Clinical trial NCT03180762: A Study to Investigate Safety and Tolerability, Pharmacokinetics and Pharmacodynamics of JNJ-64140284 in Healthy Participants
Official title: A 3-Part, Randomized, Placebo-controlled, Double-blind, Single Ascending Dose Study to Investigate Safety and Tolerability, Pharmacokinetics and Pharmacodynamics of JNJ-64140284 in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2017-06-08
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: The purpose of this study is to investigate the safety and tolerability of JNJ-64140284 versus placebo after single oral dose administration (ascending dose levels) under fasted condition, to characterize the pharmacokinetics (PK) of JNJ-64140284 in plasma, cerebrospinal fluid (CSF) and urine after single oral dose administration and to investigate the effect of food (high fat/high calorie) on the PK of JNJ-64140284 following single oral dose administration.


Eligibility criteria: Inclusion Criteria:

Part 1 and 2:

- Healthy male participants between 18 and 58 years of age, inclusive

Part 1, 2 and 3:

- Participants must be healthy on the basis of clinical laboratory tests performed at screening. If the results of the serum chemistry panel, hematology, or urinalysis are outside the normal reference ranges, retesting of an abnormal lab value(s) that may lead to exclusion will be allowed once during the screening phase. The participant may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant or to be appropriate and reasonable for the population under study according to both the investigator and to the Janssen Safety Physician, are acceptable

Part 3:

* Healthy male and female participants between 59 and 75 years of age, inclusive
* Participants must be healthy and medically stable on the basis of clinical laboratory tests (at screening) and physical and neurological examination (at screening and at admission to the clinical unit). If the participant is medically stable with medication, inclusion can be allowed on a case by case basis with written agreement of the sponsor's responsible safety physician
* Women must not be of childbearing potential (must be postmenopausal with amenorrhea for at least 12 months) or permanently sterilized (for example, tubal occlusion, hysterectomy, bilateral salpingectomy)

Exclusion Criteria:

Part 1, 2 and 3:

* Participants with a history of or current significant medical illness including (but not limited to) cardiac arrhythmias or other cardiac disease, hematological disease, lipid abnormalities, bronchospastic respiratory disease, diabetes mellitus, renal or hepatic insufficiency, thyroid disease, Parkinson's disease, infection, or any other illness that the Investigator considers should exclude the participant
* Participants with a serology positive for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibodies or human immunodeficiency virus (HIV) antibodies
* Participants with a clinically significant acute illness within 7 days prior to study drug administration
* Donation of 1 or more units (approximately 450 milliliter \[mL\]) of blood or acute loss of an equivalent amount of blood within 90 days prior to study drug administration

Part 3:

- participants having a contraindication for spinal puncture including:

1. A relevant history of lower back pain or scoliosis or kyphosis and/or major (lumbar) back surgery (microdiscectomy is allowed) in the opinion of the investigator
2. Allergy to local anesthetics and/or iodine/disinfectants
3. Clinically significant abnormal values for coagulation at screening
4. Use of aspirin (even low dose) within 5 days prior to lumbar puncture
5. Use of low molecular weight heparin (LMWH) within 12 hours prior to lumbar puncture
6. Use of any anticoagulant treatment (besides LMWH described above) within 1 week prior to lumbar puncture
7. Has a topical infection or local dermatological condition at the puncture site prior to puncture
8. Has papilloedema or signs of increased intracranial pressure based on fundoscopy at screening

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability: Part 1, Part 2, and Part 3
timeFrame: Approximately 40 days
measure: Maximum Plasma Concentration (Cmax) of JNJ-64140284: Part 1, Part 2, and Part 3
timeFrame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose
measure: Maximum Cerebrospinal Fluid (CSF) Concentration (Cmax) of JNJ-64140284: Part 3
timeFrame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
measure: Last Quantifiable Plasma Concentration (Clast) of JNJ-64140284: Part 1, Part 2, and Part 3
timeFrame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose
measure: Last Quantifiable CSF Concentration (Clast) of JNJ-64140284: Part 3
timeFrame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
measure: Time to Reach Maximum Plasma Concentration (Tmax) of JNJ-64140284: Part 1, Part 2, and Part 3
timeFrame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose
measure: Time to Reach Maximum CSF Concentration (Tmax) of JNJ-64140284: Part 1, Part 2, and Part 3
timeFrame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
measure: Time of the Last Quantifiable Plasma Concentration (Tlast) of JNJ-64140284: Part 1, Part 2, and Part 3
timeFrame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose
measure: Time of the Last Quantifiable CSF Concentration (Tlast) of JNJ-64140284: Part 3
timeFrame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Time of the Last Quantifiable Concentration (AUC [0-last]) of JNJ-64140284: Part 1, Part 2, and Part 3
timeFrame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose
measure: Area Under the CSF Concentration-Time Curve From Time Zero to Time of the Last Quantifiable Concentration (AUC [0-last]) of JNJ-64140284: Part 1, Part 2, and Part 3
timeFrame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of JNJ-64140284: Part 1, Part 2, and Part 3
timeFrame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose
measure: Area Under the CSF Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of JNJ-64140284: Part 3
timeFrame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
measure: Elimination Rate Constant (Lambda[z]) of JNJ-64140284: Part 1, Part 2, and Part 3
timeFrame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose
measure: Elimination Half-life (t1/2) of JNJ-64140284: Part 1, Part 2, and Part 3
timeFrame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post dose
measure: Total Clearance (CL/F) of JNJ-64140284: Part 1, Part 2, and Part 3
timeFrame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose
measure: Creatinine Clearance (CLcr) of JNJ-64140284: Part 1, Part 2, and Part 3
timeFrame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose
measure: Amount of Drug Excreted in Urine From Time Zero to Infinite Time (Aeinf): Part 1
timeFrame: 0-1, 1-2, 2-4, 4-12, and 12-24 hours post dose
measure: Renal Clearance (CLr): Part 1
timeFrame: 0-1, 1-2, 2-4, 4-12, and 12-24 hours post dose
Secondary outcomes:
measure: Bond & Lader Visual Analogue Scale (VAS) Score: Part 1 and Part 3
timeFrame: Days -1, 1, 2 and 3
measure: Karolinska Sleepiness Scale (KSS) Score: Part 1 and Part 3
timeFrame: Days -1, 1, 2 and 3
measure: Profile of Mood States (POMS) Score: Part 1 and Part 3
timeFrame: Days -1, 1, 2 and 3
measure: Body Sway: Part 1
timeFrame: Days -1, 1, 2 and 3
measure: Cognitive Test Battery: International Shopping List Test (ISLT): Part 1
timeFrame: Days -21 to -2, Day -1, and Day 1 (6 hours post dose)
measure: Cognitive Test Battery: Groton Maze Learning Test (GMLT): Part 1
timeFrame: Days -21 to -2, Day -1, Day 1 (2, 4, 6, and 12 hours post dose), and Day 2 (24 hours post dose)
measure: Cognitive Test Battery: Detection Task (DET): Part 1
timeFrame: Days -21 to -2, Day -1, Day 1 (2, 4, 6, and 12 hours post dose), and Day 2 (24 hours post dose)
measure: Cognitive Test Battery: Identification Task (IDN): Part 1
timeFrame: Days -21 to -2, Day -1, Day 1 (2, 4, 6, and 12 hours post dose), and Day 2 (24 hours post dose)
measure: Cognitive Test Battery: One Card Learning Task (OCL): Part 1
timeFrame: Days -21 to -2, Day -1, Day 1 (2, 4, 6, and 12 hours post dose), and Day 2 (24 hours post dose)
measure: Cognitive Test Battery: One Back Task (ONB): Part 1
timeFrame: Days -21 to -2, Day -1, Day 1 (2, 4, 6, and 12 hours post dose), and Day 2 (24 hours post dose)
measure: Cognitive Test Battery: Groton Maze Learning Test (GMLT) Delayed Recall: Part 1
timeFrame: Days -21 to -2, Day -1, and Day 1 (6 hours post dose)
measure: Cognitive Test Battery: International Shopping List Test Delayed (ISLT-D): Part 1
timeFrame: Days -21 to -2, Day -1, Predose, Day 1 (6 hours post dose), and Day 2 (24 hours post dose)
measure: Sheehan Irritability Scale (SIS) Score: Part 1 and Part 3
timeFrame: Day -1, Day 1 (6 and 12 hours post dose), and Day 2 (24 hours post dose)
measure: Cerebrospinal Fluid (CSF) Biomarkers Level: Brain Derived Neurotrophic Factor (BDNF): Part 3
timeFrame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours post dose
measure: Cerebrospinal Fluid (CSF) Biomarkers Level: Monoaminergic Neurotransmitters and Their Metabolites: Part 3
timeFrame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours post dose
Other outcomes:
Locations:
city: Merksem
country: Belgium
facility: Clinical Pharmacology Unit
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: