Atomoxetine and DAW2022 on OSA Severity

NCT ID: NCT05350215

Last Updated: 2023-07-07

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-06-01
• Study Completion Date: 2024-06-01

Brief Summary

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.

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.

Conditions

Obstructive Sleep Apnea

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo oral capsules

Placebo (2 pills) before sleep for a week

Group Type: PLACEBO_COMPARATOR

Placebo oral capsule

Intervention Type: DRUG

Placebo pills for a week, 1 pill 4 hr before sleep and 1 pill 30 min before sleep

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

Group Type: ACTIVE_COMPARATOR

Atomoxetine Oral Capsule [Strattera]

Intervention Type: DRUG

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

Interventions

Placebo oral capsule

Placebo pills for a week, 1 pill 4 hr before sleep and 1 pill 30 min before sleep

Intervention Type: 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

Intervention Type: DRUG

Other Intervention Names

DAW2020 Oral Capsule

Eligibility Criteria

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.

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Brigham and Women's Hospital

OTHER

Sponsor Role: lead

Responsible Party

David Andrew Wellman

Associate Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Ludovico Messineo, MD, PhD

Role: CONTACT

lmessineo@bwh.harvard.edu

18572726188

Facility Contacts

Nicole Calianese

Role: primary

ncalianese@partners.org

617-732-8976

References

Messineo L, Preuss M, Azarbarzin A, Vena D, Gell L, Aishah A, Esmaeili N, Kim M, Burdick I, Chen T, White D, Sands SA, Wellman A. Effects of the Combination of Pimavanserin and Atomoxetine on OSA Severity: A Randomized Crossover Trial. Chest. 2025 Jul;168(1):223-235. doi: 10.1016/j.chest.2025.03.013. Epub 2025 Mar 28.

Reference Type: DERIVED

PMID: 40158847 (View on PubMed)

Other Identifiers

2020P002760

Identifier Type: -

Identifier Source: org_study_id