Crossover Trial of AD109 in Obstructive Sleep Apnea

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

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.

Study Overview

• Status: Completed
• Conditions: Obstructive Sleep Apnea
• Intervention / Treatment: Drug: AD109; Diagnostic test: Digit System Substitution Test; Drug: Atomoxetine; Drug: R-oxybutynin; Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Preferred Research Partners, Inc.
  • California
    • Pomona, California, United States, 91767
      • Empire Clinical Research
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Yale University
  • Florida
    • Brandon, Florida, United States, 33511
      • Teradan Clinical Trials
    • Miami, Florida, United States, 33186
      • Clinical Trials of Florida
  • Georgia
    • Gainesville, Georgia, United States, 30501
      • The Neurological Center of North Georgia
  • Ohio
    • Cincinnati, Ohio, United States, 45212
      • CTI Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

4

Arms and Interventions

Participant Group / 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 Names: DSST
ACTIVE_COMPARATOR: Atomoxetine; Oral capsule administered before sleep	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 Names: DSST; Drug: Atomoxetine; Oral administration before bed
ACTIVE_COMPARATOR: R-oxybutynin; Oral capsule administered before sleep	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 Names: DSST; Drug: R-oxybutynin; Oral administration before bed
PLACEBO_COMPARATOR: Placebo; Oral capsule administered before sleep	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 Names: DSST; Drug: Placebo; Oral administration before bed

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Hypoxic Burden (HB) Log10HB[(%*Min)/Hour]	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.	1 night (treatment duration) (0-8 hours collected continuously)

Collaborators and Investigators

• Sponsor: Apnimed

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 27, 2020
• Primary Completion (ACTUAL): May 28, 2021
• Study Completion (ACTUAL): May 28, 2021

Study Registration Dates

• First Submitted: October 2, 2020
• First Submitted That Met QC Criteria: October 2, 2020
• First Posted (ACTUAL): October 8, 2020

Study Record Updates

• Last Update Posted (ACTUAL): January 31, 2023
• Last Update Submitted That Met QC Criteria: January 12, 2023
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Signs and Symptoms, Respiratory; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Apnea; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Urological Agents; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Adrenergic Uptake Inhibitors; Oxybutynin; Atomoxetine Hydrochloride
• Other Study ID Numbers: APC-003

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No