A Study to Investigate Safety and Tolerability, Pharmacokinetics and Pharmacodynamics of JNJ-64140284 in Healthy Participants

NCT03180762 | Terminated Phase 1

• 3 other identifiers: CR1083182017-000283-1664140284EDI1001
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (19)

• Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability: Part 1, Part 2, and Part 3

  An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.

  Approximately 40 days

• Maximum Plasma Concentration (Cmax) of JNJ-64140284: Part 1, Part 2, and Part 3

  The Cmax is the maximum observed plasma concentration.

  Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose

• Maximum Cerebrospinal Fluid (CSF) Concentration (Cmax) of JNJ-64140284: Part 3

  The Cmax is the maximum observed CSF concentration.

  Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose

• Last Quantifiable Plasma Concentration (Clast) of JNJ-64140284: Part 1, Part 2, and Part 3

  The Clast is the last quantifiable plasma concentration.

  Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose

• Last Quantifiable CSF Concentration (Clast) of JNJ-64140284: Part 3

  The Clast is the last quantifiable CSF concentration.

  Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose

• Time to Reach Maximum Plasma Concentration (Tmax) of JNJ-64140284: Part 1, Part 2, and Part 3

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

  Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose

• Time to Reach Maximum CSF Concentration (Tmax) of JNJ-64140284: Part 1, Part 2, and Part 3

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

  Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose

• Time of the Last Quantifiable Plasma Concentration (Tlast) of JNJ-64140284: Part 1, Part 2, and Part 3

  The Tlast is defined as the time of the last quantifiable plasma concentration.

  Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose

• Time of the Last Quantifiable CSF Concentration (Tlast) of JNJ-64140284: Part 3

  The Tlast is defined as the time of the last quantifiable CSF concentration.

  Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose

• 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

  The (AUC \[0-last\]) is the area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration.

  Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose

• 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

  The (AUC \[0-last\]) is the area under the CSF concentration-time curve from time 0 to time of the last quantifiable concentration.

  Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose

• 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

  The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(0-last) and C(0-last)/lambda(z), wherein AUC(0-last) is the area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentrations; C(0-last) is the last observed quantifiable concentration; and lambda(z) is elimination rate constant.

  Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose

• Area Under the CSF Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of JNJ-64140284: Part 3

  The AUC (0-infinity) is the area under the CSF concentration-time curve from time zero to infinite time, calculated as the sum of AUC(0-last) and C(0-last)/lambda(z), wherein AUC(0-last) is the area under the CSF concentration-time curve from time 0 to time of the last quantifiable concentrations; C(0-last) is the last observed quantifiable concentration; and lambda(z) is elimination rate constant.

  Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose

• Elimination Rate Constant (Lambda[z]) of JNJ-64140284: Part 1, Part 2, and Part 3

  Lambda(z) is first-order rate constant associated with the terminal portion of the curve, determined as the negative slope of the terminal log-linear phase of the drug concentration-time curve.

  Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose

• Elimination Half-life (t1/2) of JNJ-64140284: Part 1, Part 2, and Part 3

  The 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).

  Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post dose

• Total Clearance (CL/F) of JNJ-64140284: Part 1, Part 2, and Part 3

  CL/F is the total clearance of drug after extravascular administration, uncorrected for absolute bioavailability.

  Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose

• Creatinine Clearance (CLcr) of JNJ-64140284: Part 1, Part 2, and Part 3

  CLcr will be determined with the Cockcroft-Gault formula.

  Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose

• Amount of Drug Excreted in Urine From Time Zero to Infinite Time (Aeinf): Part 1

  Aeinf is the cumulative amount of study drug excreted into urine from time of dosing extrapolated to time infinity.

  0-1, 1-2, 2-4, 4-12, and 12-24 hours post dose

• Renal Clearance (CLr): Part 1

  The CLr is the renal clearance of the drug.

  0-1, 1-2, 2-4, 4-12, and 12-24 hours post dose

Secondary Outcomes (15)

• Bond & Lader Visual Analogue Scale (VAS) Score: Part 1 and Part 3

  Days -1, 1, 2 and 3

• Karolinska Sleepiness Scale (KSS) Score: Part 1 and Part 3

  Days -1, 1, 2 and 3

• Profile of Mood States (POMS) Score: Part 1 and Part 3

  Days -1, 1, 2 and 3

• Body Sway: Part 1

  Days -1, 1, 2 and 3

• Cognitive Test Battery: International Shopping List Test (ISLT): Part 1

  Days -21 to -2, Day -1, and Day 1 (6 hours post dose)

Study Arms (8)

Part 1: Cohort 1 (JNJ-64140284 or Placebo)

EXPERIMENTAL

Participants will receive 0.1 milligram (mg) JNJ-64140284 or matching placebo under fasted condition on Day 1.

Drug: JNJ-64140284 0.1 mg; Drug: Placebo

Part 1: Cohort 2 (JNJ-64140284 or Placebo)

EXPERIMENTAL

Participants will receive 0.5 mg JNJ-64140284 or matching placebo under fasted condition on Day 1.

Drug: JNJ-64140284 0.5 mg; Drug: Placebo

Part 1: Cohort 3 (JNJ-64140284 or Placebo)

EXPERIMENTAL

Participants will receive 2.5 mg JNJ-64140284 or matching placebo under fasted condition on Day 1.

Drug: JNJ-64140284 2.5 mg; Drug: Placebo

Part 1: Cohort 4 (JNJ-64140284 or Placebo)

EXPERIMENTAL

Participants will receive 10 mg JNJ-64140284 or matching placebo under fasted condition on Day 1.

Drug: JNJ-64140284 10 mg; Drug: Placebo

Part 1: Cohort 5 (JNJ-64140284 or Placebo)

EXPERIMENTAL

Participants will receive 50 mg JNJ-64140284 or matching placebo under fasted condition on Day 1.

Drug: JNJ-64140284 50 mg; Drug: Placebo

Part 1: Cohort 6 (JNJ-64140284 or Placebo)

EXPERIMENTAL

Participants will receive 150 mg JNJ-64140284 or matching placebo under fasted condition on Day 1.

Drug: JNJ-64140284 150 mg; Drug: Placebo

Part 2: Cohort 7 (JNJ-64140284)

EXPERIMENTAL

Participants will receive JNJ-64140284 (dose to be determined - the dose of JNJ-64140284 will be determined on the basis of acceptable safety, tolerability and pharmacokinetics \[PK\] of preceding dose levels; no more than 50 percent (%) of the highest dose tested \[though as high as possible within this restriction\] and considered well tolerated in Part 1) under fed conditions on Day 1.

Drug: JNJ-64140284 (dose to be determined [TBD])

Part 3: Cohort 8 (JNJ-64140284 or Placebo)

EXPERIMENTAL

Participants will receive JNJ-64140284 or matching placebo (dose to be determined - dose will be determined based on PK data from previous cohorts and which will be well-tolerated in Part 1) under fasted condition on Day 1.

Drug: JNJ-64140284 (dose to be determined [TBD]); Drug: Placebo

Interventions

JNJ-64140284 0.1 mg DRUG

0.1 mg of JNJ-64140284 will be administered as an oral solution.

Part 1: Cohort 1 (JNJ-64140284 or Placebo)

JNJ-64140284 0.5 mg DRUG

0.5 mg of JNJ-64140284 will be administered as an oral solution.

Part 1: Cohort 2 (JNJ-64140284 or Placebo)

JNJ-64140284 2.5 mg DRUG

2.5 mg of JNJ-64140284 will be administered as an oral solution.

Part 1: Cohort 3 (JNJ-64140284 or Placebo)

JNJ-64140284 10 mg DRUG

10 mg of JNJ-64140284 will be administered as an oral solution.

Part 1: Cohort 4 (JNJ-64140284 or Placebo)

JNJ-64140284 50 mg DRUG

50 mg of JNJ-64140284 will be administered as an oral solution.

Part 1: Cohort 5 (JNJ-64140284 or Placebo)

JNJ-64140284 150 mg DRUG

150 mg of JNJ-64140284 will be administered as an oral solution.

Part 1: Cohort 6 (JNJ-64140284 or Placebo)

JNJ-64140284 (dose to be determined [TBD]) DRUG

JNJ-64140284 (dose to be determined) will be administered as an oral solution.

Part 2: Cohort 7 (JNJ-64140284); Part 3: Cohort 8 (JNJ-64140284 or Placebo)

Placebo DRUG

Matching placebo will be administered.

Part 1: Cohort 1 (JNJ-64140284 or Placebo); Part 1: Cohort 2 (JNJ-64140284 or Placebo); Part 1: Cohort 3 (JNJ-64140284 or Placebo); Part 1: Cohort 4 (JNJ-64140284 or Placebo); Part 1: Cohort 5 (JNJ-64140284 or Placebo); Part 1: Cohort 6 (JNJ-64140284 or Placebo); Part 3: Cohort 8 (JNJ-64140284 or Placebo)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Part 1 and 2:
• \- Healthy male participants between 18 and 58 years of age, inclusive
• Part 1, 2 and 3:
• Part 3:
• Healthy male and female participants between 59 and 75 years of age, inclusive
• 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)

You may not qualify if:

• 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:
• 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
• Allergy to local anesthetics and/or iodine/disinfectants
• Clinically significant abnormal values for coagulation at screening
• Use of aspirin (even low dose) within 5 days prior to lumbar puncture
• Use of low molecular weight heparin (LMWH) within 12 hours prior to lumbar puncture
• Use of any anticoagulant treatment (besides LMWH described above) within 1 week prior to lumbar puncture
• Has a topical infection or local dermatological condition at the puncture site prior to puncture
• Has papilloedema or signs of increased intracranial pressure based on fundoscopy at screening

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (1)

Clinical Pharmacology Unit

Merksem, 2170, Belgium

Location

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 30, 2017
• First Posted: June 8, 2017
• Study Start: May 30, 2017
• Primary Completion: September 25, 2017
• Study Completion: September 25, 2017
• Last Updated: October 30, 2018

Record last verified: 2018-10

Locations

BE (1)