Obstructive Sleep Apnea
Conditions
Brief summary
This trial is a 6-week, double-blind, placebo-controlled, randomized-withdrawal, multicenter study of safety and efficacy of JZP-110 in the treatment of excessive sleepiness in adult subjects with OSA.
Interventions
DRUGJZP-110
Sponsors
Jazz Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Major Inclusion Criteria: 1. Male or female between 18 and 75 years of age, inclusive 2. Diagnosis of OSA according to ICSD-3 criteria 3. Body mass index from 18 to \<45 kg/m2 4. Consent to use a medically acceptable method of contraception 5. 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 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. History or 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 principal investigator 5. History of bariatric surgery within the past year or a history of any gastric bypass 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 in the past 30 days or five half-lives (whichever is longer) 9. Previous exposure to or participation in a clinical trial of JZP-110 (ADX-N05, R228060, or YKP10A) 10. History of phenylketonuria (PKU) or history of hypersensitivity to phenylalanine-derived products
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in the Maintenance of Wakefulness Test (MWT) | Week 4 to Week 6 | 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. |
| Change in the Epworth Sleepiness Scale (ESS) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patient Global Impression of Change (PGIc) | 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. |
| Clinical Global Impression of Change (CGIc) | 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. |
| Change in Functional Outcomes of Sleep Questionnaire (FOSQ-10) | 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. |
Countries
Finland, France, Germany, Sweden, United States
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Double-Blind Withdrawal Phase | 124 |
| Total | 124 |
Baseline characteristics
| Characteristic | Double-Blind Withdrawal Phase |
|---|---|
| Age, Continuous JZP-110 | 56.3 years STANDARD_DEVIATION 11.36 |
| Age, Continuous Placebo | 56.2 years STANDARD_DEVIATION 9.75 |
| Race (NIH/OMB) JZP-110 American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) JZP-110 Asian | 0 Participants |
| Race (NIH/OMB) JZP-110 Black or African American | 12 Participants |
| Race (NIH/OMB) JZP-110 More than one race | 0 Participants |
| Race (NIH/OMB) JZP-110 Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) JZP-110 Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) JZP-110 White | 50 Participants |
| Race (NIH/OMB) Placebo American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Placebo Asian | 2 Participants |
| Race (NIH/OMB) Placebo Black or African American | 15 Participants |
| Race (NIH/OMB) Placebo More than one race | 0 Participants |
| Race (NIH/OMB) Placebo Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Placebo Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) Placebo White | 45 Participants |
| Sex: Female, Male JZP-110 Female | 26 Participants |
| Sex: Female, Male JZP-110 Male | 36 Participants |
| Sex: Female, Male Placebo Female | 21 Participants |
| Sex: Female, Male Placebo Male | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 174 | 0 / 62 |
| other Total, other adverse events | 58 / 174 | 0 / 62 |
| serious Total, serious adverse events | 0 / 174 | 0 / 62 |
Outcome results
Primary
Change in the Epworth Sleepiness Scale (ESS)
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.
Time frame: Week 4 to Week 6
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| JZP-110 | Change in the Epworth Sleepiness Scale (ESS) | -0.1 points on a scale | Standard Error 0.73 |
| Placebo | Change in the Epworth Sleepiness Scale (ESS) | 4.5 points on a scale | Standard Error 0.71 |
Primary
Change in the Maintenance of Wakefulness Test (MWT)
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.
Time frame: Week 4 to Week 6
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| JZP-110 | Change in the Maintenance of Wakefulness Test (MWT) | -0.96 minutes | Standard Error 1.35 |
| Placebo | Change in the Maintenance of Wakefulness Test (MWT) | -12.11 minutes | Standard Error 1.326 |
Secondary
Change in Functional Outcomes of Sleep Questionnaire (FOSQ-10)
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.
Time frame: Week 4 to Week 6
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| JZP-110 | Change in Functional Outcomes of Sleep Questionnaire (FOSQ-10) | -0.15 units on a scale | Standard Error 0.393 |
| Placebo | Change in Functional Outcomes of Sleep Questionnaire (FOSQ-10) | -1.31 units on a scale | Standard Error 0.381 |
Secondary
Clinical Global Impression of Change (CGIc)
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.
Time frame: Week 4 to Week 6
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| JZP-110 | Clinical Global Impression of Change (CGIc) | 22 percentage of subjects |
| Placebo | Clinical Global Impression of Change (CGIc) | 59 percentage of subjects |
Secondary
Patient Global Impression of Change (PGIc)
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.
Time frame: Week 4 to Week 6
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| JZP-110 | Patient Global Impression of Change (PGIc) | 20 percentage of subjects |
| Placebo | Patient Global Impression of Change (PGIc) | 50 percentage of subjects |