Trial of AD036 in Obstructive Sleep Apnea
Primary Purpose
Obstructive Sleep Apnea
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
AD036 Dose 1
AD036 Dose 2
AD036 Dose 3
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Obstructive Sleep Apnea
Eligibility Criteria
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.
Sites / Locations
- Pulmonary Associates
- Preferred Research Partners, Inc.
- Stanford Sleep Medicine
- SDS Clinical Trials, Inc.
- Santa Monica Clinical Trials
- Northwestern University
- Norton Clinical Research Group
- The Center for Sleep and Wake Disorders
- Sleep Medicine & Research Center, St. Luke's Hospital
- Clinilabs Drug Development Corporation
- CTI Clinical Research Center
- Sleep Therapy & Research Center
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Placebo Comparator
Experimental
Experimental
No Intervention
Arm Label
2-Night at Home
3-Night Run In
7-Night
End of Study
Arm Description
An initial 2-night, at-home blinded baseline period in which all subjects received placebo
AD036 Dose 1 (Low Dose: 25/5) or Placebo
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
End of Study Visit
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03845023
Brief Title
Trial of AD036 in Obstructive Sleep Apnea
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
November 2022
Overall Recruitment Status
Completed
Study Start Date
March 7, 2019 (Actual)
Primary Completion Date
October 23, 2019 (Actual)
Study Completion Date
October 23, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Apnimed
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
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.
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obstructive Sleep Apnea
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
140 (Actual)
8. Arms, Groups, and Interventions
Arm Title
2-Night at Home
Arm Type
Placebo Comparator
Arm Description
An initial 2-night, at-home blinded baseline period in which all subjects received placebo
Arm Title
3-Night Run In
Arm Type
Experimental
Arm Description
AD036 Dose 1 (Low Dose: 25/5) or Placebo
Arm Title
7-Night
Arm Type
Experimental
Arm Description
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
Arm Title
End of Study
Arm Type
No Intervention
Arm Description
End of Study Visit
Intervention Type
Drug
Intervention Name(s)
AD036 Dose 1
Other Intervention Name(s)
25/5
Intervention Description
AD036 Dose 1 oral capsule administered before sleep
Intervention Type
Drug
Intervention Name(s)
AD036 Dose 2
Other Intervention Name(s)
75/1.5
Intervention Description
AD036 Dose 2 oral capsule administered before sleep
Intervention Type
Drug
Intervention Name(s)
AD036 Dose 3
Other Intervention Name(s)
75/5
Intervention Description
AD036 Dose 3 oral capsule administered before sleep
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo oral capsule administered before sleep
Primary Outcome Measure Information:
Title
Apnea Hypopnea Index (AHI)
Description
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.
Time Frame
10 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
25 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ron Farkas, MD
Organizational Affiliation
Apnimed
Official's Role
Study Director
Facility Information:
Facility Name
Pulmonary Associates
City
Glendale
State/Province
Arizona
ZIP/Postal Code
85306
Country
United States
Facility Name
Preferred Research Partners, Inc.
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72211
Country
United States
Facility Name
Stanford Sleep Medicine
City
Redwood City
State/Province
California
ZIP/Postal Code
94063
Country
United States
Facility Name
SDS Clinical Trials, Inc.
City
Santa Ana
State/Province
California
ZIP/Postal Code
92705
Country
United States
Facility Name
Santa Monica Clinical Trials
City
Santa Monica
State/Province
California
ZIP/Postal Code
90404
Country
United States
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Norton Clinical Research Group
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40218
Country
United States
Facility Name
The Center for Sleep and Wake Disorders
City
Chevy Chase
State/Province
Maryland
ZIP/Postal Code
20815
Country
United States
Facility Name
Sleep Medicine & Research Center, St. Luke's Hospital
City
Chesterfield
State/Province
Missouri
ZIP/Postal Code
63017
Country
United States
Facility Name
Clinilabs Drug Development Corporation
City
New York
State/Province
New York
ZIP/Postal Code
10019
Country
United States
Facility Name
CTI Clinical Research Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45212
Country
United States
Facility Name
Sleep Therapy & Research Center
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
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Trial of AD036 in Obstructive Sleep Apnea
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