A Study of the Safety and Pharmacokinetics of JNJ-38518168 in Japanese and Caucasian Male Participants and the Effect of JNJ-38518168 on the Blood Levels of Midazolam

A Double-Blind, Randomized, Single- and Multiple-Dose Study to Investigate the Safety, Tolerability, and Pharmacokinetics of JNJ-38518168 in Japanese and Caucasian Healthy Adult Male Subjects and an Open-Label Drug-Drug Interaction Study to Evaluate the Effect of JNJ-38518168 on the Pharmacokinetics of Midazolam, a CYP3A4 Substrate

The purpose of Part 1 of this study is to evaluate the safety, tolerability, and pharmacokinetics ("PK", how the drug is absorbed in the body, distributed within the body, and how it is removed from the body over time) of JNJ-38518168 in comparison with placebo following single dose and 14 days of consecutive dosing in healthy Japanese and Caucasian adult male participants. Part 2 of this study will evaluate the effect of JNJ-38518168 on the pharmacokinetics of midazolam in healthy participants.

Study Overview

• Status: Completed
• Conditions: Healthy Male Volunteer
• Intervention / Treatment: Drug: JNJ-38518168 (30 mg); Drug: JNJ-38518168 (10 mg); Drug: JNJ-38518168 (3 mg); Drug: Placebo; Drug: Midazolam and JNJ-38518168

Detailed Description

Participants will be assigned to either Part 1 or Part 2 of this study. Part 1 will be a single-center, double-blind (participants and study personnel will not know the identity of the treatments), randomized (treatment will be assigned by chance), single- and multiple-dose study. There will be 3 groups in Part 1, and the dosing will be as follows: Group A will receive a single oral dose of 30 mg JNJ-38518168 (given as three 10-mg tablets of JNJ-38518168) or placebo (a treatment identical in appearance to JNJ-38518168 but not containing active drug) (Period 1), and multiple oral doses of 30 mg JNJ 38518168 (given as three 10-mg tablets of JNJ-38518168) or matching placebo once daily for 14 consecutive days (Period 2); Group B will receive a single oral dose of 10 mg JNJ-38518168 or placebo (Period 1), and multiple oral doses of 10 mg JNJ-38518168 or placebo once daily for 14 consecutive days (Period 2); and Group C will receive a single oral dose of 3 mg JNJ-38518168 or placebo (Period 1), and multiple oral doses of 3 mg JNJ-38518168 or placebo once daily for 14 consecutive days (Period 2). At least a 20-day washout period will separate the dose administration in Period 1 and the first dose administration of Period 2. The duration of Part 1 will be approximately 78 days. Part 2 of this study will be a single-center, open-label (participants and study personnel will know the identity of the treatments), non-randomized, multiple dose, drug-drug interaction study. Eligible participants will receive a single oral dose of 2.5 mg of midazolam as oral solution on Day 1, three 10-mg tablets of JNJ-38518168 (30 mg) once daily for 14 consecutive days (Day 2 through Day 15); and another single oral dose of 2.5 mg midazolam on Day 15. The duration of Part 2 of the study will be approximately 42 days. Following an interim safety and PK data analysis, one additional treatment group may be studied to evaluate the effect of JNJ-38518168 at a dose lower than 30 mg once daily on the PK of midazolam. During Parts 1 or 2, participants may be admitted to the clinical unit for periods of up to 7 and 18 days, and follow-up return visits to the clinic will also be required.

• Study Type: Interventional
• Enrollment (Actual): 94
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Cypress, California, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

Part 1 only:

• Male, 20 to 55 years of age.
• Be either:
• Of Japanese descent who has resided outside of Japan for no more than 5 years and whose parents and maternal and paternal grandparents are Japanese, as determined by participant's verbal report. Japanese participants must have a valid Japanese passport.

or

• A non-Hispanic Caucasian participant who has Caucasian parents as determined by participant's verbal report.
• Have a body mass index (BMI) of 18.5 kg/m2 to 25 kg/m2 for participants of Japanese descent and between 18.5 kg/m2 and 30 kg/m2 for Caucasian participants.
• Have a body weight of not less than 50 kg.

Part 2 only:

• Male, 18 to 55 years of age
• Have a BMI of 18.5 kg/m2 to 30 kg/m2 and have a body weight of not less than 50 kg.

For both Parts 1 and 2:

• Be otherwise healthy with no clinically significant abnormalities as determined by medical history, physical examination, blood chemistry assessments, hematologic assessments, coagulation and urinalysis, measurement of vital signs, and ECG. If the results of the serum chemistry panel, hematology, or urinalysis are outside the normal reference ranges, the participant may be included only if the investigator judge the abnormalities or deviations from normal to be not clinically significant.
• If a man is heterosexually active with a woman of childbearing potential, he must be surgically sterile or 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.
• Have a blood pressure measurement between 90 and 140 mmHg systolic, inclusive, and between 50 and 90 mmHg diastolic, at screening.
• Have a 12-lead ECG consistent with normal cardiac conduction and function at screening.
• Non-smoker.

Exclusion Criteria:

• History of or current clinically significant medical illness including (but not limited to) cardiac arrhythmias or other cardiac disease, hematologic disease, coagulation disorders (including any abnormal bleeding or blood dyscrasias), lipid abnormalities, significant pulmonary disease, including bronchospastic respiratory disease, diabetes mellitus, renal or hepatic insufficiency, thyroid disease, neurologic or psychiatric disease, infection, or any other illness that the investigator considers should exclude the participant or that could interfere with the interpretation of the study results.
• History of hypersensitivity to or intolerance of midazolam (Part 2 only)
• Clinically significant abnormal values for hematology, clinical chemistry, or urinalysis at screening or admission to the study center in Period 1 as deemed appropriate by the investigator.
• Clinically significant abnormal physical examination, vital signs, or 12-lead ECG at screening or admission to the study center in Period 1 as deemed appropriate by the investigator.
• Has any known malignancy or a history of malignancy (with the exception of basal cell carcinoma, squamous cell carcinoma in situ of the skin, or squamous cell carcinoma of the skin that has been treated with no evidence of recurrence within 5 years prior to the first administration of study drug).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: JNJ-38518168 (30 mg); Type=range, unit=mg, number=30, form=tablet, route=oral use, in single and multiple doses for 14 days
Experimental: 2	Drug: JNJ-38518168 (10 mg); Type=range, unit=mg, number=10, form=tablet, route=oral use, in single and multiple doses for 14 days
Experimental: 3	Drug: JNJ-38518168 (3 mg); Type=range, unit=mg, number=3, form=tablet, route=oral use, in single and multiple doses for 14 days
Placebo Comparator: 4	Drug: Placebo; Form=tablet, route=oral use, for 14 days
Experimental: 5	Drug: Midazolam and JNJ-38518168; Midazolam: Type=exact, unit=mg, number=2.5, form=oral solution; route=oral use, on Days 1 and 15; JNJ-38518168: Type=exact, unit=mg, number=30, form=tablet, route=oral use, once daily from Day 2 through Day 15

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The number of Japanese participants with adverse events	Up to 10 weeks
Blood tests in Japanese participants	Up to 10 weeks
Clinical laboratory tests in Japanese participants	Up to 10 weeks
Electrocardiograms in Japanese participants	Up to 10 weeks
Blood levels of JNJ-38518168 in all participants	Up to 10 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
The number of Caucasian participants with adverse events	Up to 10 weeks
Blood tests in Caucasian participants	Up to 10 weeks
Clinical laboratory tests in Caucasian participants	Up to 10 weeks
Electrocardiograms in Caucasian participants	Up to 10 weeks

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research & Development, LLC & Development, L.L.C., Clinical Trial, Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): July 1, 2012
• Study Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: September 27, 2011
• First Submitted That Met QC Criteria: September 27, 2011
• First Posted (Estimate): September 28, 2011

Study Record Updates

• Last Update Posted (Estimate): March 4, 2013
• Last Update Submitted That Met QC Criteria: March 1, 2013
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Keywords: Midazolam; JNJ-38518168; Healthy male volunteer
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Midazolam
• Other Study ID Numbers: CR100669; 38518168ARA1002 (Other Identifier: Janssen Research & Development, LLC)