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 | 12.0 |
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 |
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 (using the average of weekly measurements [Weeks 1, 2, 3 and 4]). .
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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. Patient understands the study procedures, alternative treatments available, and risks involved with the study, and voluntarily agrees to participate by giving written informed consent. 4. Patient is able to read, understand and complete questionnaires and diaries, including operation of the eDiary. 5. For patients who have no secondary education, the patients will read the first 2 paragraphs of the informed consent. Patients with any secondary education (any formal education beyond 8th grade) do not need to conduct a reading assessment. 6. 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 in the opinion of the investigator administration of the MMSE to the patient <65 is indicated. 7. 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. 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. Patients taking oral contraceptives may continue use during the trial, but must use 2 additional forms of non-hormonal contraception throughout the study. The contraceptive requirements have been modified in amendment 03 by the SPONSOR after data regarding lack of interaction of MK-4305 with oral contraceptives become available. 8. Patient demonstrates compliance with the morning and evening e-diary for the period between Visit 2 and 3. E-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 e-diaries.
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E.4 | Principal exclusion criteria |
1. If female, patient is pregnant, breastfeeding, or expecting to conceive within the projected duration of the study. 2. Patient is expecting to donate egg or sperm during the study. 3. Patient has a history of hypersensitivity or idiosyncratic reaction to more than two chemical classes of drugs, including prescriptions and over-the-counter medications. 4. Patient has a history or current evidence of any condition, therapy, lab or ECG abnormality or other circumstances that might confound the results of the study, or interfere with the patient's participation for the full duration of the study, such that it's not in the best interest of the patient to participate. 5. Patient has a recent and/or active history of a confounding neurological disorder, including but not limited to: seizure disorder, 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. 6. 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 7. Patient at Screening Visit 1 has a clinically significant ECG abnormality such as AV conduction disturbance, sick sinus syndrome, bradycardia, accessory bypass tract, or current evidence of long QT syndrome or Torsades de pointe. 8. 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 9. 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 • 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 • Hypnotics: 2 weeks or 5 t½ lives • Any CNS depressants: 2 weeks • Over-the-counter medications that could affect sleep: 2 weeks • Stimulants: 2 weeks • Diet pills: 2 weeks 10. Patient has a positive screening urine drug screen 11. Patient has any of the following: •A lifetime history of bipolar disorder, a psychotic disorder, or posttraumatic stress disorder; •A psychiatric condition requiring treatment with a prohibited medication; or •Other current psychiatric condition that would interfere with the patient's ability to participate in the study. 12. Patient has evidence of suicidality or is otherwise impaired in such a way as to be unable to complete the study procedures in a safe and appropriate fashion. 13. Patient has a history of substance abuse or dependence. 14. Patient has difficulty sleeping due to tobacco, caffeine, or alcohol use. 15. 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. 16. Patient has a history of transmeridian travel within the past 2 weeks. 17. Patient has a history of shift work within the past 2 weeks or anticipates need to perform shift work during the study. 18. Patient has a history or diagnosis of any of following conditions: •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 •Periodic Limb Movement Disorder •Restless Legs Syndrome •Primary Hypersomia 19. Patient has difficulty sleeping due to a confounding medical condition. 20. The patient has a Body Mass Index (BMI) > 40 kg/m2. 21. Patient has donated blood products or has had phlebotomy of > 300 mL within 8 weeks of signing informed consent, or intends to donate or receive blood products during participation in the study. 22. Patient is unlikely to adhere to the study procedures and restrictions, keep appointments or is planning to relocate during the study. 23. Patient is currently participating or has participated in a study with an investigational compound or device within 30 days of signing informed consent, or is unwilling to refrain from participating in other concurrent studies. 24. Patient has participated in another investigational study of MK4305.
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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 | 9 |
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 | 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 |