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

• Sponsor: Janssen-Cilag International NV (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02515955
• Collaborator: (none)
• Enrollment: 76
• Location: 1
• Arms: 8
• Duration (Months): 7
• Patients Per Site Per Month: 10.9

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: JNJ-54175446; Drug: Minocycline; Drug: JNJ 54175446 Matching Placebo; Drug: D Amphetamine; Drug: D Amphetamine Matching Placebo	Phase 1

Detailed 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 76 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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
• Study Start Date: Aug 1, 2015
• Actual Primary Completion Date: Mar 1, 2016
• Actual Study Completion Date: Mar 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1 Participants will be receiving either JNJ-54175446 at increasing dose levels using 2 oral formulation as suspension for oral dose once daily from Day 1 to Day 17 or minocycline 100 mg capsule twice daily from Day 1 to Day 17 or placebo matching with JNJ 54175446 once daily from Day 1 to Day 17.	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.; Drug: Minocycline; Participants will receive minocycline 100 mg as capsule twice daily.; Drug: JNJ 54175446 Matching Placebo; Participants will receive placebo matching with JNJ 54175446 once daily orally.; Drug: 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.; Drug: 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.
Experimental: Cohort 2 Participants will be receiving either JNJ-54175446 at increasing dose levels using 2 oral formulation as suspension for oral dose once daily from Day 1 to Day 17 or minocycline 100 mg capsule twice daily from Day 1 to Day 17 or placebo matching with JNJ 54175446 once daily from Day 1 to Day 17.	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.; Drug: Minocycline; Participants will receive minocycline 100 mg as capsule twice daily.; Drug: JNJ 54175446 Matching Placebo; Participants will receive placebo matching with JNJ 54175446 once daily orally.; Drug: 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.; Drug: 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.
Experimental: Cohort 3 Participants will be receiving either JNJ-54175446 at increasing dose levels using 2 oral formulation as suspension for oral dose once daily from Day 1 to Day 17 or minocycline 100 mg capsule twice daily from Day 1 to Day 17 or placebo matching with JNJ 54175446 once daily from Day 1 to Day 17.	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.; Drug: Minocycline; Participants will receive minocycline 100 mg as capsule twice daily.; Drug: JNJ 54175446 Matching Placebo; Participants will receive placebo matching with JNJ 54175446 once daily orally.; Drug: 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.; Drug: 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.
Experimental: Cohort 4 Participants will be receiving either JNJ-54175446 at increasing dose levels using 2 oral formulation as suspension for oral dose once daily from Day 1 to Day 17 or minocycline 100 mg capsule twice daily from Day 1 to Day 17 or placebo matching with JNJ 54175446 once daily from Day 1 to Day 17.	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.; Drug: Minocycline; Participants will receive minocycline 100 mg as capsule twice daily.; Drug: JNJ 54175446 Matching Placebo; Participants will receive placebo matching with JNJ 54175446 once daily orally.; Drug: 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.; Drug: 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.
Experimental: Cohort 5 Participants will be receiving either JNJ-54175446 at increasing dose levels using 2 oral formulation as suspension for oral dose once daily from Day 1 to Day 17 or minocycline 100 mg capsule twice daily from Day 1 to Day 17 or placebo matching with JNJ 54175446 once daily from Day 1 to Day 17.	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.; Drug: Minocycline; Participants will receive minocycline 100 mg as capsule twice daily.; Drug: JNJ 54175446 Matching Placebo; Participants will receive placebo matching with JNJ 54175446 once daily orally.; Drug: 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.; Drug: 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.
Experimental: Cohort 6 Participants will be receiving either JNJ-54175446 at increasing dose levels using 2 oral formulation as suspension for oral dose once daily from Day 1 to Day 17 or minocycline 100 mg capsule twice daily from Day 1 to Day 17 or placebo matching with JNJ 54175446 once daily from Day 1 to Day 17.	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.; Drug: Minocycline; Participants will receive minocycline 100 mg as capsule twice daily.; Drug: JNJ 54175446 Matching Placebo; Participants will receive placebo matching with JNJ 54175446 once daily orally.; Drug: 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.; Drug: 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.
Experimental: Cohort 7 Participants will be receiving either JNJ-54175446 at increasing dose levels using 2 oral formulation as suspension for oral dose once daily from Day 1 to Day 17 or placebo matching with JNJ 54175446 once daily from Day 1 to Day 17.	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.; Drug: JNJ 54175446 Matching Placebo; Participants will receive placebo matching with JNJ 54175446 once daily orally.; Drug: 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.; Drug: 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.
Experimental: Cohort 8 Participants will be receiving either JNJ-54175446 at increasing dose levels using 2 oral formulation as suspension for oral dose once daily from Day 1 to Day 17 or placebo matching with JNJ 54175446 once daily from Day 1 to Day 17.	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.; Drug: JNJ 54175446 Matching Placebo; Participants will receive placebo matching with JNJ 54175446 once daily orally.; Drug: 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.; Drug: 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.

Outcome Measures

Primary Outcome Measures

1. Number of Participants with Adverse Events [Baseline up to 14 or 21 days after study drug administration]

   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.

2. Maximum Observed Plasma Concentration (Cmax) [Baseline up to Day 17]

   The Cmax is the maximum observed concentration.

3. Minimum Observed Plasma Concentration (Cmin) [Baseline up to Day 17]

   The Cmin is the minimum observed plasma concentration.

4. Trough Plasma Concentration (Ctrough) [Baseline up to Day 17]

   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.

5. Average Plasma Concentration at Steady State (Cavg,ss) [Baseline up to Day 17]

   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).

6. Time to Reach Maximum Observed Plasma Concentration (Tmax) [Baseline up to Day 17]

   The Tmax is defined as actual sampling time to reach maximum observed analyte concentration.

7. Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) [Baseline up to Day 17]

   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.

8. Area Under the Plasma Concentration-Time Curve From Time Zero to Time 't' (AUC[0-t]) [Baseline up to Day 17]

   The AUC(0-t) is the area under the plasma concentration-time curve from time zero to any time 't'.

9. Elimination Half-Life (t1/2) [Baseline up to Day 17]

   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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Leiden		Netherlands

Sponsors and Collaborators

• Janssen-Cilag International NV

Investigators

• Study Director: Janssen-Cilag International NV Clinical trials, Janssen-Cilag International NV

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Janssen-Cilag International NV
• ClinicalTrials.gov Identifier: NCT02515955
• Other Study ID Numbers: CR107762; 54175446EDI1002; 2015-001300-55
• First Posted: Aug 5, 2015
• Last Update Posted: Jun 6, 2016
• Last Verified: Jun 1, 2016

• Keywords provided by Janssen-Cilag International NV: Healthy; JNJ-54175446
• Additional relevant MeSH terms: Minocycline; Amphetamine; Dextroamphetamine

Study Results

No Results Posted as of Jun 6, 2016