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

NCT01932320 | Completed Phase 1

• 3 other identifiers: CR01676540411813EDI10042009-016638-28
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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).

Conditions

Healthy

Keywords

Healthy; Relative Bioavailability; Food effect; JNJ-40411813; Positive allosteric modulator; Solid Dosage Formulation of JNJ-40411813; Ketoconazole

Outcome Measures

Primary Outcomes (10)

• 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])

• 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])

• 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])

• 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])

• 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])

• 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])

• 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])

• 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])

• 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])

• 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])

Secondary Outcomes (1)

• Number of participants with adverse events

  Up to 8 weeks (for Part 1, Part 2, and Part 3)

Study Arms (3)

Part 1

EXPERIMENTAL

Participants will receive single dose of all the 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 in 3 periods (Period 1, Period 2, and Period 3). The sequences will be based on a computer-generated randomization schedule prepared by the sponsor before the study. Each period will be separated by a wash out period (no treatment) of at least 1 week.

Drug: JNJ-40411813: Formulation A; Drug: JNJ-40411813: Formulation B; Drug: JNJ-40411813: Formulation C

Part 2

EXPERIMENTAL

Participants will receive single dose of the selected solid dose formulation of JNJ-40411813 (Formulation A or Formulation B) from Part 1 without food and with food in 2 periods (Period 1 and Period 2). The sequences will be based on a computer generated randomization schedule prepared by the sponsor before the study. Each period will be separated by a wash out period of at least 1 week.

Drug: JNJ-40411813: Formulation A; Drug: JNJ-40411813: Formulation B

Part 3

EXPERIMENTAL

Participants will receive single dose of the selected solid dose formulation of JNJ-40411813 (Formulation A or Formulation B) from Part 1 on two occasions (Day 1 and Day 10) without food along with ketoconazole from Day 6 to Day 14 with food.

Drug: JNJ-40411813: Formulation A; Drug: JNJ-40411813: Formulation B; Drug: Ketoconazole

Interventions

JNJ-40411813: Formulation A DRUG

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.

Part 1; Part 2; Part 3

JNJ-40411813: Formulation B DRUG

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.

Part 1; Part 2; Part 3

JNJ-40411813: Formulation C DRUG

Participants will receive JNJ-40411813 100 mg nanosuspension orally as a single dose for Part 1 (Period 1, Period 2, and Period 3).

Part 1

Ketoconazole DRUG

Participants will receive ketoconazole 200 mg tablet orally twice daily with food from Day 6 to Day 14 in Part 3.

Part 3

Eligibility Criteria

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

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Johnson & Johnson Pharmaceutical Research & Development, L.L.C.: lead

Study Sites (1)

Unknown Facility

Antwerp, Belgium

Location

MeSH Terms

Interventions

Ketoconazole

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Johnson & Johnson Pharmaceutical Research & Development Clinical Trial

  Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

  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: August 27, 2013
• First Posted: August 30, 2013
• Study Start: February 1, 2010
• Primary Completion: May 1, 2010
• Study Completion: May 1, 2010
• Last Updated: September 9, 2013

Record last verified: 2013-09

Locations

BE (1)