A Crossover Study to Evaluate the Bioavailability of Ibrutinib Suspension and Sprinkle Formulations Compared to Capsules in Healthy Adults

NCT02390609 | Completed Phase 1

• 3 other identifiers: CR1069462015-000155-25PCI-32765CLL1015
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Keywords

Healthy; Ibrutinib; Bioavailability

Outcome Measures

Primary Outcomes (11)

• Maximum Plasma Concentration (Cmax) of Ibrutinib

  The Cmax is the maximum observed plasma concentration of Ibrutinib.

  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

• Time to Reach the Maximum Plasma Concentration (Tmax) of Ibrutinib

  The Tmax is the time to reach the maximum observed plasma concentration of Ibrutinib.

  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

• Area Under the Plasma Concentration-Time Curve From 0 to 24 Hours (AUC[0-24]) Post Dose of Ibrutinib

  The AUC (0-24hrs) is the area under the plasma Ibrutinib concentration-time curve from 0 to 24 hours post dosing.

  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

• Area Under the Plasma Concentration-Time Curve From Time 0 to Time of the Last Observed Quantifiable Concentration (AUC [0-last]) of Ibrutinib

  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\[last\]).

  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

• Area Under the Plasma Concentration-Time Curve From 0 to Infinite Time (AUC[0-infinity]) Post Dose of Ibrutinib

  The AUC (0-infinity) is the area under the plasma Ibrutinib concentration-time curve from time 0 to infinite time, calculated as the sum of AUC (0-last) and C(last)/lambda(z), in which AUC(0-last) is area under the plasma Ibrutinib concentration-time curve from time zero to time of the last quantifiable concentration, C(last) is the last observed quantifiable concentration and lambda(z) is elimination rate constant.

  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

• Percentage of Area Under the Plasma Concentration-Time Curve Obtained by Extrapolation (%AUC[infinity,ex])

  The %AUC(infinity,ex) is calculated by dividing the difference of AUC(0-infinity) and AUC(0-last) by AUC(0-infinity) and then multiplying by 100, (AUC\[0-infinity\] - AUC\[0-last\])\*100/AUC\[0-infinity\].

  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

• Terminal Half-life (t[1/2]) of Ibrutinib

  The t(1/2) is defined as 0.693/Lambda (z).

  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

• Elimination Rate Constant (Lambda [z]) of Ibrutinib

  The Lambda (z) determined by linear regression of the terminal points of the ln-linear plasma concentration-time curve.

  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

• Adjusted Coefficient of Determination (r^2 [adjusted])

  The r\^2 \[adjusted\] for the number of points used in the estimation of lambda\[z\].

  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

• Relative Bioavailability (Frel) of Ibrutinib

  The Frel will be calculated as individual Cmax and AUC treatment ratios (for the comparison of food effect). Calculated as: \[(AUC\[0-infinity\]\[test\]/AUC\[0-infinity\]\[ref\])\*(Dose\[ref\]/Dose\[test\])\]\*100.

  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

• Metabolite to Parent Ratio for Maximum Plasma Concentration (Cmax) of Ibrutinib

  Metabolite to parent drug ratio for maximum observed plasma concentration of Ibrutinib.

  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 (1)

• Number of Participants with Adverse Events (AEs) and Serious AEs

  Screening up to follow-up (10 plus [+] / minus [-] 2 days after last dose administration)

Study Arms (10)

Group 1: Sequence 1 (ABC)

EXPERIMENTAL

Participants will receive Treatment A (Ibrutinib 560 milligram \[mg\] capsules \[reference\] under fasted conditions) in Period 1; followed by Treatment B (Ibrutinib 560 mg suspension under fasted conditions) in Period 2; followed by Treatment C (Ibrutinib 560 mg suspension under fed conditions) in Period 3. A washout period of 7 (plus \[+\] / minus \[-\] 2) days will be maintained between each treatment period.

Drug: Ibrutinib (Treatment A) [Reference]; Drug: Ibrutinib (Treatment B); Drug: Ibrutinib (Treatment C)

Group 1: Sequence 2 (BCA)

EXPERIMENTAL

Participants will receive Treatment B (Ibrutinib 560 mg suspension under fasted conditions) in Period 1; followed by Treatment C (Ibrutinib 560 mg suspension under fed conditions) in Period 2; followed by Treatment A (Ibrutinib 560 mg capsules \[reference\] under fasted conditions) in Period 3. A washout period of 7 (+/- 2) days will be maintained between each treatment period.

Drug: Ibrutinib (Treatment A) [Reference]; Drug: Ibrutinib (Treatment B); Drug: Ibrutinib (Treatment C)

Group 1: Sequence 3 (CAB)

EXPERIMENTAL

Participants will receive Treatment C (Ibrutinib 560 mg suspension under fed conditions) in Period 1; followed by Treatment A (Ibrutinib 560 mg capsules \[reference\] under fasted conditions) in Period 2; followed by Treatment B (Ibrutinib 560 mg suspension under fasted conditions) in Period 3. A washout period of 7 (+/- 2) days will be maintained between each treatment period.

Drug: Ibrutinib (Treatment A) [Reference]; Drug: Ibrutinib (Treatment B); Drug: Ibrutinib (Treatment C)

Group 1: Sequence 4 (ACB)

EXPERIMENTAL

Participants will receive Treatment A (Ibrutinib 560 mg capsules \[reference\] under fasted conditions) in Period 1; followed by Treatment C (Ibrutinib 560 mg suspension under fed conditions) in Period 2; followed by Treatment B (Ibrutinib 560 mg suspension under fasted conditions) in Period 3. A washout period of 7 (+/- 2) days will be maintained between each treatment period.

Drug: Ibrutinib (Treatment A) [Reference]; Drug: Ibrutinib (Treatment B); Drug: Ibrutinib (Treatment C)

Group 1: Sequence 5 (BAC)

EXPERIMENTAL

Participants will receive Treatment B (Ibrutinib 560 mg suspension under fasted conditions) in Period 1; followed by Treatment A (Ibrutinib 560 mg capsules \[reference\] under fasted conditions) in Period 2; followed by Treatment C (Ibrutinib 560 mg suspension under fed conditions) in Period 3. A washout period of 7 (+/- 2) days will be maintained between each treatment period.

Drug: Ibrutinib (Treatment A) [Reference]; Drug: Ibrutinib (Treatment B); Drug: Ibrutinib (Treatment C)

Group 1: Sequence 6 (CBA)

EXPERIMENTAL

Participants will receive Treatment C (Ibrutinib 560 mg suspension under fed conditions) in Period 1; followed by Treatment B (Ibrutinib 560 mg suspension under fasted conditions) in Period 2; followed by Treatment A (Ibrutinib 560 mg capsules \[reference\] under fasted conditions) in Period 3. A washout period of 7 (+/- 2) days will be maintained between each treatment period.

Drug: Ibrutinib (Treatment A) [Reference]; Drug: Ibrutinib (Treatment B); Drug: Ibrutinib (Treatment C)

Group 2: Sequence 1 (AFDE)

EXPERIMENTAL

Participants will receive Treatment A (Ibrutinib 560 mg capsules \[reference\] under fasted conditions) in Period 1; followed by Treatment F (Ibrutinib 560 mg sprinkle capsule granules suspended in water under fasted conditions) in Period 2; followed by Treatment D (Ibrutinib 560 mg sprinkle capsule granules under fasted conditions) in Period 3; followed by Treatment E (Ibrutinib 560 mg sprinkle capsule granules under fed conditions) in Period 4. A washout period of 7 (+/- 2) days will be maintained between each treatment period.

Drug: Ibrutinib (Treatment A) [Reference]; Drug: Ibrutinib (Treatment D); Drug: Ibrutinib (Treatment E); Drug: Ibrutinib (Treatment F)

Group 2: Sequence 2 (DAEF)

EXPERIMENTAL

Participants will receive Treatment D (Ibrutinib 560 mg sprinkle capsule granules under fasted conditions) in Period 1; followed by Treatment A (Ibrutinib 560 mg capsules \[reference\] under fasted conditions) in Period 2; followed by Treatment E (Ibrutinib 560 mg sprinkle capsule granules under fed conditions) in Period 3; followed by Treatment F (Ibrutinib 560 mg sprinkle capsule granules suspended in water under fasted conditions) in Period 4. A washout period of 7 (+/- 2) days will be maintained between each treatment period.

Drug: Ibrutinib (Treatment A) [Reference]; Drug: Ibrutinib (Treatment D); Drug: Ibrutinib (Treatment E); Drug: Ibrutinib (Treatment F)

Group 2: Sequence 3 (EDFA)

EXPERIMENTAL

Participants will receive Treatment E (Ibrutinib 560 mg sprinkle capsule granules under fed conditions) in Period 1; followed by Treatment D (Ibrutinib 560 mg sprinkle capsule granules under fasted conditions) in Period 2; followed by Treatment F (Ibrutinib 560 mg sprinkle capsule granules suspended in water under fasted conditions) in Period 3; followed by Treatment A (Ibrutinib 560 mg capsules \[reference\] under fasted conditions) in Period 4. A washout period of 7 (+/- 2) days will be maintained between each treatment period.

Drug: Ibrutinib (Treatment A) [Reference]; Drug: Ibrutinib (Treatment D); Drug: Ibrutinib (Treatment E); Drug: Ibrutinib (Treatment F)

Group 2: Sequence 4 (FEAD)

EXPERIMENTAL

Participants will receive Treatment F (Ibrutinib 560 mg sprinkle capsule granules suspended in water under fasted conditions) in Period 1; followed by Treatment E (Ibrutinib 560 mg sprinkle capsule granules under fed conditions) in Period 2; followed by Treatment A (Ibrutinib 560 mg capsules \[reference\] under fasted conditions) in Period 3; followed by Treatment D (Ibrutinib 560 mg sprinkle capsule granules under fasted conditions) in Period 4. A washout period of 7 (+/- 2) days will be maintained between each treatment period.

Drug: Ibrutinib (Treatment A) [Reference]; Drug: Ibrutinib (Treatment D); Drug: Ibrutinib (Treatment E); Drug: Ibrutinib (Treatment F)

Interventions

Ibrutinib (Treatment A) [Reference] DRUG

Participants will receive Ibrutinib 560 milligram (mg) (4\*140 mg) capsule as Treatment A under fasted conditions in one of the treatment periods.

Group 1: Sequence 1 (ABC); Group 1: Sequence 2 (BCA); Group 1: Sequence 3 (CAB); Group 1: Sequence 4 (ACB); Group 1: Sequence 5 (BAC); Group 1: Sequence 6 (CBA); Group 2: Sequence 1 (AFDE); Group 2: Sequence 2 (DAEF); Group 2: Sequence 3 (EDFA); Group 2: Sequence 4 (FEAD)

Ibrutinib (Treatment B) DRUG

Participants will receive Ibrutinib 560 mg suspension as Treatment B under fasted conditions in one of the treatment periods.

Group 1: Sequence 1 (ABC); Group 1: Sequence 2 (BCA); Group 1: Sequence 3 (CAB); Group 1: Sequence 4 (ACB); Group 1: Sequence 5 (BAC); Group 1: Sequence 6 (CBA)

Ibrutinib (Treatment C) DRUG

Participants will receive Ibrutinib 560 mg suspension as Treatment C under fed (high-fat) conditions in one of the treatment periods.

Group 1: Sequence 1 (ABC); Group 1: Sequence 2 (BCA); Group 1: Sequence 3 (CAB); Group 1: Sequence 4 (ACB); Group 1: Sequence 5 (BAC); Group 1: Sequence 6 (CBA)

Ibrutinib (Treatment D) DRUG

Participants will receive Ibrutinib 560 mg sprinkle capsule granules as Treatment D under fasted conditions in one of the treatment periods.

Group 2: Sequence 1 (AFDE); Group 2: Sequence 2 (DAEF); Group 2: Sequence 3 (EDFA); Group 2: Sequence 4 (FEAD)

Ibrutinib (Treatment E) DRUG

Participants will receive Ibrutinib 560 mg sprinkle capsule granules as Treatment E under fed (high-fat) conditions in one of the treatment periods.

Group 2: Sequence 1 (AFDE); Group 2: Sequence 2 (DAEF); Group 2: Sequence 3 (EDFA); Group 2: Sequence 4 (FEAD)

Ibrutinib (Treatment F) DRUG

Participants will receive Ibrutinib 560 mg sprinkle capsule granules suspended in water as Treatment F under fasted conditions in one of the treatment periods.

Group 2: Sequence 1 (AFDE); Group 2: Sequence 2 (DAEF); Group 2: Sequence 3 (EDFA); Group 2: Sequence 4 (FEAD)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (1)

Unknown Facility

Antwerp, Belgium

Location

MeSH Terms

Interventions

ibrutinib

Study Officials

• Janssen Research & Development Clinical Trial

  Janssen Research & Development

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2015
• First Posted: March 17, 2015
• Study Start: March 1, 2015
• Primary Completion: November 1, 2015
• Study Completion: November 1, 2015
• Last Updated: December 23, 2015

Record last verified: 2015-12

Locations

BE (1)