| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| 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 |
|
| 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-6096 compared with placebo in improving sleep efficiency (SE) as measured by polysomnography (PSG) on Night 1 and at the end of 4 weeks of treatment, where SE is defined as 100 times total sleep time (minutes) divided by time in bed (minutes). And, to evaluate the safety and tolerability of MK-6096. |
|
| E.2.2 | Secondary objectives of the trial |
| To evaluate the efficacy of MK-6096 compared with placebo in improving wake after sleep onset (WASO) as measured by PSG on Night 1 and at the end of 4 weeks of treatment. And, to evaluate the efficacy of MK-6096 compared with placebo in improving latency to persistent sleep (LPS) as measured by PSG on Night 1 and at the end of 4 weeks of treatment. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Patient is male or female between 18 and < 65 years of age on the day of signing
informed consent.
2. Patient has a DSM-IV-TR 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. Patient has completed at least 6 years of formal education; patient obtains a score
6th grade level on Reading Subtest of Wide Range Achievement Test Version 4
(WRAT-4) at screening. For languages other than English, the SPONSOR will
specify other tests or methods of assessing. NOTE: Patients with any secondary
education (any formal education beyond 8th grade) do not need to conduct a reading
assessment.
6. Patient is in good physical and mental health in the opinion of the investigator.
7. Patient reports on at least 3 out of 7 nights each week during the 4 weeks prior to
Visit 1 each of the following:
7.1. Total sleep time of 6.5 hours;
7.2. Sleep latency of 30 minutes;
7.3. 1 hour of wakefulness after sleep onset; and
7.4. Spending 6.5 to 9 hours nightly in bed.
8. Patient is willing to stay overnight at a sleep laboratory.
9. Patient is willing to stay in bed for at least 8 hours each night while at the sleep
laboratory.
10. The patient’s regular bedtime is between 9 PM (21:00) and 12 AM (00:00).
11. During the study, the patient is willing to refrain from napping.
12. During the study, patient is willing to limit alcohol to 2 drinks a day, at least 3 hours before going to bed on non-PSG visit days, and refrains from drinking alcohol at least 24 hours prior to a PSG visit.
13. 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) on non-PSG nights, and avoid caffeine after 1 PM (13:00) on PSG
visits.
14. A female patient who is of reproductive potential has a serum -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.
15. A female patient that is postmenopausal or status post hysterectomy, bilateral tubal ligation, or bilateral oophorectomy is eligible without requiring the use of
contraception. Postmenopausal status is defined as age 43 years and (1) no menses
for > 1 year but < 3 years and confirmed by FSH levels elevated into the
postmenopausal range, as defined by the designated laboratory, or (2) no menses for at least 3 years.
16. Patient has latency to persistent sleep (LPS) > 20 minutes during the Screening PSG at Visit 2.
17. Patient has WASO > 45 minutes during the Screening PSG at Visit 2.
18. Patient has LPS > 20 minutes on both Screening and Baseline PSG nights.
19. Patient has a mean WASO 60 minutes on the combined Screening and Baseline
PSG nights, where neither night is 45 minutes. |
|
| 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 eggs or sperm during the study or within 90 days of
their last dose of study medication.
3. Patient has a history or diagnosis of any of following conditions, in the opinion of the investigator:
3.1. Narcolepsy
3.2. Idiopathic cataplexy
3.3. Circadian rhythm sleep disorder
3.4. Parasomnia including nightmare disorder, sleep terror disorder, sleepwalking
disorder, and REM behavior disorder
3.5. Sleep-related breathing disorder (such as central sleep apna syndromes,
obstructive sleep apnea syndromes, sleep-related hypoventilation/hypoxemic
syndrome, and other sleep-related breathing disorders)
3.6. Periodic limb movement disorder
3.7. Restless legs syndrome
3.8. Primary hypersomnia
3.9. Excessive daytime sleepiness (EDS) that is not attributable to primary insomnia
4. Patient has any history of a neurological disorder in the last 10 years.
5. Patient has history within the past 6 months prior to the Screening Visit or current
evidence of unstable or otherwise clinically significant cardiovascular disorder including:
5.1. acute coronary syndrome
5.2. unstable angina
5.3. congestive heart failure
5.4. cardiogenic syncope
5.5. cardiomyopathy
5.6. any symptomatic arrhythmia
6. Patient has clinically significant AV conduction disturbance, sick sinus syndrome, bradycardia, accessory bypass tract.
7. Patient has a history or current evidence of long QT syndrome, Torsades de pointe, or a QTcB interval of > 450.
8. Patient has a screening blood pressure > 150 mmHg systolic or > 90 mmHg diastolic or a pulse rate > 100 beats/min in a sitting position. Blood pressure and pulse measurements exceeding these limits, may be repeated as warranted by the investigator, but values must be within the specified limits for the patient to be eligible for the study.
9. Patient has any of the following:
9.1. A lifetime history of bipolar disorder, a psychotic disorder, or posttraumatic
stress disorder;
9.2. A psychiatric condition requiring treatment with a prohibited medication; or
9.3. Other current psychiatric condition that, in the investigator’s opinion, would
interfere with the patient’s ability to participate in the study.
10. Patient has evidence of ongoing depression or suicidality.
11. Patient has a history of substance abuse or dependence.
12. Patient has a positive screening urine drug screen.
13. 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.
14. Patient has a history of hypersensitivity or idiosyncratic reaction to more than two chemical classes of drugs, including prescriptions and over-the-counter medications.
15. 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.
16. Patient has abnormal screening laboratory values per the guidelines below or other clinically significant, unexplained 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
17. Patient has a history of transmeridian travel or shift work within the past 2
weeks or anticipates needing to travel at any time during the study.
18. 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.
19. Patient has recent history (within the last 3 months) of tobacco use associated with initiation or interruption of sleep or requires a cigarette within 30 minutes of waking in the morning.
20. Patient consumes the equivalent of > 15 cigarettes a day, and the Primary Investigator confirms that the patient’s sleep disturbance is in part the result of this consumption and the patient is unable to refrain from smoking during the night.
21. The patient has a Body Mass Index (BMI) > 40 kg/m2.
22. Patient has an underlying pathology of sleep identified during the screening PSG:
22.1. An Apnea Hypopnea Index > 10 or
22.2. >10 periodic leg movements associated with an arousal per hour of sleep.
23. Patient has a positive alcohol breath test or urine drug screen. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Sleep efficiency (SE) at Night 1 and at the end of 4 weeks of treatment, as derived from total sleep time (TST), based on polysomnography (PSG) results |
|
| 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 | 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| 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 | No |
| E.8.1.6 | Cross over | Yes |
| 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
| Information not present in EudraCT |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 14 |
| 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 |
|
| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| 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
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 18 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 18 |
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