Clinical trial NCT01674322: A Study to Determine the Absorption, Metabolism, and Routes of Excretion of (14C) Radiolabeled Ibrutinib in Healthy Male Participants
Official title: An Open-Label Phase 1 Study to Determine the Pharmacokinetics, Metabolism, and Routes of Excretion of (14C) Radiolabeled PCI-32765 in Healthy Male Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Participants
Keywords: Healthy participants
Ibrutinib
PCI-32765
B-cell malignancies
CYP3A4
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2012-08-28
Enrollment: 6
Sex: MALE
Minimum age (years): 30
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Maximum concentration (Cmax) of ibrutinib
timeFrame: 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)
measure: Time to reach the maximum concentration (tmax) of ibrutinib
timeFrame: 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)
measure: Area under the concentration-time curve (AUC) of ibrutinib
timeFrame: 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)
measure: Amount excreted into the urine (Ae) of ibrutinib
timeFrame: 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 outcomes:
measure: Number of patients with adverse events
timeFrame: Up to 73 days
Other outcomes:
Locations:
city: Merksem
country: Belgium
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: 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.