E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10022437 |
E.1.2 | Term | Insomnia |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To demonstrate an effect of ACT 078573 at 200 mg at treatment start and at 16 days on a set of objective sleep-maintenance endpoints and over 2 weeks on subjective sleep-maintenance endpoint. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are to demonstrate an effect of ACT 078573 • at 200 and 100 mg at treatment start and at 16 days on a set of objective endpoints (Sleep-Initiation, Total Sleep Time, Sleep Quality and delayed Word Recall Test) and over 2 weeks on a set of subjective endpoints (Sleep Initiation, Total Sleep Time, Sleep Quality and delayed Word Recall Test). • at 100 mg at treatment start and at 16 days on a set of objective Sleep Maintenance endpoints and over 2 weeks on a subjective Sleep Maintenance endpoint.
Also included in the secondary objectives is an evaluation of the safety and tolerability of a 16-day oral administration of AC 078573 at doses of 200 and 100 mg.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed informed consent prior to any study mandated procedure. 2. Male or female aged 18–64 years (inclusive) at screening. • Women of childbearing potential must have negative pregnancy tests before randomization and consistently and correctly use (from screening, during the entire study, and for at least 1 month after study drug intake) a reliable method of contraception with a failure rate of < 1% per year (such as implants, injectables, combined oral hormonal contraceptives, some intrauterine devices), sexual abstinence, or vasectomised partner. • Women not of childbearing potential are defined as postmenopausal (i.e., amenorrhea at least 1 year), or surgically or naturally sterile. 3. Body mass index ≥18.5 and < 32 kg/m2. 4. Primary insomnia by Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision (DSM IV TR®) criteria. 5. Self reported history of the following for at least 3 months prior to the screening visit: - Usual time to fall asleep ≥ 30 min - Usual wake time during sleep ≥ 30 min - Usual total sleep time < 6.5 h. confirmed on at least 3 nights (out of 7 consecutive nights prior to Visit 2) on the screening Sleep Diary. 6. Usual bedtime between 20:00 and 01:00 confirmed on at least 5 nights (out of 7 consecutive nights prior to Visit 2) on the screening Sleep Diary. 7. Mean LPS ≥ 20 min (with no night < 15 min), mean WASO ≥ 20 min (with no night < 15 min), and mean TST < 420 min on the 2 PSG screening nights. 8. Ability to communicate well with the investigator, and to understand the study requirements.
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E.4 | Principal exclusion criteria |
a. History of any sleep disorder other than primary insomnia. b. Any axis I disorder other than primary insomnia according to the DSM IV TR® criteria within 6 months prior to the screening visit. c. Apnea / hypopnea index (AHI) ≥ 10/h on the first PSG screening night. d. Apnea or hypopnea event associated with oxygen saturation by pulse oximetry (SpO2) < 80%, on the first PSG screening night. e. Periodic limb movement arousal index (PLMAI) ≥ 10/h on the first PSG screening night. f. Usual daytime napping ≥ 1 hour per day, and ≥ 3 days per week. g. Important caffeine consumption (≥ 500 mg per day). h. Pregnancy or breast feeding. i. Shift work within 3 months prior to the screening visit, planned shift work during study, travel ≥ 3 time zones within 1 week prior to the screening visit, planned travel ≥ 3 time zones during study, or history of circadian rhythm disorders. j. Hematology or biochemistry test results deviating from the normal range to a clinically relevant extent. k. Alcohol or drug abuse within 1 year prior to the screening visit, or inability to refrain from drinking alcohol for at least 3 consecutive days. l. Positive drug test (for benzodiazepines, barbiturates, cannabinoids, opiates, amphetamines, or cocaine) or positive alcohol test on the evening of the PSG screening nights. m. Inability to refrain from smoking for at least 14 hours during the night. n. Unstable medical condition, significant medical disorder within 1 month prior to the screening visit or acute illness at the screening visit. o. Any known factor or disease that might interfere with treatment compliance, study conduct or interpretation of the results such as psychiatric disease, history of non compliance to medical regimens, or unwillingness to comply with study requirements. p. Treatment with Cognitive Behavioral Therapy (CBT) within 1 week prior to the first day of completion of the screening Sleep Diary. q. Unwillingness to refrain from prohibited CNS active drugs (see Appendix 2) for 5 half lives of the respective drug (but at least 1 week) prior to the first day of completion of the screening Sleep Diary, until 24 hours after the last administration of study treatment. r. Treatment with moderate or strong inhibitors of CYP3A4 (see Appendix 12) within 1 week prior to the first PSG screening night. s. Treatment containing simvastatin or lovastatin, at daily doses higher than 20 mg, within 1 day prior to the first PSG screening night. t. Known hypersensitivity or contraindication to drugs of the same class as the study treatment, or any excipients of the drug formulations, or to zolpidem. u. Treatment with another investigational drug within 1 month prior to the screening visit. v. Treatment with drugs metabolized by CYP2D6 isoenzyme with a narrow therapeutic index (see Appendix 12), within 1 day prior to the first PSG screening night. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The change in sleep-maintenance as compared to pre treatment is chosen as the primary endpoint; it includes the following components: • Change from Baseline* to Day 1&2* in WASO. • Change from Baseline* to Day 15&16*in WASO. • Change from Baseline# to Week 1&2# in sWASO.
* ‘Baseline’ is the mean of the 2 PSG screening nights. ‘Day 1&2’, ‘Day 15&16’ are the mean of the corresponding 2 PSG treatment nights.
# ‘Baseline’ is the mean value of the screening Sleep Dairy entries at home between Visit 2 and 3. ‘Week 1&2’ is the mean value based on the Sleep Diary entries at home under double-blind study treatment (between Visit 3 and 4).
WASO is the time spent awake after onset of persistent sleep (time spent in epochs scored as wake after onset of persistent sleep – see the definition of LPS) until ‘lights on’ as determined by PSG.
sWASO is the self-reported time spent awake after sleep onset as reported in the Sleep Diary.
Assumptions for sample size estimation: • a WASO difference of 20 min compared to placebo is to be detected. • normal distribution of the change from Baseline* in WASO with a standard deviation of 40 min. • an sWASO difference of 20 min compared to placebo is to be detected. • normal distribution of the change from Baseline# in sWASO with a standard deviation of 50 min.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 55 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 4 |