A Pilot Study of Suvorexant for Insomnia in Parkinson Disease

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.

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.