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

Phase 1

Completed

• Conditions: Advanced Solid Tumors
• Interventions: Drug: [14C]-pamiparib

• Registration Number: NCT03991494
• Lead Sponsor: BeiGene

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2019-05-29
• Study First Submitted: 2019-06-14
• Study First Submitted QC: 2019-06-17
• Study First Posted: 2019-06-19
• Primary Completion: 2019-10-21
• Study Completion: 2020-08-05
• Status Verified: 2021-08
• Results First Submitted: 2021-08-02
• Results First Submitted QC: 2021-08-30
• Last Update Submitted: 2021-08-30
• Results First Posted: 2021-09-27
• Last Update Posted: 2021-09-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 4

Inclusion Criteria

1. 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
2. A total body weight between 50 and 100 kg, inclusive at Screening
3. Measurable disease by CT/MRI
4. Eastern Cooperative Oncology Group (ECOG) performance status of ≤1
5. Adequate organ function

Key

Exclusion Criteria

1. Clinically significant cardiovascular disease
2. Have a previous complete gastric resection, chronic diarrhea, active inflammatory gastrointestinal disease, or any other disease causing malabsorption syndrome.
3. Poor peripheral venous access
4. 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
5. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Pamiparib	[14C]-pamiparib	-

Primary Outcome Measures

Name	Time	Method
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 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 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
Fecal Recovery of Total Radioactivity	192 hours of [14C]-Pamiparib Administration
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 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 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 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
Percentage of Total Radioactivity Excreted in Urine	192 hours of [14C]-Pamiparib Administration
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: 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 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
Renal Clearance of Pamiparib (CLR)	192 hours of [14C]-Pamiparib Administration
Cumulative Recovery of Total Radioactivity in Total Excreta	192 hours of [14C]-Pamiparib Administration
Cumulative Urinary Excretion of Pamiparib	192 hours of [14C]-Pamiparib Administration

Secondary Outcome Measures

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

Trial Locations

Locations (2)

The Clatterbridge Cancer Centre NHS Foundation Trust; 🇬🇧 Bebington, Wirral, United Kingdom

Royal Liverpool University Hospital Clinical Research Unit; 🇬🇧 Liverpool, United Kingdom