Atomoxetine and DAW2022 on OSA Severity

Effect of Atomoxetine and DAW2022 on OSA Severity

Obstructive sleep apnea (OSA) is common and has major health implications but treatment options are limited. In previous research atomoxetine and oxybutynin showed promising effect at reducing OSA severity, however they reduced arousal threshold, one of the key traits responsible for OSA. Since oxybutynin was used mainly as a hypnotic, but it is burdened by several anti-cholinergic side effects, DAW2020, a hypnotic which prolonged the total sleep time in a previous trial in OSA patients, could be a better candidate to associate with atomoxetine.

Study Overview

• Status: Recruiting
• Conditions: Obstructive Sleep Apnea
• Intervention / Treatment: Drug: Placebo oral capsule; Drug: Atomoxetine Oral Capsule [Strattera]

Detailed Description

Two overnight sleep studies will be performed: a drug night and a placebo night, with a month of washout between treatments. The patient will breath spontaneously (without CPAP) for both nights. On the study nights, subjects will present to the laboratory in the evening and be instrumented with a full polysomnography for monitoring sleep, physiological variables (endotypes), and respiratory events. A history and physical examination will be performed on each night prior to beginning the study, as will a urine pregnancy test in premenopausal women. The drugs will be administered as follows. There will be a 3-day run in of atomoxetine 40 mg followed by atomoxetine 80 mg starting on the fourth night until the night of the study. DAW2020 34 mg will be administered for 1-week to allow adequate plasma concentrations to be reached. For the sleep study, at least four hours of sleep (50% in the supine position) will be monitored to assess sleep and respiratory variables.

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Ludovico Messineo, MD, PhD; Phone Number: 18572726188; Email: lmessineo@bwh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02135
      • Recruiting
      • Brigham and Women's Hospital
      • Contact: Nicole Calianese; Phone Number: 617-732-8976; Email: ncalianese@partners.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Moderate-to-severe OSA (AHI ≥ 15 events/hr)

Exclusion Criteria:

• All participants will be healthy and without major organ system disease that would preclude undergoing the physiological measurements.
• Use of medications expected to stimulate or depress respiration (including opioids, barbiturates, acetazolamide, doxapram, almitrine, theophylline, 4-hydroxybutanoic acid).
• Use of SNRIs/SSRIs.
• Conditions likely to affect OSA physiology: neuromuscular disease or other major neurological disorder, heart failure (also below), or any other unstable major medical condition.
• Sleep disordered breathing or respiratory disorders other than obstructive sleep apnea:
• Other sleep disorders: periodic limb movements (periodic limb movement arousal index > 10/hr), narcolepsy, or parasomnias.
• Hypersensitivity to the study drug (angioedema or urticaria)
• Contraindications to DAW2020
• Use of medications that lengthen QTc interval
• Hypokaliemia, hypomagnesemia, uncontrolled thyroid disease
• Severe claustrophobia.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo oral capsules; Placebo (2 pills) before sleep for a week	Drug: Placebo oral capsule; Placebo pills for a week, 1 pill 4 hr before sleep and 1 pill 30 min before sleep
Active Comparator: Atomoxetine and DAW2020 oral capsules; DAW2020 34 mg 4 h before sleep, single night administration for a week. Simultaneous administration of atomoxetine 40 mg for 3 days 30 min before sleep, 80 mg for the following 4 days, 30 min before sleep	Drug: Atomoxetine Oral Capsule [Strattera]; Atomoxetine for a week: 40 mg for 3 days 30 min before sleep, 80 mg for 4 days 30 min before sleep Simultaneous administration of DAW2020 for a week, 34 mg 4 h before sleep; Other Names: DAW2020 Oral Capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of atomoxetine and DAW2020 on OSA severity	OSA severity will be quantified by the number of respiratory events/h (AHI)	1 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of atomoxetine and DAW2020 on arousal index	Arousal index will be calculated as the number of arousal per hour	1 week
Effect of atomoxetine and DAW2020 on nadir oxygen desaturation	Nadir oxygen desaturation will be calculated as the lowest oxygen saturation value during sleep	1 week

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2022
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: April 22, 2022
• First Submitted That Met QC Criteria: April 22, 2022
• First Posted (Actual): April 28, 2022

Study Record Updates

• Last Update Posted (Actual): July 7, 2023
• Last Update Submitted That Met QC Criteria: July 5, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Apnea; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Adrenergic Uptake Inhibitors; Atomoxetine Hydrochloride
• Other Study ID Numbers: 2020P002760

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No