Narcolepsy
Conditions
Brief summary
This is a study to evaluate the safety and effectiveness of ADX-N05 compared to placebo in the treatment of excessive daytime sleepiness in adults with narcolepsy.
Interventions
DRUGADX-N05
150 mg once a day for seven days followed by 300 mg once a day for seven days
DRUGPlacebo
Placebo to match ADX-N05 once a day for 2 consecutive weeks
Sponsors
Jazz Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of narcolepsy * Good general health * Willing and able to comply with the study design and schedule and other requirements
Exclusion criteria
* If female, pregnant or lactating * Customary bedtime later than midnight * History of significant medical condition, behavioral or psychiatric disorder (including suicidal ideation), or surgical history * Any other clinically relevant medical, behavioral or psychiatric disorder other than narcolepsy that is associated with excessive sleepiness * History of significant cardiovascular disease * Body mass index \>34 * Excessive caffeine use - \> 600 mg/day of caffeine or \> 6 cups of coffee/day * History of alcohol or drug abuse within the past two years * Nicotine dependence that has an affect on sleep
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Average Sleep Latency Time (in Minutes) as Determined From the Maintenance of Wakefulness Test (MWT) Following Two Weeks of Treatment With ADX-N05 vs. Two Weeks of Treatment With Placebo | Baseline up to 2 weeks post-dose. | The MWT is a validated objective measure of the ability to stay awake for a defined period of time. The change from baseline in the mean sleep latency from the MWT was the average of sleep latency from the four trials of the MWT. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Epworth Sleepiness Scale (ESS) Score During Weeks 1 and 3 | Baseline up to Week 3 post-dose. | The ESS is a questionnaire intended to measure daytime sleepiness. In this test, participants answer questions with regard to the level of sleepiness they experienced over approximately the 7 days prior to the assessment while performing eight common, non-stimulating activities. The ESS total score range is 1 to 24. Each activity is rated on a 4-point scale ranging from a minimum of would never doze to a maximum of a high chance of dozing. Thus, the ESS scale range is as follows: 0=would never doze, 1=slight chance of dozing, 2=moderate chance of dozing, 3=high chance of dozing; 0 indicates a better outcome, and 3 indicates a worse outcome. A negative mean change value indicates a decrease in score from baseline and an improvement in daytime sleepiness. |
| Change From Baseline in Epworth Sleepiness Scale (ESS) Score During Weeks 2 and 4 | Baseline up to Week 4 post-dose. | The ESS is a questionnaire intended to measure daytime sleepiness. In this test, participants answer questions with regard to the level of sleepiness they experienced over approximately the 7 days prior to the assessment while performing eight common, non-stimulating activities. The ESS total score range is 1 to 24. Each activity is rated on a 4-point scale ranging from a minimum of would never doze to a maximum of a high chance of dozing. Thus, the ESS scale range is as follows: 0=would never doze, 1=slight chance of dozing, 2=moderate chance of dozing, 3=high chance of dozing; 0 indicates a better outcome, and 3 indicates a worse outcome. A negative mean change value indicates a decrease in score from baseline and an improvement in daytime sleepiness. |
| Number of Participants With Improved Clinical Global Impression of Change (CGI-C) Scores During Weeks 1 and 3 | Week 1 and Week 3 post-dose. | The CGI-C scale was completed at Week 1 through 4 visits. The participant was rated on a 7-point scale ranging from a minimum of Very much improved to a maximum of Very much worse. The proportion of participants experiencing at least minimal improvement on the CGI-C was calculated and summarized for each of the two weeks of each of the treatment periods. The CGI-C scale consists of the following ratings: 1-Very Much improved, 2-Much improved, 3-Minimally improved, 4-No change, 5-Minimally worse, 6-Much worse, 7-Very much worse; a rating of 1 indicates a better outcome, and a rating of 7 indicates a worse outcome. Improvement was defined as a CGI-rating of 1, 2, or 3. |
| Number of Participants With Improved Clinical Global Impression of Change (CGI-C) Scores During Weeks 2 and 4 | Week 2 and Week 4 post-dose. | The CGI-C scale was completed at Week 1 through 4 visits. The participant was rated on a 7-point scale ranging from a minimum of Very much improved to a maximum of Very much worse. The proportion of participants experiencing at least minimal improvement on the CGI-C was calculated and summarized for each of the two weeks of each of the treatment periods. The CGI-C scale consists of the following ratings: 1-Very Much improved, 2-Much improved, 3-Minimally improved, 4-No change, 5-Minimally worse, 6-Much worse, 7-Very much worse; a rating of 1 indicates a better outcome, and a rating of 7 indicates a worse outcome. Improvement was defined as a CGI-rating of 1, 2, or 3. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo, Then ADX-N05 Participants first received a placebo to match ADX-N05 once a day for 2 consecutive weeks (Weeks 1 and 2). They then received ADX-N05 150 mg tablet once a day for seven days (Week 3) followed by 300 mg (2 tablets) once a day for seven days (Week 4). | 17 |
| ADX-N05, Then Placebo Participants first received ADX-N05 150 mg tablet once a day for seven days (Week 1) followed by 300 mg (2 tablets) once a day for seven days (Week 2). They then received a placebo to match ADX-N05 once a day for 2 consecutive weeks (Weeks 3 and 4). | 16 |
| Total | 33 |
Baseline characteristics
| Characteristic | ADX-N05, Then Placebo | Total | Placebo, Then ADX-N05 |
|---|---|---|---|
| Age, Continuous | 42.81 years STANDARD_DEVIATION 10.72 | 37.1 years STANDARD_DEVIATION 12.35 | 31.71 years STANDARD_DEVIATION 11.56 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants | 33 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 10 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 23 Participants | 12 Participants |
| Sex: Female, Male Female | 5 Participants | 14 Participants | 9 Participants |
| Sex: Female, Male Male | 11 Participants | 19 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 33 | 0 / 33 |
| other Total, other adverse events | 20 / 33 | 0 / 33 |
| serious Total, serious adverse events | 0 / 33 | 0 / 33 |
Outcome results
Primary
Change From Baseline in the Average Sleep Latency Time (in Minutes) as Determined From the Maintenance of Wakefulness Test (MWT) Following Two Weeks of Treatment With ADX-N05 vs. Two Weeks of Treatment With Placebo
The MWT is a validated objective measure of the ability to stay awake for a defined period of time. The change from baseline in the mean sleep latency from the MWT was the average of sleep latency from the four trials of the MWT.
Time frame: Baseline up to 2 weeks post-dose.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ADX-N05 300 mg | Change From Baseline in the Average Sleep Latency Time (in Minutes) as Determined From the Maintenance of Wakefulness Test (MWT) Following Two Weeks of Treatment With ADX-N05 vs. Two Weeks of Treatment With Placebo | 12.7 minutes | Standard Deviation 10.64 |
| Placebo | Change From Baseline in the Average Sleep Latency Time (in Minutes) as Determined From the Maintenance of Wakefulness Test (MWT) Following Two Weeks of Treatment With ADX-N05 vs. Two Weeks of Treatment With Placebo | 0.9 minutes | Standard Deviation 6.02 |
Secondary
Change From Baseline in Epworth Sleepiness Scale (ESS) Score During Weeks 1 and 3
The ESS is a questionnaire intended to measure daytime sleepiness. In this test, participants answer questions with regard to the level of sleepiness they experienced over approximately the 7 days prior to the assessment while performing eight common, non-stimulating activities. The ESS total score range is 1 to 24. Each activity is rated on a 4-point scale ranging from a minimum of would never doze to a maximum of a high chance of dozing. Thus, the ESS scale range is as follows: 0=would never doze, 1=slight chance of dozing, 2=moderate chance of dozing, 3=high chance of dozing; 0 indicates a better outcome, and 3 indicates a worse outcome. A negative mean change value indicates a decrease in score from baseline and an improvement in daytime sleepiness.
Time frame: Baseline up to Week 3 post-dose.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ADX-N05 300 mg | Change From Baseline in Epworth Sleepiness Scale (ESS) Score During Weeks 1 and 3 | -5.3 score on a scale | Standard Deviation 5.2 |
| Placebo | Change From Baseline in Epworth Sleepiness Scale (ESS) Score During Weeks 1 and 3 | -1.2 score on a scale | Standard Deviation 4.09 |
Secondary
Change From Baseline in Epworth Sleepiness Scale (ESS) Score During Weeks 2 and 4
The ESS is a questionnaire intended to measure daytime sleepiness. In this test, participants answer questions with regard to the level of sleepiness they experienced over approximately the 7 days prior to the assessment while performing eight common, non-stimulating activities. The ESS total score range is 1 to 24. Each activity is rated on a 4-point scale ranging from a minimum of would never doze to a maximum of a high chance of dozing. Thus, the ESS scale range is as follows: 0=would never doze, 1=slight chance of dozing, 2=moderate chance of dozing, 3=high chance of dozing; 0 indicates a better outcome, and 3 indicates a worse outcome. A negative mean change value indicates a decrease in score from baseline and an improvement in daytime sleepiness.
Time frame: Baseline up to Week 4 post-dose.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ADX-N05 300 mg | Change From Baseline in Epworth Sleepiness Scale (ESS) Score During Weeks 2 and 4 | -6.7 score on a scale | Standard Deviation 6.15 |
| Placebo | Change From Baseline in Epworth Sleepiness Scale (ESS) Score During Weeks 2 and 4 | -2.4 score on a scale | Standard Deviation 3.82 |
Secondary
Number of Participants With Improved Clinical Global Impression of Change (CGI-C) Scores During Weeks 1 and 3
The CGI-C scale was completed at Week 1 through 4 visits. The participant was rated on a 7-point scale ranging from a minimum of Very much improved to a maximum of Very much worse. The proportion of participants experiencing at least minimal improvement on the CGI-C was calculated and summarized for each of the two weeks of each of the treatment periods. The CGI-C scale consists of the following ratings: 1-Very Much improved, 2-Much improved, 3-Minimally improved, 4-No change, 5-Minimally worse, 6-Much worse, 7-Very much worse; a rating of 1 indicates a better outcome, and a rating of 7 indicates a worse outcome. Improvement was defined as a CGI-rating of 1, 2, or 3.
Time frame: Week 1 and Week 3 post-dose.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ADX-N05 300 mg | Number of Participants With Improved Clinical Global Impression of Change (CGI-C) Scores During Weeks 1 and 3 | 29 Participants |
| Placebo | Number of Participants With Improved Clinical Global Impression of Change (CGI-C) Scores During Weeks 1 and 3 | 9 Participants |
Secondary
Number of Participants With Improved Clinical Global Impression of Change (CGI-C) Scores During Weeks 2 and 4
The CGI-C scale was completed at Week 1 through 4 visits. The participant was rated on a 7-point scale ranging from a minimum of Very much improved to a maximum of Very much worse. The proportion of participants experiencing at least minimal improvement on the CGI-C was calculated and summarized for each of the two weeks of each of the treatment periods. The CGI-C scale consists of the following ratings: 1-Very Much improved, 2-Much improved, 3-Minimally improved, 4-No change, 5-Minimally worse, 6-Much worse, 7-Very much worse; a rating of 1 indicates a better outcome, and a rating of 7 indicates a worse outcome. Improvement was defined as a CGI-rating of 1, 2, or 3.
Time frame: Week 2 and Week 4 post-dose.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ADX-N05 300 mg | Number of Participants With Improved Clinical Global Impression of Change (CGI-C) Scores During Weeks 2 and 4 | 25 Participants |
| Placebo | Number of Participants With Improved Clinical Global Impression of Change (CGI-C) Scores During Weeks 2 and 4 | 13 Participants |