A Study in Healthy Participants Investigating the Safety, Tolerability and Plasma Pharmacokinetics (PK) of Single Oral Doses of JNJ-47910382

NCT ID: NCT01482611

Last Updated: 2013-02-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-11-30
• Study Completion Date: 2012-04-30

Brief Summary

The purpose of this study is to investigate the safety, tolerability and plasma pharmacokinetics (PK) of JNJ-47910382 after increasing single oral doses (taken with food) from 10 mg up to 600 mg or up to the maximum tolerated dose or up to the dose that yields a JNJ-47910382 plasma level that approaches the predefined maximum mean exposure (whichever comes first) in healthy Caucasian and Japanese participants. The foreseen maximum dose is 600 mg. In addition, the effect of fasting (ie JNJ-47910382 is taken without food) on the plasma pharmacokinetics of JNJ-47910382 after one selected oral dose given to healthy Caucasian participants will be studied. JNJ-47910382 is a drug that is being developed to treat Hepatitis C infection and is an inhibitor of the reproduction machinery of the Hepatitis C virus (HCV). Pharmacokinetics (PK) means how the drug is absorbed into the bloodstream, distributed in the body and eliminated from the body.

Detailed Description

This is a Phase I, single-center, first-in-human, double-blind (neither the participant nor the investigator/medical staff knows whether placebo or JNJ-47910382 is given at a certain moment), randomized (treatment with placebo or JNJ-47910382 is assigned by chance), placebo-controlled trial in 18 healthy Caucasian and 16 healthy Japanese participants to investigate the safety, tolerability and plasma pharmacokinetics of single oral doses of JNJ-47910382. This trial consists of 3 Parts: 1. a single dose escalation part in healthy male and female Caucasians, 2. a single dose study investigating the effect of fasting in healthy male and female Caucasians and 3. a single dose escalation part in healthy male Japanese participants. Part 1 holds 6 sessions, each testing another dose of JNJ-47910382. Part 2 holds 1 session testing one dose and Part 3 holds 3 sessions, each testing another dose of JNJ-47910382. The doses pre-defined for the Caucasian cohort in Part 1 are 10 mg, 30 mg, 75 mg, 150 mg, 300 mg, and 600 mg, given in Session I till and including Session VI, respectively. These doses may be adjusted based on results obtained from previous sessions, but will not exceed 600 mg, the predefined maximal tolerated dose or a dose that yields a JNJ-47910382 plasma levels that approaches the predefined maximum mean exposure. The foreseen maximum dose is 600 mg.The doses for the Japanese cohort, given in Session VIII till and including Session X, respectively, and the dose for the fasting-session (Session VII) will be defined during the conduct of the study, based on the safety, tolerability and PK profiles obtained in the previously completed sessions. The Caucasian cohort is divided over 2 panels (Panel 1 and 2) of 9 participants, and to each Panel, 3 different doses are assigned, respecting a washout period of at least 10 days. The Japanese cohort is divided over 2 panels (Panel 3 and 4) of 8 participants and to Panel 3, 2 different doses are assigned, respecting a washout period of at least 10 days, and to Panel 4 only 1 dose of JNJ-47910382 is assigned. Either Panel 1 or 2 will be selected for the fasting-study Session, depending on the dose that has been selected for this fasting-study. Both, JNJ-47910382 and the placebo are liquids and will be administered in the mouth of the participants via an oral dispenser. The decision to escalate to the next dose in Part 1 and 3 will be taken with caution. After each session, the safety and tolerability (till and including 96h post dose) and the PK (till and including 24h post dose) results will be evaluated by the sponsor and principle investigator - in a blinded fashion. Only in case the previous dose is shown to be generally safe and tolerable and the maximum tolerated dose and the maximal mean plasma JNJ-47910382 levels have not been reached and the PK profile is satisfactory, the next session can start, using a selected and agreed dose. Safety evaluations between sessions include adverse events, vital signs (blood pressure and heart rate), electrocardiogram (ECG) (evaluation of the activity of the heart at certain time points), heart telemetry (continuous evaluation of the activity of the heart, for 12 hours), physical examination and clinical laboratory tests. Throughout the trial, in each session, the plasma PK profiles of JNJ-47910382 will be determined up to 96 hours after dosing. Also the amount of JNJ-47910382 recovered in the urine will be determined over 72 hours after intake of study medication in Session IV and in the Japanese Session with the same dose (either Session VIII, IX or X). A blood sample dedicated for the analysis of specific genes involved in the PK (metabolism) and transport of JNJ-47910382 will be collected from each participant, preferentially on Day-2 of one of the sessions. Also safety and tolerability of JNJ-47910382 will be determined throughout the trial. In each session a triplicate ECG is taken, vital signs are recorded, urinalysis is performed and biochemical and blood parameters are assessed on Days 1, 2 and 4. On Day3, vital signs are recorded and a triplicate ECG taken. On Day-1, a triplicate ECG is taken. Heart telemetric recordings are performed on Day-1 and Day1 for 12 hours. Physical examination occurs on Day-1 and Day5.

Conditions

Hepatitis C Virus Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Panel 1: Caucasian

10, 75 and 300 mg JNJ-47910382 or placebo

Group Type: EXPERIMENTAL

JNJ-47910382

Intervention Type: DRUG

Type = exact number, unit = mg, number = 10, 75, 300, form = suspension, route = oral use.

Placebo

Intervention Type: DRUG

Type = exact number, unit = mg, number = equivalent of 10, 75, 300, form = suspension, route = oral use.

Panel 2: Caucasian

30, 150, 600 mg JNJ-47910382 or placebo

Group Type: EXPERIMENTAL

JNJ-47910382

Intervention Type: DRUG

Type = exact number, unit = mg, number = 30, 150, 600, form = suspension, route = oral use.

Placebo

Intervention Type: DRUG

Type = exact number, unit = mg, number = equivalent of 30, 150, 600, form = suspension, route = oral use

Panel 3: Japanese

Session VIII and X: Doses of JNJ-47910382 or placebo to be determined

Group Type: EXPERIMENTAL

JNJ-47910382

Intervention Type: DRUG

Type = exact number, unit = mg, number = To be determined, form = suspension, route = oral use.

Placebo

Intervention Type: DRUG

Type = exact number, unit = mg, number = equivalent dose to be determined, form = suspension, route = oral use.

Panel 4: Japanese

Session IX: Dose of JNJ-47910382 or placebo to be determined

Group Type: EXPERIMENTAL

JNJ-47910382

Intervention Type: DRUG

Type = exact number, unit = mg, number = To be determined, form = suspension, route = oral use.

Placebo

Intervention Type: DRUG

Type = exact number, unit = mg, number = equivalent dose to be determined, form = suspension, route = oral use

Interventions

JNJ-47910382

Type = exact number, unit = mg, number = 10, 75, 300, form = suspension, route = oral use.

Intervention Type: DRUG

JNJ-47910382

Type = exact number, unit = mg, number = 30, 150, 600, form = suspension, route = oral use.

Intervention Type: DRUG

JNJ-47910382

Type = exact number, unit = mg, number = To be determined, form = suspension, route = oral use.

Intervention Type: DRUG

JNJ-47910382

Type = exact number, unit = mg, number = To be determined, form = suspension, route = oral use.

Intervention Type: DRUG

Placebo

Type = exact number, unit = mg, number = equivalent of 10, 75, 300, form = suspension, route = oral use.

Intervention Type: DRUG

Placebo

Type = exact number, unit = mg, number = equivalent of 30, 150, 600, form = suspension, route = oral use

Intervention Type: DRUG

Placebo

Type = exact number, unit = mg, number = equivalent dose to be determined, form = suspension, route = oral use.

Intervention Type: DRUG

Placebo

Type = exact number, unit = mg, number = equivalent dose to be determined, form = suspension, route = oral use

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Caucasian subjects between 18 and 45 years of age, inclusive.
• Japanese subjects between 20 and 45 years of age, inclusive.
• MALE Japanese subjects who has resided outside of Japan for no more than 5 years and whose parents and maternal and paternal grandparents are Japanese
• A body weight above 50 kg at screening
• Non-smoking for at least 3 months prior to screening

Exclusion Criteria

• Female Caucasian, except if postmenopausal for at least 2 years or be surgically sterile.
• Hepatitis A, B or C infection
• Human Immunodeficiency Virus Type 1 (HIV-1) or Human Immunodeficiency Virus Type 2 (HIV-2) infection

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Janssen R&D Ireland

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen R&D Ireland Clinical Trial

Role: STUDY_DIRECTOR

Janssen R&D Ireland

Locations

Neuss, , Germany

Countries

Germany

Other Identifiers

47910382HPC1001

Identifier Type: OTHER

Identifier Source: secondary_id

2011-003196-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR018547

Identifier Type: -

Identifier Source: org_study_id