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 | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036701 |
E.1.2 | Term | Primary 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 |
All Main/Primary objectives are MK-4305 high dose compared to placebo, as measured by change from baseline: MAINTENANCE: 1. Mean subjective total sleep time (sTSTm) at Month 1. 2. Wakefulness after persistent sleep onset (WASO) by PSG at Month 1. 3. Mean subjective total sleep time (sTSTm) at Month 3. 4. Wakefulness after persistent sleep onset (WASO) by PSG at Month 3. ONSET: 5. Mean subjective time to sleep onset (sTSOm) at Month 1. 6. Latency to onset of persistent sleep (LPS) by PSG at Month 1. 7. Mean subjective time to sleep onset (sTSOm) at Month 3. 8. Latency to onset of persistent sleep (LPS) by PSG at Month 3. SAFETY: 9. Safety and tolerability of MK-4305 for up to 3 months of treatment.
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E.2.2 | Secondary objectives of the trial |
MAINTENANCE: Objectives 1 to 2 are MK-4305 high dose compared to placebo, as measured by change from baseline: 1. sTSTm at Week 1 2. WASO at Night 1 Objectives 3 to 8 are MK-4305 low dose compared to placebo, as measured by change from baseline 3. sTSTm at Month 1 4. WASO at Month 1 5. sTSTm at Month 3 6. WASO at Month 3 7. sTSTm at Week 1 8. WASO at Night 1 ONSET: Objectives 9 to 10 are MK-4305 high dose compared to placebo, as measured by change from baseline: 9. sTSOm at Week 1 10. LPS at Night 1 Objectives 11 to 16 are MK-4305 low dose compared to placebo, as measured by change from baseline: 11. sTSOm at Month 1 12. LPS at Month 1 13. sTSOm at Month 3 14. LPS at Month 3 15. sTSOm at Week 1 16. LPS at Night 1 SAFETY: 17. Safety and tolerability of MK-4305 for up to 6 months of treatment
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patient is/reports: 1. Age ≥18 yrs on the day of signing informed consent. 2. Diagnosed with primary insomnia. 3. In good physical and mental health. 4. If ≥ 65 yrs old, scores ≥ 25 on the Mini Mental State Exam. 5. A female who is of reproductive potential, has a negative serum pregnancy test, and agrees to use contraception. 6. Difficulty with initiating and maintaining sleep during the 4 weeks prior to Visit 1 (accordingly to specific protocol criteria). 7. Spending 6.5 to 9 hours nightly in bed on at least 3 out of 7 nights prior to Visit 1. 8. Regular bedtime between 9pm-1am. 9. Willing to refrain from napping while in study. 10. Able to read, understand and complete questionnaires and all diaries. 11. Willing to limit alcohol, caffeine, and nicotine consumption.
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E.4 | Principal exclusion criteria |
Patient is/reports: 1. A female who is pregnant and breastfeeding at Prestudy visit, or expecting to conceive while in study. 2. A history or diagnosis of sleeping disorders. 3. Difficulty sleeping due to a medical condition. 4. A history of neurological disorders. 5. A history of any clinically severe psychological disorder or current psychiatric disorder that requires a prohibited medication. 6. Ongoing depression. 7. A history of substance abuse or dependence. 8. A history or current evidence of a clinically significant cardiovascular disorder or clinically significant ECG at Prestudy Visit. 9. Taking certain prohibited medications. 10. Consuming the equivalent of >15 cigarettes a day. 11. A history of malignancy ≤ 5 years prior to signing informed consent, with the exception of basal cell or squamous cell skin cancer. 12. Morbidly obese. 13. Was previously randomized in another investigational study of MK-4305. 14. Currently participating or has participated in a clinical study within 30 days of signing informed consent.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoints in this study will be derived from polysomnographic measures and from responses in the patient's daily e-diary. PSG values for statistical analysis will be based on standardized readings from a PSG reading center. Subjective data for statistical analysis will be based on patient responses to the morning and evening questionnaires provided in the e-diary.
The following parameters will be evaluated for the high dose vs. placebo comparison as the primary comparison: •MAINTENANCE: o MK-4305 high dose: Change from baseline in mean subjective total sleep time (sTSTm) on the daily e-diary at Month 1 and Month 3. o MK-4305 high dose: Change from baseline in wakefulness after persistent sleep onset (WASO) by PSG at Month 1 and Month 3. •ONSET: o MK-4305 high dose: Change from baseline in mean subjective time to sleep onset (sTSOm) by daily e-diary at Month 1 and Month 3. o MK-4305 high dose: Change from baseline in latency to onset of persistent sleep (LPS) by PSG at Month 1 and Month 3.
Safety endpoints: •Adverse Experience Reporting •Laboratory evaluations (hematology, chemistry, urinalysis) •Urine drug screen •Pregnancy test •Alcohol breath test (PQ-cohort only) •Physical examination •Electrocardiogram (ECG) •Vital signs •Tyrer Withdrawal Symptom Questionnaire via the evening e-diary questionnaire •Digit Symbol Substitution Test (PQ-cohort only) •Columbia Suicide Severity Rating Scale •Motor Vehicle Accidents and Violations
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
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) | No |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 36 |
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 | No |
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 | 2 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial months | 4 |