A Study to Determine the Absorption, Metabolism, and Routes of Excretion of (14C) Radiolabeled Ibrutinib in Healthy Male Participants

An Open-Label Phase 1 Study to Determine the Pharmacokinetics, Metabolism, and Routes of Excretion of (14C) Radiolabeled PCI-32765 in Healthy Male Subjects

The purpose of this study is to investigate the absorption, the metabolic pathways and the excretion of ibrutinib in healthy male adult participants after administration of a single oral dose of 50 mg to 140 mg (5 mg/mL solution) of unlabeled ibrutinib admixed with 14C ibrutinib.

Study Overview

• Status: Completed
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: Ibrutinib

Detailed Description

This is an open-label (all people know the identity of the intervention), single-center, single-dose study in healthy male participants. Six men will be enrolled to allow a minimum of 4 participants to complete the study. All participants will receive a single oral solution dose of 50 to 140 mg ibrutinib containing 1480 kBq (40 µCi) of 14C labeled ibrutinib, constituting a total radiation burden of approximately 0.916 mSv (ICRP risk category IIa). The duration of the study is approximately 73 days including screening period of 28 days, treatment period of 15 days, and follow-up period of 30 days. Safety will include adverse events, laboratory safety, 12 lead electrocardiogram, physical examination, and vital signs.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Merksem, Belgium

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Participant must sign an informed consent document indicating they understand the purpose of and procedures required for the study, including DNA analysis, and are willing to participate in the study
• Must agree to use an adequate contraception method as deemed appropriate by the investigator (eg, vasectomy, double-barrier, partner using effective contraception) during the study and for 3 months after receiving the study drug
• Must agree to not donate sperm during the study and for 3 months after receiving the study drug
• Blood pressure (after the participant is supine for 5 minutes) between 90 and 140 mmHg systolic, inclusive, and no higher than 90 mmHg diastolic
• Non-smoker (not smoked for 6 months prior to screening)

Exclusion Criteria:

• History of or current clinically significant medical illness including cardiac arrhythmias or other cardiac disease, hematologic disease, coagulation disorders, lipid abnormalities, significant pulmonary disease, including bronchospastic respiratory disease, diabetes mellitus, renal or hepatic insufficiency, thyroid disease, neurologic or psychiatric disease
• Clinically significant abnormal values for hematology, coagulation and platelet function, clinical chemistry or urinalysis at screening as deemed appropriate by the investigator
• Clinically significant abnormal physical examination, vital signs or 12 lead electrocardiogram (ECG) at screening as deemed appropriate by the investigator
• History of clinically significant allergies, especially known hypersensitivity or intolerance to β-lactam antibiotics or sulfonamides
• Known allergy to heparin or history of heparin induced thrombocytopenia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ibrutinib; All participants will receive a single oral solution dose of 50 mg to 140 mg -ibrutinib containing 1480 kBq (40 µCi) of 14C-labeled ibrutinib, with a total radiation burden of approximately 0.916 mSv.	Drug: Ibrutinib; Type=exact number, unit=mg, number=50-140, form=solution, route=oral. Participants will receive a single oral solution dose of 50 mg to 140 mg -ibrutinib containing 1480 kBq (40 µCi) of 14C-labeled ibrutinib, with a total radiation burden of approximately 0.916 mSv.; Other Names: PCI-32765

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum concentration (Cmax) of ibrutinib	Pharmacokinetic parameter Cmax of ibrutinib will be determined.	Day 1 (Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 hours), Day 2 (24 hours), Day 3 (48 hours), Day 4 (72 hours)
Time to reach the maximum concentration (tmax) of ibrutinib	Pharmacokinetic parameter tmax of ibrutinib will be determined.	Predose, Day 1 (0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 hours), Day 2 (24 hours), Day 3 (48 hours), Day 4 (72 hours)
Area under the concentration-time curve (AUC) of ibrutinib	Pharmacokinetic parameter AUC of ibrutinib will be determined.	Predose, Day 1 (0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 hours), Day 2 (24 hours), Day 3 (48 hours), Day 4 (72 hours)
Amount excreted into the urine (Ae) of ibrutinib	Pharmacokinetic parameter Ae of ibrutinib will be determined by multiplying the urinary volume with the urinary concentration.	Day -1, Day 1 over intervals 0-2, 2-4, 4-8, 8-24, 24-48, 48-72, 72-96, 96-120, 120-144, 144-168 hours, Days 9-15

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of patients with adverse events	Up to 73 days

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Publications and helpful links

General Publications

• Scheers E, Leclercq L, de Jong J, Bode N, Bockx M, Laenen A, Cuyckens F, Skee D, Murphy J, Sukbuntherng J, Mannens G. Absorption, metabolism, and excretion of oral (1)(4)C radiolabeled ibrutinib: an open-label, phase I, single-dose study in healthy men. Drug Metab Dispos. 2015 Feb;43(2):289-97. doi: 10.1124/dmd.114.060061. Epub 2014 Dec 8.

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (Actual): September 1, 2012
• Study Completion (Actual): September 1, 2012

Study Registration Dates

• First Submitted: August 9, 2012
• First Submitted That Met QC Criteria: August 24, 2012
• First Posted (Estimate): August 28, 2012

Study Record Updates

• Last Update Posted (Estimate): November 5, 2014
• Last Update Submitted That Met QC Criteria: November 4, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Keywords: Healthy participants; Ibrutinib; B-cell malignancies; CYP3A4; PCI-32765
• Other Study ID Numbers: CR100885; PCI-32765CLL1004 (Other Identifier: Janssen Research & Development, LLC); 2012-002087-27 (EudraCT Number)