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

Healthy Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01932320
• Other study ID #: CR016765
• Secondary ID: 40411813EDI10042
• Status: Completed
• Phase: Phase 1
• First received: August 27, 2013
• Last updated: September 5, 2013
• Start date: February 2010
• Est. completion date: May 2010

Study information

• Verified date: September 2013
• Source: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicinal Products and Health Products
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: May 2010
• Est. primary completion date: May 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 55 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Bio-availability Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• JNJ-40411813: Formulation A
Participants will receive JNJ-40411813 100 mg hard gelatin capsule orally (by mouth) as a single dose for Part 1 (Period 1, Period 2, and Period 3). If selected this formulation from Part 1, participants will receive this formulation at the dose of 50 mg to 150 mg orally without food and with food in Part 2 (Period 1, Period 2); and at the dose of 50 mg to 150 mg orally without food on Day 1 and Day 10 in Part 3.
• JNJ-40411813: Formulation B
Participants will receive JNJ-40411813 100 mg immediate release tablet orally as a single dose for Part 1 (Period 1, Period 2, and Period 3). If selected this formulation from Part 1, participants will receive this formulation at the dose of 50 mg to 150 mg orally without food and with food in Part 2 (Period 1, Period 2); and at the dose of 50 mg to 150 mg orally without food on Day 1 and Day 10 in Part 3.
• JNJ-40411813: Formulation C
Participants will receive JNJ-40411813 100 mg nanosuspension orally as a single dose for Part 1 (Period 1, Period 2, and Period 3).
• Ketoconazole
Participants will receive ketoconazole 200 mg tablet orally twice daily with food from Day 6 to Day 14 in Part 3.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Peak plasma concentration of JNJ-40411813	This pharmacokinetics parameter will be analyzed for 3 formulations of JNJ-40411813: Formulation A: hard gelatin capsule filled with beads; Formulation B: immediate release tablet; and Formulation C: nanosuspension formulation.	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])	No
Primary	Time to reach the peak plasma concentration of JNJ-40411813	This pharmacokinetics parameter will be analyzed for 3 formulations of JNJ-40411813: Formulation A: hard gelatin capsule filled with beads; Formulation B: immediate release tablet; and Formulation C: nanosuspension formulation.	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])	No
Primary	Area under the plasma concentration of JNJ-40411813-time curve from 0 to t hours post dosing	This pharmacokinetics parameter will be analyzed for 3 formulations of JNJ-40411813: Formulation A: hard gelatin capsule filled with beads; Formulation B: immediate release tablet; and Formulation C: nanosuspension formulation.	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])	No
Primary	Area under the plasma concentration of JNJ-40411813 time curve from 0 to infinity post dosing	This pharmacokinetics parameter will be analyzed for 3 formulations of JNJ-40411813: Formulation A: hard gelatin capsule filled with beads; Formulation B: immediate release tablet; and Formulation C: nanosuspension formulation.	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])	No
Primary	Elimination rate constant of JNJ-40411813	This pharmacokinetics parameter will be analyzed for 3 formulations of JNJ-40411813: Formulation A: hard gelatin capsule filled with beads; Formulation B: immediate release tablet; and Formulation C: nanosuspension formulation.	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])	No
Primary	Terminal half-life of JNJ-40411813	This pharmacokinetics parameter will be analyzed for 3 formulations of JNJ-40411813: Formulation A: hard gelatin capsule filled with beads; Formulation B: immediate release tablet; and Formulation C: nanosuspension formulation.	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])	No
Primary	Relative bioavailability of JNJ-40411813	This pharmacokinetics parameter will be analyzed for 3 formulations of JNJ-40411813: Formulation A: hard gelatin capsule filled with beads; Formulation B: immediate release tablet; and Formulation C: nanosuspension formulation.	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])	No
Primary	Cumulative amount of JNJ-40411813 excreted in urine	This pharmacokinetics parameter will be analyzed for solid formulation of JNJ-40411813.	1 hour predose to 120 hours postdose (for Part 3 [after each single-dose administration])	No
Primary	Renal clearance of JNJ-40411813	This pharmacokinetics parameter will be analyzed for solid formulation of JNJ-40411813.	1 hour predose to 120 hours postdose (for Part 3 [after each single-dose administration])	No
Primary	Fraction of JNJ-40411813 excreted in urine until time 't'	This pharmacokinetics parameter will be analyzed for solid formulation of JNJ-40411813.	1 hour predose to 120 hours postdose (for Part 3 [after each single-dose administration])	No
Secondary	Number of participants with adverse events		Up to 8 weeks (for Part 1, Part 2, and Part 3)	Yes