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

• ClinicalTrials.gov Identifier: NCT02841150
• Recruitment Status: Completed
• First Posted: July 22, 2016
• Last Update Posted: March 29, 2018
• Sponsor: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Janssen Research & Development, LLC

Tracking Information

• First Submitted Date: June 15, 2016
• First Posted Date: July 22, 2016
• Last Update Posted Date: March 29, 2018
• Actual Study Start Date: June 2016
• Actual Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 19, 2016)

• Maximum Plasma Concentration (Cmax) of Ibrutinib [ Time Frame: Day 1 (Pre-dose) up to Day 3 ]
  The Cmax is the maximum observed plasma concentration.
• Time to reach maximum concentration (tmax) of Ibrutinib [ Time Frame: Day 1 (Pre-dose) up to Day 3 ]
  The Tmax is defined as actual sampling time to reach maximum observed analyte concentration.
• Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-last]) of Ibrutinib [ Time Frame: Day 1 (Pre-dose) up to Day 3 ]
  The AUC (0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable time.
• Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of Ibrutinib [ Time Frame: Day 1 (Pre-dose) up to Day 3 ]
  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.
• Elimination Rate Constant (Lambda[z]) of Ibrutinib [ Time Frame: Day 1 (Pre-dose) up to Day 3 ]
  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.
• Terminal Half-Life (t[1/2]) of Ibrutinib [ Time Frame: Day 1 (Pre-dose) up to Day 3 ]
  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).
• Maximum Plasma Concentration (Cmax) of IMBRUVICA [ Time Frame: Day 1 (Pre-dose) up to Day 3 ]
  The Cmax is the maximum observed plasma concentration.
• Time to reach maximum concentration (tmax) of IMBRUVICA [ Time Frame: Day 1 (Pre-dose) up to Day 3 ]
  The Tmax is defined as actual sampling time to reach maximum observed analyte concentration.
• Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-last]) of IMBRUVICA [ Time Frame: Day 1 (Pre-dose) up to Day 3 ]
  The AUC (0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable time.
• Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of IMBRUVICA [ Time Frame: Day 1 (Pre-dose) up to Day 3 ]
  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.
• Elimination Rate Constant (Lambda[z]) of IMBRUVICA [ Time Frame: Day 1 (Pre-dose) up to Day 3 ]
  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.
• Terminal Half-Life (t[1/2]) of IMBRUVICA [ Time Frame: Day 1 (Pre-dose) up to Day 3 ]
  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).

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures (submitted: July 19, 2016): Number of participants with adverse events and serious adverse events as a measure of safety and tolerability [ Time Frame: Baseline up to 14 days after last dose of study drug (Day 17) ]
• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study to Assess the Bioequivalence of Ibrutinib 560- Milligram (mg) Tablet to Four 140 -mg IMBRUVICA Capsules
• Official Title: 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
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: None (Open Label); Primary Purpose: Other
• Condition: Healthy

Intervention

• Drug: IMBRUVICA (Treatment A)
  IMBRUVICA (reference treatment), 4*140 milligram (mg), capsules.
  Other Name: Ibrutinib
• Drug: Ibrutinib (Treatment B)
  Ibrutinib (test treatment), 1*560 mg, tablet.

Study Arms

• 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.
  Interventions:

  • Drug: IMBRUVICA (Treatment A)
  • Drug: Ibrutinib (Treatment B)
• 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.
  Interventions:

  • Drug: IMBRUVICA (Treatment A)
  • Drug: Ibrutinib (Treatment B)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 19, 2016): 102
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: August 2016
• Actual Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 55 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02841150
• Other Study ID Numbers: CR108171; 54179060CLL1021 ( Other Identifier: Janssen Research & Development, LLC )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes

• IPD Sharing Statement: Not Provided
• Responsible Party: Janssen Research & Development, LLC
• Study Sponsor: Janssen Research & Development, LLC
• Collaborators: Not Provided

Investigators

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

• PRS Account: Janssen Research & Development, LLC
• Verification Date: March 2018