To evaluate the effects of JNJ-42847922, compared to zolpidem and placebo, on driving performance as assessed by the mean difference of standard deviation of lateral position (SDLP) after forced awakening using a validated driving simulator test at…
ID
Source
Brief title
Condition
- Sleep disorders and disturbances
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To evaluate the effects of JNJ-42847922, zolpidem and placebo on driving
performance
as assessed by the Mean Lateral Position (MLP), distance-keeping, mean speed,
SD of
speed, head movement, reaction-time, inhibition, alertness and Drive safety
Score (DSS)
after forced awakening using a validated driving simulator test at 2, 4, 6 and
8 hours
post-evening dose.
Secondary outcome
To evaluate the effects of JNJ-42847922, zolpidem and placebo on the subjective
driving performance of the subjects after the driving simulator test at 2, 4, 6
and 8 hours postevening dose.
To evaluate the effects of JNJ-42847922, zolpidem and placebo on a cognitive
test battery at 2, 4, 6 and 8 hours post-evening dose.
To evaluate the effects of JNJ-42847922, zolpidem and placebo on sleepiness at
2, 4, 6 and 8 hours post-evening dose using the Karolinska Sleepiness Scale
(KSS).
To evaluate the effects of JNJ-42847922, zolpidem and placebo on postural
stability (body sway) at 2, 4, 6 and 8 hours post-evening dose.
To investigate the safety and tolerability of 40 mg JNJ-42847922 in healthy
subjects.
To evaluate the potential relationship between duration of changes in driving
ability and plasma concentrations of JNJ-42847922, its metabolites M12 and M16,
and zolpidem.
Background summary
JNJ-42847922 is a potent and selective antagonist of the human orexin-2
receptor (OX2R) that is being developed for the treatment of insomnia and major
depressive disorder (MDD). In rats, JNJ-42847922 quickly and reversibly binds
to the OX2R in the brain after oral administration and reduces sleep latency
and increases total sleep duration whilst not affecting Rapid Eye Movement
(REM) sleep. JNJ-42847922 induced dose-related somnolence in healthy subjects
after daytime administration and decreased the latency to persistent sleep
(LPS) and increased the total sleep time (TST) in MDD patients with insomnia
after nighttime administration of a single dose of 10 mg or higher. During the
phase 1 program, single dose levels of 10 to 80 mg of JNJ-42847922 have been
administered to healthy subjects and single dose levels of 10 to 40 mg have
been administered to subjects with MDD and comorbid insomnia. Dose levels of 5
to 60 mg once daily (q.d.) over 10 days were administered to healthy subjects.
JNJ-42847922 was well tolerated by both healthy subjects and subjects with MDD
with comorbid insomnia.
The results of this study will contribute to a better understanding of the
absence or of possible adverse effects of JNJ-42847922 on driving performance
and cognition. In addition, effects of JNJ-42847922 on driving performance and
cognition will be compared to those elicited by intake of a 10mg dose of
zolpidem to investigate potentially differentiating features.
Study objective
To evaluate the effects of JNJ-42847922, compared to zolpidem and placebo, on
driving performance as assessed by the mean difference of standard deviation of
lateral position (SDLP) after forced awakening using a validated driving
simulator test at 2, 4, 6 and 8 hours post-evening dose.
Study design
This will be a single center, double-blind, randomized, 3-way cross-over, pilot
study in healthy male and female subjects.
Intervention
On Day 1 of each study period, subjects will take the study medication 15
minutes prior to bedtime, The dose of the study medication is: JNJ-42847922: 2
capsules containing 20 mg JNJ-42847922 each
Zolpidem: 1 capsule containing 10 mg zolpidem + 1 capsule placebo
Placebo: 2 capsules placebo.
Study burden and risks
JNJ-42487922 has been administered to healthy male and female subjects for 10
days in doses up to 60-mg [42847922EDI1003] and was well tolerated.
JNJ-42847922 causes somnolence/sedation when administered at daytime. When
administered in the evening, JNJ-42847922 decreases LPS and increases TST
[42847922EDI1002] at all doses tested (10, 20, and 40 mg).
A 40-mg JNJ-42847922 dose level is selected for this study because it has been
demonstrated to be well tolerated, has shown significant benefit on sleep
parameters, and is expected to be in the range of the highest effective dose.
Zolpidem has been selected as a comparator, because it is one of the most
commonly prescribed sleep medications in the EU and USA, and has a well-known
profile of residual effects as assessed during on-the-road driving tests
(Vermeeren 2004, Verster 2004). Zolpidem has been approved in the European
Union and the USA for the treatment of
insomnia. According to the product label of zolpidem in the EU, the dose is 10
mg.
Turnhoutseweg 30
Beerse 2340
BE
Turnhoutseweg 30
Beerse 2340
BE
Listed location countries
Age
Inclusion criteria
-Body mass index (BMI) (weight [kg]/height2[m2]) between 18 and 30 kg/m2 (inclusive)
-Men who are sexually active with a woman of childbearing potential must agree to use a condom, and all men must not donate sperm during the study and for 3 months after receiving the last dose of study drug. In addition, for men who have not had a vasectomy, their female partners should also use an appropriate method of birth control for at least the same duration
-A woman of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test predose on Day 1 of each period
-A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for at least 3 months after receiving the last dose of study drug
-Participant has a valid driving license for more than 3 years, has driven at least 5000 kilometer (km) in the past year and is driving a car regularly
- Women of childbearing potential must practice a highly effective method of birth control consistent with local regulations regarding the use of birth control methods for participants participating in clinical studies (that is, one that results in a less than 1 percent per year failure rate when used consistently and correctly)
Exclusion criteria
-Participant has clinically significant liver or renal insufficiency* cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic (including cataplexy and cognitive
impairment), hematologic, rheumatologic, psychiatric, or metabolic disturbances. A significant primary sleep disorder is exclusionary
-Clinically significant abnormal values for hematology, clinical chemistry, or urinalysis at screening as deemed appropriate by the investigator
- Subject has a history of substance or alcohol use disorder according to Diagnostic and Statistical Manual of Mental Disorders (5th edition) (DSM5) criteria within 6 months before screening or positive test result(s) for alcohol and/or drugs of abuse (opiates [including methadone], cocaine, amphetamines, methamphetamines, cannabinoids, barbiturates, ecstasy and benzodiazepines) at screening or admission on Day 1 of each study period
- Current suicidal or homicidal ideation/intent/behavior
- Serology positive for hepatitis B surface antigen (HBsAg), hepatitis C antibodies (HCV) or Human immunodeficiency virus (HIV) antibodies
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
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Other (possibly less up-to-date) registrations in this register
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In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2015-004203-24-NL |
| CCMO | NL55279.056.15 |