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

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT02475148
• Date of registration: 16/06/2015
• Prospective Registration: No
• Primary sponsor: Janssen-Cilag International NV
• Public title: A Study to Investigate Safety and Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of JNJ-54175446 in Healthy Participants
• Scientific title: A Randomized, Placebo-controlled, Double-blind, Single Ascending Dose Study to Investigate Safety and Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of JNJ-54175446 in Healthy Subjects
• Date of first enrolment: June 2015
• Target sample size: 76
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02475148
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 1

Countries of recruitment

Belgium

Contacts

• Name: Janssen-Cilag International NV Clinical Trial
• Affiliation: Janssen-Cilag International NV

Key inclusion & exclusion criteria

Inclusion Criteria:

- Participants must have a body mass index (BMI) between 18 and 32 kg/m^2, inclusive
(BMI = weight/height^2)

- Participants must be healthy on the basis of clinical laboratory tests performed at
screening. If the results of the serum chemistry panel[excluding liver function
tests], hematology, or urinalysis are outside the normal reference ranges, the
participant 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

For Part 1 and 3:

- Healthy male participants between 18 and 54 years of age, inclusive

For Part 2:

- Healthy male or female participants between 55 and 75 years of age, inclusive

- Participant must be healthy on the basis of both physical and neurological examination
performed at screening and at admission to the clinical unit

- Women must not be of childbearing potential (i.e., must be postmenopausal with
amenorrhea for at least 12 months); permanently sterilized (e.g., tubal occlusion,
hysterectomy, bilateral salpingectomy); or otherwise be incapable of pregnancy

Exclusion Criteria:

- Participant has a history of or current liver or renal insufficiency; significant
cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic
(including coagulation disorders), rheumatologic, psychiatric, or metabolic
disturbances, any inflammatory illness or any other illness that the Investigator
considers should exclude the participant

- Participant has any liver function test (including alanine aminotransferase [ALT],
aspartate aminotransferase [AST], gamma-glutamyltransferase [gamma-GT], alkaline
phosphatase [ALP] and bilirubin) at screening exceeding the upper limit of normal

- 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

- Participant has a Prothrombin time [PT] >14 seconds and/or an activated partial
thromboplastin time [aPTT] >35 seconds



Age minimum: 18 Years
Age maximum: 75 Years
Gender: All

Health Condition(s) or Problem(s) studied

Healthy

Intervention(s)

Drug: JNJ 54175446

Drug: Placebo

Other: High fat/high Calorie Breakfast

Primary Outcome(s)

Area Under Curve From Time of Administration up to the Last Time Point with a Measurable Plasma and Cerebrospinal Fluid Concentration (AUClast) [Time Frame: Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 18, 24, 36, 48, 72, 96, 120, 144 hours after study drug administration]

Maximum Observed Plasma and Cerebrospinal Fluid (CSF) Concentration (Cmax) [Time Frame: Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 18, 24, 36, 48, 72, 96, 120, 144 hours after study drug administration]

Creatinine Clearance [Time Frame: Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 18, 24, 36, 48, 72, 96, 120, 144 hours after study drug administration]

Area Under the Plasma and Cerebrospinal Fluid Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) [Time Frame: Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 18, 24, 36, 48, 72, 96, 120, 144 hours after study drug administration]

Number of Participants with Adverse Events [Time Frame: Baseline up to 14 or 21 days after study drug administration]

Last Quantifiable Plasma and Cerebrospinal Fluid (CSF) Concentration (Clast) [Time Frame: Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 18, 24, 36, 48, 72, 96, 120, 144 hours after study drug administration]

Total Clearance (CL/F) [Time Frame: Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 18, 24, 36, 48, 72, 96, 120, 144 hours after study drug administration]

Maximum Tolerated Dose of JNJ-54175446 in Part 1 [Time Frame: Baseline up to 24 Hours after study drug administration]

Time to Reach Maximum Observed Plasma and Cerebrospinal Fluid Concentration (Tmax) [Time Frame: Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 18, 24, 36, 48, 72, 96, 120, 144 hours after study drug administration]

Elimination Half-Life (t1/2) [Time Frame: Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 18, 24, 36, 48, 72, 96, 120, 144 hours after study drug administration]

First-order Rate Constant (Lambda[z]) [Time Frame: Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 18, 24, 36, 48, 72, 96, 120, 144 hours after study drug administration]

Time to Last Quantifiable Plasma and Cerebrospinal Fluid Concentration (Tlast) [Time Frame: Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 18, 24, 36, 48, 72, 96, 120, 144 hours after study drug administration]

Secondary ID(s)

54175446EDI1001

2015-000942-53

CR107482

Source(s) of Monetary Support

Please refer to primary and secondary sponsors