Clinical trial NCT01932320: A Study to Evaluate the Relative Bioavailability, Food Effect and Effect of Ketoconazole on the Rate and Extent of Absorption of Solid Dosage Formulation(s) of JNJ-40411813
Official title: An Open Label Study to Investigate the Relative Bioavailability, Food Effect and Effect of Ketoconazole on the Rate and Extent of Absorption of Solid Dosage Formulation(s) of JNJ-40411813
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Healthy
Relative Bioavailability
Food effect
JNJ-40411813
Positive allosteric modulator
Solid Dosage Formulation of JNJ-40411813
Ketoconazole
Lead sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Sponsor class: INDUSTRY
First posted: 2013-08-30
Enrollment: 36
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare the rate and extent of absorption of a single dose of two solid dose formulations relative to a nanosuspension formulation of JNJ-40411813 (Part 1); to evaluate the effect of a high-fat/high-calorie breakfast on the rate and extent of absorption of the selected JNJ-40411813 solid dose formulation from Part 1 (Part 2); and to explore the influence of a potent inhibitor of CYP3A4, ketoconazole, on the rate and extent of absorption of the selected JNJ-40411813 solid dose formulation from Part 1 (Part 3).

Detailed description: This is an open-label (both physician and participants know the identity of the intervention) and single centre study. This study will be conducted in 3 parts (Part 1, Part 2, and Part 3). The study consists of 3 phases including, the screening phase (within 21 days prior to the start of study medication), treatment phase (Part 1: 20 days; Part 2: 12 days; Part 3: 16 days), and the follow-up phase (Part 1 and Part 2: approximately 14 days after the last administration of study medication and Part 3: 14 days after the last administration of ketaconazole). Approximately 36 participants will be enrolled in the study (12 participants in each part). Part 1 is randomized (study medication is assigned by chance) and 3-way cross-over (method used to switch participants from one treatment arm to another in a clinical study) part of the study. Participants in Part 1 will be randomly assigned to 1 of 3 treatment sequences (Period 1, Period 2, and Period 3) to receive single dose of 3 formulations of JNJ-40411813 (Formulation A: hard gelatin capsule filled with beads; Formulation B: immediate release tablet; and Formulation C: nanosuspension formulation) without food. Each period will be separated by a wash out period (no treatment) of at least 1 week. Part 2 is randomized and 2-way cross-over part of the study. Participants in Part 2 will be randomly assigned 1 of 2 treatment sequences (Period 1 and Period 2) to receive single dose of the selected solid dose formulation of JNJ-40411813 from Part 1 without food and with food separated by a wash out period of at least 1 week. Part 3 is single-arm sequential (carried out in a staged approach) part of the study. Participants in Part 3 will receive single dose of the selected solid dose formulation of JNJ-40411813 from Part 1 on two occasions (Day 1 and Day 10) without food along with ketoconazole from Day 6 to Day 14 with food. Safety will be evaluated by the assessment of adverse events, vital signs, physical examination, 12-lead electrocardiogram, and clinical laboratory tests which will be monitored throughout the study. The total duration of study participation for a participant will be 8 weeks.

Eligibility criteria: Inclusion Criteria:

* Men must agree to use a double barrier method of birth control and to not donate sperm during the study and for 3 months after receiving the last dose of study drug
* Body mass index (BMI) between 18 and 30 kg/m2 (BMI is calculated as weight \[kilogram\] divided by square of height \[meter\])
* Non-smoker (not smoked for 3 months prior to screening)

Exclusion Criteria:

* Clinically significant abnormal values for laboratory tests and abnormal physical examination
* History of or current significant unstable medical illness including (but not limited to) cardiac arrhythmias or other cardiac disease, hematological disease, lipid abnormalities, bronchospastic respiratory disease, diabetes mellitus, renal or hepatic insufficiency, thyroid disease, Parkinson's disease, infection
* History of epilepsy or fits or unexplained black-outs and significant history of or current psychiatric or neurological illness
* Serology positive for hepatitis B surface antigen, hepatitis C antibodies or HIV antibodies at screening
* Positive urine screen for drugs of abuse and positive alcohol breath test at screening or start of study medication
* Clinically significant acute illness within 7 days prior to start of study medication
* Use of any prescription medication or over-the-counter medication (not including paracetamol), or herbal medication within 2 weeks of start of study medication

Primary outcomes:
measure: Peak plasma concentration of JNJ-40411813
timeFrame: 1 hour predose to 96 hours postdose (for Part 1 and Part 2 [after each single-dose administration]) and 1 hour predose to 120 hours postdose (for Part 3 [after each single-dose administration])
measure: Time to reach the peak plasma concentration of JNJ-40411813
timeFrame: 1 hour predose to 96 hours postdose (for Part 1 and Part 2 [after each single-dose administration]) and 1 hour predose to 120 hours postdose (for Part 3 [after each single-dose administration])
measure: Area under the plasma concentration of JNJ-40411813-time curve from 0 to t hours post dosing
timeFrame: 1 hour predose to 96 hours postdose (for Part 1 and Part 2 [after each single-dose administration]) and 1 hour predose to 120 hours postdose (for Part 3 [after each single-dose administration])
measure: Area under the plasma concentration of JNJ-40411813 time curve from 0 to infinity post dosing
timeFrame: 1 hour predose to 96 hours postdose (for Part 1 and Part 2 [after each single-dose administration]) and 1 hour predose to 120 hours postdose (for Part 3 [after each single-dose administration])
measure: Elimination rate constant of JNJ-40411813
timeFrame: 1 hour predose to 96 hours postdose (for Part 1 and Part 2 [after each single-dose administration]) and 1 hour predose to 120 hours postdose (for Part 3 [after each single-dose administration])
measure: Terminal half-life of JNJ-40411813
timeFrame: 1 hour predose to 96 hours postdose (for Part 1 and Part 2 [after each single-dose administration]) and 1 hour predose to 120 hours postdose (for Part 3 [after each single-dose administration])
measure: Relative bioavailability of JNJ-40411813
timeFrame: 1 hour predose to 96 hours postdose (for Part 1 and Part 2 [after each single-dose administration]) and 1 hour predose to 120 hours postdose (for Part 3 [after each single-dose administration])
measure: Cumulative amount of JNJ-40411813 excreted in urine
timeFrame: 1 hour predose to 120 hours postdose (for Part 3 [after each single-dose administration])
measure: Renal clearance of JNJ-40411813
timeFrame: 1 hour predose to 120 hours postdose (for Part 3 [after each single-dose administration])
measure: Fraction of JNJ-40411813 excreted in urine until time 't'
timeFrame: 1 hour predose to 120 hours postdose (for Part 3 [after each single-dose administration])
Secondary outcomes:
measure: Number of participants with adverse events
timeFrame: Up to 8 weeks (for Part 1, Part 2, and Part 3)
Other outcomes:
Locations:
city: Antwerpen
country: Belgium
Study officials:
affiliation: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
name: Johnson & Johnson Pharmaceutical Research & Development Clinical Trial
role: STUDY_DIRECTOR
References: