Insomnia
Conditions
Brief summary
The purpose of this study is to see if the study drug, suvorexant, is safe and effective in treating symptoms of insomnia in people with Parkinson's Disease. It is anticipated that a total of 20 subjects, 30 to 80 years of age, with Parkinson's Disease and symptoms of insomnia will participate in the study at this site
Detailed description
The proposed study is a randomized, double-blind, placebo-controlled, cross-over trial to assess the safety, tolerability, and efficacy of suvorexant specifically in a cohort of 20 Parkinson's Disease patients between the ages of 30 and 80 (inclusive) who have a complaint of insomnia. After informed consent is given, potential subjects will be screened to ensure they meet eligibility criteria. This will include an overnight polysomnogram, which will serve both as a baseline and a screening polysomnogram. Active drug will be suvorexant 10 mg orally at bed time with an optional up-titration to 15 mg orally at bedtime after 2 weeks. The first treatment period will be 4 weeks long, in which subjects will be randomized 1:1 to receive active drug or matching placebo. At the end of treatment period 1, subjects will undergo efficacy assessment with repeat polysomnogram and clinical scales. This will be followed by a 2-week washout period with placebo; this period only will be single-blinded, as subjects only will be blinded to treatment. Subjects will then be crossed over into the alternate treatment group, which will once again be double-blinded; those on active treatment for period 1 will be switched to placebo, and those on placebo in period 1 will be switched to active treatment. Treatment period 2 will also be 4 weeks long, and at the end of this, subjects will undergo final assessment with polysomnogram and clinical scales.
Interventions
DRUGSuvorexant
10 mg Suvorexant or matching Placebo orally at bedtime with optional up-titration to 15 mg Suvorexant or matching Placebo orally at bedtime after 2 weeks.
DRUGPlacebo
10 mg Suvorexant or matching Placebo orally at bedtime with optional up-titration to 15 mg Suvorexant or matching Placebo orally at bedtime after 2 weeks.
Sponsors
Merck Sharp & Dohme LLC
Burdick, Daniel, M.D.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
30 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Has signed and dated an Institutional Review Board-approved informed consent form before any protocol-specific screening procedures are performed; * Has a diagnosis of Parkinson disease according to the United Kingdom Parkinson Disease Society Brain Bank Criteria; * Has a modified Hoehn and Yahr Stage of 1-3, inclusive; * Is aged 30-80 years old, inclusive; * Has had no change in Parkinson's Disease medications during the 4 weeks preceding screening, with no dose changes during the study, except that as needed doses of carbidopa/levodopa will be allowed to address periodic worsening of parkinsonian symptoms; * Is willing and able to complete polysomnogram; * Is subject willing and able to limit alcohol use to 1 alcoholic drink per day during the study period and abstain from alcohol for 6 hours prior to each study-related polysomnogram? * Is subject willing and able to abstain from caffeine and marijuana for 6 hours prior to and during each study-related polysomnogram * Is subject willing and able to abstain from products containing nicotine during each study-related polysomnogram? * Has Insomnia Disorder defined by diagnostic criteria published in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition; 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; * On screening polysomnogram, has a latency to persistent sleep \> 20 minutes OR total wakefulness after sleep onset \> 45 minutes; * 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; and * Has valid health insurance coverage at the time of study enrollment and expects this coverage to remain valid for the duration of the study period.
Exclusion criteria
* Is a woman 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); * Does subject have an implanted deep brain stimulator? * Has a history of narcolepsy; * Has a diagnosis of severe chronic obstructive pulmonary disease, defined by forced expiratory volume in 1 second \< 50% of predicted on most recent available pulmonary function test (a 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 or evidence of severe obstructive sleep apnea on screening polysomnogram, with severe obstructive sleep apnea defined as having an apnea-hypopnea index \> 30; * Is concurrently using other central nervous system 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, and no alcohol will be permitted for 24 hours before polysomnogram visits; * Is concurrently using digoxin; * Is concurrently using any moderate or strong inhibitor of cytochrome P450 3A; * Is concurrently using any strong inducer of cytochrome P450 3A; * Has evidence at screening of severe hepatic impairment as defined by a Child-Pugh score \> 10; * Has evidence at screening of severe cognitive impairment as defined by a Montreal Cognitive Assessment score \< 15, or has cognitive impairment that in the opinion of the investigator would prevent completion of study procedures or the ability to provide informed consent. * Has evidence at screening of suicidal ideation in the past 6 months as defined by a positive response to any one of Questions 2-5 on the Columbia Suicide Severity Rating Scale or of a lifetime history of suicidal behavior as defined by any positive response to the suicidal behavior section of the Columbia Suicide Severity Rating Scale.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Sleep Efficiency as Measured by Polysomnogram | 4 weeks | Sleep efficiency is defined as total sleep time divided by total time in bed, expressed as a percent. Polysomnograms were performed at baseline, end of treatment period 1, and end of treatment period 2. A positive change indicates improvement in sleep efficiency. Assessing difference between change in sleep efficiency during suvorexant period and change in sleep efficiency during placebo period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Latency to Persistent Sleep (LPS) | 4 weeks | Latency to Persistent Sleep (LPS) is defined as total time between lights out and first epoch of sleep. Measured on polysomnogram performed at baseline, end of treatment period 1, and end of treatment period 2. A negative change indicates improvement in LPS. |
| Insomnia Severity Index (ISI) | 4 weeks | The Insomnia Severity Index (ISI) is a 7-question survey assessing symptoms of insomnia. Scores range from 0 to 28, with higher scores indicating greater severity. Thus, a negative change in the ISI score indicates improvement in sleep. Performed at baseline, end of treatment period 1, start of treatment period 2, and end of treatment period 2. |
| Wakefulness After Sleep Onset (WASO) | 4 weeks | Wakefulness after sleep onset (WASO) is defined as total time spent awake after first epoch of sleep and before final awakening. Captured during polysomnograms performed at baseline, end of treatment period 1, and end of treatment period 2. Measured in minutes. A negative change indicates improvement in WASO. |
| Subject's Global Impression of Change (SGI-C) | 4 weeks | The Subject's Global Impression of Change (SGI-C) is a rating scale that asks a single question: Since baseline (when first starting this study), how have your sleep symptoms changed? Answers will be on a 7-point scale: 1 = much improved; 2 = somewhat improved; 3 = minimally improved; 4 = no change; 5 = minimally worse; 6 = somewhat worse; and 7 = much worse. Evaluated at end of treatment period 1 and end of treatment period 2. |
| Clinician's Global Impression of Change (CGI-C) | 4 weeks | The Clinician's Global Impression of Change (CGI-C) is a rating scale that asks the single question: Since baseline (when first starting this study), how have the subject's sleep symptoms changed? Answers will be on a 7-point scale: 1 = much improved; 2 = somewhat improved; 3 = minimally improved; 4 = no change; 5 = minimally worse; 6 = somewhat worse; and 7 = much worse. |
| Epworth Sleepiness Scale (ESS) | 4 weeks | The Epworth Sleepiness Scale (ESS) is an 8-question survey assessing symptoms of daytime sleepiness. Scores range from 0 to 24, with higher scores indicating greater severity of daytime sleepiness. Thus, a negative change indicates improvement in daytime sleepiness. The ESS has been validated for use in the general population and in PD. Administered at start of treatment period 1, end of treatment period 1, start of treatment period 2, and end of treatment period 2. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Suvorexant Then Placebo 10 Suvorexant or Placebo mg orally at bedtime with an optional up-titration to 15 mg Suvorexant or Placebo orally at bedtime after 2 weeks. The first treatment period will be 4 weeks. In this group, subjects were randomized 1:1 to receive Suvorexant in the first period. Following a 2 week washout period with placebo, subjects in this group were crossed over into the placebo group for the second treatment period, also 4 weeks. | 11 |
| Placebo Then Suvorexant 10 Suvorexant or Placebo mg orally at bedtime with an optional up-titration to 15 mg Suvorexant or Placebo orally at bedtime after 2 weeks. The first treatment period will be 4 weeks. In this group, subjects were randomized 1:1 to receive Placebo in the first period. Following a 2 week washout period with placebo, subjects in this group were crossed over into the suvorexant group for the second treatment period, also 4 weeks. | 10 |
| Total | 21 |
Baseline characteristics
| Characteristic | Placebo Then Suvorexant | Total | Suvorexant Then Placebo |
|---|---|---|---|
| Age, Continuous | 55.9 years STANDARD_DEVIATION 5.6 | 60.2 years STANDARD_DEVIATION 8.7 | 64.1 years STANDARD_DEVIATION 9.4 |
| Hoehn & Yahr Stage | 2 Stage | 2 Stage | 2 Stage |
| Levodopa-Equivalent Daily Dose | 676.9 mg STANDARD_DEVIATION 213.6 | 682.6 mg STANDARD_DEVIATION 277.5 | 687.8 mg STANDARD_DEVIATION 336 |
| MDS-UPDRS Part 3 Score | 24.5 units on a scale | 24 units on a scale | 24 units on a scale |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 19 Participants | 10 Participants |
| Region of Enrollment United States | 10 participants | 21 participants | 11 participants |
| Sex: Female, Male Female | 1 Participants | 6 Participants | 5 Participants |
| Sex: Female, Male Male | 9 Participants | 15 Participants | 6 Participants |
| Years since diagnosis of Parkinson disease | 3.9 years STANDARD_DEVIATION 2.3 | 3.7 years STANDARD_DEVIATION 2.7 | 3.4 years STANDARD_DEVIATION 3 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 21 |
| other Total, other adverse events | 2 / 21 | 3 / 21 |
| serious Total, serious adverse events | 0 / 21 | 0 / 21 |
Outcome results
Primary
Change in Sleep Efficiency as Measured by Polysomnogram
Sleep efficiency is defined as total sleep time divided by total time in bed, expressed as a percent. Polysomnograms were performed at baseline, end of treatment period 1, and end of treatment period 2. A positive change indicates improvement in sleep efficiency. Assessing difference between change in sleep efficiency during suvorexant period and change in sleep efficiency during placebo period.
Time frame: 4 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Suvorexant Period | Change in Sleep Efficiency as Measured by Polysomnogram | 8.9 Percentage (see sleep efficiency def) |
| Placebo | Change in Sleep Efficiency as Measured by Polysomnogram | 9.4 Percentage (see sleep efficiency def) |
p-value: 0.72Wilcoxon (Mann-Whitney)
Secondary
Clinician's Global Impression of Change (CGI-C)
The Clinician's Global Impression of Change (CGI-C) is a rating scale that asks the single question: Since baseline (when first starting this study), how have the subject's sleep symptoms changed? Answers will be on a 7-point scale: 1 = much improved; 2 = somewhat improved; 3 = minimally improved; 4 = no change; 5 = minimally worse; 6 = somewhat worse; and 7 = much worse.
Time frame: 4 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Suvorexant Period | Clinician's Global Impression of Change (CGI-C) | 3 score on a scale |
| Placebo | Clinician's Global Impression of Change (CGI-C) | 4 score on a scale |
p-value: 0.2Wilcoxon (Mann-Whitney)
Secondary
Epworth Sleepiness Scale (ESS)
The Epworth Sleepiness Scale (ESS) is an 8-question survey assessing symptoms of daytime sleepiness. Scores range from 0 to 24, with higher scores indicating greater severity of daytime sleepiness. Thus, a negative change indicates improvement in daytime sleepiness. The ESS has been validated for use in the general population and in PD. Administered at start of treatment period 1, end of treatment period 1, start of treatment period 2, and end of treatment period 2.
Time frame: 4 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Suvorexant Period | Epworth Sleepiness Scale (ESS) | -0.5 units on a scale |
| Placebo | Epworth Sleepiness Scale (ESS) | 0.0 units on a scale |
p-value: 0.32Wilcoxon (Mann-Whitney)
Secondary
Insomnia Severity Index (ISI)
The Insomnia Severity Index (ISI) is a 7-question survey assessing symptoms of insomnia. Scores range from 0 to 28, with higher scores indicating greater severity. Thus, a negative change in the ISI score indicates improvement in sleep. Performed at baseline, end of treatment period 1, start of treatment period 2, and end of treatment period 2.
Time frame: 4 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Suvorexant Period | Insomnia Severity Index (ISI) | -1 units on a scale |
| Placebo | Insomnia Severity Index (ISI) | 1 units on a scale |
p-value: 0.004Wilcoxon (Mann-Whitney)
Secondary
Latency to Persistent Sleep (LPS)
Latency to Persistent Sleep (LPS) is defined as total time between lights out and first epoch of sleep. Measured on polysomnogram performed at baseline, end of treatment period 1, and end of treatment period 2. A negative change indicates improvement in LPS.
Time frame: 4 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Suvorexant Period | Latency to Persistent Sleep (LPS) | -9.4 Minutes |
| Placebo | Latency to Persistent Sleep (LPS) | -4.2 Minutes |
p-value: 0.81Wilcoxon (Mann-Whitney)
Secondary
Subject's Global Impression of Change (SGI-C)
The Subject's Global Impression of Change (SGI-C) is a rating scale that asks a single question: Since baseline (when first starting this study), how have your sleep symptoms changed? Answers will be on a 7-point scale: 1 = much improved; 2 = somewhat improved; 3 = minimally improved; 4 = no change; 5 = minimally worse; 6 = somewhat worse; and 7 = much worse. Evaluated at end of treatment period 1 and end of treatment period 2.
Time frame: 4 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Suvorexant Period | Subject's Global Impression of Change (SGI-C) | 3 score on a scale |
| Placebo | Subject's Global Impression of Change (SGI-C) | 4 score on a scale |
p-value: 0.098Wilcoxon (Mann-Whitney)
Secondary
Wakefulness After Sleep Onset (WASO)
Wakefulness after sleep onset (WASO) is defined as total time spent awake after first epoch of sleep and before final awakening. Captured during polysomnograms performed at baseline, end of treatment period 1, and end of treatment period 2. Measured in minutes. A negative change indicates improvement in WASO.
Time frame: 4 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Suvorexant Period | Wakefulness After Sleep Onset (WASO) | -54.1 Minutes |
| Placebo | Wakefulness After Sleep Onset (WASO) | -36.5 Minutes |
p-value: 0.51Wilcoxon (Mann-Whitney)