Crossover Trial of AD109 in Obstructive Sleep Apnea

• ClinicalTrials.gov Identifier: NCT04580394
• Recruitment Status: Completed
• First Posted: October 8, 2020
• Results First Posted: January 31, 2023
• Last Update Posted: January 31, 2023
• Sponsor: Apnimed
• Information provided by (Responsible Party): Apnimed

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Obstructive Sleep Apnea	Drug: AD109; Drug: Atomoxetine; Drug: R-oxybutynin; Drug: Placebo; Diagnostic Test: Digit System Substitution Test	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Phase 2 Randomized Double-Blind Placebo-Controlled 4-Period Single-Dose Crossover Factorial Study to Evaluate the Contribution of the Individual Drug Components to the Efficacy of AD109 in Obstructive Sleep Apnea
• Actual Study Start Date: October 27, 2020
• Actual Primary Completion Date: May 28, 2021
• Actual Study Completion Date: May 28, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: AD109; Oral capsule administered before sleep	Drug: AD109; Oral administration before bed; Diagnostic Test: Digit 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.; Other Name: DSST
Active Comparator: Atomoxetine; Oral capsule administered before sleep	Drug: Atomoxetine; Oral administration before bed; Diagnostic Test: Digit 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.; Other Name: DSST
Active Comparator: R-oxybutynin; Oral capsule administered before sleep	Drug: R-oxybutynin; Oral administration before bed; Diagnostic Test: Digit 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.; Other Name: DSST
Placebo Comparator: Placebo; Oral capsule administered before sleep	Drug: Placebo; Oral administration before bed; Diagnostic Test: Digit 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.; Other Name: DSST

Outcome Measures

Primary Outcome Measures :

1. Change in Hypoxic Burden (HB) Log10HB[(%*Min)/Hour] [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 25 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, Arkansas

Preferred Research Partners, Inc.

Little Rock, Arkansas, United States, 72211

United States, California

Empire Clinical Research

Pomona, California, United States, 91767

United States, Connecticut

Yale University

New Haven, Connecticut, United States, 06511

United States, Florida

Teradan Clinical Trials

Brandon, Florida, United States, 33511

Clinical Trials of Florida

Miami, Florida, United States, 33186

United States, Georgia

The Neurological Center of North Georgia

Gainesville, Georgia, United States, 30501

United States, Ohio

CTI Clinical Research Center

Cincinnati, Ohio, United States, 45212

Sponsors and Collaborators

Apnimed

  Study Documents (Full-Text)

Documents provided by Apnimed:

Study Protocol  [PDF] January 6, 2021

Statistical Analysis Plan  [PDF] May 13, 2021

More Information

• Responsible Party: Apnimed
• ClinicalTrials.gov Identifier: NCT04580394
• Other Study ID Numbers: APC-003
• First Posted: October 8, 2020
• Results First Posted: January 31, 2023
• Last Update Posted: January 31, 2023
• Last Verified: December 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Apnea; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Oxybutynin; Atomoxetine Hydrochloride; Adrenergic Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Adrenergic Agents; Neurotransmitter Agents; Physiological Effects of Drugs; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Urological Agents