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

NCT03991494 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: BGB-290-1062018-001156-36
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 2

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.

Conditions

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (19)

• 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 Outcomes (4)

• 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)

  0.5, 1, 2, 6, 12, 24, 48, 72, 96, 120, and 144 hours post dose on Days 1 to 7

Study Arms (1)

Pamiparib

EXPERIMENTAL

Drug: [14C]-pamiparib

Interventions

[14C]-pamiparib DRUG

During the treatment phase, pamiparib 60 mg administered orally twice daily

Pamiparib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• BeiGene: lead

Study Sites (2)

The Clatterbridge Cancer Centre NHS Foundation Trust

Bebington, Wirral, CH63 4JY, United Kingdom

Location

Royal Liverpool University Hospital Clinical Research Unit

Liverpool, United Kingdom

Location

Related Publications (1)

• Mu S, Palmer D, Fitzgerald R, Andreu-Vieyra C, Zhang H, Tang Z, Su D, Sahasranaman S. Human Mass Balance and Metabolite Profiling of [14 C]-Pamiparib, a Poly (ADP-Ribose) Polymerase Inhibitor, in Patients With Advanced Cancer. Clin Pharmacol Drug Dev. 2021 Sep;10(9):1108-1120. doi: 10.1002/cpdd.943. Epub 2021 Apr 19.

  PMID: 33876576 DERIVED

Results Point of Contact

• Title: Study Director
• Organization: BeiGene

clinicaltrials@beigene.com

+1-877-828-5568

Study Officials

• Study Director

  BeiGene

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2019
• First Posted: June 19, 2019
• Study Start: May 29, 2019
• Primary Completion: October 21, 2019
• Study Completion: August 5, 2020
• Last Updated: September 27, 2021
• Results First Posted: September 27, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will share

Locations

GB (2)