To investigate the effect of JNJ-42847922 given as monotherapy as compared to placebo on symptoms of depression in male and female MDD patients
ID
Source
Brief title
Condition
- Mood disorders and disturbances NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Depressive symptoms: the structured interview guide for the Hamilton Depression
Scale (SIGH-D) will be completed at baseline and during the visits.
Secondary outcome
Mood Symptoms:
• the MADRS
• the QIDS-SR16, B&L VAS and the POMS
Cognitive function:
• A cognitive test battery that includes tests to evaluate attention, immediate
and delayed verbal and visual memory, working memory, and executive function.
Sleep quality:
• the time to sleep onset, total sleep time (TST), time awake during the night
and time of awakening will be recorded in a sleep diary.
• For polysomnography (PSG) measurements subjects will be instructed to go to
bed between 10:00 pm and 12:00 am (midnight) and remain in bed for 8 hours.
TST, wake after sleep onset, latency to persistent sleep, time spent awake,
time spent in deep sleep, and sleep efficiency will be registered.
Rumination:
• the Ruminative Response Scale (RRS), a 22 item self-report measure of
rumination, the Sleep and worry VAS which asks the subjects in the morning
after wake up whether they could not sleep due to worrying and ongoing
thoughts.
Hyperarousal:
Heart Rate Variability (HRV) will be derived from Holter recordings overnight
and will be evaluated for arousal. Quantitative EEG (qEEG) will be recorded in
a quiet environment with the eyes open for 2 minute and the eyes closed for 2
minutes.
Pharmacokinetic endpoints
Venous blood samples of 3 mL will be collected for determination of
JNJ-42847922 plasma concentrations and metabolites.
Tolerability / safety endpoints
Adverse events will be reported from screening until follow-up. Because of the
mechanism of action, investigators should pay special attention to parasomnias
and episodes of cataplexy. Safety parameters like blood pressure, pulse/heart
rate measurements, temperature physical examination and ECG will be performed
for safety monitoring. An interview (the C-SSRS) to assess the risk of suicidal
ideation and behavior will be conducted.
Background summary
The selectivity of JNJ-42847922 for the OX2R (approximate 2 logs selectivity
ratio versus OX1R) confers blunting of the stress response of the HPA axis
(ACTH release). This inhibition of the HPA axis response is only partially
attenuated by pre-treatment with DORAs in preclinical psychological stress
models. Since the administration of JNJ-42847922 still reduces response of the
HPA axis after treatment with DORAs, antagonism of OX1R is thought to
counteract the stress inhibition produced by antagonism of the OX2R. MDD is
associated with sustained increases in cortisol levels and it is hypothesized
that JNJ-42847922 can attenuate this HPA axis activation and subsequently
reduce symptoms of depression. This hypothesis was tested in study
42847922MDD1001/CHDR1504 in which a potentially relevant antidepressant effect
with early onset (as early as Day 11 of exposure) of 20 mg JNJ-42847922 versus
placebo and diphenhydramine was demonstrated in a small number of patients with
MDD. Since this was an exploratory study in a small sample, these initial
results warranted a study in a larger sample of MDD patients.
Study objective
To investigate the effect of JNJ-42847922 given as monotherapy as compared to
placebo on symptoms of depression in male and female MDD patients
Study design
This will be a multi-center, placebo-controlled, randomized, double-blind study
in subjects with MDD not currently treated with antidepressant drugs.
For each subject, the study will consist of four phases: a screening phase of
up to 3 weeks, a baseline period including a 48-hour in-house baseline visit, a
double-blind treatment phase lasting up to 8 weeks, and a 1 week post-treatment
(follow up) phase. The double-blind treatment phase of the trial will consist
of 3 periods:
o period 1: a double-blind placebo lead-in period of variable duration
o period 2: at the end of the lead-in period subjects will be divided into 2
groups: placebo lead-in responders and placebo lead-in non-responders. Each
group will be randomized to receive 20 or 40 mg JNJ 42847922 or continue
placebo for 5 weeks during the double-blind treatment period.
o period 3: subjects who complete the treatment period prior to the end of Week
8, will then enter the double-blind withdrawal period and be treated with
placebo for the remaining time of the double-blind phase of the study. The
withdrawal period will be used to assess whether there are signs of withdrawal.
The duration of the withdrawal period will vary depending on the duration of
the placebo lead-in period for the specific subject.
The total study duration for each subject will be approximately 13 weeks. There
will be 11 scheduled visits to the clinical research center including screening
and follow-up during the study period.
Intervention
JNJ-42847922 is a potent and selective antagonist of the human orexin-2
receptor (OX2R) that is being developed for the treatment of major depressive
disorder (MDD) and the treatment of insomnia disorder.
Study burden and risks
To date, 11 Phase 1 clinical studies and 1 Phase 2 study have been completed
with oral suspension and solid dosage formulations of JNJ-42847922. Overall, an
estimated 389 subjects, have been exposed to JNJ-42847922 in the clinical
development. All of these subjects were exposed to JNJ-42847922 in either Phase
1 or Phase 2 clinical trials. Subject may not benefit from the study in terms
of long term improvement of their symptoms, however they may benefit from the
extensive medical review and disease follow-up during the study. Additionally,
the safety and tolerability data so far accumulated for JNJ-42847922 in both
healthy subjects and subjects with MDD and/or insomnia were generally
acceptable based on a thorough review of the safety information from completed
clinical studies. No death or SAEs have been reported after subjects received
JNJ-42847922. The most commonly reported TEAEs were somnolence, headache, and
dizziness with most TEAEs being mild or moderate in intensity. ADRs attributed
to JNJ-42847922 were sleep paralysis, somnolence, and abnormal dreams. Few
subjects reported these events at doses planned for this study and
all were self-limiting and mild or moderate in intensity.
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Listed location countries
Age
Inclusion criteria
1. 18 to 55 years of age (inclusive).
2. Body Mass Index (BMI) between 18 and 35 kg/m2 inclusive
3. Meets DSM (edition IV or 5) diagnostic criteria for MDD (ICD-code F32.x and F33.x), without psychotic features, and confirmed by the MINI. The length of the current depressive episode must be <=2 years.
4. MADRS total score >25 at screening and must not demonstrate a clinically significant change (i.e., an improvement of >20% on their MADRS total score) from the screening to baseline visit, i.e., subjects must have a MADRS total score of at least 20 at the baseline visit.
5. Not currently receive antidepressant drug therapy for >= 2 weeks before screening.
Exclusion criteria
1. Current or past clinically significant disease of the renal, hepatic, musculoskeletal, gastrointestinal, cardiovascular systems, immunological, endocrine, metabolic, or neurological disease.
2. Signs or symptoms of Cushing*s Disease, Addison*s Disease, primary amenorrhea, or other evidence of significant medical disorders of the HPA axis.
3. Primary DSM (4th or 5th edition) diagnosis of general anxiety disorder (GAD), panic disorder, obsessive compulsive disorder (OCD), posttraumatic stress disorder (PTSD).
4. Current or recent history of clinically significant suicidal ideation within the past 6 months.
5. History of drug or alcohol abuse or dependence according to DSM-IV or 5 criteria, except nicotine or caffeine, within 6 months before screening.
6. Prior electroconvulsive therapy (ECT), vagal nerve stimulation (VNS), or a deep brain stimulation (DBS) device.
7. Narcolepsy, severe obstructive sleep apnea/hypopnea, central sleep apnea, sleep-related, hypoventilation, circadian rhythm sleep-wake disorders, diagnosed with severe restless legs syndrome, substance/medication-induced sleep disorder or parasomnias (NREM sleep arousal disorders, nightmare disorder, REM sleep behavior disorder).
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2017-002633-28-NL |
| CCMO | NL63487.056.17 |