Study to Investigate the Absorption, Metabolism, and Excretion of [14C]-Pamiparib in Participants With Advanced Cancer

Study Overview
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Brief Summary
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This is an open-label study, in participants with advanced and/or metastatic solid tumors, which consists of 2 parts: a research phase (inpatient) and a treatment phase. The research phase (Part 1) of the study will assess the disposition of a single oral dose of [14C]-pamiparib. In the treatment phase (Part 2) participants will be allowed to have continued access to pamiparib.

Official Title
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A Phase 1 Study to Investigate the Absorption, Metabolism, and Excretion of [14C]Pamiparib Following Single Oral Dose Administration in Patients With Advanced and/or Metastatic Solid Tumors

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: [14C]-pamiparib


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Histologically and/or cytologically confirmed advanced or metastatic solid tumor that has progressed after treatment with approved therapies for which there are no standard therapies available A total body weight between 50 and 100 kg, inclusive at Screening Measurable disease by CT/MRI Eastern Cooperative Oncology Group (ECOG) performance status of ≤1 Adequate organ function Key Exclusion Criteria: Clinically significant cardiovascular disease Have a previous complete gastric resection, chronic diarrhea, active inflammatory gastrointestinal disease, or any other disease causing malabsorption syndrome. Poor peripheral venous access Major surgical procedure, open biopsy, or significant traumatic injury ≤ 2 weeks prior to Day 1, or anticipation of need for major surgical procedure during the course of the study Use or have anticipated need for food or drugs known to be strong or moderate CYP3A inhibitors or strong CYP3A inducers NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pamiparib<br> | Drug: [14C]-pamiparib<br>* During the treatment phase, pamiparib 60 mg administered orally twice daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Pamiparib Pharmacokinetics: Area Under the Concentration-time Curve (AUC) From Time Zero to Infinity (AUC0-∞) |  | Pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 6, 12, 24, 48, 72, 96, 120, and 144 hours post-dose on Day 1 to Day 7 | 
| Plasma Total Radioactivity and Whole Blood Total Radioactivity Pharmacokinetics: AUC From Time Zero to Infinity (AUC0-∞) |  | Pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 6, 12, 24, 48, 72, 96, 120, and 144 hours post-dose on Day 1 to Day 7 | 
| Plasma Pamiparib Pharmacokinetics: AUC From Time Zero to the Last Quantifiable Concentration (AUC0-t) |  | Pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 6, 12, 24, 48, 72, 96, 120, and 144 hours post-dose on Day 1 to Day 7 | 
| Plasma Total Radioactivity and Whole Blood Total Radioactivity Pharmacokinetics: AUC From Time Zero to the Last Quantifiable Concentration (AUC-t) |  | Pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 6, 12, 24, 48, 72, 96, 120, and 144 hours post-dose on Day 1 to Day 7 | 
| Plasma Pamiparib Pharmacokinetics: Maximum Observed Concentration (Cmax) of Pamiparib |  | Pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 6, 12, 24, 48, 72, 96, 120, and 144 hours post-dose on Day 1 to Day 7 | 
| Plasma Total Radioactivity and Whole Blood Total Radioactivity Pharmacokinetics: Maximum Observed Concentration (Cmax) |  | Pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 6, 12, 24, 48, 72, 96, 120, and 144 hours post-dose on Day 1 to Day 7 | 
| Plasma Pamiparib Pharmacokinetics: Time of Cmax (Tmax) |  | Pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 6, 12, 24, 48, 72, 96, 120, and 144 hours post-dose on Day 1 to Day 7 | 
| Plasma Total Radioactivity Whole Blood Total Radioactivity Pharmacokinetics: Time of Cmax (Tmax) |  | Pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 6, 12, 24, 48, 72, 96, 120, and 144 hours post-dose on Day 1 to Day 7 | 
| Plasma Pamiparib Pharmacokinetics: Apparent Terminal Elimination Half-Life (t1/2) |  | Pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 6, 12, 24, 48, 72, 96, 120, and 144 hours post-dose on Day 1 to Day 7 | 
| Plasma Total Radioactivity and Whole Blood Total Radioactivity Pharmacokinetics: Apparent Terminal Elimination Half-Life (t1/2) |  | Pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 6, 12, 24, 48, 72, 96, 120, and 144 hours post-dose on Day 1 to Day 7 | 
| Plasma Pamiparib Pharmacokinetics: Apparent Total Clearance (CL/F) |  | Pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 6, 12, 24, 48, 72, 96, 120, and 144 hours post-dose on Day 1 to Day 7 | 
| Plasma Pamiparib Pharmacokinetics: Apparent Volume of Distribution (Vz/F) |  | Pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 6, 12, 24, 48, 72, 96, 120, and 144 hours post-dose on Day 1 to Day 7 | 
| Plasma Pamiparib Pharmacokinetics: AUC0-∞ of Plasma Pamiparib Relative to AUC0-∞ of Plasma Total Radioactivity |  | Pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 6, 12, 24, 48, 72, 96, 120, and 144 hours post-dose on Day 1 to Day 7 | 
| Plasma Pharmacokinetics: AUC0-∞ of Whole Blood Total Radioactivity to AUC0-∞ of Plasma Total Radioactivity |  | Pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 6, 12, 24, 48, 72, 96, 120, and 144 hours post-dose on Day 1 to Day 7 | 
| Percentage of Total Radioactivity Excreted in Urine |  | 192 hours of [14C]-Pamiparib Administration | 
| Cumulative Urinary Excretion of Pamiparib |  | 192 hours of [14C]-Pamiparib Administration | 
| Renal Clearance of Pamiparib (CLR) |  | 192 hours of [14C]-Pamiparib Administration | 
| Fecal Recovery of Total Radioactivity |  | 192 hours of [14C]-Pamiparib Administration | 
| Cumulative Recovery of Total Radioactivity in Total Excreta |  | 192 hours of [14C]-Pamiparib Administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Emergent Adverse Events in Part1 and Part 2 |  | Up to 6 months | 
| Number of Participants With Clinically Significant Laboratory Abnormalities |  | Up to 6 months | 
| Number of Participants With Clinically Significant Abnormalities in 12-lead ECG Parameters, Vital Signs Data, Physical Examinations and Weight Data |  | Up to 6 months | 
| Pamiparib Metabolite Identified and Metabolic Profile Using Measured Mass (M3) | Human plasma, urine, and feces samples were analyzed by LC-MS. | 0.5, 1, 2, 6, 12, 24, 48, 72, 96, 120, and 144 hours post dose on Days 1 to 7 |