Trial Outcomes & Findings for Crossover Trial of AD109 in Obstructive Sleep Apnea (NCT NCT04580394)
NCT ID: NCT04580394
Last Updated: 2023-01-31
Results Overview
Change in Hypoxic Burden (HB) is calculated as the oxygen desaturation 'area under the curve' in association with individual apneas and hypopneas. Due to the known logarithmic distribution of HB, data are primarily expressed and analyzed as Log10HB 4%\[% min/hour\]. Events with 4% or greater desaturations were included in the calculation of HB.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
60 participants
Primary outcome timeframe
1 night (treatment duration) (0-8 hours collected continuously)
Results posted on
2023-01-31
Participant Flow
Seven clinical sites screened 146 participants, 60 participants were randomized. This was a double-blind, single dose crossover study. Participants underwent initial pre-screening to determine potential study eligibility. Overall study duration was up to 14 weeks. Participants who withdrew from the study were not replaced.
Participants underwent initial pre-screening to determine potential study eligibility. Patients selected for further screening had either a previous history of OSA of a severity consistent with enrollment criteria or had high risk.
Participant milestones
| Measure |
All Participants
Oral capsules were administered before sleep in random order of each of the following: AD109 (Treatment A: Atomoxetine 75 mg and R-Oxbutynin 2.5 mg), Treatment B: Atomoxetine 75 mg and Placebo, Treatment C:R-Oxbutynin 2.5 mg and placebo, Treatment D:Placebo and Placebo. Each participant received single doses of each of the four treatments, the order in which each treatment was assigned was random.
|
|---|---|
|
First Intervention
STARTED
|
60
|
|
First Intervention
75mg/2.5mg
|
16
|
|
First Intervention
75mg and Placebo
|
14
|
|
First Intervention
2.5mg and Placebo
|
15
|
|
First Intervention
Placebo and Placebo
|
15
|
|
First Intervention
COMPLETED
|
57
|
|
First Intervention
NOT COMPLETED
|
3
|
|
Washout (One Week)
STARTED
|
51
|
|
Washout (One Week)
COMPLETED
|
49
|
|
Washout (One Week)
NOT COMPLETED
|
2
|
|
Second Intervention
STARTED
|
56
|
|
Second Intervention
75mg/2.5mg
|
15
|
|
Second Intervention
75mg and Placebo
|
15
|
|
Second Intervention
2.5mg and Placebo
|
13
|
|
Second Intervention
Placebo and Placebo
|
14
|
|
Second Intervention
COMPLETED
|
56
|
|
Second Intervention
NOT COMPLETED
|
0
|
|
Third Intervention
STARTED
|
53
|
|
Third Intervention
75mg /2.5mg
|
13
|
|
Third Intervention
75mg and Placebo
|
13
|
|
Third Intervention
2.5mg and Placebo
|
15
|
|
Third Intervention
Placebo and Placebo
|
14
|
|
Third Intervention
COMPLETED
|
51
|
|
Third Intervention
NOT COMPLETED
|
2
|
|
Fourth Intervention
STARTED
|
49
|
|
Fourth Intervention
75mg/2.5mg
|
12
|
|
Fourth Intervention
75mg and Placebo
|
12
|
|
Fourth Intervention
2.5mg and Placebo
|
11
|
|
Fourth Intervention
Placebo and Placebo
|
14
|
|
Fourth Intervention
COMPLETED
|
49
|
|
Fourth Intervention
NOT COMPLETED
|
0
|
Reasons for withdrawal
| Measure |
All Participants
Oral capsules were administered before sleep in random order of each of the following: AD109 (Treatment A: Atomoxetine 75 mg and R-Oxbutynin 2.5 mg), Treatment B: Atomoxetine 75 mg and Placebo, Treatment C:R-Oxbutynin 2.5 mg and placebo, Treatment D:Placebo and Placebo. Each participant received single doses of each of the four treatments, the order in which each treatment was assigned was random.
|
|---|---|
|
First Intervention
Incorrectly Randomized
|
1
|
|
First Intervention
Physician Decision
|
1
|
|
First Intervention
Lost to Follow-up
|
1
|
|
Washout (One Week)
Withdrawal by Subject
|
2
|
|
Washout (One Week)
Adverse Event
|
1
|
|
Third Intervention
Adverse Event
|
1
|
|
Third Intervention
Withdrawal by Subject
|
1
|
Baseline Characteristics
Crossover Trial of AD109 in Obstructive Sleep Apnea
Baseline characteristics by cohort
| Measure |
All Study Participants
n=60 Participants
Oral capsule administered before sleep
AD109 Atomoxetine R-Oxybutynin Placebo
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
60 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
25 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
35 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
16 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
44 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
11 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
47 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
60 participants
n=5 Participants
|
|
Body Mass Index (BMI)
|
33 kg/m^2
n=5 Participants
|
PRIMARY outcome
Timeframe: 1 night (treatment duration) (0-8 hours collected continuously)Population: The efficacy was analyzed using the mITT Set comprised of all participants who took at least 1 dose of any of the study treatments and had at least 1 measurement for the primary endpoint. Fifty-nine (98.3%) participants were included in the mITT Population
Change in Hypoxic Burden (HB) is calculated as the oxygen desaturation 'area under the curve' in association with individual apneas and hypopneas. Due to the known logarithmic distribution of HB, data are primarily expressed and analyzed as Log10HB 4%\[% min/hour\]. Events with 4% or greater desaturations were included in the calculation of HB.
Outcome measures
| Measure |
AD109
n=59 Participants
Oral capsule administered before sleep
AD109: Oral administration before bed
|
Atomoxetine
n=59 Participants
Oral capsule administered before sleep
Atomoxetine: Oral administration before bed
|
R-oxybutynin
n=59 Participants
Oral capsule administered before sleep
R-oxybutynin: Oral administration before bed
|
Placebo
n=59 Participants
Oral capsule administered before sleep
Placebo: Oral administration before bed
|
|---|---|---|---|---|
|
Change in Hypoxic Burden (HB) Log10HB[(%*Min)/Hour]
|
-0.41 Log10HB4%[%min/hour]
Interval -0.54 to -0.28
|
-0.36 Log10HB4%[%min/hour]
Interval -0.49 to -0.23
|
-0.04 Log10HB4%[%min/hour]
Interval -0.17 to 0.09
|
-0.06 Log10HB4%[%min/hour]
Interval -0.18 to 0.07
|
Adverse Events
A: AD109
Serious events: 1 serious events
Other events: 2 other events
Deaths: 0 deaths
B: Atomoxetine 75 mg + Placebo
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
C: R-oxybutynin 2.5 mg + Placebo
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
D:Placebo + Placebo
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
A: AD109
n=56 participants at risk
Treatment A: AD109 (Atomoxetine 75 mg + R-oxybutynin 2.5 mg)
|
B: Atomoxetine 75 mg + Placebo
n=54 participants at risk
Treatment B: Atomoxetine 75 mg + Placebo
|
C: R-oxybutynin 2.5 mg + Placebo
n=54 participants at risk
Treatment C:R-oxybutynin 2.5 mg + Placebo
|
D:Placebo + Placebo
n=57 participants at risk
Treatment D: Placebo + Placebo
|
|---|---|---|---|---|
|
Nervous system disorders
Seizure
|
1.8%
1/56 • Number of events 1 • Adverse Events were monitored for 14 weeks (Screening period, up to 4 weeks; 3-period crossover, up to 8 weeks; End of Study Evaluation, 2 weeks post crossover period).
The study analysis did not analyze data by period. AEs were reported for the safety analysis by number and percent for treatment group only.
|
0.00%
0/54 • Adverse Events were monitored for 14 weeks (Screening period, up to 4 weeks; 3-period crossover, up to 8 weeks; End of Study Evaluation, 2 weeks post crossover period).
The study analysis did not analyze data by period. AEs were reported for the safety analysis by number and percent for treatment group only.
|
0.00%
0/54 • Adverse Events were monitored for 14 weeks (Screening period, up to 4 weeks; 3-period crossover, up to 8 weeks; End of Study Evaluation, 2 weeks post crossover period).
The study analysis did not analyze data by period. AEs were reported for the safety analysis by number and percent for treatment group only.
|
0.00%
0/57 • Adverse Events were monitored for 14 weeks (Screening period, up to 4 weeks; 3-period crossover, up to 8 weeks; End of Study Evaluation, 2 weeks post crossover period).
The study analysis did not analyze data by period. AEs were reported for the safety analysis by number and percent for treatment group only.
|
|
Cardiac disorders
Atrial Fibrillation
|
1.8%
1/56 • Number of events 1 • Adverse Events were monitored for 14 weeks (Screening period, up to 4 weeks; 3-period crossover, up to 8 weeks; End of Study Evaluation, 2 weeks post crossover period).
The study analysis did not analyze data by period. AEs were reported for the safety analysis by number and percent for treatment group only.
|
0.00%
0/54 • Adverse Events were monitored for 14 weeks (Screening period, up to 4 weeks; 3-period crossover, up to 8 weeks; End of Study Evaluation, 2 weeks post crossover period).
The study analysis did not analyze data by period. AEs were reported for the safety analysis by number and percent for treatment group only.
|
0.00%
0/54 • Adverse Events were monitored for 14 weeks (Screening period, up to 4 weeks; 3-period crossover, up to 8 weeks; End of Study Evaluation, 2 weeks post crossover period).
The study analysis did not analyze data by period. AEs were reported for the safety analysis by number and percent for treatment group only.
|
0.00%
0/57 • Adverse Events were monitored for 14 weeks (Screening period, up to 4 weeks; 3-period crossover, up to 8 weeks; End of Study Evaluation, 2 weeks post crossover period).
The study analysis did not analyze data by period. AEs were reported for the safety analysis by number and percent for treatment group only.
|
|
Cardiac disorders
Cardiac Arrythmia
|
1.8%
1/56 • Number of events 1 • Adverse Events were monitored for 14 weeks (Screening period, up to 4 weeks; 3-period crossover, up to 8 weeks; End of Study Evaluation, 2 weeks post crossover period).
The study analysis did not analyze data by period. AEs were reported for the safety analysis by number and percent for treatment group only.
|
0.00%
0/54 • Adverse Events were monitored for 14 weeks (Screening period, up to 4 weeks; 3-period crossover, up to 8 weeks; End of Study Evaluation, 2 weeks post crossover period).
The study analysis did not analyze data by period. AEs were reported for the safety analysis by number and percent for treatment group only.
|
0.00%
0/54 • Adverse Events were monitored for 14 weeks (Screening period, up to 4 weeks; 3-period crossover, up to 8 weeks; End of Study Evaluation, 2 weeks post crossover period).
The study analysis did not analyze data by period. AEs were reported for the safety analysis by number and percent for treatment group only.
|
0.00%
0/57 • Adverse Events were monitored for 14 weeks (Screening period, up to 4 weeks; 3-period crossover, up to 8 weeks; End of Study Evaluation, 2 weeks post crossover period).
The study analysis did not analyze data by period. AEs were reported for the safety analysis by number and percent for treatment group only.
|
|
Nervous system disorders
Headache
|
1.8%
1/56 • Number of events 1 • Adverse Events were monitored for 14 weeks (Screening period, up to 4 weeks; 3-period crossover, up to 8 weeks; End of Study Evaluation, 2 weeks post crossover period).
The study analysis did not analyze data by period. AEs were reported for the safety analysis by number and percent for treatment group only.
|
0.00%
0/54 • Adverse Events were monitored for 14 weeks (Screening period, up to 4 weeks; 3-period crossover, up to 8 weeks; End of Study Evaluation, 2 weeks post crossover period).
The study analysis did not analyze data by period. AEs were reported for the safety analysis by number and percent for treatment group only.
|
0.00%
0/54 • Adverse Events were monitored for 14 weeks (Screening period, up to 4 weeks; 3-period crossover, up to 8 weeks; End of Study Evaluation, 2 weeks post crossover period).
The study analysis did not analyze data by period. AEs were reported for the safety analysis by number and percent for treatment group only.
|
0.00%
0/57 • Adverse Events were monitored for 14 weeks (Screening period, up to 4 weeks; 3-period crossover, up to 8 weeks; End of Study Evaluation, 2 weeks post crossover period).
The study analysis did not analyze data by period. AEs were reported for the safety analysis by number and percent for treatment group only.
|
Other adverse events
| Measure |
A: AD109
n=56 participants at risk
Treatment A: AD109 (Atomoxetine 75 mg + R-oxybutynin 2.5 mg)
|
B: Atomoxetine 75 mg + Placebo
n=54 participants at risk
Treatment B: Atomoxetine 75 mg + Placebo
|
C: R-oxybutynin 2.5 mg + Placebo
n=54 participants at risk
Treatment C:R-oxybutynin 2.5 mg + Placebo
|
D:Placebo + Placebo
n=57 participants at risk
Treatment D: Placebo + Placebo
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
3.6%
2/56 • Number of events 2 • Adverse Events were monitored for 14 weeks (Screening period, up to 4 weeks; 3-period crossover, up to 8 weeks; End of Study Evaluation, 2 weeks post crossover period).
The study analysis did not analyze data by period. AEs were reported for the safety analysis by number and percent for treatment group only.
|
3.7%
2/54 • Number of events 2 • Adverse Events were monitored for 14 weeks (Screening period, up to 4 weeks; 3-period crossover, up to 8 weeks; End of Study Evaluation, 2 weeks post crossover period).
The study analysis did not analyze data by period. AEs were reported for the safety analysis by number and percent for treatment group only.
|
0.00%
0/54 • Adverse Events were monitored for 14 weeks (Screening period, up to 4 weeks; 3-period crossover, up to 8 weeks; End of Study Evaluation, 2 weeks post crossover period).
The study analysis did not analyze data by period. AEs were reported for the safety analysis by number and percent for treatment group only.
|
0.00%
0/57 • Adverse Events were monitored for 14 weeks (Screening period, up to 4 weeks; 3-period crossover, up to 8 weeks; End of Study Evaluation, 2 weeks post crossover period).
The study analysis did not analyze data by period. AEs were reported for the safety analysis by number and percent for treatment group only.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee PIs agreed that because the Study is part of a Multi-center Study, individual publication could not be made until the publication of the Multi-center study results, notification that that a Multi-center publication was not planned, or after 18 months had passed
- Publication restrictions are in place
Restriction type: OTHER