Trial Outcomes & Findings for "A Long-Term Safety Study of JZP-110 in the Treatment of Excessive Sleepiness in Subjects With Narcolepsy or OSA" (NCT NCT02348632)

NCT ID: NCT02348632

Last Updated: 2019-06-25

Results Overview

Change in Epworth Sleepiness Scale (ESS) score during the 2-week randomized withdrawal period. The beginning of the randomized withdrawal period represents efficacy baseline. 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. This analysis included treatment group and randomization stratification factor (narcolepsy vs. OSA) as fixed effects. The ESS score at the beginning of the randomized withdrawal period was used as the covariate. The response variable was the change in ESS score from the beginning to the end of 2- week randomized withdrawal period.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 645 participants
• Primary outcome timeframe: Start of randomized withdrawal phase to end of randomized withdrawal (2 weeks)
• Results posted on: 2019-06-25

Participant Flow

A total of 645 subjects were enrolled in the study; 2 subjects withdrew from the study prior to receiving study drug. A total of 643 subjects received at least 1 dose of JZP-110 in the open-label phase and were included in the Safety Population.

Participant milestones

Measure	JZP-110 Subjects completed a 2-week Titration phase. They then entered the maintenance phase of up to 50 weeks at the stable dose that was reached at the end of the Titration Phase.	Placebo Placebo administered orally, QD, for the 2-week randomized withdrawal period.
Open-label Period STARTED	643	0
Open-label Period COMPLETED	458	0
Open-label Period NOT COMPLETED	185	0
Randomized Withdrawal Period STARTED	140	142
Randomized Withdrawal Period COMPLETED	137	141
Randomized Withdrawal Period NOT COMPLETED	3	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

"A Long-Term Safety Study of JZP-110 in the Treatment of Excessive Sleepiness in Subjects With Narcolepsy or OSA"

Baseline characteristics by cohort

Measure	Open-label Period n=643 Participants 643 subjects comprised the safety population.
Age, Continuous	49.31 years STANDARD_DEVIATION 14.155 • n=5 Participants
Sex: Female, Male Female	306 Participants n=5 Participants
Sex: Female, Male Male	337 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=5 Participants
Race (NIH/OMB) Asian	15 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	3 Participants n=5 Participants
Race (NIH/OMB) Black or African American	109 Participants n=5 Participants
Race (NIH/OMB) White	506 Participants n=5 Participants
Race (NIH/OMB) More than one race	8 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Start of randomized withdrawal phase to end of randomized withdrawal (2 weeks)

Population: 282 subjects were randomized into the randomized withdrawal period. Two subjects who were treated in the randomized withdrawal period did not have evaluable efficacy data during that period. Therefore, the mITT Population comprised 280 subjects, 141 who received placebo and 139 who received JZP-110.

Change in Epworth Sleepiness Scale (ESS) score during the 2-week randomized withdrawal period. The beginning of the randomized withdrawal period represents efficacy baseline. 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. This analysis included treatment group and randomization stratification factor (narcolepsy vs. OSA) as fixed effects. The ESS score at the beginning of the randomized withdrawal period was used as the covariate. The response variable was the change in ESS score from the beginning to the end of 2- week randomized withdrawal period.

Outcome measures

Measure	JZP-110 n=139 Participants Subjects completed a 2-week Titration phase. They then entered the maintenance phase of up to 50 weeks at the stable dose that was reached at the end of the Titration Phase.	Placebo n=141 Participants JZP-110 administered orally, QD, for the 2-week randomized withdrawal period, at the same dose subjects were currently receiving.
Change in Epworth Sleepiness Scale (ESS) Score	1.6 points on a scale Standard Error 0.41	5.3 points on a scale Standard Error 0.41

SECONDARY outcome

Timeframe: Beginning of randomized withdrawal phase to end of the randomized withdrawal phase (2 weeks)

Population: 282 subjects were randomized into the randomized withdrawal period. Two subjects who were treated in the randomized withdrawal period did not have evaluable efficacy data during that period. Therefore, the mITT Population comprised 280 subjects, 141 who received placebo and 139 who received JZP-110.

Percentage of subjects reported as worse (minimally worse, much worse, or very much worse) on the PGIc during the 2-week randomized withdrawal period. The beginning of the randomized withdrawal period represents efficacy baseline.

Outcome measures

Measure	JZP-110 n=139 Participants Subjects completed a 2-week Titration phase. They then entered the maintenance phase of up to 50 weeks at the stable dose that was reached at the end of the Titration Phase.	Placebo n=141 Participants JZP-110 administered orally, QD, for the 2-week randomized withdrawal period, at the same dose subjects were currently receiving.
Subjects Reported as Worse on the Patient Global Impression of Change (PGIc)	28.2 percentage of subjects	64.5 percentage of subjects

SECONDARY outcome

Timeframe: Beginning of randomized withdrawal phase to end of the randomized withdrawal phase (2 weeks)

Population: 282 subjects were randomized into the randomized withdrawal period. Two subjects who were treated in the randomized withdrawal period did not have evaluable efficacy data during that period. Therefore, the mITT Population comprised 280 subjects, 141 who received placebo and 139 who received JZP-110.

Subjects reported as worse (very much worse, much worse, and minimally worse) on the CGIc during the 2-week randomized withdrawal period. The beginning of the randomized withdrawal period represents efficacy baseline.

Outcome measures

Measure	JZP-110 n=139 Participants Subjects completed a 2-week Titration phase. They then entered the maintenance phase of up to 50 weeks at the stable dose that was reached at the end of the Titration Phase.	Placebo n=141 Participants JZP-110 administered orally, QD, for the 2-week randomized withdrawal period, at the same dose subjects were currently receiving.
Subjects Reported as Worse on the Clinical Global Impression of Change (CGIc)	28.7 percentage of subjects	63.8 percentage of subjects

Adverse Events

JZP-110

Serious events: 27 serious events

Other events: 269 other events

Deaths: 1 deaths

Placebo

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Measure	JZP-110 n=643 participants at risk Subjects completed a 2-week Titration phase. They then entered the maintenance phase of up to 50 weeks at the stable dose that was reached at the end of the Titration Phase.	Placebo n=142 participants at risk JZP-110 administered orally, QD, for the 2-week randomized withdrawal period, at the same dose subjects were currently receiving.
Vascular disorders Deep vein thrombosis	0.16% 1/643 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).	0.00% 0/142 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer stage I	0.16% 1/643 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).	0.00% 0/142 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma	0.16% 1/643 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).	0.00% 0/142 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).
Immune system disorders Anaphylactic reaction	0.16% 1/643 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).	0.00% 0/142 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	0.16% 1/643 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).	0.00% 0/142 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).
Pregnancy, puerperium and perinatal conditions Stillbirth	0.16% 1/643 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).	0.00% 0/142 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).
General disorders Chest pain	0.16% 1/643 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).	0.00% 0/142 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).
General disorders Chest discomfort	0.16% 1/643 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).	0.00% 0/142 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).
General disorders Non-cardiac chest pain	0.16% 1/643 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).	0.00% 0/142 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).
Psychiatric disorders Agitation	0.31% 2/643 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).	0.00% 0/142 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).
Psychiatric disorders Bipolar I disorder	0.16% 1/643 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).	0.00% 0/142 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).
Psychiatric disorders Hallucination, auditory	0.31% 2/643 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).	0.00% 0/142 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).
Psychiatric disorders Suicide attempt	0.16% 1/643 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).	0.00% 0/142 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).
Psychiatric disorders Depression	0.16% 1/643 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).	0.00% 0/142 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).
Reproductive system and breast disorders Prostatomegaly	0.16% 1/643 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).	0.00% 0/142 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).
Injury, poisoning and procedural complications Anaemia postoperative	0.16% 1/643 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).	0.00% 0/142 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).
Injury, poisoning and procedural complications Alcohol poisoning	0.31% 2/643 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).	0.00% 0/142 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).
Injury, poisoning and procedural complications Ear canal injury	0.16% 1/643 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).	0.00% 0/142 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).
Injury, poisoning and procedural complications Fall	0.16% 1/643 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).	0.00% 0/142 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).
Injury, poisoning and procedural complications Head injury	0.16% 1/643 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).	0.00% 0/142 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).
Injury, poisoning and procedural complications Skull fracture	0.16% 1/643 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).	0.00% 0/142 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).
Injury, poisoning and procedural complications Skull fractured base	0.16% 1/643 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).	0.00% 0/142 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).
Injury, poisoning and procedural complications Procedural hypotension	0.16% 1/643 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).	0.00% 0/142 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).
Injury, poisoning and procedural complications Intentional overdose	0.16% 1/643 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).	0.00% 0/142 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).
Cardiac disorders Acute myocardial infarction	0.16% 1/643 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).	0.00% 0/142 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).
Cardiac disorders Atrial fibrillation	0.62% 4/643 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).	0.00% 0/142 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).
Cardiac disorders Angina pectoris	0.16% 1/643 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).	0.00% 0/142 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.16% 1/643 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).	0.00% 0/142 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).
Nervous system disorders Cerebrovascular accident	0.16% 1/643 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).	0.00% 0/142 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).
Nervous system disorders Dizziness	0.31% 2/643 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).	0.00% 0/142 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).
Nervous system disorders Migraine	0.16% 1/643 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).	0.00% 0/142 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).
Nervous system disorders Cluster headache	0.31% 2/643 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).	0.00% 0/142 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).
Eye disorders Retinal vein occlusion	0.16% 1/643 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).	0.00% 0/142 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).
Ear and labyrinth disorders Vertigo	0.16% 1/643 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).	0.00% 0/142 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).
Ear and labyrinth disorders Abdominal pain	0.31% 2/643 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).	0.00% 0/142 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).
Ear and labyrinth disorders Duodenal ulcer haemorrhage	0.16% 1/643 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).	0.00% 0/142 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).
Ear and labyrinth disorders Gastrointestinal inflammation	0.16% 1/643 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).	0.00% 0/142 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).
Ear and labyrinth disorders Nausea	0.16% 1/643 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).	0.00% 0/142 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).
Ear and labyrinth disorders Vomiting	0.16% 1/643 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).	0.00% 0/142 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).
Hepatobiliary disorders Cholecystitis acute	0.16% 1/643 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).	0.00% 0/142 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).
Renal and urinary disorders Haematuria	0.16% 1/643 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).	0.00% 0/142 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).
Metabolism and nutrition disorders Dehydration	0.16% 1/643 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).	0.00% 0/142 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).
Infections and infestations Bronchitis	0.16% 1/643 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).	0.00% 0/142 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).
Infections and infestations Cellulitis	0.16% 1/643 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).	0.00% 0/142 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).
Infections and infestations Clostridium difficile infection	0.16% 1/643 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).	0.00% 0/142 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).
Infections and infestations Sepsis	0.16% 1/643 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).	0.00% 0/142 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).
Infections and infestations Staphylococcal infection	0.16% 1/643 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).	0.00% 0/142 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).

Other adverse events

Measure	JZP-110 n=643 participants at risk Subjects completed a 2-week Titration phase. They then entered the maintenance phase of up to 50 weeks at the stable dose that was reached at the end of the Titration Phase.	Placebo n=142 participants at risk JZP-110 administered orally, QD, for the 2-week randomized withdrawal period, at the same dose subjects were currently receiving.
Nervous system disorders Headache	11.0% 71/643 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).	0.00% 0/142 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).
Psychiatric disorders Anxiety	7.2% 46/643 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).	0.00% 0/142 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).
Psychiatric disorders Insomnia	7.9% 51/643 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).	0.70% 1/142 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).
Gastrointestinal disorders Nausea	8.9% 57/643 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).	0.70% 1/142 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).
Gastrointestinal disorders Dry mouth	7.3% 47/643 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).	0.00% 0/142 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).
Metabolism and nutrition disorders Decreased appetite	5.0% 32/643 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).	0.00% 0/142 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).
Infections and infestations Nasopharyngitis	8.4% 54/643 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).	0.70% 1/142 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).
Infections and infestations Upper respiratory tract infection	5.0% 32/643 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).	0.00% 0/142 • The Safety Population consisted of all subjects who received at least 1 dose of study medication. Adverse events are reported across the entire study (e.g., the open-label and randomized withdrawal periods combined).

Additional Information

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Jazz Pharmaceuticals

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Email: ClinicalTrialDisclosure@JazzPharma.com

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