Obstructive Sleep Apnea
Conditions
Brief summary
This is a randomized, 3-Period, Placebo-Controlled, Crossover, phase 2 clinical study to examine the efficacy and safety of AD036 versus placebo or atomoxetine in patients with obstructive sleep apnea.
Detailed description
The study is designed to examine the efficacy and safety of AD036 to treat obstructive sleep apnea. The study is a three-period single-dose randomized crossover design in which patients will undergo overnight Home Sleep Apnea Testing (HSAT) with dosing of one of the following 3 treatments: AD036, Atomoxetine, or Placebo. Participants will return 1 week after their final crossover HSAT for an end of study (EOS) Visit.
Interventions
DRUGAD036
Oral administration before bed
DRUGAtomoxetine
Oral administration before bed
DRUGPlacebo
Oral administration before bed
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 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 |
|---|---|---|
| Apnea-Hypopnea Index | 1 day | Apnea-Hypopnea Index(Disease severity is often defined based on the number of apneas and hypopneas per hour during sleep), AD036 vs. placebo |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hypoxic Burden | 1 day | Hypoxic burden (a way to measure oxygen desaturation) determined by measuring the respiratory event-associated area under the desaturation curve from pre-event baseline, AD036 vs. placebo. Hypoxic Burden was measured during polysomnography (type of sleep study), while the patient was asleep |
| ODI | 1 day | Oxygen Desaturation Index, measured by pulse-oximetry, AD036 vs. placebo |
Countries
United States
Participant flow
Recruitment details
5 clinical sites screened 101 participants 62 were randomized. This was an unblinded three period placebo controlled study. Participants who withdrew were not replaced.
Pre-assignment details
All participants were centrally randomized to one of 6 sequences (A - B - C, B - C - A, C - B - A, A - C - B, B - A - C, C - A - B). A 1-week minimum washout period occurred between each of the 3 arm assignments.
Participants by arm
| Arm | Count |
|---|---|
| All Participants oral capsules administered before bedtime. Treatment A: AD036, Treatment B: atomoxetine + placebo, Treatment C: placebo + placebo | 62 |
| Total | 62 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Washout (One Week) | Adverse Event | 2 |
| Washout (One Week) | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 59 Participants |
| Age, Continuous | 53 years |
| BMI (kg/m^2) | 32.30 kg/m^2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 58 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 17 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 | 41 Participants |
| Sex: Female, Male Female | 31 Participants |
| Sex: Female, Male Male | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 59 | 0 / 62 | 0 / 59 |
| other Total, other adverse events | 8 / 59 | 11 / 62 | 5 / 59 |
| serious Total, serious adverse events | 0 / 59 | 0 / 62 | 0 / 59 |
Outcome results
Primary
Apnea-Hypopnea Index
Apnea-Hypopnea Index(Disease severity is often defined based on the number of apneas and hypopneas per hour during sleep), AD036 vs. placebo
Time frame: 1 day
Population: The efficacy was analyzed using the mITT Population comprised of all participants who took at least 1 dose of any of the study treatments and had at least 1 measurement on the primary endpoint. Sixty (96.8%) patients were included in the mITT Population. Patients were analyzed for efficacy according to the treatment sequence into which they were randomized. Due to insufficient data quality of the home sleep test, AHI could not be determined in some treatment conditions.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AD036 | Apnea-Hypopnea Index | 11.5 events/hour |
| Atomoxetine | Apnea-Hypopnea Index | 11.5 events/hour |
| Placebo | Apnea-Hypopnea Index | 18.8 events/hour |
p-value: <0.000195% CI: [-10.2, -4.4]ANOVA
Secondary
Hypoxic Burden
Hypoxic burden (a way to measure oxygen desaturation) determined by measuring the respiratory event-associated area under the desaturation curve from pre-event baseline, AD036 vs. placebo. Hypoxic Burden was measured during polysomnography (type of sleep study), while the patient was asleep
Time frame: 1 day
Population: The efficacy was analyzed using the mITT Population comprised of all participants who took at least 1 dose of any of the study treatments and had at least 1 measurement on the primary endpoint. Sixty (96.8%) patients were included in the mITT Population. Patients were analyzed for efficacy according to the treatment sequence into which they were randomized. Due to insufficient data quality of the home sleep test, hypoxic burden could not be determined in some treatment conditions.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AD036 | Hypoxic Burden | 24.3 %min/hour |
| Atomoxetine | Hypoxic Burden | 26.8 %min/hour |
| Placebo | Hypoxic Burden | 46.1 %min/hour |
p-value: <0.000195% CI: [-29.5, -14.1]ANOVA
Secondary
ODI
Oxygen Desaturation Index, measured by pulse-oximetry, AD036 vs. placebo
Time frame: 1 day
Population: The efficacy was analyzed using the mITT Population comprised of all participants who took at least 1 dose of any of the study treatments and had at least 1 measurement on the primary endpoint. Sixty (96.8%) patients were included in the mITT Population. Patients were analyzed for efficacy according to the treatment sequence into which they were randomized. Mean (SD) of ODI (4%). Due to insufficient data quality of the home sleep test, ODI could not be determined in some treatment conditions.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AD036 | ODI | 12.8 events/hour |
| Atomoxetine | ODI | 13.3 events/hour |
| Placebo | ODI | 20.1 events/hour |
p-value: <0.000195% CI: [-10.5, -4.2]ANOVA