Clinical trial NCT02515955: A Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of JNJ-54175446 in Healthy Male Participants
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Healthy
JNJ-54175446
Lead sponsor: Janssen-Cilag International NV
Sponsor class: INDUSTRY
First posted: 2015-08-05
Enrollment: 76
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants with Adverse Events
timeFrame: Baseline up to 14 or 21 days after study drug administration
measure: Maximum Observed Plasma Concentration (Cmax)
timeFrame: Baseline up to Day 17
measure: Minimum Observed Plasma Concentration (Cmin)
timeFrame: Baseline up to Day 17
measure: Trough Plasma Concentration (Ctrough)
timeFrame: Baseline up to Day 17
measure: Average Plasma Concentration at Steady State (Cavg,ss)
timeFrame: Baseline up to Day 17
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax)
timeFrame: Baseline up to Day 17
measure: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau)
timeFrame: Baseline up to Day 17
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Time 't' (AUC[0-t])
timeFrame: Baseline up to Day 17
measure: Elimination Half-Life (t1/2)
timeFrame: Baseline up to Day 17
Secondary outcomes:
Other outcomes:
Locations:
city: Leiden
country: Netherlands
Study officials:
affiliation: Janssen-Cilag International NV
name: Janssen-Cilag International NV Clinical trials
role: STUDY_DIRECTOR
References: