected life expectancy of ≥ 3 months.
- •Able to swallow the study drug (no contra indication to oral agents).
- •Renal function at screening and enrollment as defined by the Modification of Diet in Renal Disease (MDRD) equation.
- •Patient has had no clinically significant change in renal status within 3 months prior to screening, according to Investigator's review of clinical patient records.
- •Patient is not currently on hemodialysis and/or peritoneal dialysis for management of chronic kidney disease or acute failure/conditions.
- •Patient has no unstable renal function, defined as a change in estimated glomerular filtration rate (eGFR) (calculated with the MDRD equation) of > 25% for patients with mild and moderate renal impaired or as a change in eGFR > 30% for patients with severe renal impaired, from screening to enrollment.
- •Adequate other organ function at screening and enrollment.
- •Female patients of childbearing potential must have a negative serum pregnancy test at screening, and must agree to use a highly effective birth control method from the time of the first dose of study drug through 45 days after the last dose of study drug.
- •Male patients must agree to use a condom when having sex with a pregnant woman or with a non-pregnant female partner of childbearing potential, from 21 days before the first dose of study drug through 105 days after last dose of study drug.
- •Female patients must not be breastfeeding at screening nor during the study participation until 45 days after the last dose of study drug.
- •Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures.
排除标准
- •Treatment within 14 days or five half lives prior to enrollment with any type of systemic anticancer-therapy or any investigational drug, whichever is longer.
- •Have not recovered (recovery is defined as CTCAE grade ≤ 1) from the acute toxicities of previous anticancer standard or investigational therapy, except treatment-related alopecia or laboratory abnormalities otherwise meeting eligibility requirements.
- •Major surgery within 28 days prior to enrollment.
- •Serious accompanying cardiac disorder.
- •Active known or suspected brain metastasis or active leptomeningeal disease undergoing or requiring treatment.
- •Symptomatic or impending spinal cord compression or cauda equina syndrome.
- •Has undergone a liver transplant, kidney transplant or nephrectomy.
- •Prior allergic reaction or severe intolerance (meeting the criteria for a serious adverse event, a grade 3 or 4 AE, or permanent treatment discontinuation) to a poly ADP ribose polymerase (PARP) inhibitor.
- •Known myelodysplastic syndrome.
- •Seropositive for human immunodeficiency virus (HIV).
- •Any serious or unstable medical condition that interferes with ability to tolerate treatment or assessments associated with the protocol.
- •Gastrointestinal disorder affecting absorption.
- •Known or suspected hypersensitivity to any of the talazoparib capsule components.
- •Any condition or reason that interferes with ability to participate in the study, tolerate treatment or assessments associated with the protocol, causes undue risk, or complicates the interpretation of safety data, in the opinion of the Investigator or Medical Monitor.
研究组 & 干预措施
Group A (control, normal renal function)
Experimental
干预措施: Talazoparib (Drug)
Group B (mild renal impairment)
Experimental
干预措施: Talazoparib (Drug)
Group C (moderate renal impairment)
Experimental
干预措施: Talazoparib (Drug)
Group D (severe renal impairment)
Experimental
干预措施: Talazoparib (Drug)
结局指标
主要结局
Multiple Dose: Area Under the Curve From Time 0 to 24 Hours for Unbound (AUC0-24u) Talazoparib
时间窗: Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 22
AUC0-24u for unbound talazoparib was defined as the area under the concentration time curve from time 0 to 24 hours post-dose.
Multiple Dose: Maximum Observed Plasma Concentration for Unbound (Cmaxu) Talazoparib
时间窗: Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 22
Cmaxu was defined as the maximum observed plasma concentration for unbound talazoparib.
Multiple Dose: Area Under the Concentration Time Curve From 0 to 24 Hours (AUC0-24) of Talazoparib
时间窗: Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 22
AUC0-24 of talazoparib was defined as the area under the concentration time curve from time 0 to 24 hours post-dose.
Multiple Dose: Maximum Observed Plasma Concentration (Cmax) of Talazoparib
时间窗: Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 22
Cmax was defined as the maximum observed plasma concentration of talazoparib.
次要结局
- Single Dose: Area Under the Concentration Time Curve From 0 to 24 Hours (AUC0-24) of Talazoparib(Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 1)
- Multiple Dose: Plasma Trough Concentration (Ctrough) of Talazoparib(Predose on Day 22)
- Single Dose: Fraction of Unbound Drug (Fu) in Plasma in Talazoparib(Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 1)
- Single Dose: Maximum Observed Plasma Concentration (Cmax) of Talazoparib(Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 1)
- Single Dose: Area Under the Curve From Time 0 to 24 Hour for Unbound (AUC0-24u) Talazoparib(Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 1)
- Single Dose: Maximum Observed Plasma Concentration for Unbound (Cmaxu) Talazoparib(Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 1)
- Single Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib(Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 1)
- Multiple Dose: Apparent Oral Clearance (CL/F) of Talazoparib(Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 22)
- Multiple Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib(Predose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 22)
- Multiple Dose: Accumulation Ratio (Rac) of AUC (0-24)(Pre-dose, 0.5, 1, 2, 4, 6, 8 to 12, and 24 hours post-dose on Day 1 and Day 22)
- Single Dose: Amount of Talazoparib Excreted Unchanged in Urine From Time 0 to 24 Hours (Ae 0-24)(0 to 24 hours on Day 1)
- Multiple Dose: Unbound Apparent Oral Clearance (CLu/F) of Talazoparib(Predose, 0.5, 1, 2, 4, 6, 8-12, and 24 hours post-dose on Day 22)
- Multiple Dose: Fraction of Unbound Drug (Fu) in Plasma in Talazoparib(Predose, 0.5, 1, 2, 4, 6, 8-12, and 24 hours post-dose on Day 22)
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)(Baseline up to 30 days after last dose of study drug (up to 52 days))
- Change From Baseline in Respiratory Rate of Participants(Baseline, Day 8, Day 15, Day 22, Safety follow up (Day 52))
- Change From Baseline in Body Weight of Participants(Baseline, Day 8, Day 15, Day 22, Safety follow up (Day 52))
- Number of Participants With Electrocardiogram (ECG) Abnormalities(Baseline up to 30 days after last dose of study drug (up to 52 days))
- Single Dose: Percentage of Dose of Talazoparib Excreted in Urine From Time 0 to 24 Hours (Ae 0-24%) at Day 1(0 to 24 hours on Day 1)
- Multiple Dose: Amount of Talazoparib Excreted in Urine From Time 0 to 24 Hours (Ae 0-24%)(0 to 24 hours on Day 22)
- Multiple Dose: Renal Clearance (CLr) of Talazoparib at Day 22(0 to 24 hours on Day 22)
- Multiple Dose: Percentage of Talazoparib Excreted in Urine From Time 0 to 24 Hours (Ae 0-24 %) of Talazoparib at Day 22(0 to 24 hours on Day 22)
- Number of Participants With Abnormalities in Physical Examination(Baseline up to 30 days after last dose of study drug (up to 52 days))
- Change From Baseline in Systolic Blood Pressure (SBP) of Participants(Baseline, Day 8, Day 15, Day 22, Safety follow up (Day 52))
- Change From Baseline in Diastolic Blood Pressure (DBP) of Participants(Baseline, Day 8, Day 15, Day 22, Safety follow up (Day 52))
- Change From Baseline in Heart Rate of Participants(Baseline, Day 8, Day 15, Day 22, Safety follow up (Day 52))
- Number of Participants With Laboratory Abnormalities(Baseline up to 30 days after last dose of study drug (up to 52 days))
- Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status(Baseline, Safety follow up (Day 52))
研究者
研究点 (9)
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