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 2 doses of AD109 vs placebo in patients with mild obstructive sleep apnea.
Detailed description
Participants underwent initial pre-screening to determine potential study eligibility. Participants selected for further screening had either a previous history of OSA of a severity consistent with enrollment criteria or were at high risk (e.g. as assessed by STOP-Bang Questionnaire score). Only participants who met all non polysomnography (PSG) enrollment criteria at Visit 1 were eligible for a screening PSG.
Interventions
DRUGAD109 dose1- A
Oral administration at bedtime
DRUGAD109 dose2- B
Oral administration at bedtime
DRUGPlacebo- C
Oral administration at bedtime
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
* AHI between 5 and 20 events/h * PGI-S equal to or higher than 1, or one or more of the following symptoms: * Snoring or nightime gasping/choking * Daytime sleepiness, fatigue or decreased concentration * Nonrefreshing sleep, sleep fragmentation (including from nocturia), or morning headache * Irritability, decreased mood or libido
Exclusion criteria
* History of narcolepsy. * Clinically significant craniofacial malformation. * Clinically significant cardiac disease (e.g. rhythm disturbances, coronary artery disease or heart failure or hypertension requiring more than 2 medications for control). * CPAP should not be used for at least 2 weeks prior to the study * 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) Log Transformed - Log10HB[(%*Min)/h] | 1 night (8 hours) | 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%\[% min/h\]. Raw measurement of HB (%min/h) is defined as the sum of individual areas (%min) divided by total sleep time (h). Events with 4% or greater desaturations were included in the calculation of HB. |
| Change in Hypoxic Burden (HB) Raw Values - HB[(%*Min)/h] | 1 night (8 hours) | Change in Hypoxic Burden (HB) is calculated as the oxygen desaturation 'area under the curve' in association with individual apneas and hypopneas. Raw measurement of HB (%min/h) is defined as the sum of individual areas (%min) divided by total sleep time (h). Events with 4% or greater desaturations were included in the calculation of HB. |
Countries
United States
Participant flow
Recruitment details
A total of 65 participants were screened in the study. Thirty-two participants were randomized.
Pre-assignment details
Participants who met all enrollment criteria were planned to be randomized to receive the following oral experimental treatments, 1 treatment on each of 3 PSG nights, separated by at least a 1 week washout period. One ineligible participant was inadvertently randomized but not treated. Twenty-seven participants completed the study. Four participants were treated but early terminated from the study.
Participants by arm
| Arm | Count |
|---|---|
| All Participants AD109 dose1 75mg, AD109 Dose 2 37.5 mg, and Placebo: Oral administration at bedtime, randomly sequence of all three study products. | 31 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| First Intervention (1 Night) | ineligible participant was inadvertently randomized but not treated | 1 |
| Second Intervention (1 Night) | Adverse Event | 1 |
| Second Intervention (1 Night) | Withdrawal by Subject | 1 |
| Third Intervention (1 Night) | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 31 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 25 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Hypoxic Burden (HB) | 11.8 (%*min)/hour |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 7 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 | 1 Participants |
| Race (NIH/OMB) White | 22 Participants |
| Region of Enrollment United States | 31 participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 28 | 0 / 29 |
| other Total, other adverse events | 4 / 30 | 2 / 28 | 2 / 29 |
| serious Total, serious adverse events | 0 / 30 | 0 / 28 | 0 / 29 |
Outcome results
Primary
Change in Hypoxic Burden (HB) Log Transformed - Log10HB[(%*Min)/h]
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%\[% min/h\]. Raw measurement of HB (%min/h) is defined as the sum of individual areas (%min) divided by total sleep time (h). Events with 4% or greater desaturations were included in the calculation of HB.
Time frame: 1 night (8 hours)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| AD109 dose1 vs Placebo | Change in Hypoxic Burden (HB) Log Transformed - Log10HB[(%*Min)/h] | -0.40 difference in log10HB[(%*min)/h] |
| AD109 dose2 vs Placebo | Change in Hypoxic Burden (HB) Log Transformed - Log10HB[(%*Min)/h] | -0.21 difference in log10HB[(%*min)/h] |
| Dose 2 vs Dose 1 | Change in Hypoxic Burden (HB) Log Transformed - Log10HB[(%*Min)/h] | 0.18 difference in log10HB[(%*min)/h] |
Primary
Change in Hypoxic Burden (HB) Raw Values - HB[(%*Min)/h]
Change in Hypoxic Burden (HB) is calculated as the oxygen desaturation 'area under the curve' in association with individual apneas and hypopneas. Raw measurement of HB (%min/h) is defined as the sum of individual areas (%min) divided by total sleep time (h). Events with 4% or greater desaturations were included in the calculation of HB.
Time frame: 1 night (8 hours)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| AD109 dose1 vs Placebo | Change in Hypoxic Burden (HB) Raw Values - HB[(%*Min)/h] | -6.90 (%*min)/h |
| AD109 dose2 vs Placebo | Change in Hypoxic Burden (HB) Raw Values - HB[(%*Min)/h] | -4.70 (%*min)/h |
| Dose 2 vs Dose 1 | Change in Hypoxic Burden (HB) Raw Values - HB[(%*Min)/h] | 2.20 (%*min)/h |