A Drug Interaction Study to Assess the Effect of Omeprazole on the Pharmacokinetics of Ibrutinib in Healthy Adults

• ClinicalTrials.gov Identifier: NCT02638116
• Recruitment Status: Completed
• First Posted: December 22, 2015
• Last Update Posted: April 15, 2016
• Sponsor: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Janssen Research & Development, LLC

Study Description

Brief Summary:

The purpose of this study is to evaluate the Effect of Omeprazole on the Pharmacokinetics of Ibrutinib in Healthy Adults.

Condition or disease	Intervention/treatment	Phase
Healthy	Drug: Ibrutinib; Drug: Omeprazole	Phase 1

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Open-Label, Sequential-Design Drug Interaction Study of the Effect of Omeprazole on the Pharmacokinetics of Ibrutinib in Healthy Adults
• Study Start Date: January 2016
• Actual Primary Completion Date: March 2016
• Actual Study Completion Date: March 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: Ibrutinib + Omeprazole; Participants will receive a dose of Ibrutinib 560 milligram (mg) orally (4 x 140 mg capsules) on Day 1 and Day 7 and Omeprazole at a dose of 40 mg tablets orally once on Days 3 through 7.	Drug: Ibrutinib; Ibrutinib will be administered at a dose of 560 milligram (mg) orally (4 x 140 mg capsules) on Day 1 and Day 7.; Drug: Omeprazole; Omeprazole will be administered at dose of 40 mg tablets orally once daily from Day 3 to Day 7.

Outcome Measures

Primary Outcome Measures :

1. Maximum Plasma Concentration (Cmax) of Ibrutinib [ Time Frame: 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 ]
   The Cmax is the maximum observed plasma concentration of Ibrutinib.
2. Time to Reach the Maximum Plasma Concentration (Tmax) of Ibrutinib [ Time Frame: 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 ]
   The Tmax is the time to reach the maximum observed plasma concentration of Ibrutinib.
3. Area Under the Plasma Concentration-Time Curve From 0 to 48 Hours (AUC[0-48]) Post Dose of Ibrutinib [ Time Frame: 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 ]
   The AUC (0-48hrs) is the area under the plasma Ibrutinib concentration-time curve from 0 to 48 hours post dosing.
4. Area Under the Plasma Concentration-Time Curve From Time 0 to Time of the Last Observed Quantifiable Concentration (AUC [0-last]) of Ibrutinib [ Time Frame: 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 ]
   The AUC (0-last) is the area under the plasma Ibrutinib concentration-time curve from time 0 to time of the last observed quantifiable concentration (C[last]).
5. Metabolite to Parent (M/P) Ratio of Ibrutinib [ Time Frame: 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 ]
   Ratio of ibrutinib metabolite concentration to parent compound (ibrutinib) concentration will be assessed.

Secondary Outcome Measures :

1. Maximum Plasma Concentration (Cmax) of PCI-45227 [ Time Frame: 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 ]
   The Cmax is the maximum observed plasma concentration of PCI-45227.
2. Time to Reach the Maximum Plasma Concentration (Tmax) of PCI-45227 [ Time Frame: 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 ]
   The Tmax is the time to reach the maximum observed plasma concentration of PCI-45227.
3. Area Under the Plasma Concentration-Time Curve From 0 to 48 Hours (AUC[0-48]) Post Dose of PCI-45227 [ Time Frame: 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 ]
   The AUC (0-48hrs) is the area under the plasma PCI-45227 concentration-time curve from 0 to 48 hours post dosing.
4. Area Under the Plasma Concentration-Time Curve From Time 0 to Time of the Last Observed Quantifiable Concentration (AUC [0-last]) of PCI-45227 [ Time Frame: 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 ]
   The AUC (0-last) is the area under the plasma PCI-45227 concentration-time curve from time 0 to time of the last observed quantifiable concentration (C[last]).
5. Number of Participants with Adverse Events (AEs) and Serious AEs [ Time Frame: Screening up to follow-up (10 plus [+] / minus [-] 2 days after last dose administration) ]
   An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

Belgium

Antwerpen, Belgium

Sponsors and Collaborators

Janssen Research & Development, LLC

Investigators

• Study Director: Janssen Research & Development, LLC Clinical Trial; Janssen Research & Development, LLC

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Janssen Research & Development, LLC
• ClinicalTrials.gov Identifier: NCT02638116
• Other Study ID Numbers: CR108106; 2015-005015-32 ( EudraCT Number ); PCI-32765CLL1005 ( Other Identifier: Janssen Research & Development, LLC )
• First Posted: December 22, 2015
• Last Update Posted: April 15, 2016
• Last Verified: April 2016

Keywords provided by Janssen Research & Development, LLC:

Ibrutinib; Proton pump inhibitors; Pharmacokinetics; Drug Interaction

Additional relevant MeSH terms:

Omeprazole; Anti-Ulcer Agents; Gastrointestinal Agents; Proton Pump Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action