Trial Outcomes & Findings for "Six-week Study of the Safety and Efficacy of JZP-110 in the Treatment of Excessive Sleepiness in OSA" (NCT NCT02348619)

Last Updated: 2019-09-09

Results Overview

Change in the mean sleep latency time as determined from the first four trials of a 40-minute MWT from the end of the Stable Dose Phase to the end of the Double-blind Withdrawal Phase. Mean sleep latency defined as the average of the first four MWT trial's measurements.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

174 participants

Primary outcome timeframe

Week 4 to Week 6

Results posted on

2019-09-09

Participant Flow

Following screening, subjects entered the Titration phase. Subjects who were titrated to an efficacious and tolerable dose in the Titration phase remained on the same dose regimen in the Stable-Dose phase. Subjects in the Double-Blind Withdrawal phase who did not receive JZP-110 received placebo for 2 weeks.

Participant milestones

Participant milestones
Measure	JZP-110 Start at 75 mg, titrate up to 150 or 300 mg, or down at any time.	Placebo Subjects in the Double-Blind Withdrawal phase who did not receive JZP-110 received placebo for 2 weeks.
Titration Phase STARTED	174	0
Titration Phase COMPLETED	157	0
Titration Phase NOT COMPLETED	17	0
Stable-Dose Phase STARTED	157	0
Stable-Dose Phase COMPLETED	124	0
Stable-Dose Phase NOT COMPLETED	33	0
Double-Blind Withdrawal Phase STARTED	62	62
Double-Blind Withdrawal Phase COMPLETED	60	62
Double-Blind Withdrawal Phase NOT COMPLETED	2	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A total of 124 subjects were randomized into the Double-Blind Withdrawal phase of the study and comprised the Safety population for that phase. Two of these subjects were excluded.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Double-Blind Withdrawal Phase n=124 Participants
Age, Continuous Placebo	56.2 years STANDARD_DEVIATION 9.75 • n=124 Participants
Age, Continuous JZP-110	56.3 years STANDARD_DEVIATION 11.36 • n=124 Participants
Sex: Female, Male Placebo · Female	21 Participants n=62 Participants • A total of 124 subjects were randomized into the Double-Blind Withdrawal phase of the study and comprised the Safety population for that phase. Two of these subjects were excluded.
Sex: Female, Male Placebo · Male	41 Participants n=62 Participants • A total of 124 subjects were randomized into the Double-Blind Withdrawal phase of the study and comprised the Safety population for that phase. Two of these subjects were excluded.
Sex: Female, Male JZP-110 · Female	26 Participants n=62 Participants • A total of 124 subjects were randomized into the Double-Blind Withdrawal phase of the study and comprised the Safety population for that phase. Two of these subjects were excluded.
Sex: Female, Male JZP-110 · Male	36 Participants n=62 Participants • A total of 124 subjects were randomized into the Double-Blind Withdrawal phase of the study and comprised the Safety population for that phase. Two of these subjects were excluded.
Race (NIH/OMB) Placebo · American Indian or Alaska Native	0 Participants n=62 Participants • A total of 124 subjects were randomized into the Double-Blind Withdrawal phase of the study and comprised the Safety population for that phase. Two of these subjects were excluded.
Race (NIH/OMB) Placebo · Asian	2 Participants n=62 Participants • A total of 124 subjects were randomized into the Double-Blind Withdrawal phase of the study and comprised the Safety population for that phase. Two of these subjects were excluded.
Race (NIH/OMB) Placebo · Native Hawaiian or Other Pacific Islander	0 Participants n=62 Participants • A total of 124 subjects were randomized into the Double-Blind Withdrawal phase of the study and comprised the Safety population for that phase. Two of these subjects were excluded.
Race (NIH/OMB) Placebo · Black or African American	15 Participants n=62 Participants • A total of 124 subjects were randomized into the Double-Blind Withdrawal phase of the study and comprised the Safety population for that phase. Two of these subjects were excluded.
Race (NIH/OMB) Placebo · White	45 Participants n=62 Participants • A total of 124 subjects were randomized into the Double-Blind Withdrawal phase of the study and comprised the Safety population for that phase. Two of these subjects were excluded.
Race (NIH/OMB) Placebo · More than one race	0 Participants n=62 Participants • A total of 124 subjects were randomized into the Double-Blind Withdrawal phase of the study and comprised the Safety population for that phase. Two of these subjects were excluded.
Race (NIH/OMB) Placebo · Unknown or Not Reported	0 Participants n=62 Participants • A total of 124 subjects were randomized into the Double-Blind Withdrawal phase of the study and comprised the Safety population for that phase. Two of these subjects were excluded.
Race (NIH/OMB) JZP-110 · American Indian or Alaska Native	0 Participants n=62 Participants • A total of 124 subjects were randomized into the Double-Blind Withdrawal phase of the study and comprised the Safety population for that phase. Two of these subjects were excluded.
Race (NIH/OMB) JZP-110 · Asian	0 Participants n=62 Participants • A total of 124 subjects were randomized into the Double-Blind Withdrawal phase of the study and comprised the Safety population for that phase. Two of these subjects were excluded.
Race (NIH/OMB) JZP-110 · Native Hawaiian or Other Pacific Islander	0 Participants n=62 Participants • A total of 124 subjects were randomized into the Double-Blind Withdrawal phase of the study and comprised the Safety population for that phase. Two of these subjects were excluded.
Race (NIH/OMB) JZP-110 · Black or African American	12 Participants n=62 Participants • A total of 124 subjects were randomized into the Double-Blind Withdrawal phase of the study and comprised the Safety population for that phase. Two of these subjects were excluded.
Race (NIH/OMB) JZP-110 · White	50 Participants n=62 Participants • A total of 124 subjects were randomized into the Double-Blind Withdrawal phase of the study and comprised the Safety population for that phase. Two of these subjects were excluded.
Race (NIH/OMB) JZP-110 · More than one race	0 Participants n=62 Participants • A total of 124 subjects were randomized into the Double-Blind Withdrawal phase of the study and comprised the Safety population for that phase. Two of these subjects were excluded.
Race (NIH/OMB) JZP-110 · Unknown or Not Reported	0 Participants n=62 Participants • A total of 124 subjects were randomized into the Double-Blind Withdrawal phase of the study and comprised the Safety population for that phase. Two of these subjects were excluded.

PRIMARY outcome

Timeframe: Week 4 to Week 6

Outcome measures

Outcome measures
Measure	JZP-110 n=60 Participants Start at 75 mg, titrate up to 150 or 300 mg, or down at any time.	Placebo n=62 Participants Subjects in the Double-Blind Withdrawal phase who did not receive JZP-110 received placebo for 2 weeks.
Change in the Maintenance of Wakefulness Test (MWT)	-0.96 minutes Standard Error 1.350	-12.11 minutes Standard Error 1.326

PRIMARY outcome

Timeframe: Week 4 to Week 6

Change in Epworth Sleepiness Scale (ESS) score from the end of the Stable Dose Phase to the end of the Double-blind Withdrawal Phase. A negative change from baseline represents improvement in excessive sleepiness. The ESS is a self-administered questionnaire with 8 questions. Each activity is scored on a scale ranging from 0-3, with 0 = would never fall asleep, and 3 = high chance of falling asleep. The total score ranges from 0-24, with a higher number representing an increased propensity for sleepiness. An analysis of covariance (ANCOVA) was used for the analysis of ESS scores. The response variable was the change in ESS score from week 4 to week 6.

Outcome measures

Outcome measures
Measure	JZP-110 n=60 Participants Start at 75 mg, titrate up to 150 or 300 mg, or down at any time.	Placebo n=62 Participants Subjects in the Double-Blind Withdrawal phase who did not receive JZP-110 received placebo for 2 weeks.
Change in the Epworth Sleepiness Scale (ESS)	-0.1 points on a scale Standard Error 0.73	4.5 points on a scale Standard Error 0.71

SECONDARY outcome

Timeframe: Week 4 to Week 6

Percentage of subjects reported as worse (minimally, much, or very much) on the PGIc at the end of the Double-blind Withdrawal Phase. PGIc was rated by subjects and measures the change in their condition since treatment starts on a 7-point scale ranging from 1= very much improved to 7= very much worse.

Outcome measures

Outcome measures
Measure	JZP-110 n=60 Participants Start at 75 mg, titrate up to 150 or 300 mg, or down at any time.	Placebo n=62 Participants Subjects in the Double-Blind Withdrawal phase who did not receive JZP-110 received placebo for 2 weeks.
Patient Global Impression of Change (PGIc)	20 percentage of subjects	50 percentage of subjects

SECONDARY outcome

Timeframe: Week 4 to Week 6

Percentage of subjects reported as worse (minimally, much, or very much) on the CGIc at the end of the Double-blind Withdrawal Phase. CGIc was rated by clinicians and measures the change in the subject's condition since treatment starts on a 7-point scale ranging from 1= very much improved to 7= very much worse.

Outcome measures

Outcome measures
Measure	JZP-110 n=60 Participants Start at 75 mg, titrate up to 150 or 300 mg, or down at any time.	Placebo n=62 Participants Subjects in the Double-Blind Withdrawal phase who did not receive JZP-110 received placebo for 2 weeks.
Clinical Global Impression of Change (CGIc)	22 percentage of subjects	59 percentage of subjects

SECONDARY outcome

Timeframe: Week 4 to Week 6

Change is total score from the end of the stable dose phase to the end of the double blind withdrawal phase. Functional Outcomes of Sleep Questionnaire Short Version (FOSQ-10) is a 10-item disease-specific quality of life questionnaire to assess the effect of excessiveness sleepiness on multiple activities of everyday living. The FOSQ-10 consists of 10 questions, each scored on a scale from 1-4. The questionnaire has a 4-point response format for each question (1 = extreme difficulty, 2 = moderate difficulty, 3 = a little difficulty, and 4 = no difficulty). The total score is derived by the mean of the 5 subscale scores, multiplied by 5, resulting in a possible range of scores between 5 to 20; lower FOSQ-10 scores are worse, indicating more difficulty carrying out activities; higher FOSQ-10 scores are better, indicating less difficulty carrying out activities.

Outcome measures

Outcome measures
Measure	JZP-110 n=60 Participants Start at 75 mg, titrate up to 150 or 300 mg, or down at any time.	Placebo n=62 Participants Subjects in the Double-Blind Withdrawal phase who did not receive JZP-110 received placebo for 2 weeks.
Change in Functional Outcomes of Sleep Questionnaire (FOSQ-10)	-0.15 units on a scale Standard Error 0.393	-1.31 units on a scale Standard Error 0.381

Adverse Events

JZP-110 (Entire Study)

Serious events: 0 serious events

Other events: 58 other events

Deaths: 0 deaths

Placebo (Randomized Withdrawal)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	JZP-110 (Entire Study) n=174 participants at risk Across the entire study.	Placebo (Randomized Withdrawal) n=62 participants at risk During the randomized withdrawal phase only.
Nervous system disorders Headache	11.5% 20/174	0.00% 0/62
Nervous system disorders Dizziness	8.0% 14/174	0.00% 0/62
Gastrointestinal disorders Dry mouth	7.5% 13/174	0.00% 0/62
Gastrointestinal disorders Nausea	7.5% 13/174	0.00% 0/62
Psychiatric disorders Insomnia	6.3% 11/174	0.00% 0/62
Cardiac disorders Palpitations	5.2% 9/174	0.00% 0/62

Additional Information

Director, Disclosure & Transparency

Jazz Pharmaceuticals

Phone: 2158709177

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The sponsor can review trial results communications prior to public release and can embargo such communications for a period of at least 60 days from the time submitted to sponsor for review. If requested by sponsor, the PI will withhold publication for up to an additional 30 days. Furthermore, the first publication of study results must be a joint publication of all study sites unless a joint manuscript has not been submitted for publication within 12 months of completion of the study.
Publication restrictions are in place

Restriction type: OTHER