Suvorexant (Belsomra) for the Treatment of Bipolar Depression With Insomnia

NCT03764683 | Withdrawn Phase 4 FDA Drug

• 1 other identifier: 2018P002157
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The investigators are doing this research study to find out if suvorexant (Belsomra) can help people with bipolar depression when added to their usual treatment. The investigators also want to find out if suvorexant (Belsomra) is safe to take without causing too many side effects in people with bipolar disorder. Suvorexant (Belsomra) is approved by the U.S. Food and Drug Administration (FDA) to treat insomnia. It has not yet been studied in people with bipolar disorder who have problems sleeping. This research study will compare suvorexant (Belsomra) to placebo. The placebo looks exactly like suvorexant (Belsomra), but contains no suvorexant (Belsomra). During this study participants may get a placebo instead of suvorexant (Belsomra). Placebos are used in research studies to see if the results are due to the study drug or due to other reasons. This study has two parts, each lasting 6 weeks. During each part, participants may receive either Belsomra or placebo. Some participants will receive suvorexant for both parts, some will receive placebo for both parts, and others will receive suvorexant during one part and placebo during the other part. Placebos are used in research studies to see if the results are due to the study drug or due to other reasons. This study is open to people with bipolar disorder who have trouble sleeping. Bipolar disorder is a brain disorder associated with episodes of mood swings ranging from depressive lows to manic highs. About 80 subjects will take part in this research study. All subjects will be enrolled at Massachusetts General Hospital (MGH).

Conditions

Bipolar Disorder; Insomnia

Outcome Measures

Primary Outcomes (4)

• Change in sleep quality via Pittsburgh Sleep Quality Index (PSQI)

  The PSQI assesses perceived sleep quality more generally and consists of 7 components: \[1\] subjective sleep quality (1 item) \[2\] sleep latency (2 items) \[3\] sleep duration (1 item) \[4\] habitual sleep efficiency (3 items) \[5\] sleep disturbances (9 items) \[6\] use of sleeping medications (1 item), and \[7\] daytime dysfunction (2 items).19 items are included in scoring. Five additional items, to be completed by a bed partner, are included in the questionnaire and may be useful for clinical purposes but are not used for scoring. The client self rates each of these seven areas of sleep. Scoring of the answers is based on a 0 to 3 scale, whereby 3 reflects the negative extreme on the Likert Scale. A global sum of "5"or greater indicates a "poor" sleeper. Lower scores indicate better sleep quality and better outcome. Minimum score is 0, maximum score is 21.

  The PSQI will assess change in perceived sleep quality from Week 1 to Week 8 to Week 10 to Week 12 to Week 14.

• Change in depressive symptoms via the Bipolar Inventory of Symptoms Scale (BISS)

  The BISS is a 45-item scale completed by the physician or trained rater, using a structured interview to assess for symptoms of mania and depression (Bowden et al., 2007; Gonzalez et al., 2008). The BISS includes all items from the Montgomery Asberg Depression Rating Scale (MADRS) and the Young Mania Rating Scale (YMRS), plus additional items that are either absent or indirectly addressed in the MADRS and YMRS scales. Items are scored from 0 to 4, based on the most recent 7 day period, utilizing information from self report, and family and clinician observation both outside and during the interview. Items are scored both on the basis of frequency and severity. A score of 3, in most cases, also entails behavior that is observable to others. A score of 0 means the symptom is completely absent. The Depression subscale of the BISS includes 21 items. Minimum score is 0 and maximum score is 84. Lower scores indicate less severe depressive symptoms and better outcome.

  The BISS will be administered at Screen visit, Baseline visit (Week 0), Week 2, Week 4, Week 6, Week 8, Week 10, Week 12, and Week 14.

• Change in manic symptoms via the Bipolar Inventory of Symptoms Scale (BISS)

  The BISS is a 45-item scale completed by the physician or trained rater, using a structured interview to assess for symptoms of mania and depression (Bowden et al., 2007; Gonzalez et al., 2008). The BISS includes all items from the Montgomery Asberg Depression Rating Scale (MADRS) and the Young Mania Rating Scale (YMRS), plus additional items that are either absent or indirectly addressed in the MADRS and YMRS scales. Items are scored from 0 to 4, based on the most recent 7 day period, utilizing information from self report, and family and clinician observation both outside and during the interview. Items are scored both on the basis of frequency and severity. A score of 3, in most cases, also entails behavior that is observable to others. A score of 0 means the symptom is completely absent. The Mania subscale of the BISS includes 21 items. Minimum score is 0 and maximum score is 84. Lower scores indicate less severe manic symptoms and better outcome.

  The BISS will be administered at Screen visit, Baseline visit (Week 0), Week 2, Week 4, Week 6, Week 8, Week 10, Week 12, and Week 14.

• Change in psychosocial functioning via Quality of Life Satisfaction Questionnaire (Q-LES-Q)

  The Q-LES-Q is a patient-administered instrument, which has a "long" and "short" form (Endicott, 1993). The "long" form asks questions in 8 modules of 6-16 questions each, about physical health/activities, general feelings of well-being and relaxation, function at work, household duties, school or course work, leisure activities, social relations, and general activities over the past week. Patients will be administered the "long form" version.

  The Q-LES-Q will be administered at Screen visit, Baseline visit (Week 0), Week 2, Week 4, Week 6, Week 8, Week 10, Week 12, and Week 14.

Secondary Outcomes (5)

• Change in insomnia measured via Insomnia Severity Index (ISI)

  This will be administered at Screen visit, Baseline visit (Week 0), Week 2, Week 4, Week 6, Week 8, Week 10, Week 12, and Week 14.

• Change in bipolar symptom severity via Clinical Global Impressions - Severity (CGI-S)

  This will be administered at Baseline visit (Week 0), Week 2, Week 4, Week 6, Week 8, Week 10, Week 12, and Week 14.

• Change in suicidal ideation score on The Columbia Suicide Severity Rating Scale (C-SSRS)

  This will be administered at Screen visit, Baseline visit (Week 0), Week 2, Week 4, Week 6, Week 8, Week 10, Week 12, and Week 14.

• Change in functioning via MGH Cognitive and Physical Functioning Questionnaire (MGH-CPFQ)

  This will be administered at Screen visit, Baseline visit (Week 0), Week 2, Week 4, Week 6, Week 8, Week 10, Week 12, and Week 14.

• Change in depressive symptoms via Quick Inventory of Depression Symptomatology-Self Report (QIDS-SR)

  This will be administered at Screen visit, Baseline visit (Week 0), Week 2, Week 4, Week 6, Week 8, Week 10, Week 12, and Week 14.

Study Arms (3)

Drug-Drug

EXPERIMENTAL

This arm will receive the active drug in the first and second phase of the study.

Drug: Suvorexant (Belsomra)

Placebo-Drug

OTHER

This arm will receive placebo in the first phase of the study and the active drug in the second phase.

Drug: Suvorexant (Belsomra); Drug: Placebo

Placebo-Placebo

PLACEBO COMPARATOR

This arm will receive placebo in the first phase and second phase of the study.

Drug: Placebo

Interventions

Suvorexant (Belsomra) DRUG

Suvorexant (Belsomra) is approved by the U.S. Food and Drug Administration (FDA) to treat insomnia. It has not yet been studied in people with bipolar disorder who have problems sleeping.

Drug-Drug; Placebo-Drug

Placebo DRUG

Subjects will take placebo capsules (containing no active substance) identical in appearance to those containing Suvorexant

Placebo-Drug; Placebo-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:

• Men or women between the ages of 18 and 75.
• DSM V diagnosis of Bipolar Disorder Type I and II.
• Ability to sign the Informed Consent Form.
• Not taking an antidepressant medication within the past 14 days.
• Meets criteria for a current major depressive episode as defined and operationalized by the MINI.
• Scores \>15 on the QIDS-SR.
• Does not meet criteria for current hypomanic or manic episode as defined and operationalized by the MINI 7.0.2.
• Patients must be stable on their bipolar medications for at least 1 month (4 weeks) prior to screening.

You may not qualify if:

• Unable to sign the Informed Consent Form.
• Declines to participate.
• DSM-V diagnosis of Psychosis, Schizophrenia, Schizoaffective Bipolar type.
• Meets criteria for current hypomanic or manic episode as defined and operationalized by the MINI.
• Pregnant women or women of child bearing potential who are not using a medically accepted means of contraception (e.g. oral contraceptives, intrauterine device, barrier methods, or total abstinence from intercourse; Depo Provera is acceptable if it is started 3 months prior to enrollment).
• Suicidal ideation associated with actual intent and a method or plan in the past year: "Yes" answers on items 4 or 5 of the C-SSRS
• Previous history of suicidal behaviors in the past one year: "Yes" answer (for events that occurred in the past year) to any of the suicidal behavior items of the C-SSRS. (Non-suicidal self-injurious behavior is not included unless in the investigator's judgment it is indicated).
• Any lifetime history of serious or recurrent suicidal behavior.
• Unstable medical illness including cardiovascular, hepatic, renal, respiratory, endocrine, neurological, or hematological disease.
• The following DSM-V diagnoses: 1) organic mental disorders; 2) substance use disorders, including alcohol but excluding tobacco, active within the 3 months; 3) schizophrenia; 4) delusional disorder; 5) psychotic disorders not elsewhere classified; 6) schizoaffective disorder; 7) acute bereavement; 9) severe borderline or antisocial personality disorder.
• a. Subjects who have a positive urine drug screen which cannot be explained by prescribed medications, or for which patients do not have a valid prescription for a valid medical reason.
• Patients meeting criteria for current bipolar mixed episode as defined and operationalized by the MINI.
• Patients with mood congruent or mood incongruent psychotic features.
• Clinical or laboratory evidence of hypothyroidism.
• Patients previously treated with Suvorexant (Belsomra)

Sponsors & Collaborators

• Massachusetts General Hospital: lead

MeSH Terms

Conditions

Bipolar Disorder; Sleep Initiation and Maintenance Disorders

Interventions

suvorexant

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases

Study Officials

• Gustavo Kinrys, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Physician

Model Details: The investigators are proposing the use of SPCD for this study. The Sequential Parallel Comparison Design aims to reduce the impact of high placebo response and decrease sample size. The design has been accepted by and published on by FDA. The SPCD model has two relatively short phases of treatment of equal duration. Only non-responders to placebo (P) during the first phase are included in the analyses of the second phase. Randomization is unbalanced (for example, a 2:3:3 assignment of DD, PP, and PD).

Study Record Dates

• First Submitted: November 29, 2018
• First Posted: December 5, 2018
• Study Start: February 26, 2019
• Primary Completion: January 6, 2021
• Study Completion: January 6, 2021
• Last Updated: February 21, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share