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

NCT01097616 | Completed Phase 3 Results

• 2 other identifiers: 4305-0282010_520
• Study Type: interventional
• Target: 1,023
• Locations: 0 countries
• Sites: N/A

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

Outcome Measures

Primary Outcomes (10)

• Suvorexant HD Versus Placebo: Change From Baseline in Mean Subjective Total Sleep Time (sTSTm) at Month 1

  sTSTm is the average over a defined day range of the participant's report of the total amount of time spent asleep before waking for the day, as recorded in a daily electronic diary (e-diary). Averages were derived by taking the mean of all available daily measurements (excluding the mornings following any polysomnography \[PSG\] nights) falling within the day range; Month 1 range is Days 23-30 (Day 1 is day of first double-blind dose). A participant must have at least 3 days of data during the defined day range to calculate an average for the day range; otherwise, the mean value was considered missing for that day range. The baseline value is the mean of the last 7 daily measurements obtained during the placebo Run-in period.

  Baseline and Month 1

• Suvorexant HD Versus Placebo: Change From Baseline in sTSTm at Month 3

  sTSTm is the average over a defined day range of the participant's report of the total amount of time spent asleep before waking for the day, as recorded in a daily e-diary. Averages were derived by taking the mean of all available daily measurements (excluding the mornings following any PSG nights) falling within the day range; Month 3 range is Days 76-90 (Day 1 is day of first double-blind dose). A participant must have at least 3 days of data during the defined day range to calculate an average for the day range; otherwise, the mean value was considered missing for that day range. The baseline value is the mean of the last 7 daily measurements obtained during the placebo Run-in period.

  Baseline and Month 3

• Suvorexant HD Versus Placebo: Change From Baseline in Wakefulness After Persistent Sleep Onset (WASO) at Month 1

  WASO is measured during overnight sleep laboratory (PSG) assessments at baseline, Night 1, Month 1 and Month 3, and is defined as the duration of wakefulness from the onset of persistent sleep (i.e., 10 consecutive minutes of sleep) to the end of PSG assessment the following morning. Beginning of PSG assessment ("Lights-Off") is at approximately the participant's habitual bedtime. The participant is awakened, or allowed to get out of bed if already awake, after 8 hours of PSG recording ("Lights-On"). PSG assessments consist of electronic measurement of brain activity and eye and muscle movements. PSG data was scored by a Centralized PSG reading center.

  Baseline and Month 1

• Suvorexant HD Versus Placebo: Change From Baseline in WASO at Month 3

  WASO is measured during overnight sleep laboratory (PSG) assessments at baseline, Night 1, Month 1 and Month 3, and is defined as the duration of wakefulness from the onset of persistent sleep (i.e., 10 consecutive minutes of sleep) to the end of PSG assessment the following morning. Beginning of PSG assessment ("Lights-Off") is at approximately the participant's habitual bedtime. The participant is awakened, or allowed to get out of bed if already awake, after 8 hours of PSG recording ("Lights-On"). PSG assessments consist of electronic measurement of brain activity and eye and muscle movements. PSG data was scored by a Centralized PSG reading center.

  Baseline and Month 3

• Suvorexant HD Versus Placebo: Change From Baseline in Mean Subjective Time to Sleep Onset (sTSOm) at Month 1

  sTSOm is the average over a defined day range of the participant's report of the duration of time that it took to fall asleep, as recorded in a daily e-diary. Averages were derived by taking the mean of all available daily measurements (excluding the mornings following any PSG nights) falling within the day range; Month 1 range is Days 23-30 (Day 1 is day of first double-blind dose). A participant must have at least 3 days of data during the defined day range to calculate an average for the day range; otherwise, the mean value was considered missing for that day range. The baseline value is the mean of the last 7 daily measurements obtained during the placebo Run-in period.

  Baseline and Month 1

• Suvorexant HD Versus Placebo: Change From Baseline in sTSOm at Month 3

  sTSOm is the average over a defined day range of the participant's report of the duration of time that it took to fall asleep, as recorded in a daily e-diary. Averages were derived by taking the mean of all available daily measurements (excluding the mornings following any PSG nights) falling within the day range; Month 3 range is Days 76-90 (Day 1 is day of first double-blind dose). A participant must have at least 3 days of data during the defined day range to calculate an average for the day range; otherwise, the mean value was considered missing for that day range. The baseline value is the mean of the last 7 daily measurements obtained during the placebo Run-in period.

  Baseline and Month 3

• Suvorexant HD Versus Placebo: Change From Baseline in Latency to Onset of Persistent Sleep (LPS) at Month 1

  LPS is measured during overnight sleep laboratory (PSG) assessments at baseline, Night 1, Month 1 and Month 3, and is defined as the duration of time from the beginning of PSG assessment ("Lights-Off") to the first interval of 10 consecutive minutes of sleep. Beginning of PSG assessment ("Lights-Off") is at approximately the participant's habitual bedtime. The participant is awakened, or allowed to get out of bed if already awake, after 8 hours of PSG recording ("Lights-On"). PSG assessments consist of electronic measurement of brain activity and eye and muscle movements. PSG data was scored by a Centralized PSG reading center.

  Baseline and Month 1

• Suvorexant HD Versus Placebo: Change From Baseline in LPS at Month 3

  LPS is measured during overnight sleep laboratory (PSG) assessments at baseline, Night 1, Month 1 and Month 3, and is defined as the duration of time from the beginning of PSG assessment ("Lights-Off") to the first interval of 10 consecutive minutes of sleep. Beginning of PSG assessment ("Lights-Off") is at approximately the participant's habitual bedtime. The participant is awakened, or allowed to get out of bed if already awake, after 8 hours of PSG recording ("Lights-On"). PSG assessments consist of electronic measurement of brain activity and eye and muscle movements. PSG data was scored by a Centralized PSG reading center.

  Baseline and Month 3

• Number of Participants With an Adverse Event (AE) During Initial 3-Month DB TRT Phase

  An AE is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration, whether or not considered related to the study drug. Participants with an AE occurring during the initial 3-month DB TRT Phase are counted once in this summary.

  Up to 3 months

• Number of Participants Who Discontinued Study Drug Due to an AE Occurring During Initial 3-Month DB TRT Phase

  An AE is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration, whether or not considered related to the study drug. Participants who discontinued study drug treatment due to an AE occurring during the initial 3-month DB TRT Phase are counted once in this summary.

  Up to 3 months

Secondary Outcomes (12)

• Suvorexant LD/HD Versus Placebo: Change From Baseline in sTSTm at Week 1

  Baseline and Week 1

• Suvorexant LD Versus Placebo: Change From Baseline in sTSTm at Month 1

  Baseline and Month 1

• Suvorexant LD Versus Placebo: Change From Baseline in sTSTm at Month 3

  Baseline and Month 3

• Suvorexant LD/HD Versus Placebo: Change From Baseline in WASO at Night 1

  Baseline and Night 1

• Suvorexant LD Versus Placebo: Change From Baseline in WASO at Month 1

  Baseline and Month 1

Study Arms (3)

Suvorexant HD

EXPERIMENTAL

Drug

Drug: Suvorexant High Dose (HD)

Suvorexant LD

EXPERIMENTAL

Drug

Drug: Suvorexant Low Dose (LD)

Placebo

PLACEBO COMPARATOR

Placebo Comparator

Drug: Comparator: Placebo

Interventions

Suvorexant High Dose (HD) 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.

Also known as: MK-4305

Suvorexant HD

Suvorexant Low Dose (LD) 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.

Also known as: MK-4305

Suvorexant LD

Comparator: Placebo 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.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (10)

• 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.

  PMID: 25526970 RESULT

• 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.

  PMID: 36529106 DERIVED

• 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.

  PMID: 33210445 DERIVED

• 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.

  PMID: 31926466 DERIVED

• 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.

  PMID: 30522875 DERIVED

• 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.

  PMID: 29112763 DERIVED

• 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.

  PMID: 28427826 DERIVED

• 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.

  PMID: 28265715 DERIVED

• 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.

  PMID: 27397664 DERIVED

• 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.

  PMID: 27198953 DERIVED

MeSH Terms

Conditions

Sleep Initiation and Maintenance Disorders

Interventions

suvorexant

Condition Hierarchy (Ancestors)

Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Monitor

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 26, 2010
• First Posted: April 1, 2010
• Study Start: May 5, 2010
• Primary Completion: September 9, 2011
• Study Completion: December 7, 2011
• Last Updated: September 21, 2018
• Results First Posted: September 1, 2014

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will share