| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Patients with Primary Insomnia. |
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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 | 10036701 |
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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 evaluate the efficacy of MK-4305 high dose compared with placebo in improving insomnia: 1.as measured by change from baseline in mean subjective total sleep time (sTSTm) on the daily sleep e-diary at Month 1. 2.as measured by the change from baseline in wakefulness after persistent sleep onset (WASO) at Month1. 3.as measured by change from baseline in mean subjective total sleep time (sTSTm) on the daily sleep e-diary at Month 3. 4.as measured by the change from baseline in wakefulness after persistent sleep onset (WASO) at Month3. 5.as measured by change from baseline in mean subjective time to sleep onset (sTSOm) on the daily sleep e-diary at Month 1. 6.as measured by the change from baseline in latency to onset of persistent sleep (LPS) at Month 1. 7.as measured by change from baseline in mean subjective time to sleep onset (sTSOm) on the daily sleep e-diary at Month 3. 8. as measured by the change from baseline in latency to onset of persistent sleep (LPS) at Month 3. |
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| E.2.2 | Secondary objectives of the trial |
| Maintainence 1.to evaluate the efficacy of MK-4305 high dose compared with placebo in improving insomnia, as measured by change from baseline in mean subjective total sleep time (sTSTm) on the daily sleep e-diary at Week 1. 2.To evaluate the efficacy of MK-4305 high dose compared with placebo in improving insomnia, as measured by the change from baseline in wakefulness after persistent sleep onset (WASO) at Night 1. Onset 3.To evaluate the efficacy of MK-4305 high dose compared with placebo in improving insomnia, as measured by change from baseline in mean subjective time to sleep onset (sTSOm) on the daily sleep e-diary at Week 1. 4.To evaluate the efficacy of MK-4305 high dose compared with placebo in improving insomnia, as measured by the change from baseline in latency to onset of persistent sleep (LPS) at Night 1. |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
| 1. Patient is male or female and ≥18 years of age on the day of signing informed consent. 2. Patient has a DSM-IV-TR (Appendix 6.2) diagnosis of Primary Insomnia based on the investigator’s judgment and the patient’s sleep history as assessed on the Sleep Diagnostic Interview/Sleep History. 3. For a patient ≥65 years of age, (s)he scores ≥25 on the Mini Mental State Examination (MMSE) 4. A female patient who is of reproductive potential has a serum β-hCG level consistent with the nongravid state at Screening Visit 1 and agrees to use acceptable contraception. Acceptable contraception is defined as abstinence (where abstinence is a locally accepted form of contraception) or use of 2 regionally accepted effective forms of contraception including: partner using condom with spermicide or status post vasectomy, and patient using hormonal contraceptives, intra-uterine device (IUD), diaphragm with spermicide, contraceptive sponge. Note that if a male partner does not use an effective form of contraception, a female patient MUST use 2 acceptable forms of contraception to satisfy the study requirement. 5. Patient reports total sleep time of < 6.5 hours on at least 3 out of 7 nights each week during the 4 weeks prior to Visit 1. 6. Patient reports sleep latency of ≥ 30 minutes on at least 3 out of 7 nights each week during the 4 weeks prior to Visit 1. 7. Patient reports ≥ 1 hour of wakefulness after sleep onset on at least 3 out of 7 nights each week during the 4 weeks prior to Visit 1. 8. Patient reports spending 6.5 to 9 hours nightly in bed on at least 3 out of 7 nights each week during the 4 weeks prior to Visit 1. 9. The patient’s regular bedtime is between 9 pm (21:00) and 1 am (01:00). 10. During the study, patient is willing to limit alcohol to 2 drinks a day and at least 3 hours before going to bed. (A drink is defined as a 12 ounce bottle/can of beer (~14 grams alcohol) or a 4-ounce glass of wine (~12 grams alcohol) or 1 ounce of liquor (80 proof or 40 % alcohol, ~9 grams alcohol)). 11. During the study, the patient is willing to limit caffeine consumption to ≤ 5 standard 6-ounce cups of caffeinated beverages a day, or ≤ 600 mg caffeine, avoid caffeine after 4 pm (16:00) 12. Patient demonstrates compliance with the morning and evening diary for the period between Visit 2 and 3. Diary compliance is defined as patient having completed at least 70% [e.g. 5 out of 7 days/nights] of both the morning and evening diaries. |
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| E.4 | Principal exclusion criteria |
| 1.a Patient has a history or diagnosis of any of the following conditions, in the opinion of the investigator: • Narcolepsy • Cataplexy (familial or idiopathic) • Circadian Rhythm Sleep Disorder • Parasomnia including nightmare disorder, sleep terror disorder, sleepwalking disorder, and REM behavior disorder • Sleep-related Breathing Disorder (i.e., obstructive or central sleep apnea syndrome or central alveolar hypoventilation syndrome) • Periodic Limb Movement Disorder • Restless Legs Syndrome • Primary Hypersomnia • Excessive Daytime Sleepiness (EDS), not attributable to Primary Insomnia 1.b In the opinion of the investigator, patient has difficulty sleeping due to a confounding medical condition. NOTE: “Medical Conditions” may include chronic pain syndromes, chronic migraine, cardiac disease, nocturia (> 3 times/night), asthma, gastroesophageal reflux disease (GERD), or hot flashes. 1.c Patient has any history of a neurological disorder, including but not limited to seizure disorder (other than single episodes of childhood febrile seizures), stroke, transient ischemic attack, multiple sclerosis, cognitive impairment, or significant head trauma with sustained loss of consciousness within the last 10 years). 1.d Patient has any of the following: • Lifetime history of bipolar disorder, a psychotic disorder, or posttraumatic stress disorder; or • A psychiatric condition requiring treatment with a prohibited medication; or, • Other psychiatric condition that, in the investigator`s opinion, would interfere with the patient`s ability to participate in the study. 1.e Patient has evidence of ongoing major depression (per MINI), significant depressive symptoms (e.g., a score ≥ 20 on the Quick Inventory of Depressive Symptomatology – Self Report Scale (QIDS-SR16) or suicidal ideation (i.e., scores ≥ 2 on the QIDS-SR16 suicide item #12) or, in the investigator`s opinion, is unable to complete the study procedures in a safe and appropriate fashion (regardless of QIDS-SR16 score). 1.f Patient has a history of substance abuse or dependence (EXCEPTION: patient is currently in sustained full remission for at least one year or meets criteria for early full remission, according to DSM-IV-TR). Substances include alcohol, marijuana, hypnotics, other prescription drugs, and drugs of abuse, but exclude nicotine dependence. A patient who fulfills DSM-IV-TR criteria for sustained remission can be included if he/she, in the investigator’s opinion, is at low risk for further drug dependence or abuse. 1.g Patient has either a history within the past 6 months prior to the Prestudy visit or current evidence of an unstable or clinically significant cardiovascular disorder, including but not limited to: • Acute coronary syndrome • Unstable angina • Congestive heart failure • Cardiogenic syncope • Cardiomyopathy • Any symptomatic arrhythmia 1.h Patient has abnormal pre-randomization laboratory values per the guidance below or other clinically significant, unexplained laboratory abnormality in the opinion of the investigator: • Alanine transaminase (SGPT or ALT) > 1.5 x the upper limit of normal (x ULN) • Aspartate transaminase (SGOT or AST) > 1.5 x ULN • Total bilirubin > 1.5 x ULN • Serum Creatinine of > 2 mg/dL 1.i Patient has a positive screening urine drug screen (e.g., positive for benzodiazepines, cannabinoids, cocaine, etc.). NOTE: The screen may be repeated at investigator`s discretion and as warranted by medical history and concomitant medications. A repeat drug screen must be negative prior to randomization or it must be discussed with the SPONSOR. 1.j Patient is taking, or plans to take, one or more of the following medications (non-inclusive), shown below within the specified washout period prior to Visit 2-Screening (unless specified by a note below) and throughout the course of the study Investigational compounds-4 weeks |
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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 as the primary endpoints: • Maintenance: o Change from baseline in mean subjective total sleep time (sTSTm) on the daily e-diary at Month 1 and Month 3 o Change from baseline in wakefulness after persistent sleep onset (WASO) by PSG at Month 1 and Month 3 • Onset: o Change from baseline in mean subjective time to sleep onset (sTSOm) by daily e-diary at Month 1 and Month 3 o 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 | 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 | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | Yes |
| 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 | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| 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
| 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 | 6 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 0 |
| 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 | 1 |
| E.8.9.1 | In the Member State concerned days | 0 |
| 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 | 1 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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