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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03301207
• Date of registration: 29/09/2017
• Prospective Registration: Yes
• Primary sponsor: Janssen Research & Development, LLC
• Public title: 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
• Scientific title: 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
• Date of first enrolment: October 20, 2017
• Target sample size: 25
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03301207
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Other. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

Poland, Spain

Contacts

• Name: Janssen Research & Development, LLC Clinical Trial
• Affiliation: Janssen Research & Development, LLC

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: N/A
Gender: Female

Health Condition(s) or Problem(s) studied

Leukemia, Lymphocytic, Chronic, B-Cell

Intervention(s)

Drug: Bupropion

Drug: Ibrutinib

Drug: Midazolam

Drug: OC: Ethinylestradiol (EE) 30 mcg and Levonorgestrel (LN) 150 mcg

Primary Outcome(s)

Area Under the Plasma Concentration-Time Curve From Time Zero to Time 't' (AUC[0-t]) of Midazolam and 1-Hydroxymidazolam When Co-Administered With Repeat Doses of Ibrutinib [Time Frame: Day 3: predose, 15 min, and 0.5,1,2,3,4,5,6,8,10,12, and 24 h post-dose; Day 24: predose, 15 min, and 0.5,1,2,3,4,5,6,8,10, and 24 h post-dose]

Area Under the Plasma Concentration-Time Curve From Time Zero to Time 't' (AUC[0-t]) of EE and LN When Co-administered With Repeat Doses of Ibrutinib Compared to Administration Alone [Time Frame: Days 1 and 22: predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, and 72 h post-dose]

Area Under the Plasma Concentration-Time Curve From Time Zero to Time 't' (AUC[0-t]) of Midazolam and 1-Hydroxymidazolam When Co-Administered With Single Dose of Ibrutinib [Time Frame: Day 3: predose, 15 min, and 0.5,1,2,3,4,5,6,8,10,12, and 24 h post-dose; Day 8: predose, 15 min, and 0.5,1,2,3,4,5,6,8,10, and 12 h post-dose]

Maximum Observed Plasma Concentration (Cmax) of Bupropion and 4-Hydroxybupropion When Co-administered With Repeat Doses of Ibrutinib Compared to Administration Alone [Time Frame: Days 3 and 24: predose, 0.5, 1, 2, 3, 4, 6, 10, 24, 34, 48, 58 h post-dose]

Area Under the Plasma Concentration-Time Curve From Time Zero to Time 't' (AUC[0-t]) of Bupropion and 4-Hydroxybupropion When Co-administered With Repeat Doses of Ibrutinib Compared to Administration Alone [Time Frame: Days 3 and 24: predose, 0.5, 1, 2, 3, 4, 6, 10, 24, 34, 48, 58 h post-dose]

Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of EE and LN When Co-administered With Repeat Doses of Ibrutinib Compared to Administration Alone [Time Frame: Days 1 and 22: predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, and 72 h post-dose]

Maximum Observed Plasma Concentration (Cmax) of Ethinylestradiol (EE) and Levonorgestrel (LN) When Co-administered With Repeat Doses of Ibrutinib Compared to Administration Alone [Time Frame: Days 1 and 22: predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, and 72 hours (h) post-dose]

Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Bupropion and 4-Hydroxybupropion When Co-administered With Repeat Doses of Ibrutinib Compared to Administration Alone [Time Frame: Days 3 and 24: predose, 0.5, 1, 2, 3, 4, 6, 10, 24, 34, 48, 58 h post-dose]

Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Midazolam and 1-Hydroxymidazolam When Co-Administered With Repeat Doses of Ibrutinib [Time Frame: Day 3: predose, 15 min, and 0.5,1,2,3,4,5,6,8,10,12, and 24 h post-dose; Day 24: predose, 15 min, and 0.5,1,2,3,4,5,6,8,10, and 24 h post-dose]

Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Midazolam and 1-Hydroxymidazolam When Co-Administered With Single Dose of Ibrutinib [Time Frame: Day 3: predose, 15 min, and 0.5,1,2,3,4,5,6,8,10,12, and 24 h post-dose; Day 8: predose, 15 min, and 0.5,1,2,3,4,5,6,8,10, and 12 h post-dose]

Maximum Observed Plasma Concentration (Cmax) of Midazolam and 1-Hydroxymidazolam When Co-Administered With Repeat Doses of Ibrutinib [Time Frame: Day 3: predose, 15 minutes (min), and 0.5,1,2,3,4,5,6,8,10,12, and 24 h post-dose; Day 24: predose, 15 min, and 0.5,1,2,3,4,5,6,8,10, and 24 h post-dose]

Maximum Observed Plasma Concentration (Cmax) of Midazolam and 1-Hydroxymidazolam When Co-Administered With Single Dose of Ibrutinib [Time Frame: Day 3: predose, 15 min, and 0.5,1,2,3,4,5,6,8,10,12, and 24 h post-dose; Day 8: predose, 15 min, and 0.5,1,2,3,4,5,6,8,10, and 12 h post-dose]

Secondary Outcome(s)

Number of Participants With Vital Sign Abnormalities as a Measure of Safety and Tolerability [Time Frame: Screening, Days 8 and 36, and End of Treatment (approximately 7 months)]

Number of Participants With Electrocardiogram (ECG) Abnormalities Findings as a Measure of Safety and Tolerability [Time Frame: Screening and End of Treatment (approximately 7 months)]

Number of Participants With Laboratory Abnormalities as a Measure of Safety and Tolerability [Time Frame: Screening, Days 8 and 36, and End of Treatment (approximately 7 months)]

Number of Participants With Adverse Events as a Measure of Safety and Tolerability [Time Frame: Screening up to end of the 6 month treatment or 30 days after the last dose of study drug for Participants discontinuing treatment before 6 months]

Plasma Concentration of Ibrutinib and its Metabolite PCI-45227 [Time Frame: Predose, 1, 2, 4, and 6 h post-dose on Days 8, 22, and 24]

Secondary ID(s)

2017-000496-84

54179060CLL1017

CR108347

Source(s) of Monetary Support

Please refer to primary and secondary sponsors