Clinical trial NCT02638116: A Drug Interaction Study to Assess the Effect of Omeprazole on the Pharmacokinetics of Ibrutinib in Healthy Adults
Official title: Open-Label, Sequential-Design Drug Interaction Study of the Effect of Omeprazole on the Pharmacokinetics of Ibrutinib in Healthy Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Ibrutinib
Proton pump inhibitors
Pharmacokinetics
Drug Interaction
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2015-12-22
Enrollment: 20
Sex: ALL
Minimum age (years): 18
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 evaluate the Effect of Omeprazole on the Pharmacokinetics of Ibrutinib in Healthy Adults.

Detailed description: This is an open-label (all people know the identity of the intervention), single-center, sequential-design drug interaction study to assess the effect of omeprazole on pharmacokinetics of ibrutinib and metabolite PCI-45227 in healthy participants. The study mainly consists of 3 Phases: Screening Phase (within 21 days prior to the first dose of study medication), treatment Phase, and a follow up Phase (10 to 12 days after the last dose of study medication). In the treatment Phase, participants will receive Ibrutinib 560 milligram (mg) orally (4 x 140 mg capsules) on Day 1 and Day 7. participants will receive Omeprazole at a dose of 40 mg tablets orally once on Days 3 through 7. The total duration of study for each participant will be approximately for 29 to 32 days. Blood samples will be collected for evaluation of pharmacokinetics of Ibrutinib. 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
* Willing to adhere to the prohibitions and restrictions specified in the protocol
* 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 (example, 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

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 (5th 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

Primary outcomes:
measure: Maximum Plasma Concentration (Cmax) of Ibrutinib
timeFrame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48 hours post-dose on Day 1 and Day 7
measure: Time to Reach the Maximum Plasma Concentration (Tmax) of Ibrutinib
timeFrame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48 hours post-dose on Day 1 and Day 7
measure: Area Under the Plasma Concentration-Time Curve From 0 to 48 Hours (AUC[0-48]) Post Dose of Ibrutinib
timeFrame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48 hours post-dose on Day 1 and Day 7
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, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48 hours post-dose on Day 1 and Day 7
measure: Metabolite to Parent (M/P) Ratio of Ibrutinib
timeFrame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48 hours post-dose on Day 1 and Day 7
Secondary outcomes:
measure: Maximum Plasma Concentration (Cmax) of PCI-45227
timeFrame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48 hours post-dose on Day 1 and Day 7
measure: Time to Reach the Maximum Plasma Concentration (Tmax) of PCI-45227
timeFrame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48 hours post-dose on Day 1 and Day 7
measure: Area Under the Plasma Concentration-Time Curve From 0 to 48 Hours (AUC[0-48]) Post Dose of PCI-45227
timeFrame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48 hours post-dose on Day 1 and Day 7
measure: Area Under the Plasma Concentration-Time Curve From Time 0 to Time of the Last Observed Quantifiable Concentration (AUC [0-last]) of PCI-45227
timeFrame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48 hours post-dose on Day 1 and Day 7
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, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: de Jong J, Haddish-Berhane N, Hellemans P, Jiao J, Sukbuntherng J, Ouellet D. The pH-altering agent omeprazole affects rate but not the extent of ibrutinib exposure. Cancer Chemother Pharmacol. 2018 Aug;82(2):299-308. doi: 10.1007/s00280-018-3613-9. Epub 2018 Jun 7.