Narcolepsy, Obstructive Sleep Apnea
Conditions
Brief summary
This is a Phase 3 study to assess the long-term safety and maintenance of efficacy of JZP-110 in subjects who have completed Study 14-002, 14-003, 14-004, 15-004, 15-005, ADX-N05 201, or ADX-N05 202.
Interventions
DRUGJZP-110
Sponsors
Jazz Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Major Inclusion Criteria: 1. Subject meets one of the following: 1. Completed Study 14-002 or 14-003 (Group A) 2. Completed Study 14-004, 15-004, 15-005, ADX-N05 201 or ADX-N05 202 (Group B) 2. Body mass index from 18 to \<45 kg/m2 3. Consent to use a medically acceptable method of contraception 4. Willing and able to provide written informed consent Major
Exclusion criteria
1. Female subjects who are pregnant, nursing, or lactating 2. Any other clinically relevant medical, behavioral, or psychiatric disorder other than narcolepsy or OSA that is associated with excessive sleepiness 3. History or presence of bipolar disorder, bipolar related disorders, schizophrenia, schizophrenia spectrum disorders, or other psychotic disorders according to DSM-5 criteria 4. Presence of any acutely unstable medical condition, behavioral or psychiatric disorder (including active suicidal ideation), or surgical history that could affect the safety of the subject or interfere with study efficacy or safety assessments, or the ability of the subject to complete the trial per the judgment of the Investigator 5. History of bariatric surgery within the past year or a history of roux-en-y procedure 6. Presence or history of significant cardiovascular disease 7. Use of any over the counter (OTC) or prescription medications that could affect the evaluation of excessive sleepiness 8. Received an investigational drug other than JZP-110 in the past 30 days or five half-lives (whichever is longer) 9. History of phenylketonuria (PKU) or history of hypersensitivity to phenylalanine-derived products
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Epworth Sleepiness Scale (ESS) Score | Start of randomized withdrawal phase to end of randomized withdrawal (2 weeks) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Subjects Reported as Worse on the Patient Global Impression of Change (PGIc) | Beginning of randomized withdrawal phase to end of the randomized withdrawal phase (2 weeks) | 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. |
| Subjects Reported as Worse on the Clinical Global Impression of Change (CGIc) | Beginning of randomized withdrawal phase to end of the randomized withdrawal phase (2 weeks) | 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. |
Countries
Canada, Finland, France, Germany, Netherlands, United States
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Open-label Period 643 subjects comprised the safety population. | 643 |
| Total | 643 |
Baseline characteristics
| Characteristic | Open-label Period |
|---|---|
| Age, Continuous | 49.31 years STANDARD_DEVIATION 14.155 |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants |
| Race (NIH/OMB) Asian | 15 Participants |
| Race (NIH/OMB) Black or African American | 109 Participants |
| Race (NIH/OMB) More than one race | 8 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 3 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 506 Participants |
| Sex: Female, Male Female | 306 Participants |
| Sex: Female, Male Male | 337 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 643 | 0 / 142 |
| other Total, other adverse events | 269 / 643 | 3 / 142 |
| serious Total, serious adverse events | 27 / 643 | 0 / 142 |
Outcome results
Primary
Change in Epworth Sleepiness Scale (ESS) Score
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| JZP-110 | Change in Epworth Sleepiness Scale (ESS) Score | 1.6 points on a scale | Standard Error 0.41 |
| Placebo | Change in Epworth Sleepiness Scale (ESS) Score | 5.3 points on a scale | Standard Error 0.41 |
Secondary
Subjects Reported as Worse on the Clinical Global Impression of Change (CGIc)
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| JZP-110 | Subjects Reported as Worse on the Clinical Global Impression of Change (CGIc) | 28.7 percentage of subjects |
| Placebo | Subjects Reported as Worse on the Clinical Global Impression of Change (CGIc) | 63.8 percentage of subjects |
Secondary
Subjects Reported as Worse on the Patient Global Impression of Change (PGIc)
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| JZP-110 | Subjects Reported as Worse on the Patient Global Impression of Change (PGIc) | 28.2 percentage of subjects |
| Placebo | Subjects Reported as Worse on the Patient Global Impression of Change (PGIc) | 64.5 percentage of subjects |