E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
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 safety and tolerability of of MK-4305 for up to 12 months of treatment. |
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E.2.2 | Secondary objectives of the trial |
1. To evaluate the efficacy of MK-4305 compared with placebo in improving insomnia, as measured by change from baseline in subjective total sleep time (sTST) on the sleep diary during the first month of treatment (using the average of weekly measurements [Weeks 1, 2, 3 and 4]).
2. To evaluate the efficacy of MK-4305 compared with placebo in improving insomnia, as measured by change from baseline in subjective time to sleep onset (sTSO) on the sleep diary during the first month of treatment.
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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), to rule out cognitive impairment in the interest of safety for the patient. NOTE: If <65 years old, answer "YES" except in cases where administration of the MMSE to the patient <65 seems indicated in the opinion of the investigator. 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 non-hormonal forms of contraception including: partner using condom with spermicide or status post vasectomy, and patient using 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 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. Patient has a recent and/or active history of a confounding 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 and residual impairment within the last 10 years. 2. Patient has either a history within the past 6 months prior to the Screening Visit 1 or current evidence of an unstable or otherwise clinically significant cardiovascular disorder, including but not limited to: acute coronary syndrome unstable angina, congestive heart failure cardiogenic syncope cardiomyopathy any symptomatic arrhythmia 3. Patient has abnormal screening laboratory values per the guidelines below, or in the opinion of the investigator has any other clinically significant laboratory abnormality: Alanine transaminase (SGPT or ALT) > 1.5 times 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 4. Patient is taking, or plans to take, one or more of the following medications (non-inclusive), shown below, within the specified washout periods prior to Screening Visit 2 and throughout the course of the study: Investigational compounds-4 weeks or 5 t½ lives (which ever is longer) Clinically relevant CYP3A4 Inhibitors and Inducers-2 weeks or 5 t½ lives (which ever is longer) Centrally acting anticholinergics or antihistamines-2 weeks Melatonin-2 weeks Anticonvulsants-2 weeks Antipsychotics-2 weeks Anxiolytics-2 weeks Benzodiazepines-2 weeks or 5 t½ lives (which ever is longer) Hypnotics-2 weeks or 5 t½ lives (which ever is longer) Any CNS depressants-2 weeks Over-the-counter medications that could affect sleep [e.g., kava-kava, valerian, Benadryl (diphenhydramine) St. Johns wort] -2 weeks Stimulants-2 weeks Diet pills-2 weeks
5. Patient has any of the following: a. A lifetime history of bipolar disorder, a psychotic disorder, or posttraumatic stress disorder; b. A psychiatric condition requiring treatment with a prohibited medication; or c. Other current psychiatric condition that, in the investigator's opinion, would interfere with the patient's ability to participate in the study. 6. Patient has evidence of suicidality (based on a score of ≥ 2 on the QIDS-SR16 suicide item #12) or, in the investigator's opinion, is otherwise impaired in such a way as to be unable to complete the study procedures in a safe and appropriate fashion (regardless of QIDS-SR16 score). 7. Patient, in the opinion of the Investigator, has difficulty sleeping due to tobacco, caffeine, or alcohol use. 8. Patient has a history of malignancy ≤ 5 years prior to signing informed consent, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer. 9. Patient has a history of transmeridian travel (across > 3 time zones or > 3 hour time difference) within the past 2 weeks. 10. Patient has a history of shift work (defined as permanent night shift or rotating day/night shift work) within the past 2 weeks or anticipates need to perform shift work during the study. 11. Patient has a history or diagnosis of any of following conditions, in the opinion of the investigator: a. Narcolepsy b. Cataplexy (familial or idiopathic) c. Circadian Rhythm Sleep Disorder d. Parasomnia including nightmare disorder, sleep terror disorder, sleepwalking disorder, and REM behavior disorder e. Sleep-related Breathing Disorder (obstructive or central sleep apnea syndrome, central alveolar hypoventilation syndrome) f. Periodic Limb Movement Disorder g. Restless Legs Syndrome h. Primary Hypersomia 12. 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 migraines, cardiac disease, nocturia (>3 times/night), asthma, gastroesophageal reflux disease (GERD), or hot flashes. 13. The patient has a Body Mass Index (BMI) > 40 kg/m2. BMI is calculated by taking the subject’s weight in kg and dividing by the subject’s height in meters, squared.
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E.5 End points |
E.5.1 | Primary end point(s) |
• adverse experiences (AEs), • laboratory values, • ECGs, • physical examinations, • vital signs, • rebound insomnia and withdrawal effects. • The Columbia - Classification Algorithm of Suicide Assessment (C-CASA) scores from the C-SSRS will also be evaluated
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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 | 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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 43 |
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 | 2 |
E.8.9.1 | In the Member State concerned days | 14 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial days | 14 |