Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
AD109 · 5 trials · 3 indications
AHI, Apnea-Hypopnea Index, is the number of apneas or hypopneas recorded via polysomnography during the study per hour of sleep. Apnea is defined as a cessation of airflow lasting at least 10 seconds, hypopnea as a decrease in airflow by at least 30% from baseline for at least 10 seconds occurring with a drop in oxygen saturation (SpO2) by at least 4%.
General safety and tolerability will be assessed between treatment cohorts using the occurrence of spontaneously reported adverse events (AEs) at 6 weeks
Change in AHI4 (apnea-hypopnea index, 4% oxygen desaturation criterion; average respiratory events per hour of sleep) measured by in-lab polysomnography. Baseline was the mean of two pre-treatment PSG nights (Visits 2 and 3). Change from baseline was assessed at treatment PSG nights at approximately Day 21 (Visit 5) and Day 28 (Visit 6), modeled as repeated measures, with the reported value representing the model-based LS mean using equal (0.5/0.5) weighting between the Day 21 and Day 28 visits.
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.
| Arm | Type | Description |
|---|---|---|
| AD109 | EXPERIMENTAL | - |
| Placebo | PLACEBO_COMPARATOR | - |
| Arm 1 | ACTIVE_COMPARATOR | Twenty patients who are taking GLP-1 at time of enrollment will be treated with AD109 |
| Arm 2 | ACTIVE_COMPARATOR | Twenty patients who are not taking a GLP-1 will be treated with AD109 only |
| AD109 75/5mg | EXPERIMENTAL | Atomoxetine 75 mg/Aroxybutynin 5 mg tablet |
| AD109 75/2.5mg | EXPERIMENTAL | Atomoxetine 75 mg/Aroxybutynin 2.5 mg tablet |
| AD504 75/100mg | EXPERIMENTAL | Atomoxetine 75 mg tablet/Trazodone 100 mg capsule |
| AD504 75/50mg | EXPERIMENTAL | Atomoxetine 75 mg tablet/Trazodone 50 mg capsule |
| Atomoxetine 75mg | ACTIVE_COMPARATOR | Atomoxetine 75 mg tablet |
| Atomoxetine 75mg plus placebo | ACTIVE_COMPARATOR | Atomoxetine 75 mg tablet/placebo capsule |
| Placebo tablet | PLACEBO_COMPARATOR | - |
| Placebo tablet plus placebo capsule | PLACEBO_COMPARATOR | - |
| Atomoxetine | ACTIVE_COMPARATOR | Oral capsule administered before sleep |
| R-oxybutynin | ACTIVE_COMPARATOR | Oral capsule administered before sleep |
| Name | Type | Description |
|---|---|---|
| AD109 | DRUG | Aroxybutynin 2.5 mg/atomoxetine 75 mg tablet, administered orally once daily at bedtime (Weeks 2-26). Week 1 run-in: aroxybutynin 2.5 mg/atomoxetine 37.5 mg tablet. |
| Placebo | DRUG | Matching placebo tablet administered orally once daily at bedtime for 26 weeks, with run-in and target dose matched to active arm packaging |
| AD504 | DRUG | Oral administration at bedtime |
| Atomoxetine Hydrochloride | DRUG | Oral administration at bedtime |
| Atomoxetine | DRUG | Oral administration before bed |
| R-oxybutynin | DRUG | Oral administration before bed |
| Digit System Substitution Test | DIAGNOSTIC_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. |
Inclusion Criteria: 1. ≥18 years of age at the time of informed consent. 2. PSG criteria: AHI of ≥10 and ≤45; ≤ 25% central or mixed apneas; and PLM arousal index ≤15 3. PROMIS-Fatigue: raw score ≥17 4. PAP intolerance or current PAP refusal. 5. BMI between 18.5 and 40 kg/m2 for men, or 42 kg/m2 fo...