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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: JNJ-48816274; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Guildford, United Kingdom
  • United Kingdom, United Kingdom

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 Single Dose; Part 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.	Drug: JNJ-48816274; Oral dose; dose range of 5 mg up to 250 mg; Drug: Placebo; Oral dose; appearance matched to JNJ-48816274
Experimental: Part 2 Crossover Sleep Study; Part 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).	Drug: JNJ-48816274; Oral dose; dose range of 5 mg up to 250 mg; Drug: Placebo; Oral dose; appearance matched to JNJ-48816274
Experimental: Part 3 Repeated Dose (Optional); Part 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).	Drug: JNJ-48816274; Oral dose; dose range of 5 mg up to 250 mg; Drug: Placebo; Oral dose; appearance matched to JNJ-48816274

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Treatment Emergent Adverse Events as a Measure of Safety and Tolerability		Up 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 score	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).	Day 1 in Part 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Total Sleep Time by 8-hour overnight Polysomnography	The sum of all minutes of sleep stages 1, 2, 3, and 4 will be assessed.	Part 2: Days 1-2 of each of 3 or 4 crossover periods
Mean Latency to Persistent Sleep by 8-hour overnight Polysomnography	Elapsed time from the beginning of the polysomnography recording to the onset of continuous sleep will be assessed.	Part 2: Days 1-2 of each of 3 or 4 crossover periods
Mean Leeds Sleep Evaluation Questionnaire (LSEQ) Score	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.	Part 2: Day 2 of each of 3 or 4 crossover periods
Mean Subjective Quality of Sleep Questionnaire (SQSQ) Item Scores	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.	Part 2: Day 2 of each of 3 or 4 crossover periods
Mean Karolinska Sleepiness Scale score	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).	Part 2: Days 1-2 of each of 3 or 4 crossover periods; Part 3: Days 1-7
Area Under the Plasma Concentration vs. Time Curve in Subjects who are Fasted Predose vs. Those Fed a Meal	Evaluation of the effect of food consumption on PK of JNJ-48816274.	Part 1: Days 1-2
Correlation Between Plasma Levels of JNJ-48816274 and Karolinska Sleepiness Scale Score	Evaluation of the pharmacokinetic and pharmacodynamic relationship of JNJ-48816274 using a measure of somnolence.	Day 1 of Parts 1 and 3
Correlation Between Plasma Levels of JNJ-48816274 and Duration of Sleep as Measured by 8-hour Overnight Polysomnography	Evaluation of the pharmacokinetic and pharmacodynamic relationship of JNJ-48816274 using a measure of sleep	Part 2: Days 1-2 of each of 3 or 4 crossover periods

Collaborators and Investigators

• Sponsor: Janssen-Cilag International NV
• Investigators: Study Director: Janssen-Cilag International NV Clinical Trial, Janssen-Cilag International NV

Study record dates

Study Major Dates

• Study Start (Actual): August 13, 2016
• Primary Completion (Actual): May 2, 2018
• Study Completion (Actual): May 2, 2018

Study Registration Dates

• First Submitted: July 11, 2016
• First Submitted That Met QC Criteria: July 28, 2016
• First Posted (Estimated): August 2, 2016

Study Record Updates

• Last Update Posted (Actual): April 27, 2025
• Last Update Submitted That Met QC Criteria: April 25, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: CR108090; 48816274EDI1001 (Other Identifier: Janssen-Cilag International NV); 2015-004186-89 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No