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

• Status: Completed
• Trial end date: 2018-12-04
• Target enrollment: 0
• Participant gender: Female

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Janssen Research & Development, LLC
• Treatments: Bupropion; Contraceptive Agents; Contraceptives, Oral; Ethinyl Estradiol; Ethinyl estradiol, levonorgestrel drug combination; Levonorgestrel; Midazolam

Criteria

Inclusion Criteria:

• Histologically or cytologically confirmed chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), or Waldenstrom's macroglobulinemia (WM)

1. Participants with MCL must have relapsed or refractory disease after at least 1 prior line of systemic therapy

2. Participants with MZL must have failed an anti-cluster of differentiation (CD)20 monoclonal antibody-based therapy

• Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1

• Adequate hematologic, hepatic, and renal functions

• Before the first dose of oral contraceptive (OC), a woman must be either:

1. Not of childbearing potential: postmenopausal (greater than [>]45 years of age with amenorrhea for at least 12 months and a serum follicle stimulating hormone level >40 international unit per Liter [IU/L] or milli international unit per milli Liter [mIU/mL]); permanently sterilized

2. Of childbearing potential and practicing a highly effective non-hormonal method of birth control

• Women of childbearing potential must have a negative serum (Beta-human chorionic gonadotropin [Beta-hCG]) or urine pregnancy test at screening

Exclusion Criteria:

• Major surgery planned within 2 weeks of the first dose of ibrutinib or during study participation up to Cycle 2 Day 1

• History of other malignancies, except:

1. Malignancy treated with curative intent and with no known active disease present for greater than or equal to (>=)3 years before the first dose of ibrutinib and felt to be at low risk for recurrence by treating physician

2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease

3. Adequately treated in-situ cancer without evidence of disease

• History of breast or endometrial cancer

• Prior treatment/exposure with ibrutinib or other Bruton's tyrosine kinase (BTK) inhibitor

• Requires ongoing anticoagulation treatment with warfarin or equivalent vitamin K antagonists (for example, phenprocoumon)

• Requires therapies that must be discontinued or substituted 7 days prior to Study Day 1, or must be temporally interrupted during the course of the study, including the following:

1. Medications known to induce or inhibit drug metabolizing enzymes (CYP3A4 and CYP2B6)

2. Medication which are not allowed to be used in combination with EE, LN, bupropion, or midazolam