AN OPEN-LABEL, SINGLE-ARM, PHASE 1 STUDY OF PHARMACOKINETICS, SAFETY AND ANTI-TUMOR ACTIVITY OF TALAZOPARIB MONOTHERAPY IN CHINESE PARTICIPANTS WITH ADVANCED SOLID TUMORS
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 15
- 试验地点
- 2
- 主要终点
- Maximum Observed Concentration (Cmax) of Talazoparib Following Single Oral Dose
研究概览
简要总结
A phase1 study to evaluate the PK (single dose and multiple doses) and safety of talazoparib 1 mg Once Daily in Chinese adult participants with advanced solid tumors. A maximum of approximately 15 participants will be enrolled such that approximately 12 evaluable participants complete the study.
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
- •Histological or cytological diagnosis of locally advanced or metastatic solid tumor that is resistant to standard therapy or for which no standard therapy is available.
- •ECOG Performance Status 0 or
- •Adequate Bone Marrow, Renal and Liver Function.
排除标准
- •Participants with brain metastases.
- •Current or anticipated use of P gp inhibitor and/or inducer within 7 days prior to study intervention from lead-in to end of Cycle 1; concomitant use of potent P gp inhibitor after Cycle 1 until the end of treatment.
- •Prior treatment with a PARP inhibitor.
研究组 & 干预措施
talazoparib
1 mg QD
干预措施: talazoparib (Drug)
结局指标
主要结局
Maximum Observed Concentration (Cmax) of Talazoparib Following Single Oral Dose
时间窗: Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours, 48 hours, 96 hours, 168 hours and 216 hours post Day -9 dosing
Maximum plasma concentration of talazoparib after the participant received a single oral lead-in dose of talazoparib 1 mg on Study Day -9. Cmax was directly observed from data.
Time to Cmax (Tmax) of Talazoparib Following Single Oral Dose
时间窗: Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours, 48 hours, 96 hours, 168 hours and 216 hours post Day -9 dosing
Time to reach Cmax (maximum plasma concentration) of talazoparib after the participant received a single oral lead-in dose of talazoparib 1 mg on Study Day -9.
Apparent Oral Clearance (CL/F) of Talazoparib Following Single Oral Dose
时间窗: Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours, 48 hours, 96 hours, 168 hours and 216 hours post Day -9 dosing
Apparent oral clearance of talazoparib after the participant received a single oral lead-in dose of talazoparib 1 mg on Study Day -9. Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is a quantitative measure of the rate at which a drug substance is removed from the blood. CL/F is calculated as dose/AUCinf. AUCinf = area under the plasma concentration versus time curve from time zero extrapolated to infinite time.
Cmax of Talazoparib Following Multiple Oral Doses (Steady State)
时间窗: Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours after dosing on Cycle 1 Day 22.
Maximum plasma concentration of talazoparib at steady state after the participant received multiple oral doses of talazoparib 1 mg QD from Cycle 1 Day 1 to Cycle 1 Day 22.
Area Under Plasma Concentration-Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Talazoparib Following Single Oral Dose
时间窗: Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours, 48 hours, 96 hours, 168 hours and 216 hours post Day -9 dosing
Area under the plasma concentration versus time curve from time zero to the time of the last quantifiable concentration of talazoparib after the participant received a single oral lead-in dose of talazoparib 1 mg on Study Day -9.
AUCtau of Talazoparib Following Multiple Oral Doses (Steady State)
时间窗: Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours after dosing on Cycle 1 Day 22.
Area under the plasma concentration versus time curve within a dosing interval of tau (=24 hours) at steady state after the participant received multiple oral doses of talazoparib 1 mg QD from Cycle 1 Day 1 to Cycle 1 Day 22.
Apparent Volume of Distribution (Vz/F) of Talazoparib Following Single Oral Dose
时间窗: Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours, 48 hours, 96 hours, 168 hours and 216 hours post Day -9 dosing
Apparent volume of distribution of talazoparib after the participant received a single oral lead-in dose of talazoparib 1 mg on Study Day -9. Vz/F is calculated as Dose/(AUCinf \* kel), where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. AUCinf is area under the plasma concentration versus time curve from time zero extrapolated to infinite time.
Minimum Plasma Concentration (Cmin) of Talazoparib Following Multiple Oral Doses (Steady State)
时间窗: Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours after dosing on Cycle 1 Day 22.
Minimum plasma concentration observed during the dosing interval at steady state after the participant received multiple oral doses of talazoparib 1 mg QD from Cycle 1 Day 1 to Cycle 1 Day 22.
Steady-State Accumulation Ratio (Rss) of Talazoparib Following Multiple Oral Doses (Steady State)
时间窗: Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours after dosing on Cycle 1 Day 22.
Steady-state accumulation ratio after the participant received multiple oral doses of talazoparib 1 mg QD from Cycle 1 Day 1 to Cycle 1 Day 22. Rss is calculated as AUCtau/AUCinf, where AUCtau = Area under the plasma concentration versus time curve within a dosing interval of tau (=24 hours) at steady state after multiple doses, AUCinf = Area under the plasma concentration versus time curve from time zero extrapolated to infinite time after single dose.
Area Under the Plasma Concentration-Time Profile From Time Zero to Time Tau (AUCtau) of Talazoparib Following Single Oral Dose
时间窗: Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours, 48 hours, 96 hours, 168 hours and 216 hours post Day -9 dosing
Area under the plasma concentration versus time curve from time zero to the time tau (=24 hours) of talazoparib after the participant received a single oral lead-in dose of talazoparib 1 mg on Study Day -9.
Terminal Half-Life (t1/2) of Talazoparib Following Single Oral Dose
时间窗: Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours, 48 hours, 96 hours, 168 hours and 216 hours post Day -9 dosing
Terminal half-life of talazoparib after the participant received a single oral lead-in dose of talazoparib 1 mg on Study Day -9. t1/2 is defined as the time for plasma concentration of drug to decrease by one half.
Area Under Plasma Concentration-Time Profile From Time Zero to Infinity (AUCinf) of Talazoparib Following Single Oral Dose
时间窗: Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours, 48 hours, 96 hours, 168 hours and 216 hours post Day -9 dosing
Area under the plasma concentration versus time curve from time zero extrapolated to infinite time of talazoparib after the participant received a single oral lead-in dose of talazoparib 1 mg on Study Day -9.
Tmax of Talazoparib Following Multiple Oral Doses (Steady State)
时间窗: Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours after dosing on Cycle 1 Day 22.
Time for Cmax of talazoparib at steady state after the participant received multiple oral doses of talazoparib 1 mg QD from Cycle 1 Day 1 to Cycle 1 Day 22.
CL/F of Talazoparib Following Multiple Oral Doses (Steady State)
时间窗: Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours after dosing on Cycle 1 Day 22.
Apparent clearance at steady state after the participant received multiple oral doses of talazoparib 1 mg QD from Cycle 1 Day 1 to Cycle 1 Day 22. Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is a quantitative measure of the rate at which a drug substance is removed from the blood. Steady-state CL/F is calculated as dose/AUCtau. AUCtau = area under the plasma concentration versus time curve within a dosing interval of tau (=24 hours) at steady state after multiple doses.
Observed Accumulation Ratio (Rac) of Talazoparib Following Multiple Oral Doses (Steady State)
时间窗: Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours after dosing on Cycle 1 Day 22.
Observed accumulation ratio at steady state after the participant received multiple oral doses of talazoparib 1 mg QD from Cycle 1 Day 1 to Cycle 1 Day 22. Rac is calculated as AUCtau/AUCsd,tau, where AUCtau = Area under the plasma concentration versus time curve within a dosing interval of tau (=24 hours) at steady state after multiple doses, AUCsd,tau = area under the plasma concentration versus time curve from time zero extrapolated to the time tau (=24 hours) after single dose.
次要结局
- Number of Participants With TEAEs Leading to Dose Interruption of Talazoparib by PT(Baseline (the latest non-missing value prior to or on the date of first dose of talazoparib) to at least 28 days after the last dose of talazoparib (maximum of approximately 46 weeks))
- Number of Participants With On-Treatment Maximum QT Interval (Bazett's Correction) (QTcB) and QT Interval (Fridericia's Correction) (QTcF) Data by Category(From first dose date up to at least 28 days after last dose or to the start of new anti-cancer drug therapy minus 1 day (whichever was earlier) (maximum of approximately 46 weeks))
- Number of Participants With Serious Adverse Events (SAEs)(Baseline (the latest non-missing value prior to or on the date of first dose of talazoparib) to at least 28 days after the last dose of talazoparib (maximum of approximately 46 weeks))
- Number of Participants With TEAEs Leading to Dose Reduction of Talazoparib by PT(Baseline (the latest non-missing value prior to or on the date of first dose of talazoparib) to at least 28 days after the last dose of talazoparib (maximum of approximately 46 weeks))
- Number of Participants With Grade 3 or 4 All-Causality TEAEs by Preferred Term (PT) and Maximum CTCAE Grade(Baseline (the latest non-missing value prior to or on the date of first dose of talazoparib) to at least 28 days after the last dose of talazoparib (maximum of approximately 46 weeks))
- Number of Participants With Grade 3 or 4 Treatment-Related TEAEs by PT and Maximum CTCAE Grade(Baseline (the latest non-missing value prior to or on the date of first dose of talazoparib) to at least 28 days after the last dose of talazoparib (maximum of approximately 46 weeks))
- Number of Participants With TEAEs Leading to Discontinuation From Talazoparib by PT(Baseline (the latest non-missing value prior to or on the date of first dose of talazoparib) to at least 28 days after the last dose of talazoparib (maximum of approximately 46 weeks))
- Number of Participants With On-Treatment Urinalysis Laboratory Abnormalities Shifting From <=Grade 2 at Baseline to Grade 3/4 Post-Baseline by Maximum CTCAE Grade(From first dose date up to at least 28 days after last dose or to the start of new anti-cancer drug therapy minus 1 day (whichever was earlier) (maximum of approximately 46 weeks))
- Number of Participants With On-Treatment Maximum Increase From Baseline in QTcB and QTcF Data by Category(From first dose date up to at least 28 days after last dose or to the start of new anti-cancer drug therapy minus 1 day (whichever was earlier) (maximum of approximately 46 weeks))
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs)(Baseline (the latest non-missing value prior to or on the date of first dose of talazoparib) to at least 28 days after the last dose of talazoparib (maximum of approximately 46 weeks))
- Number of Participants With On-Treatment Hematology Laboratory Abnormalities Shifting From <=Grade 2 at Baseline to Grade 3/4 Post-Baseline by Maximum CTCAE Grade(From first dose date up to at least 28 days after last dose or to the start of new anti-cancer drug therapy minus 1 day (whichever was earlier) (maximum of approximately 46 weeks))
- Number of Participants With On-Treatment Chemistry Laboratory Abnormalities Shifting From <=Grade 2 at Baseline to Grade 3/4 Post-Baseline by Maximum CTCAE Grade(From first dose date up to at least 28 days after last dose or to the start of new anti-cancer drug therapy minus 1 day (whichever was earlier) (maximum of approximately 46 weeks))
- Number of Participants With On-Treatment Vital Signs Data Meeting Pre-Specified Criteria for Potentially Clinically Significant Results(From first dose date up to at least 28 days after last dose or to the start of new anti-cancer drug therapy minus 1 day (whichever was earlier) (maximum of approximately 46 weeks))
- Number of Participants With On-Treatment Concomitant Medications With Frequency >=20% by PT(From first dose date up to at least 28 days after last dose/start day of new anti-cancer drug therapy minus 1 day (maximum of approximately 46 weeks))
- Number of Participants With On-Treatment Concomitant Nondrug Treatments/Procedures by PT(From first dose date up to at least 28 days after last dose/start day of new anti-cancer drug therapy minus 1 day (maximum of approximately 46 weeks))
- Number of Participants With On-Treatment Concomitant Medications(From first dose date up to at least 28 days after last dose/start day of new anti-cancer drug therapy minus 1 day (maximum of approximately 46 weeks))
- Percentage of Participants Achieving Objective Response (OR) (Complete Response [CR] or Partial Response [PR]) (Confirmed or Unconfirmed)(Cycle 1 Day 1 until disease progression, start of subsequent anti-cancer therapy or death due to any cause (maximum of approximately 45 weeks))
- Number of Participants With On-Treatment Concomitant Nondrug Treatments/Procedures(From first dose date up to at least 28 days after last dose/start day of new anti-cancer drug therapy minus 1 day (maximum of approximately 46 weeks))
- Duration of Response (DOR) for Participant(s) Achieving CR or PR(Cycle 1 Day 1 until disease progression, start of subsequent anti-cancer therapy or death due to any cause (maximum of approximately 45 weeks))