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A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of JNJ-48816274

Phase 1
Completed
Conditions
Healthy
Interventions
Drug: Placebo
Registration Number
NCT02852395
Lead Sponsor
Janssen-Cilag International NV
Brief Summary

This is a 3-part study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of JNJ-48816274 in healthy participants after administration of single and repeated doses, and to evaluate its potential effectiveness for treating insomnia.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
90
Inclusion Criteria
  • Must be healthy as assessed by medical history and safety evaluations performed at screening
  • Has a body mass index between 18 and 30 kilogram per square meter (kg/m2) and body weight not less than 50 kg
  • Must be willing and able to abide by the prohibitions and restrictions of the study, including requirements for contraception
  • Women must not be of childbearing potential by either being postmenapausal or permanently sterilized
  • Part 2 Only: Maintains a regular sleep-wake cycle as measured by sleep diaries and a watch that measures activity
  • Has a habitual (majority of days) bedtime and duration of sleep that meet the study requirements
Exclusion Criteria
  • Current or history of clinically significant medical or psychiatric illness, or recent major surgery or blood loss/donation
  • Any current sleep-wake disorder, recent night shift work, or history of insomnia within the last 5 years
  • Man who has a pregnant female partner
  • Woman who is breastfeeding
  • Is participating or has participated within the last 3 months in a study with an investigational drug or medical device
  • Tests positive or has a history of human immunodeficiency virus (HIV), hepatitis B, hepatitis C, or other active liver disease
  • Drug or alcohol abuse within the last 5 years, nicotine use within the last 3 months, or tests positive for alcohol, drugs of abuse, or nicotine
  • Routinely consumes an excessive amount of caffeine

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Part 1 Single DosePlaceboPart 1 single daytime oral dose of JNJ-48816274 or placebo. Doses of JNJ-48816274 will start at 5 milligram (mg) and increase sequentially to a maximum dose of 250 mg.
Part 1 Single DoseJNJ-48816274Part 1 single daytime oral dose of JNJ-48816274 or placebo. Doses of JNJ-48816274 will start at 5 milligram (mg) and increase sequentially to a maximum dose of 250 mg.
Part 2 Crossover Sleep StudyPlaceboPart 2 single nighttime oral dose of JNJ-48816274 or placebo administered during each of 3 or 4 crossover periods separated by 7-9 days. The doses of JNJ-48816274 will be selected based on data from Part 1 (not to exceed 250 mg).
Part 3 Repeated Dose (Optional)JNJ-48816274Part 3 daytime oral dose of JNJ-48816274 or placebo administered once daily for 7 consecutive days. Doses will be determined based on data from Part 1, and may increase sequentially (not to exceed 250 mg/day).
Part 3 Repeated Dose (Optional)PlaceboPart 3 daytime oral dose of JNJ-48816274 or placebo administered once daily for 7 consecutive days. Doses will be determined based on data from Part 1, and may increase sequentially (not to exceed 250 mg/day).
Part 2 Crossover Sleep StudyJNJ-48816274Part 2 single nighttime oral dose of JNJ-48816274 or placebo administered during each of 3 or 4 crossover periods separated by 7-9 days. The doses of JNJ-48816274 will be selected based on data from Part 1 (not to exceed 250 mg).
Primary Outcome Measures
NameTimeMethod
Number of Participants with Treatment Emergent Adverse Events as a Measure of Safety and TolerabilityUp to 14 days after last dose in Part 1 (approximately 5.5 weeks)
Area Under the Plasma Concentration-Time Curve From Time Zero to Time 't' (AUC[0-t])Days 1-2 in Part 1
Maximum Observed Plasma Concentration (Cmax)Day 1 in Part 1
Time to Reach the Maximum Plasma Concentration (Tmax)Day 1 in Part 1
Elimination Half Life (t1/2)Days 1-2 in Part 1
Mean Karolinska Sleepiness Scale scoreDay 1 in Part 1

A 1-item questionnaire completed by participants to rate their degree of sleepiness on a scale of 1 to 9, ranging from 'extremely alert' (1) to 'very sleepy, great effort to keep awake, fighting sleep' (9).

Secondary Outcome Measures
NameTimeMethod
Area Under the Plasma Concentration vs. Time Curve in Subjects who are Fasted Predose vs. Those Fed a MealPart 1: Days 1-2

Evaluation of the effect of food consumption on PK of JNJ-48816274.

Correlation Between Plasma Levels of JNJ-48816274 and Karolinska Sleepiness Scale ScoreDay 1 of Parts 1 and 3

Evaluation of the pharmacokinetic and pharmacodynamic relationship of JNJ-48816274 using a measure of somnolence.

Mean Total Sleep Time by 8-hour overnight PolysomnographyPart 2: Days 1-2 of each of 3 or 4 crossover periods

The sum of all minutes of sleep stages 1, 2, 3, and 4 will be assessed.

Mean Latency to Persistent Sleep by 8-hour overnight PolysomnographyPart 2: Days 1-2 of each of 3 or 4 crossover periods

Elapsed time from the beginning of the polysomnography recording to the onset of continuous sleep will be assessed.

Mean Leeds Sleep Evaluation Questionnaire (LSEQ) ScorePart 2: Day 2 of each of 3 or 4 crossover periods

A participant-reported 10-item visual analogue scale used to rate the quality of sleep. A 100 millimeter (mm) line used for ratings, with higher scores representing better sleep-wake characteristics.

Mean Subjective Quality of Sleep Questionnaire (SQSQ) Item ScoresPart 2: Day 2 of each of 3 or 4 crossover periods

A participant-reported 10-item questionnaire to estimate the time to fall asleep, duration of sleep, number of awakenings, sleep quality, and feeling upon awakening.

Mean Karolinska Sleepiness Scale scorePart 2: Days 1-2 of each of 3 or 4 crossover periods; Part 3: Days 1-7

A 1-item questionnaire completed by participants to rate their degree of sleepiness on a scale of 1 to 9, ranging from 'extremely alert' (1) to 'very sleepy, great effort to keep awake, fighting sleep' (9).

Correlation Between Plasma Levels of JNJ-48816274 and Duration of Sleep as Measured by 8-hour Overnight PolysomnographyPart 2: Days 1-2 of each of 3 or 4 crossover periods

Evaluation of the pharmacokinetic and pharmacodynamic relationship of JNJ-48816274 using a measure of sleep

Trial Locations

Locations (2)

University of Surrey

🇬🇧

Guildford, United Kingdom

Quotient Clinical Limited

🇬🇧

United Kingdom, United Kingdom

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