A Study of the Safety and Effectiveness of ADX-N05 for Excessive Daytime Sleepiness in Subjects With Narcolepsy

Study Overview
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Brief Summary
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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.

Official Title
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A Twelve-week, Double-blind, Placebo-controlled, Randomized, Parallel-group, Multi-center Study of the Safety and Efficacy of ADX-N05 in the Treatment of Excessive Daytime Sleepiness in Subjects With Narcolepsy

Conditions
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Narcolepsy

Intervention / Treatment
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* Drug: ADX-N05
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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 2 years Nicotine dependence that has an effect on sleep

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ADX-N05<br>ADX-N05 to be taken once a day for 12 weeks | Drug: ADX-N05<br>* 150 mg once a day for 4 weeks followed by 300 mg once a day for 8 weeks<br>|
| Placebo Comparator: Placebo<br>Placebo to match ADX-N05 to be taken once a day for 12 weeks | Drug: Placebo<br>* One capsule placebo to match ADX-N05 to be taken for 4 weeks followed by 2 capsules placebo to match ADX-N05 to be taken for 8 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Average Sleep Latency Time (in Minutes) as Determined From the Maintenance of Wakefulness Test (MWT) for ADX-N05 300 mg vs. Placebo at Last Assessment. | The MWT is a validated objective measure of the ability to stay awake for a defined period of time. The primary analysis was a comparison of treatments vs. control groups on change from Baseline to last available post-Baseline assessment (Week 12/Last Assessment) in the average sleep latency time (in minutes) averaged across the first four trials of the MWT using a two-sample t-test. | Baseline up to Week 12/Last Assessment post-dose. | 
| Number of Participants With Improved Clinical Global Impression of Change (CGI-C) Scores for ADX-N05 vs. Placebo at Last Assessment | The CGI-C scale rated the change in the participant's condition as compared to the Baseline visit on a 7-point scale ranging from a minimum of Very much improved to a maximum of Very much worse. The proportion of subjects experiencing at least minimal improvement on the CGI-C was calculated and summarized for each of the treatment groups at Week 4 and the last available post-Baseline assessment (Week 12/Last Assessment). 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. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Average Sleep Latency Time (in Minutes) as Determined From the Maintenance of Wakefulness Test (MWT) (Average of the First Four Trials) Following Four Weeks of Treatment With ADX-N05 150 mg vs. Placebo | The MWT is a validated objective measure of the ability to stay awake for a defined period of time. The MWT consisted of five 40-minute trials separated by 2 hour intervals. This secondary analysis repeated the primary analysis for effects at the end of Week 4. | Baseline up to Week 4 post-dose. | 
| Change From Baseline in Sleep Latency Time (in Minutes) as Determined From Each of the 5 Individual MWT Trials for ADX-N05 vs. Placebo at Week 4 | The MWT is a validated objective measure of the ability to stay awake for a defined period of time. The MWT consisted of five 40-minute trials separated by 2 hour intervals. This secondary analysis repeated the primary analysis for effects for the five MWT trials analyzed separately at Week 4. | Baseline up to Week 4 post-dose. | 
| Change From Baseline in Sleep Latency Time (in Minutes) as Determined From Each of the 5 Individual MWT Trials for ADX-N05 vs. Placebo at Last Assessment | The MWT is a validated objective measure of the ability to stay awake for a defined period of time. The MWT consisted of five 40-minute trials separated by 2 hour intervals. This secondary analysis repeated the primary analysis for effects for the five MWT trials analyzed separately at the last available post-Baseline assessment (Week 12/Last Assessment). | Baseline up to Week 12/Last Assessment post-dose. | 
| Change From Baseline in Epworth Sleepiness Scale (ESS) Scores for ADX-N05 vs. Placebo at Week 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. | Baseline up to Week 4 post-dose. | 
| Change From Baseline in ESS Scores for ADX-N05 vs. Placebo at Last Assessment | 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. | Baseline up to Week 12/Last Assessment post-dose. | 
| Number of Participants With Improved Clinical Global Impression of Change (CGI-C) Scores for ADX-N05 vs. Placebo at Week 4 | The CGI-C scale rated the change in the participant's condition as compared to the Baseline visit on a 7-point scale ranging from a minimum of Very much improved to a maximum of Very much worse. The proportion of subjects experiencing at least minimal improvement on the CGI-C was calculated and summarized for each of the treatment groups at Week 4 and the last available post-Baseline assessment (Week 12/Last Assessment). 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. | Week 4 | 
| Number of Participants With Improved Patient Global Impression Change (PGI-C) Scores for ADX-N05 vs. Placebo at Week 4 | The Patient Global Impression - Change (PGI-C) scale was completed by the subject at the Weeks 1, 2, 4, 6, 8, and 12 visits. The CGI-C scale rated the change in the participant's condition as compared to the Baseline visit on a 7-point scale ranging from a minimum of Very much improved to a maximum of Very much worse. The proportion of subjects experiencing at least minimal improvement on the CGI-C was calculated and summarized for each of the treatment groups at Week 4 and the last available post-Baseline assessment (Week 12/Last Assessment). 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. | Week 4 | 
| Number of Participants With Improved PGI-C Scores for ADX-N05 vs. Placebo at Last Assessment | The Patient Global Impression - Change (PGI-C) scale was completed by the subject at the Weeks 1, 2, 4, 6, 8, and 12 visits. The CGI-C scale rated the change in the participant's condition as compared to the Baseline visit on a 7-point scale ranging from a minimum of Very much improved to a maximum of Very much worse. The proportion of subjects experiencing at least minimal improvement on the CGI-C was calculated and summarized for each of the treatment groups at Week 4 and the last available post-Baseline assessment (Week 12/Last Assessment). 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. | Week 12/Last Assessment |