Clinical trial NCT01097616: Safety and Efficacy Study of Suvorexant in Participants With Primary Insomnia - Study A (MK-4305-028)
Official title: A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Safety and Efficacy of MK-4305 in Patients With Primary Insomnia - Study A
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Primary Insomnia
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2010-04-01
Enrollment: 1023
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multicenter study to test the hypothesis that suvorexant (MK-4305) is superior to placebo in improving insomnia as measured by change from baseline in: subjective total sleep time and time to sleep onset, wake time after persistent sleep onset, and latency to onset of persistent sleep. Participants who complete the initial 3-month Treatment (TRT) Phase may participate in an optional 3-month Extension (EXT) Phase.


Eligibility criteria: Inclusion Criteria:

* Must be ≥18 yrs old on the day of signing informed consent
* Diagnosed with Primary Insomnia
* Good physical and mental health
* Participant ≥65 yrs old score at least 25 on the Mini Mental State Examination
* A female participant who is of reproductive potential has a negative serum pregnancy test and agrees to use contraception
* Reports difficulty with initiating and maintaining sleep during the 4 weeks prior to Visit 1 (accordingly to specific protocol criteria)
* Reports spending 6.5 to 9 hours nightly in bed on at least 3 out of 7 nights prior to Visit 1
* Regular bedtime is between 9 pm-1 am
* Willing to refrain from napping while in study
* Able to read, understand and complete questionnaires and all diaries
* Willing to limit alcohol, caffeine, and nicotine consumption while in the study
* For a portion of participants: Must be willing to stay overnight in a sleep laboratory and must be willing to stay in bed for at least 8 hours each night while at the sleep laboratory

Exclusion Criteria:

* Female participant is pregnant and/or breastfeeding at Prestudy visit, or expecting to conceive while in study
* History or diagnosis of another sleep disorder
* Difficulty sleeping due to a medical condition
* History of a neurological disorder
* History of bipolar disorder, psychotic disorder, or posttraumatic stress disorder, or current psychiatric disorder that requires a prohibited medication
* Ongoing depression
* History of substance abuse or dependence
* History or current evidence of a clinically significant cardiovascular disorder or clinically significant electrocardiogram (ECG) at Prestudy Visit
* Taking certain prohibited medications
* Consumption of the equivalent of \>15 cigarettes a day
* 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
* Participant is considered morbidly obese
* Previously randomized in another investigational study of suvorexant

Primary outcomes:
measure: Suvorexant HD Versus Placebo: Change From Baseline in Mean Subjective Total Sleep Time (sTSTm) at Month 1
timeFrame: Baseline and Month 1
measure: Suvorexant HD Versus Placebo: Change From Baseline in sTSTm at Month 3
timeFrame: Baseline and Month 3
measure: Suvorexant HD Versus Placebo: Change From Baseline in Wakefulness After Persistent Sleep Onset (WASO) at Month 1
timeFrame: Baseline and Month 1
measure: Suvorexant HD Versus Placebo: Change From Baseline in WASO at Month 3
timeFrame: Baseline and Month 3
measure: Suvorexant HD Versus Placebo: Change From Baseline in Mean Subjective Time to Sleep Onset (sTSOm) at Month 1
timeFrame: Baseline and Month 1
measure: Suvorexant HD Versus Placebo: Change From Baseline in sTSOm at Month 3
timeFrame: Baseline and Month 3
measure: Suvorexant HD Versus Placebo: Change From Baseline in Latency to Onset of Persistent Sleep (LPS) at Month 1
timeFrame: Baseline and Month 1
measure: Suvorexant HD Versus Placebo: Change From Baseline in LPS at Month 3
timeFrame: Baseline and Month 3
measure: Number of Participants With an Adverse Event (AE) During Initial 3-Month DB TRT Phase
timeFrame: Up to 3 months
measure: Number of Participants Who Discontinued Study Drug Due to an AE Occurring During Initial 3-Month DB TRT Phase
timeFrame: Up to 3 months
Secondary outcomes:
measure: Suvorexant LD/HD Versus Placebo: Change From Baseline in sTSTm at Week 1
timeFrame: Baseline and Week 1
measure: Suvorexant LD Versus Placebo: Change From Baseline in sTSTm at Month 1
timeFrame: Baseline and Month 1
measure: Suvorexant LD Versus Placebo: Change From Baseline in sTSTm at Month 3
timeFrame: Baseline and Month 3
measure: Suvorexant LD/HD Versus Placebo: Change From Baseline in WASO at Night 1
timeFrame: Baseline and Night 1
measure: Suvorexant LD Versus Placebo: Change From Baseline in WASO at Month 1
timeFrame: Baseline and Month 1
measure: Suvorexant LD Versus Placebo: Change From Baseline in WASO at Month 3
timeFrame: Baseline and Month 3
measure: Suvorexant LD/HD Versus Placebo: Change From Baseline in sTSOm at Week 1
timeFrame: Baseline and Week 1
measure: Suvorexant LD Versus Placebo: Change From Baseline in sTSOm at Month 1
timeFrame: Baseline and Month 1
measure: Suvorexant LD Versus Placebo: Change From Baseline in sTSOm at Month 3
timeFrame: Baseline and Month 3
measure: Suvorexant LD/HD Versus Placebo: Change From Baseline in LPS at Night 1
timeFrame: Baseline and Night 1
measure: Suvorexant LD Versus Placebo: Change From Baseline in LPS at Month 1
timeFrame: Baseline and Month 1
measure: Suvorexant LD Versus Placebo: Change From Baseline in LPS at Month 3
timeFrame: Baseline and Month 3
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Monitor
role: STUDY_DIRECTOR
References:
citation: Herring WJ, Connor KM, Ivgy-May N, Snyder E, Liu K, Snavely DB, Krystal AD, Walsh JK, Benca RM, Rosenberg R, Sangal RB, Budd K, Hutzelmann J, Leibensperger H, Froman S, Lines C, Roth T, Michelson D. Suvorexant in Patients With Insomnia: Results From Two 3-Month Randomized Controlled Clinical Trials. Biol Psychiatry. 2016 Jan 15;79(2):136-48. doi: 10.1016/j.biopsych.2014.10.003. Epub 2014 Oct 23.
citation: Snyder ES, Tao P, Svetnik V, Lines C, Herring WJ. Use of the single-item Patient Global Impression-Severity scale as a self-reported assessment of insomnia severity. J Sleep Res. 2021 Feb;30(1):e13141. doi: 10.1111/jsr.13141. Epub 2020 Jul 30.
citation: Svetnik V, Snyder ES, Tao P, Roth T, Lines C, Herring WJ. How well can a large number of polysomnography sleep measures predict subjective sleep quality in insomnia patients? Sleep Med. 2020 Mar;67:137-146. doi: 10.1016/j.sleep.2019.08.020. Epub 2019 Sep 11.
citation: Herring WJ, Connor KM, Snyder E, Snavely DB, Morin CM, Lines C, Michelson D. Effects of suvorexant on the Insomnia Severity Index in patients with insomnia: analysis of pooled phase 3 data. Sleep Med. 2019 Apr;56:219-223. doi: 10.1016/j.sleep.2018.09.010. Epub 2018 Oct 2.
citation: Svetnik V, Snyder ES, Tao P, Scammell TE, Roth T, Lines C, Herring WJ. Insight Into Reduction of Wakefulness by Suvorexant in Patients With Insomnia: Analysis of Wake Bouts. Sleep. 2018 Jan 1;41(1). doi: 10.1093/sleep/zsx178.
citation: Herring WJ, Connor KM, Snyder E, Snavely DB, Zhang Y, Hutzelmann J, Matzura-Wolfe D, Benca RM, Krystal AD, Walsh JK, Lines C, Roth T, Michelson D. Suvorexant in Elderly Patients with Insomnia: Pooled Analyses of Data from Phase III Randomized Controlled Clinical Trials. Am J Geriatr Psychiatry. 2017 Jul;25(7):791-802. doi: 10.1016/j.jagp.2017.03.004. Epub 2017 Mar 8.
citation: Herring WJ, Connor KM, Snyder E, Snavely DB, Zhang Y, Hutzelmann J, Matzura-Wolfe D, Benca RM, Krystal AD, Walsh JK, Lines C, Roth T, Michelson D. Clinical profile of suvorexant for the treatment of insomnia over 3 months in women and men: subgroup analysis of pooled phase-3 data. Psychopharmacology (Berl). 2017 Jun;234(11):1703-1711. doi: 10.1007/s00213-017-4573-1. Epub 2017 Mar 7.
citation: Herring WJ, Connor KM, Snyder E, Snavely DB, Zhang Y, Hutzelmann J, Matzura-Wolfe D, Benca RM, Krystal AD, Walsh JK, Lines C, Roth T, Michelson D. Suvorexant in Patients with Insomnia: Pooled Analyses of Three-Month Data from Phase-3 Randomized Controlled Clinical Trials. J Clin Sleep Med. 2016 Sep 15;12(9):1215-25. doi: 10.5664/jcsm.6116.
citation: Snyder E, Ma J, Svetnik V, Connor KM, Lines C, Michelson D, Herring WJ. Effects of suvorexant on sleep architecture and power spectral profile in patients with insomnia: analysis of pooled phase 3 data. Sleep Med. 2016 Mar;19:93-100. doi: 10.1016/j.sleep.2015.10.007. Epub 2015 Nov 10.