Absorption, Metabolism, and Excretion Following a Single Oral Dose of [14C]-Rucaparib

NCT02986100 | Completed Phase 1

• 2 other identifiers: CO-338-0452015-004394-32
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to characterize the mass balance, absorption, metabolism, and elimination pathways of orally administered \[14C\] rucaparib followed by cycle by cycle treatment with rucaparib continuing until disease progression or other reason for discontinuation

Conditions

Solid Tumor

Keywords

rucaparib; CO-338; Clovis; Clovis Oncology; PARP inhibitor; Absorption; Metabolism; Excretion

Outcome Measures

Primary Outcomes (14)

• Pharmacokinetics of 14C-labeled rucaparib (radioactivity in whole blood and plasma): tmax

  Time to peak concentration (tmax)

  Days 1-13

• Pharmacokinetics of 14C-labeled rucaparib(Radioactivity in whole blood and plasma): Cmax

  peak (maximum) concentration (Cmax)

  Days 1-13

• Pharmacokinetics of 14C-labeled rucaparib(Radioactivity in whole blood and plasma): t1/2

  Elimination half-life (t1/2)

  Days 1-13

• Pharmacokinetics of 14C-labeled rucaparib(Radioactivity in whole blood and plasma): AUC

  Area under curve (AUC)

  Days 1-13

• Pharmacokinetics of 14C-labeled rucaparib(Radioactivity in whole blood and plasma): CL/F

  Oral clearance (CL/F)

  Days 1-13

• Pharmacokinetics of 14C-labeled rucaparib(Radioactivity in whole blood and plasma): V/F

  Apparent volume of distribution (V/F)

  Days 1-13

• Excretion rate of 14C-labeled rucaparib(radioactivity in feces)

  Percent of dose excreted in feces

  Days 1-13

• Excretion rate of 14C-labeled rucaparib(radioactivity in urine)

  Percent of dose excreted in urine

  Days 1-13

• Pharmacokinetics of rucaparib (in urine): CLR

  Renal clearance (CLR)

  Days 1-13

• Excretion rate of 14C-labeled rucaparib(radioactivity in vomit, if applicable)

  Percent of dose in vomit, if applicable

  Days 1-13

• Metabolite identification of rucaparib in plasma, urine and feces

  Days 1-13

• Cumulative whole blood:plasma ratio calculated for Cmax

  peak concentration (Cmax)

  Days 1-13

• Cumulative whole blood:plasma ratio calculated for AUC0-tlast

  AUC from time zero to the last time point with concentration above the lower limit of quantitation (AUC0-last)

  Day 1-13

• Cumulative whole blood:plasma ratio calculated for AUCinf

  AUC from time zero to infinity (AUCinf)

  Day 1-13

Secondary Outcomes (1)

• Tolerability and safety of rucaparib assessed by incidence of Adverse Events (AEs), clinical laboratory abnormalities, and dose modifications

  From cycle 1 Day 1 until radiologically confirmed disease progression, death, or initiation of subsequent treatment whichever comes first up to 52 weeks

Other Outcomes (1)

• To evaluate the antitumor activity of rucaparib in BRCA mutated solid tumors based on Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

  Cycle 1 Day 1 until progression of disease, unacceptable toxicity, or discontinuation for other reasons

Study Arms (1)

C-14 labeled rucaparib

EXPERIMENTAL

Each patient will receive a single oral dose of 600 mg \[14C\] rucaparib (approximately 140 µCi) in the fasted state. Patients will be confined at the study site for the collection of blood samples and excreta for a maximum of 13 days, from Day -1. The patient can be discharged sooner than Day 13, if the discharge criteria are met. After completion of Part I, patients with a deleterious BRCA mutation will have the option to participate in Part II by receiving 600 mg BID rucaparib tablets orally in 28 day cycles until disease progression, unacceptable toxicity, death, or discontinuation for other reasons

Drug: C-14 labeled Rucaparib; Drug: Rucaparib

Interventions

C-14 labeled Rucaparib DRUG

Each dosage unit consists of a hard gelatin capsule filled with cold rucaparib camsylate and \[14C\]-rucaparib camsylate salt. Each capsule contains approximately 150 mg rucaparib (free base weight) and approximately 35 µCi of \[14C\]-rucaparib. Each patient will ingest four capsules in the fasted state for a total dose of 600 mg rucaparib (free base weight) with approximately 140 µCi of \[14C\]-rucaparib

C-14 labeled rucaparib

Rucaparib DRUG

200 \& 300 mg tablet

Also known as: CO-338, Rubraca

C-14 labeled rucaparib

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed advanced solid tumor
• Part II only: Have a known deleterious BRCA1/2 mutation (germline or somatic) as determined by a local or central laboratory
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Adequate bone marrow, renal, and liver function

You may not qualify if:

• Prior treatment with chemotherapy, radiation, antibody therapy or other immunotherapy, gene therapy, vaccine therapy, or angiogenesis inhibitors within 14 days prior to Day 1
• Participation in a trial involving administration of \[14C\]-labeled compound(s) within the last 6 months prior to Day 1
• Arterial or venous thrombi (including cerebrovascular accident), myocardial infarction, admission for unstable angina, cardiac angioplasty, or stenting within the last 3 months prior to Screening
• Pre-existing duodenal stent, recent or existing bowel obstruction, and/or any gastrointestinal disorder or defect that would, in the opinion of the Investigator, interfere with absorption of rucaparib
• Untreated or symptomatic central nervous system (CNS) metastases
• Evidence or history of bleeding disorder
• Participation in another investigational drug trial within 14 days prior to Day 1 (or 5 times the half-life of the drug, whichever is longer) or exposure to more than three new investigational agents within 12 months prior to Day 1
• Acute illness (eg, nausea, vomiting, fever, diarrhea) within 14 days prior to Day 1, unless mild in severity and approved by the Investigator and Sponsor's/designated medical representative
• Active second malignancy

Sponsors & Collaborators

• pharmaand GmbH: lead

Study Sites (1)

PRA Magyarország Kft.

Budapest, Rottenbiller Utca 13, 1077, Hungary

Location

MeSH Terms

Interventions

rucaparib

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: Open Label
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2016
• First Posted: December 8, 2016
• Study Start: November 1, 2016
• Primary Completion: December 1, 2017
• Study Completion: September 1, 2018
• Last Updated: June 9, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

HU (1)