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

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

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.

Study Overview

• Status: Completed
• Conditions: Narcolepsy
• Intervention / Treatment: Drug: ADX-N05; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 93
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35213
      • Sleep Disorders Center of Alabama
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Pulmonary Associates
  • California
    • Redwood City, California, United States, 94063
      • Stanford Sleep Medicine Center
    • San Diego, California, United States, 92103
      • Pacific Research Network
  • Colorado
    • Aurora, Colorado, United States, 80012
      • Sleep-Alertness Disorders Center
  • Florida
    • Brandon, Florida, United States, 33511
      • PAB Clinical Research
    • Saint Petersburg, Florida, United States, 33707
      • Clinical Research Group of St. Petersburg
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Sleep Disorders Center of Georgia
    • Atlanta, Georgia, United States, 30342
      • NeuroTrials Research, Inc.
    • Macon, Georgia, United States, 31201
      • SleepMed of Central Georgia
  • Illinois
    • Chicago, Illinois, United States, 60634
      • Chicago Research Center
  • Kentucky
    • Crestview Hills, Kentucky, United States, 41017
      • Community Research
    • Louisville, Kentucky, United States, 40217
      • Kentucky Research Group
  • Maryland
    • Chevy Chase, Maryland, United States, 20815
      • The Center for Sleep and Wake Disorders
    • Towson, Maryland, United States, 21204
      • Pulmonary and Critical Care Associates of Baltimore
  • Massachusetts
    • Newton, Massachusetts, United States, 02459
      • Neurocare, Inc.
  • Minnesota
    • Edina, Minnesota, United States, 55435
      • Minnesota Lung Center and Sleep Institute
  • Missouri
    • Saint Louis, Missouri, United States, 63108
      • Washington University
  • North Carolina
    • Raleigh, North Carolina, United States, 27612
      • Wake Research Associates
    • Raleigh, North Carolina, United States, 27607
      • Rex Sleep Disorders Center
  • Ohio
    • Toledo, Ohio, United States, 43623
      • Mercy St. Vincent Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19118
      • Center for Sleep Medicine
  • South Carolina
    • Columbia, South Carolina, United States, 29201
      • Sleepmed of South Carolina
  • Texas
    • Austin, Texas, United States, 78731
      • Future Search Trials of Neurology
    • Dallas, Texas, United States, 75231
      • Sleep Medicine Associates of Texas
    • Houston, Texas, United States, 77063
      • Todd J. Swick, MD, PA
    • McKinney, Texas, United States, 75069
      • Metroplex Pulmonary and Sleep Center
    • San Antonio, Texas, United States, 78229
      • Sleep Therapy and Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ADX-N05; ADX-N05 to be taken once a day for 12 weeks	Drug: ADX-N05; 150 mg once a day for 4 weeks followed by 300 mg once a day for 8 weeks
Placebo Comparator: Placebo; Placebo to match ADX-N05 to be taken once a day for 12 weeks	Drug: Placebo; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Jazz Pharmaceuticals
• Investigators: Study Director: David Ward, MD, Aerial BioPharma, LLC

Publications and helpful links

General Publications

• Ruoff C, Swick TJ, Doekel R, Emsellem HA, Feldman NT, Rosenberg R, Bream G, Khayrallah MA, Lu Y, Black J. Effect of Oral JZP-110 (ADX-N05) on Wakefulness and Sleepiness in Adults with Narcolepsy: A Phase 2b Study. Sleep. 2016 Jul 1;39(7):1379-87. doi: 10.5665/sleep.5968.

Study record dates

Study Major Dates

• Study Start: September 1, 2012
• Primary Completion (Actual): August 1, 2013
• Study Completion (Actual): August 1, 2013

Study Registration Dates

• First Submitted: September 5, 2012
• First Submitted That Met QC Criteria: September 5, 2012
• First Posted (Estimate): September 7, 2012

Study Record Updates

• Last Update Posted (Actual): May 28, 2021
• Last Update Submitted That Met QC Criteria: May 27, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Disorders of Excessive Somnolence; Sleepiness; Narcolepsy
• Other Study ID Numbers: ADX-N05 202