Clinical trial NCT02390609: A Crossover Study to Evaluate the Bioavailability of Ibrutinib Suspension and Sprinkle Formulations Compared to Capsules in Healthy Adults
Official title: Open-Label, Randomized, Parallel Group, 3- or 4-Way Crossover Bioavailability Study of Ibrutinib Suspension and Sprinkle Formulations Compared to Capsules in Healthy Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Healthy
Ibrutinib
Bioavailability
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2015-03-17
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the relative bioavailability (the extent to which a drug or other substance becomes available to the body) of ibrutinib in healthy adults following single oral dose administration of suspension and sprinkle formulations under fed and fasted conditions compared with capsules under fasted conditions.

Detailed description: This is an open-label (all people know the identity of the intervention), randomized (study medication assigned to participants by chance), 3- or 4-way crossover (participants may receive different interventions sequentially during the trial), and single-center study of ibrutinib. The duration of study will be approximately 67 to 83 days per participant. The study consists of 3 parts: Screening (28 days before study commences on Day 1); Open-label Treatment (consists of 6 treatments, either Ibrutinib capsule or suspension or sprinkle capsule granules under fed or fasted condition), in subsequent 3 periods for Group 1 and 4 periods for Group 2, each separated with washout period of 7 (plus \[+\] / minus \[-\] 2) days; and follow up Phase (up to 10 + / - 2 days after last study drug administration). All the eligible participants will be randomly assigned to 1 of the 6 (Group 1) or 4 (Group 2) treatment sequences. In fasted conditions, study drug will be administered following a 10-hour overnight fast. In fed conditions, participants will also fast from food for 10 hours, but will consume a high fat breakfast within a 30-minute period. Study drug will be administered 2 hours after the breakfast. Participants will not be allowed to have food until 4 hours of drug administration. Blood samples will be collected for evaluation of pharmacokinetics at pre-dose and post-dose of study treatment. Relative bioavailability of Ibrutinib will be evaluated primarily. Participants' safety will be monitored throughout the study.

Eligibility criteria: Inclusion Criteria:

* Signed an informed consent document indicating they understand the purpose of and procedures required for the study and are willing to participate in the study
* If a woman, must not be of childbearing potential: postmenopausal ( greater than \[\>\] 45 years of age with amenorrhea for at least 2 years, or any age with amenorrhea for at least 6 months and a serum follicle stimulating hormone (FSH) \>40 International units \[IU\]/ Liter \[L\]); surgically sterile
* If a woman, must have a negative serum β-human chorionic gonadotropin (hCG) pregnancy test at Screening and a negative urine pregnancy test on Day-1 of the each treatment period
* If a man who is sexually active with a woman of childbearing potential and has not had a vasectomy, must agree to use an adequate contraception method as deemed appropriate by the investigator (eg, vasectomy, double-barrier, partner using effective contraception) and to not donate sperm during the study and for 3 months after receiving the last dose of study drug
* Body mass index (BMI; weight \[kg\]/height\^2 \[m\]\^2) between 18 and 30 Kilogram (kg)/ meter\^2 (m\^2) (inclusive), and body weight not less than 50 kg

Exclusion Criteria:

* History of or current clinically significant medical illness including (but not limited to) cardiac arrhythmias or other cardiac disease, hematologic disease, coagulation disorders (including any abnormal bleeding or blood dyscrasias), lipid abnormalities, significant pulmonary disease, including bronchospastic respiratory disease, diabetes mellitus, hepatic or renal insufficiency (creatinine clearance below 60 milliliter \[mL\]/ minute \[min\]), thyroid disease, neurologic or psychiatric disease, infection, or any other illness that the investigator considers should exclude the participant or that could interfere with the interpretation of the study results
* Clinically significant abnormal values for hematology, coagulation, clinical chemistry, 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
* Use of any prescription or nonprescription medication (including vitamins and herbal supplements), except for paracetamol and hormonal replacement therapy within 14 days before the first dose of the study drug is scheduled until completion of the study
* History of drug or alcohol abuse according to Diagnostic and Statistical Manual of Mental Disorders (4th edition) (DSM-IV) criteria within 2 years before Screening or positive test result(s) for alcohol and/or drugs of abuse (such as barbiturates, opiates, cocaine, cannabinoids, amphetamines, and benzodiazepines) at Screening and Day-1 of the each treatment period

Primary outcomes:
measure: Maximum Plasma Concentration (Cmax) of Ibrutinib
timeFrame: Pre-dose; 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose on Day 1 of each period
measure: Time to Reach the Maximum Plasma Concentration (Tmax) of Ibrutinib
timeFrame: Pre-dose; 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose on Day 1 of each period
measure: Area Under the Plasma Concentration-Time Curve From 0 to 24 Hours (AUC[0-24]) Post Dose of Ibrutinib
timeFrame: Pre-dose; 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose on Day 1 of each period
measure: Area Under the Plasma Concentration-Time Curve From Time 0 to Time of the Last Observed Quantifiable Concentration (AUC [0-last]) of Ibrutinib
timeFrame: Pre-dose; 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose on Day 1 of each period
measure: Area Under the Plasma Concentration-Time Curve From 0 to Infinite Time (AUC[0-infinity]) Post Dose of Ibrutinib
timeFrame: Pre-dose; 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose on Day 1 of each period
measure: Percentage of Area Under the Plasma Concentration-Time Curve Obtained by Extrapolation (%AUC[infinity,ex])
timeFrame: Pre-dose; 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose on Day 1 of each period
measure: Terminal Half-life (t[1/2]) of Ibrutinib
timeFrame: Pre-dose; 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose on Day 1 of each period
measure: Elimination Rate Constant (Lambda [z]) of Ibrutinib
timeFrame: Pre-dose; 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose on Day 1 of each period
measure: Adjusted Coefficient of Determination (r^2 [adjusted])
timeFrame: Pre-dose; 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose on Day 1 of each period
measure: Relative Bioavailability (Frel) of Ibrutinib
timeFrame: Pre-dose; 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose on Day 1 of each period
measure: Metabolite to Parent Ratio for Maximum Plasma Concentration (Cmax) of Ibrutinib
timeFrame: Pre-dose; 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose on Day 1 of each period
Secondary outcomes:
measure: Number of Participants with Adverse Events (AEs) and Serious AEs
timeFrame: Screening up to follow-up (10 plus [+] / minus [-] 2 days after last dose administration)
Other outcomes:
Locations:
city: Antwerpen
country: Belgium
Study officials:
affiliation: Janssen Research & Development
name: Janssen Research & Development Clinical Trial
role: STUDY_DIRECTOR
References: