Study to Assess the Bioequivalence of Ibrutinib 560- Milligram (mg) Tablet to Four 140 -mg IMBRUVICA Capsules

A Single-Dose, Open-Label, Randomized, Replicate Crossover Study in Healthy Adult Subjects to Assess the Bioequivalence of an Ibrutinib 560-mg Tablet Compared to the Four IMBRUVICA 140 mg Capsules

The purpose of this study is to demonstrate the bioequivalence (BE) of a new formulation of ibrutinib to the marketed Imbruvica formulation in healthy adults under fasted conditions.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: IMBRUVICA (Treatment A); Drug: Ibrutinib (Treatment B)

• Study Type: Interventional
• Enrollment (Actual): 102
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tempe, Arizona, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 53 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Signed an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study and is willing to participate in the study, before any study related procedures take place
• Willing and able to adhere to the prohibitions and restrictions specified in the protocol
• If a woman, must be of non-childbearing potential, defined as either: a) Postmenopausal: A postmenopausal state is defined as no menses for at least 12 months without an alternative medical cause and a serum follicle stimulating hormone (FSH) level in the postmenopausal range (greater than [>]40 international units per liter [IU/L] or milliinternational units per milliliter [mIU/mL]). b) Permanently sterile: Permanent sterilization methods include hysterectomy, bilateral salpingectomy, bilateral tubal occlusion/ligation procedures (without reversal operation), bilateral oophorectomy, and/or transcervical sterilization
• If a woman, must have a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test at screening and on Day -1 of each treatment period
• Non-smoker for at least 2 months prior to screening

Exclusion Criteria:

• Use of any prescription or nonprescription medication (including vitamins and herbal supplements), except for acetaminophen/paracetamol, topical therapies, and hormone replacement therapy within 14 days before the first dose of the study drug is scheduled
• History of clinically significant allergies, especially known hypersensitivity or intolerance to sulfonamide or beta-lactam antibiotics
• Known allergy to the study drug or any of the excipients of the formulation
• Unable to swallow solid, oral dosage forms whole with the aid of water (participants may not chew, divide, dissolve, or crush the study drug)
• Positive test for human immunodeficiency virus type 1 (HIV-1) or HIV-2 antibodies at screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Sequence 1; Participants will receive treatment A, on Day 1 of Intervention Period 1 followed by treatment B , on Day 1 of Intervention Period 2 followed by treatment A, Day 1 of Intervention Period 3 and then followed by treatment B, on Day 1 of Intervention Period 4. Each intervention Period will be separated by a washout period of 7-9 days.	Drug: IMBRUVICA (Treatment A); IMBRUVICA (reference treatment), 4*140 milligram (mg), capsules.; Other Names: Ibrutinib; Drug: Ibrutinib (Treatment B); Ibrutinib (test treatment), 1*560 mg, tablet.
Experimental: Treatment Sequence 2; Participants will receive treatment B, on Day 1 of Intervention Period 1 followed by treatment A, on Day 1 of Intervention Period 2 followed by treatment B, Day 1 of Intervention Period 3 and then followed by treatment A, on Day 1 of Intervention Period 4. Each intervention Period will be separated by a washout period of 7-9 days.	Drug: IMBRUVICA (Treatment A); IMBRUVICA (reference treatment), 4*140 milligram (mg), capsules.; Other Names: Ibrutinib; Drug: Ibrutinib (Treatment B); Ibrutinib (test treatment), 1*560 mg, tablet.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Plasma Concentration (Cmax) of Ibrutinib	The Cmax is the maximum observed plasma concentration.	Day 1 (Pre-dose) up to Day 3
Time to reach maximum concentration (tmax) of Ibrutinib	The Tmax is defined as actual sampling time to reach maximum observed analyte concentration.	Day 1 (Pre-dose) up to Day 3
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-last]) of Ibrutinib	The AUC (0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable time.	Day 1 (Pre-dose) up to Day 3
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of Ibrutinib	The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C(last)/lambda(z); wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant.	Day 1 (Pre-dose) up to Day 3
Elimination Rate Constant (Lambda[z]) of Ibrutinib	Lambda(z) is first-order elimination rate constant associated with the terminal portion of the curve, determined as the negative slope of the terminal log-linear phase of the drug concentration-time curve.	Day 1 (Pre-dose) up to Day 3
Terminal Half-Life (t[1/2]) of Ibrutinib	The elimination half-life (t1/2) is the time measured for the plasma concentration to decrease by 1 half to its original concentration. It is associated with the terminal slope of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z).	Day 1 (Pre-dose) up to Day 3
Maximum Plasma Concentration (Cmax) of IMBRUVICA	The Cmax is the maximum observed plasma concentration.	Day 1 (Pre-dose) up to Day 3
Time to reach maximum concentration (tmax) of IMBRUVICA	The Tmax is defined as actual sampling time to reach maximum observed analyte concentration.	Day 1 (Pre-dose) up to Day 3
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-last]) of IMBRUVICA	The AUC (0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable time.	Day 1 (Pre-dose) up to Day 3
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of IMBRUVICA	The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C(last)/lambda(z); wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant.	Day 1 (Pre-dose) up to Day 3
Elimination Rate Constant (Lambda[z]) of IMBRUVICA	Lambda(z) is first-order elimination rate constant associated with the terminal portion of the curve, determined as the negative slope of the terminal log-linear phase of the drug concentration-time curve.	Day 1 (Pre-dose) up to Day 3
Terminal Half-Life (t[1/2]) of IMBRUVICA	The elimination half-life (t1/2) is the time measured for the plasma concentration to decrease by 1 half to its original concentration. It is associated with the terminal slope of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z).	Day 1 (Pre-dose) up to Day 3

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of participants with adverse events and serious adverse events as a measure of safety and tolerability	Baseline up to 14 days after last dose of study drug (Day 17)

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2016
• Primary Completion (Actual): August 1, 2016
• Study Completion (Actual): August 1, 2016

Study Registration Dates

• First Submitted: June 15, 2016
• First Submitted That Met QC Criteria: July 19, 2016
• First Posted (Estimate): July 22, 2016

Study Record Updates

• Last Update Posted (Actual): March 29, 2018
• Last Update Submitted That Met QC Criteria: March 28, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Other Study ID Numbers: CR108171; 54179060CLL1021 (Other Identifier: Janssen Research & Development, LLC)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes