Delving into the Latest Updates on AD-128 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms-

Target

mAChRs

Mechanism

mAChRs antagonists(Muscarinic acetylcholine receptor antagonists)

Therapeutic Areas

Nervous System DiseasesRespiratory Diseases

Active Indication-

Inactive Indication

Sleep Apnea, Obstructive

Originator Organization

Istituto Auxologico Italiano

Active Organization-

Inactive Organization

Istituto Auxologico Italiano

Apnimed, Inc.Startup

Drug Highest PhasePendingPhase 2/3

First Approval Date-

Regulation-

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This study evaluates the combination of two drugs (AD128), to treat obstructive sleep apnea (OSA) severity. After a baseline evaluation and during 7 days, half of the participants will randomly receive this drug combination (AD128) and the other will receive a placebo, i.e. a drug without pharmaceutical effect. Neither the participants, nor the investigators will know in which arm participants are until the end of the study. After one week of trial, an evaluation will be perform and will be follow by one week without any treatment. During the third and last week of trial, there will be a crossover of the groups, i.e. the participants of the first group who took the two drugs (AD128) during the first week will take a placebo and those who took the placebo will take the drugs combination.

Start Date20 Oct 2020

Sponsor / Collaborator

Centre Hospitalier Universitaire Vaudois

[+1]

NCT04449133 / CompletedPhase 2IIT

Crossover, Double-blind, Phase 2 Study of AD128 Versus Placebo in Obstructive Sleep Apnea

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.

Start Date03 Jul 2020

Sponsor / Collaborator

Istituto Auxologico Italiano

[+2]

ACTRN12620000662965 / CompletedPhase 2IIT

Reboxetine and combination therapy with AD128 in sleep apnoea trial: A double-blind, 3-way cross-over study

Start Date09 Jun 2020

Sponsor / Collaborator

Flinders University

100 Clinical Results associated with AD-128

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100 Translational Medicine associated with AD-128

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100 Patents (Medical) associated with AD-128

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Literatures (Medical) associated with AD-128

01 Jan 2023·Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine

The norepinephrine reuptake inhibitor reboxetine alone reduces obstructive sleep apnea severity: a double-blind, placebo-controlled, randomized crossover trial

Article

Author: Altree, Thomas J. ; Eckert, Danny J. ; Grunstein, Ronald R. ; Aishah, Atqiya ; Loffler, Kelly A.

STUDY OBJECTIVES:

Recent findings indicate that noradrenergic and muscarinic processes are crucial for pharyngeal muscle control during sleep. However, to date, reductions in obstructive sleep apnea (OSA) severity have only been detected when noradrenergic agents are combined with an antimuscarinic. Accordingly, this study aimed to determine if reboxetine alone and combined with oxybutynin reduces OSA severity. The pathophysiological mechanisms underpinning the effects of these agents were also investigated via endotyping analysis.

METHODS:

Sixteen people (6 women) with OSA completed 3 polysomnograms (∼1-week washout) according to a double-blind, placebo-controlled, three-way crossover design across 2 sites. Single doses of 4 mg reboxetine, placebo, or 4 mg reboxetine + 5 mg oxybutynin were administered before sleep (order randomized).

RESULTS:

Reboxetine reduced the apnea-hypopnea index (primary outcome) by 5.4 (95% confidence interval -10.4 to -0.3) events/h, P = .03 (-24 ± 27% in men; -0.7 ± 32% in women). Oxybutynin did not cause additional reductions in apnea-hypopnea index. Reboxetine alone reduced the 4% oxygen desaturation index by (mean ± standard deviation) 5.2 ± 7.2 events/h and reboxetine+oxybutynin by 5.1 ± 10.6 events/h vs placebo, P = .02. Nadir oxygen saturation also increased by 7 ± 11% with reboxetine and 5 ± 9% with reboxetine+oxybutynin vs placebo, P = .01. Mechanistically, reboxetine and reboxetine+oxybutynin improved pharyngeal collapsibility and respiratory control (loop gain). Larger reductions in apnea-hypopnea index with reboxetine in men were associated with higher baseline loop gain.

CONCLUSIONS:

These findings show the first evidence that reboxetine alone reduces OSA severity. The data provide novel insight into the role of norepinephrine reuptake inhibitors on upper airway stability during sleep and are important to inform future pharmacotherapy development for OSA.

CLINICAL TRIAL REGISTRATION:

Registry: Australian New Zealand Clinical Trials Registry; Name: Reboxetine and Combination Therapy with AD128 in Sleep Apnoea Trial: A Double-Blind, 3-Way Cross-Over Study; URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374614&isReview=true; Identifier: ACTRN12620000662965.

CITATION:

Altree TJ, Aishah A, Loffler KA, Grunstein RR, Eckert DJ. The norepinephrine reuptake inhibitor reboxetine alone reduces obstructive sleep apnea severity: a double-blind, placebo-controlled, randomized crossover trial. J Clin Sleep Med. 2023;19(1):85-96.

100 Deals associated with AD-128

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