Excessive Sleepiness, Parkinson Disease
Conditions
Brief summary
This study is a 4-week, multicenter, randomized, double-blind, placebo-controlled, ascending dose, 4-period crossover study designed to evaluate the safety, tolerability, efficacy, and PK of JZP-110 (75, 150, and 300 mg) in the treatment of excessive sleepiness in adult subjects with idiopathic PD.
Interventions
DRUGJZP-110
75 mg, 150 mg, 300 mg
OTHERPlacebo
Sponsors
Jazz Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
35 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of idiopathic PD according to the UK PDS Brain Bank Criteria. 2. Hoehn and Yahr stage 1, 2, or 3. 3. Screening and Baseline ESS scores \>11.
Exclusion criteria
1. Diagnosis of other degenerative Parkinsonian syndromes (e.g., progressive supranuclear palsy, multiple system atrophy \[MSA\], or dementia with Lewy bodies \[DLB\]). 2. Usual nightly time in bed of \<6 hours, including the night before the Baseline visit. 3. Untreated or inadequately treated moderate to severe OSA. 4. Has evidence at screening of severe cognitive impairment or has cognitive impairment that in the opinion of the investigator would prevent completion of study procedures or the ability to provide informed consent.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) Leading to Early Discontinuation | Up to Day 35 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Epworth Sleepiness Scale (ESS) Total Score | Baseline to Weeks 1, 2, 3, and 4 | Change from Baseline ESS defined in terms of change from study baseline (prior to first dose in Period 1) to the end of each Treatment Period (Weeks 1, 2, 3, and 4). The Epworth Sleepiness Scale (ESS) is a self-administered questionnaire with 8 questions, asking subjects how likely they would be to doze off or fall asleep in different situations. Responses range from 0 = would never doze to 3 = high chance of dozing. Higher scores represent greater severity of excessive sleepiness. The total score ranges from 0 - 24, with higher scores representing greater severity of excessive sleepiness. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Mean Sleep Latency Time (in Minutes) on the Maintenance of Wakefulness Test (MWT) | Baseline to Weeks 1, 2, 3, and 4 | Change from Baseline mean sleep latency (in minutes) on the MWT defined in terms of change from study baseline (prior to first dose in Period 1) to the end of each Treatment Period (Weeks 1, 2, 3, and 4). The MWT is the standard objective measure of an individual's ability to remain awake during the daytime in a darkened, quiet environment. MWT sleep latency ranges from 0 to 40 minutes, with higher scores indicated greater ability to stay awake. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment Sequence A Subjects in Treatment Sequence A were assigned the following from Period 1, Week 1 through Period 4, Week 4: Placebo, JZP-110 75 mg, JZP 110 150 mg, and JZP 110 300 mg. | 28 |
| Treatment Sequence B Subjects in Treatment Sequence B were assigned the following from Period 1, Week 1 through Period 4, Week 4: JZP-110 75 mg, JZP 110 150 mg, JZP 110 300 mg, and Placebo. | 28 |
| Treatment Sequence C Subjects in Treatment Sequence C were assigned Placebo for each Period. | 10 |
| Total | 66 |
Baseline characteristics
| Characteristic | Treatment Sequence B | Treatment Sequence A | Treatment Sequence C | Total |
|---|---|---|---|---|
| Age, Continuous | 62.9 years STANDARD_DEVIATION 8.75 | 65.9 years STANDARD_DEVIATION 7.64 | 65.4 years STANDARD_DEVIATION 9.75 | 64.6 years STANDARD_DEVIATION 8.45 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 24 Participants | 27 Participants | 9 Participants | 60 Participants |
| Sex: Female, Male Female | 6 Participants | 10 Participants | 5 Participants | 21 Participants |
| Sex: Female, Male Male | 22 Participants | 18 Participants | 5 Participants | 45 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 56 | 0 / 55 | 0 / 54 | 0 / 64 |
| other Total, other adverse events | 4 / 56 | 5 / 55 | 4 / 54 | 0 / 64 |
| serious Total, serious adverse events | 0 / 56 | 0 / 55 | 1 / 54 | 0 / 64 |
Outcome results
Primary
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Leading to Early Discontinuation
Time frame: Up to Day 35
Population: The Safety population includes all subjects who received at least one dose of study drug
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| JZP-110 75mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Leading to Early Discontinuation | 1 Participants |
| JZP-110 150mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Leading to Early Discontinuation | 2 Participants |
| JZP-110 300mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Leading to Early Discontinuation | 0 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Leading to Early Discontinuation | 0 Participants |
Secondary
Change From Baseline in Epworth Sleepiness Scale (ESS) Total Score
Change from Baseline ESS defined in terms of change from study baseline (prior to first dose in Period 1) to the end of each Treatment Period (Weeks 1, 2, 3, and 4). The Epworth Sleepiness Scale (ESS) is a self-administered questionnaire with 8 questions, asking subjects how likely they would be to doze off or fall asleep in different situations. Responses range from 0 = would never doze to 3 = high chance of dozing. Higher scores represent greater severity of excessive sleepiness. The total score ranges from 0 - 24, with higher scores representing greater severity of excessive sleepiness.
Time frame: Baseline to Weeks 1, 2, 3, and 4
Population: The modified Intent-to-Treat population is defined as all randomized subjects who took at least one dose of study drug and have a Baseline and at least one post-Baseline efficacy assessment. Two subjects who did not have at least one post-baseline efficacy data were excluded from the mITT Population, resulting in a total of 64 subjects.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| JZP-110 75mg | Change From Baseline in Epworth Sleepiness Scale (ESS) Total Score | -4.82 score on a scale | Standard Error 0.67 |
| JZP-110 150mg | Change From Baseline in Epworth Sleepiness Scale (ESS) Total Score | -5.04 score on a scale | Standard Error 0.7 |
| JZP-110 300mg | Change From Baseline in Epworth Sleepiness Scale (ESS) Total Score | -5.72 score on a scale | Standard Error 0.68 |
| Placebo | Change From Baseline in Epworth Sleepiness Scale (ESS) Total Score | -4.78 score on a scale | Standard Error 0.58 |
Other Pre-specified
Change From Baseline in the Mean Sleep Latency Time (in Minutes) on the Maintenance of Wakefulness Test (MWT)
Change from Baseline mean sleep latency (in minutes) on the MWT defined in terms of change from study baseline (prior to first dose in Period 1) to the end of each Treatment Period (Weeks 1, 2, 3, and 4). The MWT is the standard objective measure of an individual's ability to remain awake during the daytime in a darkened, quiet environment. MWT sleep latency ranges from 0 to 40 minutes, with higher scores indicated greater ability to stay awake.
Time frame: Baseline to Weeks 1, 2, 3, and 4
Population: The MWT analysis evaluated results from subjects in the mITT population who were in Group 1 only (N=53 subjects).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| JZP-110 75mg | Change From Baseline in the Mean Sleep Latency Time (in Minutes) on the Maintenance of Wakefulness Test (MWT) | 0.4289 minutes | Standard Error 2.1254 |
| JZP-110 150mg | Change From Baseline in the Mean Sleep Latency Time (in Minutes) on the Maintenance of Wakefulness Test (MWT) | 2.6721 minutes | Standard Error 2.1961 |
| JZP-110 300mg | Change From Baseline in the Mean Sleep Latency Time (in Minutes) on the Maintenance of Wakefulness Test (MWT) | 6.8133 minutes | Standard Error 2.1351 |
| Placebo | Change From Baseline in the Mean Sleep Latency Time (in Minutes) on the Maintenance of Wakefulness Test (MWT) | 1.7670 minutes | Standard Error 1.8479 |