Clinical trial NCT04449133: Study of AD128 Versus Placebo in Obstructive Sleep Apnea
Official title: Crossover, Double-blind, Phase 2 Study of AD128 Versus Placebo in Obstructive Sleep Apnea
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Obstructive Sleep Apnea
Keywords: Obstructive Sleep Apnea
Apnea Hypopnea Index
Lead sponsor: Istituto Auxologico Italiano
Sponsor class: OTHER
Collaborators: name: YGHEA, CRO Division of Ecol Studio spa
name: STM Pharma PRO srl
name: Apnimed Inc.
First posted: 2020-06-26
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Patients who meet the eligibility criteria will be assigned alternatively to the the treatment with a AD128 or matching placebo. After 7 days of treatment and a washout period, the patients will crossover to the other arm for 7 days.
Primary purpose: TREATMENT

Brief summary: Obstructive Sleep Apnea (OSA) is the most common and serious of the sleep disorders. Long-term, OSA is associated with increased morbidity and mortality, with a number of adverse cardiovascular, neurocognitive, metabolic, and daytime functioning consequences. No drugs are currently approved for OSA treatment.

This is a randomized, double blind, placebo controlled, cross-over, inpatient phase 2 clinical trial to examine the efficacy and the safety of a fixed dose level of AD128 in patients with OSA.


Eligibility criteria: Inclusion Criteria:

* Patients who are able to understand the nature of the study and to give free informed consent
* AHI ≥ 15 on screening/baseline PSG
* Any of the following conditions should be met:

  1. Documented prior PSG within 1 year demonstrating AHI of 15 or higher
  2. Documented Continuous Positive Airway Pressure (CPAP) intolerance or poor compliance (compliance is defined as self-reported use of CPAP 4 hours per night for 70% of nights) or CPAP-naïve.
  3. Patients who have been using CPAP at least 4 hours nightly for at least 70% of the nights are eligible only if CPAP is not used for 2 weeks prior to the screening/study baseline PSG.
* Epworth Sleepiness Scale (ESS) score ≥ 4 for patients not using CPAP
* Previous surgical treatment for OSA is allowed if ≥ 1 year prior to enrollment.
* BMI between 18.5 and 40.0 kg/m2, inclusive

Exclusion Criteria:

* History of narcolepsy.
* Clinically significant craniofacial malformation.
* Clinically significant cardiac disease or hypertension requiring more than 3 medications for control.
* Clinically significant neurological disorder, including epilepsy/convulsions
* History of schizophrenia, schizoaffective disorder or bipolar disorder according to - Diagnostic and Statistical Manual of Mental Disorders-V (DSM V) or International Classification of Disease X edition criteria.
* History of attempted suicide or suicidal ideation within 1 year prior to screening, or current suicidal ideation.
* Positive history for abuse of drugs or substance use disorder as defined in DSM-V within 12 months prior to Screening Visit.
* A significant illness or infection requiring medical treatment in the past 30 days.
* Clinically significant cognitive dysfunction.
* Untreated narrow angle glaucoma.
* Women who are pregnant or nursing.
* 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.
* History of using devices to affect participant sleeping position for the treatment of OSA, e.g. to discourage supine sleeping position, may enroll as long as the devices are not used during participation in the study.
* History of oxygen therapy.
* Use of medications from the list of disallowed concomitant medications.
* Treatment with strong cytochrome P450 3A4 (CYP3A4) inhibitors, or monoamine oxidase inhibitors (MAOI) or linezolid within 14 days of the start of treatment, or concomitant with treatment.
* Use of another investigational agent within 30 days or 5 half-lives, whichever is longer, prior to dosing.
* Central apnea index \> 5/hour on baseline PSG
* Any condition that in the investigator's opinion would present an unreasonable risk to the participant, or which would interfere with their participation in the study or confound study interpretation.
* Patients considered by the investigator, for any reason, unsuitable candidates to receive AD128 treatment or unable or unlikely to understand or comply with the dosing schedule or study evaluations.

Primary outcomes:
measure: Change in Apnea-Hypopnea Index (AHI)
timeFrame: From the screening/baseline to the last day of treatment (7 days after the start of each treatment period).
Secondary outcomes:
measure: AHI decrease ≥50%
timeFrame: From screening/baseline to the last day of treatment (7 days after the start of each treatment period).
measure: AHI<15/hour
timeFrame: From screening/baseline to the last day of treatment (7 days after the start of each treatment period).
measure: Change in Epworth Sleepiness Scale (ESS)
timeFrame: From screening/baseline to the last day of treatment (7 days after the start of each treatment period).
measure: Change in Karolinska Sleepiness Scale (KSS)
timeFrame: From screening/baseline to the last day of treatment (7 days after the start of each treatment period).
measure: Patient Global Impression of OSA Severity (PGI-S)
timeFrame: From screening/baseline to the last day of treatment (7 days after the start of each treatment period).
measure: Change in Psychomotor Vigilance Test (PVT)
timeFrame: From screening/baseline to last day of treatment (7 days after the start of each treatment period).
measure: Change in Oxygen Desaturation Index (ODI) 3%
timeFrame: From screening/baseline to last day of treatment (7 days after the start of each treatment period).
measure: Change in total time with Oxygen Saturation (SaO2) <90%
timeFrame: From screening/baseline to last day of treatment (7 days after the start of each treatment period).
measure: Change in mean SaO2
timeFrame: From screening/baseline to last day of treatment (7 days after the start of each treatment period).
measure: Change in minimum SaO2
timeFrame: From screening/baseline to last day of treatment (7 days after the start of each treatment period).
measure: Change in arousal index
timeFrame: From screening/baseline to last day of treatment (7 days after the start of each treatment period).
measure: Change in periodic limb movement
timeFrame: From screening/baseline to last day of treatment (7 days after the start of each treatment period).
measure: Oxygen Desaturation Index 4%
timeFrame: For the entire at home treatment period: days 1-7 (before crossover) and days 15-20 (after crossover)
measure: Adverse Events (AE)
timeFrame: From screening/baseline to 4 weeks after last day of treatment.
Other outcomes:
Locations:
city: Milano
country: Italy
facility: Istituto Auxologico Italiano,Ospedale San Luca
Study officials:
affiliation: Istituto Auxologico Italiano
name: Elisa Perger, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Perger E, Taranto Montemurro L, Rosa D, Vicini S, Marconi M, Zanotti L, Meriggi P, Azarbarzin A, Sands SA, Wellman A, Lombardi C, Parati G. Reboxetine Plus Oxybutynin for OSA Treatment: A 1-Week, Randomized, Placebo-Controlled, Double-Blind Crossover Trial. Chest. 2022 Jan;161(1):237-247. doi: 10.1016/j.chest.2021.08.080. Epub 2021 Sep 20.