A Study of Suvorexant in Patients With Multiple Sclerosis Fatigue and Insomnia

NCT03110315 | Completed Phase 4 Results FDA Drug

• 1 other identifier: TRB 2017.2
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

This study assesses the safety, tolerability, and efficacy of suvorexant in multiple sclerosis patients. Enrolled subjects will receive 2 weeks of treatment during treatment period 1 with either suvorexant or matching placebo (1:1). After treatment period 1, subjects will undergo a washout period of 1 week then 2 weeks of the alternate treatment (either suvorexant or placebo). The primary hypothesis is that suvorexant will provide greater improvement in sleep, as measured by symptom rating scales, compared to placebo.

Conditions

Multiple Sclerosis; Fatigue; Insomnia

Keywords

Multiple Sclerosis; Fatigue; Insomnia; Suvorexant; Belsomra; Sleep disorder; Sleep

Outcome Measures

Primary Outcomes (1)

• Change in Insomnia Severity Index (ISI) Score

  7-question survey assessing symptoms of insomnia over the past week. Maximum score is 28, minimum is 0, with higher scores indicating greater severity. Guidelines for Scoring/Interpretation: Add scores for all seven items = \_\_\_\_\_ Total score ranges from 0-28 0-7 = No clinically significant insomnia 8-14 = Subthreshold insomnia 15-21 = Clinical insomnia (moderate

  Change from Baseline to 2 Weeks

Secondary Outcomes (3)

• Change in Modified Fatigue Index Scale (MFIS) Score

  Change from Baseline to 2 Weeks

• Patient Global Impression of Change

  Change from Baseline to 2 Weeks

• Fatigue Visual Analog Scale

  Change from Baseline to 2 Weeks

Other Outcomes (2)

• Sleep Latency

  Change from Baseline to 2 Weeks

• Subjective Quality of Sleep (sQUAL)

  Change from Baseline to 2 Weeks

Study Arms (2)

Suvorexant

EXPERIMENTAL

Suvorexant - 10 mg (one tablet) taken by mouth once daily at bedtime with option to up-titrate to 20 mg (two tablets) taken by mouth once daily at bedtime.

Drug: Suvorexant

Placebo

PLACEBO COMPARATOR

Placebo - one tablet taken by mouth once daily at bedtime and two tablets taken by mouth daily at bedtime if subject up-titrates.

Drug: Placebo

Interventions

Suvorexant DRUG

See detailed information in associated Arm Description.

Also known as: Belsomra

Suvorexant

Placebo DRUG

Sugar pill manufactured to mimic suvorexant 10 mg tablet.

Also known as: Sugar pill

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of multiple sclerosis made at least 3 months prior based on McDonald criteria;
• Age 18-75 inclusive;
• Expanded Disability Status Scale (EDSS) 0- 7.5;
• Clinical stability defined as no multiple sclerosis exacerbation or change in disease modifying therapy for 60 days prior to screening;
• Screening Fatigue Severity Scale score of ≥4.0;
• Has Insomnia Disorder defined by diagnostic criteria published in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5); namely, subject report of all of the following:
• One of the following: difficulty initiating sleep; difficulty maintaining sleep; or early morning waking;
• Sleep disturbance causes clinically significant distress or impairment in social, occupational, educational, academic, behavioral, or other important areas of functioning;
• Sleep difficulty has occurred on 3 or more nights per week;
• Sleep difficulty has been present for at least the past 3 months;
• Sleep difficulty occurs despite adequate opportunity for sleep;
• Insomnia is not explained by another sleep disorder;
• Insomnia is not attributable to physiological effects of a consumed substance;
• May use other medications that could influence sleep, other than those specifically prohibited, as long as the dose is stable for 4 weeks preceding screening, with no dose changes during the study;
• Signed and dated Institutional Review Board-approved informed consent form before any protocol-specific screening procedures have been performed.

You may not qualify if:

• Use of potential multiple sclerosis-associated fatigue drugs within 3 days of screening until study completion, including modafinil, armodafinil, amantadine, methylphenidate, products with amphetamine or dextroamphetamine;
• Use of any of any prohibited medication (including Digoxin, benzodiazepines, barbiturates, opiates, Zolpidem, Zaleplon, Eszopiclone, moderate or strong CYP3A inhibitors, or strong inducers of CYP3A) from 3 days prior to screening to termination visit;
• Female who is breast-feeding, pregnant, or has the potential to become pregnant during the course of the study (fertile and unwilling/unable to use effective contraceptive measures);
• History of narcolepsy;
• Has a diagnosis of severe chronic obstructive pulmonary disease (COPD), defined by forced expiratory volume 1 (FEV1) \< 50% of predicted on most recent available pulmonary function test (PFT). Pulmonary function test is not required if the subject has never been diagnosed with chronic obstructive pulmonary disease;
• Has a history of severe obstructive sleep apnea (OSA), with severe obstructive sleep apnea defined as having an apnea-hypopnea index (AHI) \> 30 on prior polysomnograph (PSG). Polysomnograph is not required if there is no history of obstructive sleep apnea;
• Is concurrently using other central nervous system (CNS) depressants, including alcohol, except that one alcoholic drink per day will be allowed for those with normal hepatic function provided the drink is consumed at least 2 hours prior to or 8 hours after taking the study drug. Medical marijuana is allowed if consumed at the patient's usual dose at least 2 hours prior to or 8 hours after taking the study drug. Recreational marijuana is not allowed from screening until end of study;
• Has evidence at screening of severe hepatic impairment as defined by a Child-Pugh score \> 10;
• Cognitive impairment that in the opinion of the investigator would prevent completion of study procedures or the ability to provide informed consent;
• Suicidality or severe depression as measured by screening Beck Depression Inventory II (BDI) score \> 28 or score of \>1 on Beck Depression Inventory II Question 9 (suicidality screen) at any time during the study;
• Any other serious and/or unstable medical condition.

Sponsors & Collaborators

• Theodore R. Brown, MD MPH: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

EvergreenHealth Multiple Sclerosis Center

Kirkland, Washington, 98034, United States

Location

MeSH Terms

Conditions

Multiple Sclerosis; Fatigue; Sleep Initiation and Maintenance Disorders; Sleep Wake Disorders

Interventions

suvorexant; Sugars

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Sleep Disorders, Intrinsic; Dyssomnias; Mental Disorders; Neurologic Manifestations

Intervention Hierarchy (Ancestors)

Carbohydrates

Limitations and Caveats

This was a small study done at two centers with treatment windows limited to two weeks including dose escalation. A two-week exposure may have been inadequate to elicit full treatment effect. It is also possible that the one-week washout period was insufficient.

Results Point of Contact

• Title: Theodore Brown
• Organization: EvergreenHealth Research

trbrown@evergreenhealthcare.org

4258995385

Study Officials

• Theodore R Brown, MD, MPH

  EvergreenHealth Multiple Sclerosis Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: investigator is blinded to randomization and results until study completion
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Model Details: randomized cross-over trial of suvorexant and placebo for people with multiple sclerosis (MS), insomnia and fatigue

Study Record Dates

• First Submitted: March 28, 2017
• First Posted: April 12, 2017
• Study Start: March 28, 2017
• Primary Completion: March 21, 2022
• Study Completion: March 21, 2022
• Last Updated: February 3, 2025
• Results First Posted: February 3, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)