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

• Sponsor: Janssen-Cilag International NV (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02852395
• Collaborator: (none)
• Enrollment: 90
• Locations: 2
• Arms: 3
• Actual Duration (Months): 20.6
• Patients Per Site: 45
• Patients Per Site Per Month: 2.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: JNJ-48816274; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 90 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of JNJ-48816274
• Actual Study Start Date: Aug 13, 2016
• Actual Primary Completion Date: May 2, 2018
• Actual Study Completion Date: May 2, 2018

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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)]

2. Area Under the Plasma Concentration-Time Curve From Time Zero to Time 't' (AUC[0-t]) [Days 1-2 in Part 1]

3. Maximum Observed Plasma Concentration (Cmax) [Day 1 in Part 1]

4. Time to Reach the Maximum Plasma Concentration (Tmax) [Day 1 in Part 1]

5. Elimination Half Life (t1/2) [Days 1-2 in Part 1]

6. Mean Karolinska Sleepiness Scale score [Day 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

1. Mean Total Sleep Time by 8-hour overnight Polysomnography [Part 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.

2. Mean Latency to Persistent Sleep by 8-hour overnight Polysomnography [Part 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.

3. Mean Leeds Sleep Evaluation Questionnaire (LSEQ) Score [Part 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.

4. Mean Subjective Quality of Sleep Questionnaire (SQSQ) Item Scores [Part 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.

5. Mean Karolinska Sleepiness Scale score [Part 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).

6. Area Under the Plasma Concentration vs. Time Curve in Subjects who are Fasted Predose vs. Those Fed a Meal [Part 1: Days 1-2]

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

7. Correlation Between Plasma Levels of JNJ-48816274 and Karolinska Sleepiness Scale Score [Day 1 of Parts 1 and 3]

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

8. Correlation Between Plasma Levels of JNJ-48816274 and Duration of Sleep as Measured by 8-hour Overnight Polysomnography [Part 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Surrey	Guildford		United Kingdom	GU2 7XP
2	Quotient Clinical Limited	United Kingdom		United Kingdom	NG11 6JS

Sponsors and Collaborators

• Janssen-Cilag International NV

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Janssen-Cilag International NV
• ClinicalTrials.gov Identifier: NCT02852395
• Other Study ID Numbers: CR108090; 48816274EDI1001; 2015-004186-89
• First Posted: Aug 2, 2016
• Last Update Posted: Jun 19, 2018
• Last Verified: Jun 1, 2018

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Study Results

No Results Posted as of Jun 19, 2018