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

Study Overview
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Brief Summary
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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.

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

Conditions
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Healthy

Intervention / Treatment
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* Drug: JNJ-48816274
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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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 |