Obstructive Sleep Apnea
Conditions
Brief summary
This is a randomized, 4-period, placebo-controlled, crossover, phase 2 clinical study to examine the efficacy and safety of AD109 versus its individual components or placebo in patients with obstructive sleep apnea.
Detailed description
The study is designed to examine the efficacy and safety of AD109 to treat obstructive sleep apnea. The study is a four-period single-dose randomized crossover design in which patients will undergo overnight polysomnographic (PSG) testing with dosing of one of the following 4 treatments: AD109, atomoxetine, R-oxybutynin or placebo. Participants will return 2 weeks after their final crossover PSG for an end of study (EOS) visit.
Interventions
DRUGAD109
Oral administration before bed
DRUGAtomoxetine
Oral administration before bed
DRUGR-oxybutynin
Oral administration before bed
DRUGPlacebo
Oral administration before bed
DIAGNOSTIC_TESTDigit System Substitution Test
a neuropsychological test sensitive to brain damage, dementia, age and depression where numbers are assigned symbols. Under each digit the subject should write down the corresponding symbol as fast as possible. The number of correct symbols within the allowed time is measured.
Sponsors
Apnimed
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
25 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Male or Female, between 25 to 65 years of age, inclusive, at the Screening Visit. * AHI 10 to \<20, or AHI ≥20 if meets other PSG criteria
Exclusion criteria
* History of narcolepsy. * 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. A medication for these purposes is defined by dosage form, such that a combination antihypertensive medication is considered 1 medication * CPAP should not be used for at least 2 weeks prior to first study PSG * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Hypoxic Burden (HB) Log10HB[(%*Min)/Hour] | 1 night (treatment duration) (0-8 hours collected continuously) | 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. |
Countries
United States
Participant flow
Recruitment details
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.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants Oral capsule administered before sleep
AD109 Atomoxetine R-Oxybutynin Placebo | 60 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| First Intervention | Incorrectly Randomized | 1 |
| First Intervention | Lost to Follow-up | 1 |
| First Intervention | Physician Decision | 1 |
| Third Intervention | Adverse Event | 1 |
| Third Intervention | Withdrawal by Subject | 1 |
| Washout (One Week) | Adverse Event | 1 |
| Washout (One Week) | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 60 Participants |
| Body Mass Index (BMI) | 33 kg/m^2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 16 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 44 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 47 Participants |
| Region of Enrollment United States | 60 participants |
| Sex: Female, Male Female | 25 Participants |
| Sex: Female, Male Male | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 56 | 0 / 54 | 0 / 54 | 0 / 57 |
| other Total, other adverse events | 2 / 56 | 2 / 54 | 0 / 54 | 0 / 57 |
| serious Total, serious adverse events | 1 / 56 | 0 / 54 | 0 / 54 | 0 / 57 |
Outcome results
Primary
Change in Hypoxic Burden (HB) Log10HB[(%*Min)/Hour]
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.
Time frame: 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
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AD109 | Change in Hypoxic Burden (HB) Log10HB[(%*Min)/Hour] | -0.41 Log10HB4%[%min/hour] |
| Atomoxetine | Change in Hypoxic Burden (HB) Log10HB[(%*Min)/Hour] | -0.36 Log10HB4%[%min/hour] |
| R-oxybutynin | Change in Hypoxic Burden (HB) Log10HB[(%*Min)/Hour] | -0.04 Log10HB4%[%min/hour] |
| Placebo | Change in Hypoxic Burden (HB) Log10HB[(%*Min)/Hour] | -0.06 Log10HB4%[%min/hour] |