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

Advanced Solid Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03991494
• Other study ID #: BGB-290-106
• Secondary ID: 2018-001156-36
• Status: Completed
• Phase: Phase 1
• Start date: May 29, 2019
• Est. completion date: August 5, 2020

Study information

• Verified date: August 2021
• Source: BeiGene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4
• Est. completion date: August 5, 2020
• Est. primary completion date: October 21, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key 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.

Related Conditions & MeSH terms

• Advanced Solid Tumors

Intervention

Drug:
• [14C]-pamiparib
During the treatment phase, pamiparib 60 mg administered orally twice daily

Locations

Country	Name	City	State
United Kingdom	The Clatterbridge Cancer Centre NHS Foundation Trust	Bebington	Wirral
United Kingdom	Royal Liverpool University Hospital Clinical Research Unit	Liverpool

Sponsors (1)

Lead Sponsor	Collaborator
BeiGene

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma Pamiparib Pharmacokinetics: Area Under the Concentration-time Curve (AUC) From Time Zero to Infinity (AUC0-8)		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
Primary	Plasma Total Radioactivity and Whole Blood Total Radioactivity Pharmacokinetics: AUC From Time Zero to Infinity (AUC0-8)		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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	Plasma Pamiparib Pharmacokinetics: AUC0-8 of Plasma Pamiparib Relative to AUC0-8 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
Primary	Plasma Pharmacokinetics: AUC0-8 of Whole Blood Total Radioactivity to AUC0-8 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
Primary	Percentage of Total Radioactivity Excreted in Urine		192 hours of [14C]-Pamiparib Administration
Primary	Cumulative Urinary Excretion of Pamiparib		192 hours of [14C]-Pamiparib Administration
Primary	Renal Clearance of Pamiparib (CLR)		192 hours of [14C]-Pamiparib Administration
Primary	Fecal Recovery of Total Radioactivity		192 hours of [14C]-Pamiparib Administration
Primary	Cumulative Recovery of Total Radioactivity in Total Excreta		192 hours of [14C]-Pamiparib Administration
Secondary	Number of Participants With Treatment Emergent Adverse Events in Part1 and Part 2		Up to 6 months
Secondary	Number of Participants With Clinically Significant Laboratory Abnormalities		Up to 6 months
Secondary	Number of Participants With Clinically Significant Abnormalities in 12-lead ECG Parameters, Vital Signs Data, Physical Examinations and Weight Data		Up to 6 months
Secondary	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