"Six-week Study of the Safety and Efficacy of JZP-110 in the Treatment of Excessive Sleepiness in OSA" (OSA)

A Six-Week, Double-Blind, Placebo-Controlled, Randomized- Withdrawal, Multicenter Study of the Safety and Efficacy of JZP-110 [(R)-2-amino-3-phenylpropylcarbamate Hydrochloride] in the Treatment of Excessive Sleepiness in Subjects With Obstructive Sleep Apnea (OSA)

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.

Study Overview

• Status: Completed
• Conditions: Obstructive Sleep Apnea
• Intervention / Treatment: Drug: JZP-110

• Study Type: Interventional
• Enrollment (Actual): 174
• Phase: Phase 3

Contacts and Locations

Study Locations

• Finland
  • Helsinki, Finland, 00420
    • Helsinki Sleep Center
  • Södra Finlands Län
    • Tampere, Södra Finlands Län, Finland, 33200
      • Tampere University Hospital
  • Västra Finlands Län
    • Turku, Västra Finlands Län, Finland, 20520
      • Turku University Hospital, Sleep Clinic
• France
  • Rhône-Alpes
    • La Tronche, Rhône-Alpes, France, 38700
      • Grenoble University Hospital
  • Vienne
    • Poitiers, Vienne, France, 86000
      • CHU de Poitiers
• Germany
  • Mecklenburg-Vorpommern
    • Schwerin, Mecklenburg-Vorpommern, Germany, 19055
      • Klinische forschung Schwerin GmbH
  • Nordrhein-Westfalen
    • Dortmund, Nordrhein-Westfalen, Germany, 44263
      • Somnolab Dortmund
• Sweden
  • Västra Götalands Län
    • Gӧteborg, Västra Götalands Län, Sweden, SE 413 45
      • Department of Sleep Medicine
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35213
      • Sleep Disorder Center of Alabama
  • California
    • Oceanside, California, United States, 92056
      • The Research Center of Southern California
    • Orange, California, United States, 92868
      • SDS Clinical Trials, Inc
    • Santa Monica, California, United States, 90404
      • Santa Monica Clinical Trials
  • Colorado
    • Lakewood, Colorado, United States, 80228
      • Critical care Pulmonary & Sleep Associates, LLC
  • Florida
    • Brandon, Florida, United States, 33511
      • PAB Clinical Research
    • Hollywood, Florida, United States, 33024
      • Broward Research Group, Inc.
    • Oviedo, Florida, United States, 32765
      • Oviedo Medical Research, LLC
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Emory Sleep Center
  • Kansas
    • Lenexa, Kansas, United States, 66214
      • Rowe Neurology Institute RNI - Lenexa
    • Topeka, Kansas, United States, 66606
      • Veritas Clinical Specialities LTD
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Advanced Neurodiagnostic Ceneter
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham & Womens Hospital
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Wilmington, North Carolina, United States, 28401
      • PMG Research of Wilmington
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Center for Sleep & Circadian Neurobiology
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC Sleep Medicine Center
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
    • Charleston, South Carolina, United States, 29406
      • Lowcountry Lung Critical Care
  • Virginia
    • Norfolk, Virginia, United States, 23510
      • EVMS Sleep Medicine
    • Vienna, Virginia, United States, 22182
      • American Sleep Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Placebo; Once Daily Dosing	Drug: JZP-110
Active Comparator: 75, 150, 300 mg of JZP-110; Once Daily Dosing	Drug: JZP-110

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Week 4 to Week 6
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.	Week 4 to Week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Week 4 to Week 6
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.	Week 4 to Week 6
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.	Week 4 to Week 6

Collaborators and Investigators

• Sponsor: Jazz Pharmaceuticals

Publications and helpful links

General Publications

• Strollo PJ Jr, Hedner J, Collop N, Lorch DG Jr, Chen D, Carter LP, Lu Y, Lee L, Black J, Pepin JL, Redline S; Tones 4 Study Investigators. Solriamfetol for the Treatment of Excessive Sleepiness in OSA: A Placebo-Controlled Randomized Withdrawal Study. Chest. 2019 Feb;155(2):364-374. doi: 10.1016/j.chest.2018.11.005. Epub 2018 Nov 22.

Study record dates

Study Major Dates

• Study Start: May 1, 2015
• Primary Completion (Actual): November 1, 2016
• Study Completion (Actual): November 1, 2016

Study Registration Dates

• First Submitted: January 15, 2015
• First Submitted That Met QC Criteria: January 22, 2015
• First Posted (Estimate): January 28, 2015

Study Record Updates

• Last Update Posted (Actual): September 9, 2019
• Last Update Submitted That Met QC Criteria: September 6, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Apnea; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Sleepiness
• Other Study ID Numbers: 14-004