NCT03301207

A Study to Evaluate the Effect of Ibrutinib on the Pharmacokinetics of Oral Contraceptives, CYP2B6, and CYP3A4 Substrates in Female Participants With B Cell Malignancy

A Drug-Drug Interaction Study to Evaluate the Effect of Ibrutinib on the Pharmacokinetics of Oral Contraceptives, CYP2B6, and CYP3A4 Substrates in Female Subjects With B Cell Malignancy

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 25 (actual)
• Sponsor: Janssen Research & Development, LLC · Industry
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The main purpose of this study is to evaluate the effects of repeat dosing of ibrutinib on the single-dose pharmacokinetics (PK) of oral contraceptives (OC - ethinylestradiol \[EE\] and levonorgestrel \[LN\]), the cytochrome P450 (CYP)2B6 probe bupropion and the CYP3A4 probe midazolam; and to evaluate the effects of single-dose ibrutinib on the single-dose PK of the CYP3A4 probe midazolam in female participants with B cell malignancy.

Detailed description

This is a multicenter study of ibrutinib (first-in-class, potent, covalently-binding inhibitor of Bruton's tyrosine kinase \[BTK\]) in female participants with B cell malignancy. The study consists of 3 phases: Screening Phase (up to 28 days), 7-day Pretreatment Phase (Days 1 to 7), Treatment Phase including PK assessment period (Days 8 to 26) and a Follow-up Phase (Day 27 to end of Cycle 6). The study procedures includes electrocardiogram (ECG), vital signs, blood samples withdrawal to evaluate PK and safety. The Antitumor activity will be assessed by means of computed tomography (CT) imaging and positron emission tomography (PET) scans. No formal statistical hypothesis will be tested. This is an estimation study designed to determine if an increase or decrease in exposure to OC or probe drugs occurs in the presence of ibrutinib.

Conditions

• Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Type	Name	Description
DRUG	Ibrutinib	Ibrutinib capsule (at dose of 420 or 560 mg) will be taken orally QD.
DRUG	OC: Ethinylestradiol (EE) 30 mcg and Levonorgestrel (LN) 150 mcg	Single dose of oral contraceptives (OC) (1 tablet containing 30 mcg EE and 150 mcg LN) will be taken orally on Study Days 1 and 22.
DRUG	Bupropion	Bupropion 75 mg tablet as a part of CYP cocktail will be taken on Study Days 3 and 24.
DRUG	Midazolam	Midazolam 2 mg (1 milliliter \[mL\]) oral solution will be taken on Study Days 3 and 24 (as a part of CYP cocktail) and on Study Day 8 (alone).

Timeline

• Start date: 2017-10-20
• Primary completion: 2018-07-17
• Completion: 2018-12-04
• First posted: 2017-10-04
• Last updated: 2019-12-05

Locations

4 sites across 2 countries: Poland, Spain

Regulatory

• FDA-regulated drug study