A Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of JNJ-54175446 in Healthy Male Participants

Healthy Clinical Trial

Official title:

A Randomized, Placebo- and Comparator-controlled, Double-blind, Multiple (Ascending) Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of JNJ-54175446 in Healthy Male Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02515955
• Other study ID #: CR107762
• Secondary ID: 54175446EDI10022
• Status: Completed
• Phase: Phase 1
• First received: August 3, 2015
• Last updated: June 3, 2016
• Start date: August 2015
• Est. completion date: March 2016

Study information

• Verified date: June 2016
• Source: Janssen-Cilag International NV
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to investigate the safety, tolerability and pharmacodynamics of JNJ-54175446 after multiple consecutive dose administrations

Description:

This will be a randomized, placebo-and comparator-controlled, double-blind, multiple dose study with JNJ-54175446 in healthy male participants. The study will consist of a Screening examination (28 to 6 days prior to dose administration), a baseline 20 mg amphetamine (AMPH) challenge at least 5 days before first dose administration, a double-blind treatment period (18 days; 11 days of dosing with JNJ-54175446, minocycline or placebo; amphetamine (AMPH)/AMPH placebo challenge sequence on Day 7 and Day 10 for each participant), and a follow-up examination between 14 and 21 days after last dose administration. The maximal study duration for each participant will not exceed 9 weeks. Safety, pharmacokinetics (PK) and pharmacodynamics of JNJ-54175446 will be primarily assessed. Safety will be monitored throughout the study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 76
• Est. completion date: March 2016
• Est. primary completion date: March 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Participant must have a body mass index (BMI) between 18 and 32 kilogram/meter^2 (kg/m^2), inclusive (BMI = weight/height^2)

• Participants must be healthy on the basis of physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) [including QTcF less than or equal to 450 millisecond (ms) (triplicate ECG)] performed at screening and admission to the clinical unit. Minor abnormalities in ECG, which are not considered to be of clinical significance by the investigator, are acceptable. The presence of Left Bundle Branch Block (LBBB), atrioventricular (AV) Block (second degree or higher), or a permanent pacemaker or implantable cardioverter defibrillator [ICD] will lead to exclusion

• Participants must be healthy on the basis of clinical laboratory tests performed at screening. If the results of the serum chemistry panel [including liver enzymes], hematology, or urinalysis are outside the normal reference ranges, the subject may be included only if the investigator judges the abnormalities to be not clinically significant. This determination must be recorded in the subject's source documents and initialed by the investigator

• A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control e.g., either condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository, and all men must also not donate sperm during the study and for 3 months after receiving the last dose of study drug. In addition, their female partner should also use an appropriate method of birth control for at least the same duration

Exclusion Criteria:

• Participant has a history of or current liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances, any inflammatory illness or any other illness that the Investigator considers should exclude the subject

• Participant has a clinically significant (history of) psychiatric illnesses or (history of) psychotic symptoms

• Participant has a family history of relevant psychiatric disorders (first degree) and/or psychotic disorders (first and second degree)

• Participant has a history of hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV) positive, or other clinically active liver disease, or tests positive for HBsAg or anti-HCV at Screening

• Participant has a history of human immunodeficiency virus (HIV) antibody positive, or tests positive for HIV at Screening

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• JNJ-54175446
Participants will receive JNJ-54175446, at increasing dose levels using 2 oral formulations i.e. 0.5 mg/ml and 20 mg/ml as suspension for oral dose once daily.
• Minocycline
Participants will receive minocycline 100 mg as capsule twice daily.
• JNJ 54175446 Matching Placebo
Participants will receive placebo matching with JNJ 54175446 once daily orally.
• D Amphetamine
Participants will receive 20 mg d-amphetamine (AMPH) 2 hours after administration of study drug (JNJ-54175446/placebo or minocycline/placebo) on Day 7 and Day 10.
• D Amphetamine Matching Placebo
Participants will receive d-amphetamine (AMPH) matching placebo, 2 hours after administration of study drug (JNJ-54175446/placebo or minocycline/placebo) on Day 7 and Day 10.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Janssen-Cilag International NV

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with Adverse Events	An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.	Baseline up to 14 or 21 days after study drug administration	Yes
Primary	Maximum Observed Plasma Concentration (Cmax)	The Cmax is the maximum observed concentration.	Baseline up to Day 17	No
Primary	Minimum Observed Plasma Concentration (Cmin)	The Cmin is the minimum observed plasma concentration.	Baseline up to Day 17	No
Primary	Trough Plasma Concentration (Ctrough)	The (Ctrough) is the plasma concentration before dosing or at the end of the dosing interval of any dose other than the first dose in a multiple dosing regimen.	Baseline up to Day 17	No
Primary	Average Plasma Concentration at Steady State (Cavg,ss)	The Cavg,ss is calculated as area under the plasma concentration-time curve during a dosing Interval (AUC[tau]) divided by the dosing interval (tau).	Baseline up to Day 17	No
Primary	Time to Reach Maximum Observed Plasma Concentration (Tmax)	The Tmax is defined as actual sampling time to reach maximum observed analyte concentration.	Baseline up to Day 17	No
Primary	Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau)	The AUCtau is the measure of the plasma drug concentration from time zero to end of dosing interval. It is used to characterize drug absorption.	Baseline up to Day 17	No
Primary	Area Under the Plasma Concentration-Time Curve From Time Zero to Time 't' (AUC[0-t])	The AUC(0-t) is the area under the plasma concentration-time curve from time zero to any time 't'.	Baseline up to Day 17	No
Primary	Elimination Half-Life (t1/2)	The elimination half-life (t1/2) is the time measured for the plasma concentration to decrease by 1 half to its original concentration. It is associated with the terminal slope of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z).	Baseline up to Day 17	No