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| ID | Type | Description | Link |
|---|---|---|---|
| 2015-000155-25 | EudraCT Number | ||
| PCI-32765CLL1015 | Other Identifier | Janssen Research & Development, LLC |
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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.
This is an open-label (all people know the identity of the intervention), randomized (study medication assigned to participants by chance), 3- or 4-way crossover (participants may receive different interventions sequentially during the trial), and single-center study of ibrutinib. The duration of study will be approximately 67 to 83 days per participant. The study consists of 3 parts: Screening (28 days before study commences on Day 1); Open-label Treatment (consists of 6 treatments, either Ibrutinib capsule or suspension or sprinkle capsule granules under fed or fasted condition), in subsequent 3 periods for Group 1 and 4 periods for Group 2, each separated with washout period of 7 (plus [+] / minus [-] 2) days; and follow up Phase (up to 10 + / - 2 days after last study drug administration). All the eligible participants will be randomly assigned to 1 of the 6 (Group 1) or 4 (Group 2) treatment sequences. In fasted conditions, study drug will be administered following a 10-hour overnight fast. In fed conditions, participants will also fast from food for 10 hours, but will consume a high fat breakfast within a 30-minute period. Study drug will be administered 2 hours after the breakfast. Participants will not be allowed to have food until 4 hours of drug administration. Blood samples will be collected for evaluation of pharmacokinetics at pre-dose and post-dose of study treatment. Relative bioavailability of Ibrutinib will be evaluated primarily. Participants' safety will be monitored throughout the study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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. |
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| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants with Adverse Events (AEs) and Serious AEs | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Janssen Research & Development Clinical Trial | Janssen Research & Development | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Antwerp | Belgium |
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| 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. |
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| 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. |
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| 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. |
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| 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. |
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| 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. |
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| 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. |
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| 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. |
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| Ibrutinib (Treatment B) | Drug | Participants will receive Ibrutinib 560 mg suspension as Treatment B under fasted conditions in one of the treatment periods. |
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| 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. |
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| 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. |
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| 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. |
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| 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. |
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| 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 |
| Screening up to follow-up (10 plus [+] / minus [-] 2 days after last dose administration) |
| ID | Term |
|---|---|
| C551803 | ibrutinib |
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