Trial Outcomes & Findings for Study to Investigate the Absorption, Metabolism, and Excretion of [14C]-Pamiparib in Participants With Advanced Cancer (NCT NCT03991494)

NCT ID: NCT03991494

Last Updated: 2021-09-27

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 4 participants
• Primary outcome timeframe: 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
• Results posted on: 2021-09-27

Participant Flow

The study consisted of 2 parts: a Research Phase (Part 1) in which participants were inpatients and a Treatment Phase (Part 2) in which participants were outpatients.

Potential participants were screened to assess their eligibility to enter the study within 28 days prior to administration of the first dose. Up to 10 participants could be enrolled to ensure that 4 participants completed Part 1 of the study.

Participant milestones

Measure	Pamiparib Research Phase (Part 1): participants received a single dose of 60 mg \[14C\]-pamiparib orally Treatment phase (Part 2): participants received pamiparib 60 mg twice daily orally
Overall Study STARTED	4
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	4

Reasons for withdrawal

Measure	Pamiparib Research Phase (Part 1): participants received a single dose of 60 mg \[14C\]-pamiparib orally Treatment phase (Part 2): participants received pamiparib 60 mg twice daily orally
Overall Study Progressive Disease	4

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Pamiparib n=4 Participants Research Phase (Part 1): participants received a single dose of 60 mg \[14C\]-pamiparib orally Treatment phase (Part 2): participants received pamiparib 60 mg twice daily orally
Age, Continuous	56 years STANDARD_DEVIATION 5.4 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United Kingdom	4 participants n=5 Participants

PRIMARY outcome

Timeframe: 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

Population: The PK population included all participants who received one dose of \[14C\]-pamiparib and had evaluable PK data.

Outcome measures

Measure	Pamiparib n=4 Participants Research Phase (Part 1): participants received a single dose of 60 mg \[14C\]-pamiparib orally Treatment phase (Part 2): participants received pamiparib 60 mg twice daily orally
Plasma Pamiparib Pharmacokinetics: Area Under the Concentration-time Curve (AUC) From Time Zero to Infinity (AUC0-∞)	29300 hours*nanograms/milliLiter (h*ng/mL) Geometric Coefficient of Variation 21.6

PRIMARY outcome

Timeframe: 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

Population: The PK population included all participants who received at least on dose of \[14C\]-pamiparib and had evaluable PK data.

Outcome measures

Measure	Pamiparib n=4 Participants Research Phase (Part 1): participants received a single dose of 60 mg \[14C\]-pamiparib orally Treatment phase (Part 2): participants received pamiparib 60 mg twice daily orally
Plasma Total Radioactivity and Whole Blood Total Radioactivity Pharmacokinetics: AUC From Time Zero to Infinity (AUC0-∞) Plasma Total Radioactivity	42200 h*ngEq/g Geometric Coefficient of Variation 21.5
Plasma Total Radioactivity and Whole Blood Total Radioactivity Pharmacokinetics: AUC From Time Zero to Infinity (AUC0-∞) Whole Blood Total Radioactivity	32200 h*ngEq/g Geometric Coefficient of Variation 16.2

PRIMARY outcome

Timeframe: 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

Population: The PK population included all participants who received at least on dose of \[14C\]-pamiparib and had evaluable PK data.

Outcome measures

Measure	Pamiparib n=4 Participants Research Phase (Part 1): participants received a single dose of 60 mg \[14C\]-pamiparib orally Treatment phase (Part 2): participants received pamiparib 60 mg twice daily orally
Plasma Pamiparib Pharmacokinetics: AUC From Time Zero to the Last Quantifiable Concentration (AUC0-t)	29200 h*ng/mL Geometric Coefficient of Variation 21.6

PRIMARY outcome

Timeframe: 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

Population: The PK population included all participants who received at least on dose of \[14C\]-pamiparib and had evaluable PK data.

Outcome measures

Measure	Pamiparib n=4 Participants Research Phase (Part 1): participants received a single dose of 60 mg \[14C\]-pamiparib orally Treatment phase (Part 2): participants received pamiparib 60 mg twice daily orally
Plasma Total Radioactivity and Whole Blood Total Radioactivity Pharmacokinetics: AUC From Time Zero to the Last Quantifiable Concentration (AUC-t) Plasma Total Radioactivity	41800 h*ngEq/g Geometric Coefficient of Variation 21.6
Plasma Total Radioactivity and Whole Blood Total Radioactivity Pharmacokinetics: AUC From Time Zero to the Last Quantifiable Concentration (AUC-t) Whole Blood Total Radioactivity	31200 h*ngEq/g Geometric Coefficient of Variation 16.1

PRIMARY outcome

Timeframe: 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

Population: The PK population included all participants who received at least on dose of \[14C\]-pamiparib and had evaluable PK data.

Outcome measures

Measure	Pamiparib n=4 Participants Research Phase (Part 1): participants received a single dose of 60 mg \[14C\]-pamiparib orally Treatment phase (Part 2): participants received pamiparib 60 mg twice daily orally
Plasma Pamiparib Pharmacokinetics: Maximum Observed Concentration (Cmax) of Pamiparib	2190 ng/mL Geometric Coefficient of Variation 12.4

PRIMARY outcome

Timeframe: 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

Population: The PK population included all participants who received at least on dose of \[14C\]-pamiparib and had evaluable PK data.

Outcome measures

Measure	Pamiparib n=4 Participants Research Phase (Part 1): participants received a single dose of 60 mg \[14C\]-pamiparib orally Treatment phase (Part 2): participants received pamiparib 60 mg twice daily orally
Plasma Total Radioactivity and Whole Blood Total Radioactivity Pharmacokinetics: Maximum Observed Concentration (Cmax) Plasma Total Radioactivity	2390 ngEq/g Geometric Coefficient of Variation 9.0
Plasma Total Radioactivity and Whole Blood Total Radioactivity Pharmacokinetics: Maximum Observed Concentration (Cmax) Whole Blood Total Radioactivity	1730 ngEq/g Geometric Coefficient of Variation 11.8

PRIMARY outcome

Timeframe: 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

Population: The PK population included all participants who received at least on dose of \[14C\]-pamiparib and had evaluable PK data.

Outcome measures

Measure	Pamiparib n=4 Participants Research Phase (Part 1): participants received a single dose of 60 mg \[14C\]-pamiparib orally Treatment phase (Part 2): participants received pamiparib 60 mg twice daily orally
Plasma Pamiparib Pharmacokinetics: Time of Cmax (Tmax)	2.00 hours Interval 1.0 to 3.05

PRIMARY outcome

Timeframe: 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

Population: The PK population included all participants who received at least on dose of \[14C\]-pamiparib and had evaluable PK data.

Outcome measures

Measure	Pamiparib n=4 Participants Research Phase (Part 1): participants received a single dose of 60 mg \[14C\]-pamiparib orally Treatment phase (Part 2): participants received pamiparib 60 mg twice daily orally
Plasma Total Radioactivity Whole Blood Total Radioactivity Pharmacokinetics: Time of Cmax (Tmax) Plasma Total Radioactivity	2.25 hours Interval 1.5 to 3.05
Plasma Total Radioactivity Whole Blood Total Radioactivity Pharmacokinetics: Time of Cmax (Tmax) Whole Blood Total Radioactivity	2.25 hours Interval 1.5 to 3.05

PRIMARY outcome

Timeframe: 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

Population: The PK population included all participants who received one dose of \[14C\]-pamiparib and had evaluable PK data.

Outcome measures

Measure	Pamiparib n=4 Participants Research Phase (Part 1): participants received a single dose of 60 mg \[14C\]-pamiparib orally Treatment phase (Part 2): participants received pamiparib 60 mg twice daily orally
Plasma Pamiparib Pharmacokinetics: Apparent Terminal Elimination Half-Life (t1/2)	29.2 hours Standard Deviation 6.02

PRIMARY outcome

Timeframe: 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

Population: The PK population included all participants who received one dose of \[14C\]-pamiparib and had evaluable PK data.

Outcome measures

Measure	Pamiparib n=4 Participants Research Phase (Part 1): participants received a single dose of 60 mg \[14C\]-pamiparib orally Treatment phase (Part 2): participants received pamiparib 60 mg twice daily orally
Plasma Total Radioactivity and Whole Blood Total Radioactivity Pharmacokinetics: Apparent Terminal Elimination Half-Life (t1/2) Plasma Total Radioactivity	21.6 hours Standard Deviation 10.3
Plasma Total Radioactivity and Whole Blood Total Radioactivity Pharmacokinetics: Apparent Terminal Elimination Half-Life (t1/2) Whole Blood Total Radioactivity	13.3 hours Standard Deviation 3.13

PRIMARY outcome

Timeframe: 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

Population: The PK population included all participants who received one dose of \[14C\]-pamiparib and had evaluable PK data.

Outcome measures

Measure	Pamiparib n=4 Participants Research Phase (Part 1): participants received a single dose of 60 mg \[14C\]-pamiparib orally Treatment phase (Part 2): participants received pamiparib 60 mg twice daily orally
Plasma Pamiparib Pharmacokinetics: Apparent Total Clearance (CL/F)	2.21 Liters/hour (L/h) Geometric Coefficient of Variation 23.2

PRIMARY outcome

Timeframe: 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

Population: The PK population included all participants who received one dose of \[14C\]-pamiparib and had evaluable PK data.

Outcome measures

Measure	Pamiparib n=4 Participants Research Phase (Part 1): participants received a single dose of 60 mg \[14C\]-pamiparib orally Treatment phase (Part 2): participants received pamiparib 60 mg twice daily orally
Plasma Pamiparib Pharmacokinetics: Apparent Volume of Distribution (Vz/F)	91.3 Liters Geometric Coefficient of Variation 18.5

PRIMARY outcome

Timeframe: 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

Population: The PK population included all participants who received at least on dose of \[14C\]-pamiparib and had evaluable PK data.

Outcome measures

Measure	Pamiparib n=4 Participants Research Phase (Part 1): participants received a single dose of 60 mg \[14C\]-pamiparib orally Treatment phase (Part 2): participants received pamiparib 60 mg twice daily orally
Plasma Pamiparib Pharmacokinetics: AUC0-∞ of Plasma Pamiparib Relative to AUC0-∞ of Plasma Total Radioactivity	0.694 Ratio Geometric Coefficient of Variation 2.7

PRIMARY outcome

Timeframe: 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

Population: The PK population included all participants who received one dose of \[14C\]-pamiparib and had evaluable PK data.

Outcome measures

Measure	Pamiparib n=4 Participants Research Phase (Part 1): participants received a single dose of 60 mg \[14C\]-pamiparib orally Treatment phase (Part 2): participants received pamiparib 60 mg twice daily orally
Plasma Pharmacokinetics: AUC0-∞ of Whole Blood Total Radioactivity to AUC0-∞ of Plasma Total Radioactivity	0.764 Ratio Geometric Coefficient of Variation 5.8

PRIMARY outcome

Timeframe: 192 hours of [14C]-Pamiparib Administration

Population: The PK population included all participants who received one dose of \[14C\]-pamiparib and had evaluable PK data.

Outcome measures

Measure	Pamiparib n=4 Participants Research Phase (Part 1): participants received a single dose of 60 mg \[14C\]-pamiparib orally Treatment phase (Part 2): participants received pamiparib 60 mg twice daily orally
Percentage of Total Radioactivity Excreted in Urine	57.84 % Excreted Standard Deviation 5.12

PRIMARY outcome

Timeframe: 192 hours of [14C]-Pamiparib Administration

Population: The PK population included all participants who received one dose of \[14C\]-pamiparib and had evaluable PK data.

Outcome measures

Measure	Pamiparib n=4 Participants Research Phase (Part 1): participants received a single dose of 60 mg \[14C\]-pamiparib orally Treatment phase (Part 2): participants received pamiparib 60 mg twice daily orally
Cumulative Urinary Excretion of Pamiparib	1.095 mg Geometric Coefficient of Variation 40.2

PRIMARY outcome

Timeframe: 192 hours of [14C]-Pamiparib Administration

Population: The PK population included all participants who received one dose of \[14C\]-pamiparib and had evaluable PK data.

Outcome measures

Measure	Pamiparib n=4 Participants Research Phase (Part 1): participants received a single dose of 60 mg \[14C\]-pamiparib orally Treatment phase (Part 2): participants received pamiparib 60 mg twice daily orally
Renal Clearance of Pamiparib (CLR)	0.03742 CLR (L/h) Geometric Coefficient of Variation 59.5

PRIMARY outcome

Timeframe: 192 hours of [14C]-Pamiparib Administration

Population: The PK population included all participants who received one dose of \[14C\]-pamiparib and had evaluable PK data.

Outcome measures

Measure	Pamiparib n=4 Participants Research Phase (Part 1): participants received a single dose of 60 mg \[14C\]-pamiparib orally Treatment phase (Part 2): participants received pamiparib 60 mg twice daily orally
Fecal Recovery of Total Radioactivity	26.89 % Excreted Standard Deviation 6.83

PRIMARY outcome

Timeframe: 192 hours of [14C]-Pamiparib Administration

Population: The PK population included all participants who received one dose of \[14C\]-pamiparib and had evaluable PK data.

Outcome measures

Measure	Pamiparib n=4 Participants Research Phase (Part 1): participants received a single dose of 60 mg \[14C\]-pamiparib orally Treatment phase (Part 2): participants received pamiparib 60 mg twice daily orally
Cumulative Recovery of Total Radioactivity in Total Excreta	84.73 % Excreted Standard Deviation 3.53

SECONDARY outcome

Timeframe: Up to 6 months

Population: The safety population for Part 1 consisted of all participants who received 1 dose of study drug, 60 mg \[14C\]-pamiparib in Part 1 and the safety population for Part 2 consisted of all participants who participated in Part 1 and received at least 1 dose of 60 mg pamiparib in Part 2.

Outcome measures

Measure	Pamiparib n=4 Participants Research Phase (Part 1): participants received a single dose of 60 mg \[14C\]-pamiparib orally Treatment phase (Part 2): participants received pamiparib 60 mg twice daily orally
Number of Participants With Treatment Emergent Adverse Events in Part1 and Part 2 Part 1: Number of Participants with AEs	4 number of participants
Number of Participants With Treatment Emergent Adverse Events in Part1 and Part 2 Part 1: Participants with SAEs	0 number of participants
Number of Participants With Treatment Emergent Adverse Events in Part1 and Part 2 Part 2: Number of Participants with AEs	3 number of participants
Number of Participants With Treatment Emergent Adverse Events in Part1 and Part 2 Part 2: Participants with SAEs	0 number of participants

SECONDARY outcome

Timeframe: Up to 6 months

Population: The safety population for Part 1 consisted of all participants who received 1 dose of study drug, 60 mg \[14C\]-pamiparib, in Part 1 and the safety population for Part 2 consisted of all participants who participated in Part 1 and received at least 1 dose of 60 mg pamiparib in Part 2.

Outcome measures

Measure	Pamiparib n=4 Participants Research Phase (Part 1): participants received a single dose of 60 mg \[14C\]-pamiparib orally Treatment phase (Part 2): participants received pamiparib 60 mg twice daily orally
Number of Participants With Clinically Significant Laboratory Abnormalities	0 number of participants

SECONDARY outcome

Timeframe: Up to 6 months

Population: The safety population for Part 1 consisted of all participants who received at least 1 dose of study drug, 60 mg \[14C\]-pamiparib, in Part 1 and the safety population for Part 2 consisted of all participants who participated in Part 1 and received at least 1 dose of 60 mg pamiparib in Part 2.

Outcome measures

Measure	Pamiparib n=4 Participants Research Phase (Part 1): participants received a single dose of 60 mg \[14C\]-pamiparib orally Treatment phase (Part 2): participants received pamiparib 60 mg twice daily orally
Number of Participants With Clinically Significant Abnormalities in 12-lead ECG Parameters, Vital Signs Data, Physical Examinations and Weight Data	0 Number of participants

SECONDARY outcome

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

Population: The PK population included all participants who received one dose of \[14C\]-pamiparib and had evaluable PK data.

Human plasma, urine, and feces samples were analyzed by LC-MS.

Outcome measures

Measure	Pamiparib n=4 Participants Research Phase (Part 1): participants received a single dose of 60 mg \[14C\]-pamiparib orally Treatment phase (Part 2): participants received pamiparib 60 mg twice daily orally
Pamiparib Metabolite Identified and Metabolic Profile Using Measured Mass (M3)	313.1098 Da

Adverse Events

Pamiparib

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Pamiparib n=4 participants at risk Research Phase (Part 1): participants received a single dose of 60 mg \[14C\]-pamiparib orally Treatment phase (Part 2): participants received 60 mg pamiparib twice daily orally
Investigations Gamma-glutamyltransferase increased	25.0% 1/4 • Approximately 30 days after the last dose of pamiparib - up to 6 months
Nervous system disorders Headache	25.0% 1/4 • Approximately 30 days after the last dose of pamiparib - up to 6 months
General disorders Influenza like illness	25.0% 1/4 • Approximately 30 days after the last dose of pamiparib - up to 6 months
Musculoskeletal and connective tissue disorders Musculoskeletal pain	25.0% 1/4 • Approximately 30 days after the last dose of pamiparib - up to 6 months
General disorders Oedema peripheral	25.0% 1/4 • Approximately 30 days after the last dose of pamiparib - up to 6 months
Nervous system disorders Radiculopathy	25.0% 1/4 • Approximately 30 days after the last dose of pamiparib - up to 6 months
Infections and infestations Sinusitis	25.0% 1/4 • Approximately 30 days after the last dose of pamiparib - up to 6 months
Nervous system disorders Tremor	25.0% 1/4 • Approximately 30 days after the last dose of pamiparib - up to 6 months
Infections and infestations Urinary tract infection	25.0% 1/4 • Approximately 30 days after the last dose of pamiparib - up to 6 months
Gastrointestinal disorders Constipation	75.0% 3/4 • Approximately 30 days after the last dose of pamiparib - up to 6 months
Gastrointestinal disorders Abdominal distension	50.0% 2/4 • Approximately 30 days after the last dose of pamiparib - up to 6 months
Nervous system disorders Dysgeusia	50.0% 2/4 • Approximately 30 days after the last dose of pamiparib - up to 6 months
Respiratory, thoracic and mediastinal disorders Dyspnoea	50.0% 2/4 • Approximately 30 days after the last dose of pamiparib - up to 6 months
General disorders Fatigue	50.0% 2/4 • Approximately 30 days after the last dose of pamiparib - up to 6 months
Gastrointestinal disorders Nausea	50.0% 2/4 • Approximately 30 days after the last dose of pamiparib - up to 6 months
Gastrointestinal disorders Abdominal discomfort	25.0% 1/4 • Approximately 30 days after the last dose of pamiparib - up to 6 months
Gastrointestinal disorders Abdominal pain	25.0% 1/4 • Approximately 30 days after the last dose of pamiparib - up to 6 months
Gastrointestinal disorders Abdominal pain upper	25.0% 1/4 • Approximately 30 days after the last dose of pamiparib - up to 6 months
Investigations Amylase increased	25.0% 1/4 • Approximately 30 days after the last dose of pamiparib - up to 6 months
Blood and lymphatic system disorders Anaemia	25.0% 1/4 • Approximately 30 days after the last dose of pamiparib - up to 6 months
Musculoskeletal and connective tissue disorders Arthralgia	25.0% 1/4 • Approximately 30 days after the last dose of pamiparib - up to 6 months
Investigations Blood alkaline phosphatase increased	25.0% 1/4 • Approximately 30 days after the last dose of pamiparib - up to 6 months
Nervous system disorders Depressed level of consciousness	25.0% 1/4 • Approximately 30 days after the last dose of pamiparib - up to 6 months
Gastrointestinal disorders Diarrhoea	25.0% 1/4 • Approximately 30 days after the last dose of pamiparib - up to 6 months
Nervous system disorders Dizziness	25.0% 1/4 • Approximately 30 days after the last dose of pamiparib - up to 6 months
Gastrointestinal disorders Dry Mouth	25.0% 1/4 • Approximately 30 days after the last dose of pamiparib - up to 6 months
Gastrointestinal disorders Flatulence	25.0% 1/4 • Approximately 30 days after the last dose of pamiparib - up to 6 months

Additional Information

Study Director

BeiGene

Phone: +1-877-828-5568

Email: clinicaltrials@beigene.com

Results disclosure agreements

• Principal investigator is a sponsor employee BeiGene has 18 months from the end of the study at all sites to publish overall study results. After the 1st multi-site publication or the expiration of publication period, Investigators are free to publish/present the results of the study. Investigators must submit all draft publications/presentations to us for review 60 days prior to the planned publication/presentation date. BeiGene may request deletion of its confidential information \& may request a further delay to protect its IP rights.
• Publication restrictions are in place

Restriction type: OTHER