Safety and Efficacy Study of Suvorexant in Participants With Primary Insomnia - Study A (MK-4305-028)

NCT ID: NCT01097616

Last Updated: 2018-09-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1023 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-05-05
• Study Completion Date: 2011-12-07

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.

Conditions

Primary Insomnia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Suvorexant HD

Drug

Group Type: EXPERIMENTAL

Suvorexant High Dose (HD)

Intervention Type: DRUG

Suvorexant 40 mg + placebo matching suvorexant 20 mg for participants \<65 years old; Suvorexant 30 mg + placebo matching suvorexant 15 mg for participants ≥65 years old; all study drug is tablet for oral administration, taken once daily at bedtime. Participants receive this dose during the 3-month TRT Phase and, if applicable, the optional 3-month EXT Phase. During the 1-week double-blind (DB) Run-out (RO) following the TRT/EXT phase, participants in this study arm receive the noted suvorexant dose or placebo, in a 1:1 ratio. During the 2-week single-blind Run-in period prior to randomization all participants receive placebo to suvorexant once daily at bedtime.

Suvorexant LD

Drug

Group Type: EXPERIMENTAL

Suvorexant Low Dose (LD)

Intervention Type: DRUG

Suvorexant 20 mg + placebo matching suvorexant 40 mg for participants \<65 years old; Suvorexant 15 mg + placebo matching suvorexant 30 mg for participants ≥65 years old; all study drug is tablet for oral administration, taken once daily at bedtime. Participants receive this dose during the 3-month TRT Phase and, if applicable, the optional 3-month EXT Phase. During the 1-week DB RO following the TRT/EXT phase, participants in this study arm receive the noted suvorexant dose or placebo, in a 1:1 ratio. During the 2-week single-blind Run-in period prior to randomization all participants receive placebo to suvorexant once daily at bedtime.

Placebo

Placebo Comparator

Group Type: PLACEBO_COMPARATOR

Comparator: Placebo

Intervention Type: DRUG

Matching placebos to suvorexant 40 mg and 20 mg for participants \<65 years old; matching placebos to suvorexant 30 mg and 15 mg for participants ≥65 years old; all study drug is tablet for oral administration, taken once daily at bedtime. Placebo is a third treatment arm for comparison to the two active (suvorexant) treatment arms during the 3-month TRT Phase and, if applicable, the optional 3-month EXT Phase. During the 1-week DB RO following the TRT/EXT phase, participants in this study arm continue to receive placebo. During the 2-week single-blind Run-in period prior to randomization all participants receive placebo to suvorexant once daily at bedtime.

Interventions

Suvorexant High Dose (HD)

Suvorexant 40 mg + placebo matching suvorexant 20 mg for participants \<65 years old; Suvorexant 30 mg + placebo matching suvorexant 15 mg for participants ≥65 years old; all study drug is tablet for oral administration, taken once daily at bedtime. Participants receive this dose during the 3-month TRT Phase and, if applicable, the optional 3-month EXT Phase. During the 1-week double-blind (DB) Run-out (RO) following the TRT/EXT phase, participants in this study arm receive the noted suvorexant dose or placebo, in a 1:1 ratio. During the 2-week single-blind Run-in period prior to randomization all participants receive placebo to suvorexant once daily at bedtime.

Intervention Type: DRUG

Suvorexant Low Dose (LD)

Suvorexant 20 mg + placebo matching suvorexant 40 mg for participants \<65 years old; Suvorexant 15 mg + placebo matching suvorexant 30 mg for participants ≥65 years old; all study drug is tablet for oral administration, taken once daily at bedtime. Participants receive this dose during the 3-month TRT Phase and, if applicable, the optional 3-month EXT Phase. During the 1-week DB RO following the TRT/EXT phase, participants in this study arm receive the noted suvorexant dose or placebo, in a 1:1 ratio. During the 2-week single-blind Run-in period prior to randomization all participants receive placebo to suvorexant once daily at bedtime.

Intervention Type: DRUG

Comparator: Placebo

Matching placebos to suvorexant 40 mg and 20 mg for participants \<65 years old; matching placebos to suvorexant 30 mg and 15 mg for participants ≥65 years old; all study drug is tablet for oral administration, taken once daily at bedtime. Placebo is a third treatment arm for comparison to the two active (suvorexant) treatment arms during the 3-month TRT Phase and, if applicable, the optional 3-month EXT Phase. During the 1-week DB RO following the TRT/EXT phase, participants in this study arm continue to receive placebo. During the 2-week single-blind Run-in period prior to randomization all participants receive placebo to suvorexant once daily at bedtime.

Intervention Type: DRUG

Other Intervention Names

MK-4305; MK-4305

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Monitor

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

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.

Reference Type: RESULT

PMID: 25526970 (View on PubMed)

Tao P, Svetnik V, Bliwise DL, Zammit G, Lines C, Herring WJ. Comparison of polysomnography in people with Alzheimer's disease and insomnia versus non-demented elderly people with insomnia. Sleep Med. 2023 Jan;101:515-521. doi: 10.1016/j.sleep.2022.11.027. Epub 2022 Dec 1.

Reference Type: DERIVED

PMID: 36529106 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33210445 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31926466 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30522875 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 29112763 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 28427826 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 28265715 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 27397664 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 27198953 (View on PubMed)

Study Documents

Document Type: CSR Synopsis

View Document

Other Identifiers

2010_520

Identifier Type: OTHER

Identifier Source: secondary_id

4305-028

Identifier Type: -

Identifier Source: org_study_id