Trial of AD036 in Obstructive Sleep Apnea

Phase 2, Placebo-Controlled, Parallel Group Dose-Finding Study to Evaluate the Efficacy and Safety of Three Dose Levels of AD036 in Adults With Obstructive Sleep Apnea

This is a randomized, double blind, placebo-controlled, repeat-dose, parallel arm, outpatient and inpatient phase 2 clinical study to examine the efficacy and safety of three dose levels of AD036 versus placebo in patients with obstructive sleep apnea.

Study Overview

• Status: Completed
• Conditions: Obstructive Sleep Apnea
• Intervention / Treatment: Drug: Placebo; Drug: AD036 Dose 1; Drug: AD036 Dose 2; Drug: AD036 Dose 3

Detailed Description

This was a randomized, double-blind, placebo-controlled, repeat-dose, parallel arm, outpatient and inpatient, multicenter, dose-finding study of the combination of atomoxetine and oxybutynin in adults with OSA documented by polysomnography (PSG).

Approximately 140 subjects were to be randomized 1:1:1:1 to receive 1 of 3 different fixed-dose combinations of oxybutynin and atomoxetine or matching placebo.

For all subjects, the study consisted of:

• A screening and baseline period in which subjects' eligibility was determined
• An initial 2-night, at-home blinded baseline period in which all subjects received placebo

• A 3-night, run-in period in which subjects received:

  • Low-dose combination for subjects randomized to one of the 3 study treatment arms
  • Placebo for subjects randomized to the placebo treatment arm
• A 7-night treatment period in which subjects received the treatment to which they were randomized, i.e., 1 of the 3 different fixed-dose combinations of drugs, or placebo
• An end of study visit

• Study Type: Interventional
• Enrollment (Actual): 140
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Glendale, Arizona, United States, 85306
      • Pulmonary Associates
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Preferred Research Partners, Inc.
  • California
    • Redwood City, California, United States, 94063
      • Stanford Sleep Medicine
    • Santa Ana, California, United States, 92705
      • SDS Clinical Trials, Inc.
    • Santa Monica, California, United States, 90404
      • Santa Monica Clinical Trials
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Kentucky
    • Louisville, Kentucky, United States, 40218
      • Norton Clinical Research Group
  • Maryland
    • Chevy Chase, Maryland, United States, 20815
      • The Center for Sleep and Wake Disorders
  • Missouri
    • Chesterfield, Missouri, United States, 63017
      • Sleep Medicine & Research Center, St. Luke's Hospital
  • New York
    • New York, New York, United States, 10019
      • Clinilabs Drug Development Corporation
  • Ohio
    • Cincinnati, Ohio, United States, 45212
      • CTI Clinical Research Center
  • Texas
    • San Antonio, Texas, United States, 78229
      • Sleep Therapy & Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Male participants between 25 to 65 years of age or female participants between 25 to 70 years of age.

Key Inclusion Criteria:

• AHI ≥ 20 based on screening polysomnography
• Epworth Sleepiness Scale (ESS) score ≥ 4 for participants not using CPAP
• Previous surgical treatment for OSA is allowed if ≥ 1 year prior to enrollment

Key Exclusion Criteria:

• Clinically significant craniofacial malformation.
• Clinically significant cardiac disease (e.g., rhythm disturbances, coronary artery disease or cardiac failure) or hypertension requiring more than 2 medications for control.
• Clinically significant neurological disorder, including epilepsy/convulsions.
• Positive screen for drugs of abuse or substance use disorder as defined in DSM-V within 24 months prior to Screening Visit.
• A significant illness or infection requiring medical treatment in the past 30 days.
• Women who are pregnant or nursing.
• History of using oral or nasal devices for the treatment of OSA may enroll as long as the devices are not used during participation in the study.
• History of using devices to affect participant sleeping position for the treatment of OSA, e.g. to discourage supine sleeping position, may enroll as long as the devices are not used during participation in the study.
• Treatment with strong cytochrome P450 3A4 (CYP3A4) inhibitors, strong cytochrome P450 2D6 (CYP2D6) inhibitors, or monoamine oxidase inhibitors (MAOI) within 14 days of the start of treatment, or concomitant with treatment.
• Use of another investigational agent within 90 days or 5 half-lives, whichever is longer, prior to dosing.
• ESS total score > 18.
• Central apnea index > 5/hour on baseline PSG.
• Periodic limb movement arousal index >15/hour on baseline PSG.
• Hepatic transaminases >3X the upper limit of normal (ULN), total bilirubin >2X ULN (unless confirmed Gilbert syndrome), serum creatinine >2X ULN.
• <6 hours typical sleep duration.
• Night- or shift-work sleep schedule.
• Employment as a commercial driver or operator of heavy or hazardous equipment.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 2-Night at Home; An initial 2-night, at-home blinded baseline period in which all subjects received placebo	Drug: Placebo; Placebo oral capsule administered before sleep
Experimental: 3-Night Run In; AD036 Dose 1 (Low Dose: 25/5) or Placebo	Drug: Placebo; Placebo oral capsule administered before sleep; Drug: AD036 Dose 1; AD036 Dose 1 oral capsule administered before sleep; Other Names: 25/5
Experimental: 7-Night; A 7-night treatment period in which subjects received the treatment to which they were randomized, i.e., 1 of the 3 different fixed-dose combinations of drugs, or placebo	Drug: Placebo; Placebo oral capsule administered before sleep; Drug: AD036 Dose 1; AD036 Dose 1 oral capsule administered before sleep; Other Names: 25/5; Drug: AD036 Dose 2; AD036 Dose 2 oral capsule administered before sleep; Other Names: 75/1.5; Drug: AD036 Dose 3; AD036 Dose 3 oral capsule administered before sleep; Other Names: 75/5
No Intervention: End of Study; End of Study Visit

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Apnea Hypopnea Index (AHI)	Number of participants with ≥50% reduction in apnea hypopnea index (AHI). AHI is the average number of apneas and hypopneas a person experiences each hour during sleep, to register as an event an apnea or hypopnea must last at least 10 seconds or longer. To measure this, doctors divide the total number of apneic and hypopneic events by the total number of hours the person was asleep.	10 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Oxygen Desaturation Index		10 days
Epworth Sleepiness Scale	The ESS is a self-administered questionnaire with 8 questions. Respondents are asked to rate, on a 4-point scale (0-3), their usual chances of dozing off or falling asleep while engaged in eight different activities. Most people engage in those activities at least occasionally, although not necessarily every day. The ESS score (the sum of 8 item scores, 0-3) can range from 0 to 24. The higher the ESS score, the higher that person's average sleep propensity in daily life (ASP), or their 'daytime sleepiness'. In general ESS scores can be interpreted as follows:0-5 Lower Normal Daytime Sleepiness 6-10 Higher Normal Daytime Sleepiness 11-12 Mild Excessive Daytime Sleepiness 13-15 Moderate Excessive Daytime Sleepiness 16-24 Severe Excessive Daytime Sleepiness	10 days

Collaborators and Investigators

• Sponsor: Apnimed
• Investigators: Study Director: Ron Farkas, MD, Apnimed

Study record dates

Study Major Dates

• Study Start (Actual): March 7, 2019
• Primary Completion (Actual): October 23, 2019
• Study Completion (Actual): October 23, 2019

Study Registration Dates

• First Submitted: February 15, 2019
• First Submitted That Met QC Criteria: February 18, 2019
• First Posted (Actual): February 19, 2019

Study Record Updates

• Last Update Posted (Estimate): January 16, 2023
• Last Update Submitted That Met QC Criteria: December 20, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Signs and Symptoms, Respiratory; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Apnea
• Other Study ID Numbers: APN-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No