Delving into the Latest Updates on Atomoxetine Hydrochloride/Oxybutynin with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

M1 receptor x M2 receptor x M3 receptor x NET

Action

antagonists, inhibitors

Mechanism

M1 receptor antagonists(Muscarinic acetylcholine receptor M1 antagonists), M2 receptor antagonists(Muscarinic acetylcholine receptor M2 antagonists), M3 receptor antagonists(Muscarinic acetylcholine receptor M3 antagonists)

+ [1]

Therapeutic Areas

Nervous System DiseasesRespiratory DiseasesOther Diseases

Active Indication-

Inactive Indication

Sleep Apnea, CentralSleep Apnea, Obstructive

Originator Organization

Apnimed, Inc.

Active Organization-

Inactive Organization

Apnimed, Inc.

License Organization-

Drug Highest PhasePendingPhase 2

First Approval Date-

RegulationFast Track (United States)

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Structure/Sequence

Molecular FormulaC17H22ClNO

InChIKeyLUCXVPAZUDVVBT-UNTBIKODSA-N

CAS Registry82248-59-7

View All Structures (2)

Currently, there is no pharmacological intervention for mild symptomatic obstructive sleep disordered breathing (SDB) in the form of loud habitual snoring, inspiratory flow limitation (i.e. upper airway resistance syndrome), or mild sleep apnea. Here the investigators study the effect on SDB of stimulating pharyngeal muscles during sleep with AD036. The key hypothesis of the study is that AD036 is superior to placebo on self-reported and objective measures of SDB severity.

Start Date02 Dec 2020

Sponsor / Collaborator

The Brigham & Women's Hospital, Inc.

[+1]

NCT04115878

/ CompletedPhase 2IIT

Evaluation of Atomoxetine and Oxybutynin for Obstructive Sleep Apnea in Children With Down Syndrome

This is a randomized, double blind, cross-over study of the combination of atomoxetine and oxybutynin (ato-oxy) in children with DS and OSA documented by polysomnography (PSG). Participants will receive high dose ato-oxy for four weeks as well as low dose ato-oxy for four weeks in random order. During the high dose ato-oxy period, participants will take 5 mg oxybutynin and 0.5mg/kg/day (max 40 mg) atomoxetine nightly for one week. Atomoxetine dose will then be increased to 1.2 mg/kg/day (max 80 mg). During the low dose ato-oxy period, participants will take 5 mg oxybutynin and 0.5mg/kg/day (max 40 mg) atomoxetine. Dosing of the study treatment will occur approximately 30 minutes prior to bedtime. Participants who withdraw from the study will not be replaced.
Study participants will undergo eligibility screening that will include an initial screening to determine whether non- PSG enrollment criteria are met, followed by a 1 night in-lab PSG and health-related quality of life assessment for participants who qualify based on non-PSG criteria. For participants who are eligible and enroll in the study, the screening PSG night will serve as the baseline measure for apnea hypopnea index (AHI) and other PSG endpoints. On the final night of dosing for both high dose ato-oxy and low-dose ato-oxy, participants will return for inpatient PSG and health-related quality of life assessment. The primary efficacy endpoint is the change in obstructive AHI from baseline (high dose ato-oxy vs. low dose ato-oxy).

Start Date21 Oct 2020

Sponsor / Collaborator

University of Arizona

[+1]

NCT04445688

/ CompletedPhase 2

Phase 2, Randomized, 3-Period, Placebo-Controlled Crossover Study to Evaluate the Efficacy and Safety in Obstructive Sleep Apnea of AD036 Versus Placebo or Atomoxetine

This is a randomized, 3-Period, Placebo-Controlled, Crossover, phase 2 clinical study to examine the efficacy and safety of AD036 versus placebo or atomoxetine in patients with obstructive sleep apnea.

Start Date15 Jul 2020

Sponsor / Collaborator

Apnimed, Inc.

100 Clinical Results associated with Atomoxetine Hydrochloride/Oxybutynin

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100 Translational Medicine associated with Atomoxetine Hydrochloride/Oxybutynin

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100 Patents (Medical) associated with Atomoxetine Hydrochloride/Oxybutynin

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86

Literatures (Medical) associated with Atomoxetine Hydrochloride/Oxybutynin

01 Dec 2023·Journal of Clinical Sleep Medicine

The combination of atomoxetine and oxybutynin for the treatment of obstructive sleep apnea in children with Down syndrome

Article

Author: Bottrill, Kenneth ; Van Vorce, Hailey ; Hsu, Chiu-Hsieh ; Parthasarathy, Sairam ; Gerken, Blake ; La Rue, Sicily ; Edgin, Jamie ; Combs, Daniel ; Matloff, Daniel

STUDY OBJECTIVESChildren with Down syndrome (DS) are at very high risk for obstructive sleep apnea (OSA). Current OSA treatments have limited effectiveness in this population. We evaluated the effectiveness of atomoxetine and oxybutynin (ato-oxy) to treat OSA in children with Down syndrome.METHODSChildren ages 6-7 years old with Down syndrome and OSA participated in a double-blind crossover clinical trial evaluating two dose regimens of ato-oxy. Participants received low-dose ato-oxy (0.5 mg/kg atomoxetine and 5 mg oxybutynin) and high-dose ato-oxy (1.2 mg/kg atomoxetine and 5 mg oxybutynin) for 1 month in random order. The primary study outcome was change in obstructive apnea-hypopnea index. Health-related quality of life as measured by the OSA-18 as well as changes in sleep architecture were secondary outcomes.RESULTSFifteen participants qualified for randomization and 11 participants had complete data at all points. Baseline obstructive apnea-hypopnea index was 7.4 ± 3.7 (mean ± standard deviation), obstructive apnea-hypopnea index with low-dose ato-oxy was 3.6 ± 3.3 (P = .001 vs baseline), and obstructive apnea-hypopnea index with high-dose ato-oxy was 3.9 ± 2.8 (P = .003 vs baseline). No significant sleep architecture differences were present with ato-oxy. No significant difference in OSA-18 score was present. OSA-18 total score was 51 ± 19 at baseline, 45 ± 17 (P = .09) at the end of 4 weeks of low-dose ato-oxy, and 45 ± 16 (P = .37) at the end of high-dose ato-oxy therapy. The most common adverse effects were irritability and fatigue, and these were generally mild.CONCLUSIONSAto-oxy is a promising treatment for OSA in children with Down syndrome.CLINICAL TRIAL REGISTRATIONRegistry: Clinicaltrials.gov; Name: Medications for Obstructive Sleep Apnea In Children With Down Syndrome (MOSAIC); URL: https://clinicaltrials.gov/ct2/show/NCT04115878; Identifier: NCT04115878.CITATIONCombs D, Edgin J, Hsu C-H, et al. The combination of atomoxetine and oxybutynin for the treatment of obstructive sleep apnea in children with Down syndrome. J Clin Sleep Med. 2023;19(12):2065-2073.

01 Aug 2023·Journal of Medical Virology

Presence of human adenovirus 36 in visceral fat tissue, viral load, and analysis of its genetic variability

Article

Author: Martinez-Hernandez, Fernando ; Rojano-Rodriguez, Martin ; Alarcon-Valdes, Patricia ; Santillan-Benitez, Jonnathan Guadalupe ; Olivo-Diaz, Angelica ; Sanchez-Aguillon, Fabiola ; Maravilla, Pablo ; Ibarra-Arce, Aurora ; Romero-Valdovinos, Mirza

AbstractIt has been proposed that infection by adipogenic viruses constitutes a “low risk” factor for obesity. Here, we report the presence of adenovirus 36 (Ad36) and its viral load copy number in fat tissue of participants with obesity and normal weight; phylogenetic analysis was performed to describe their relationship and genetic variability among viral haplotypes. Adipose tissue obtained from 105 adult patients with obesity (cases) and 26 normal‐weight adult participants as controls were analyzed by quantitative polymerase chain reaction (qPCR) amplifying the partial Ad36 E1a gene. The amplicons were examined by melting curves and submitted to sequencing. Then, genetic diversity and phylogenetic inferences were performed. Ad36 was identified at rates of 82% and 46% in the case and control groups, respectively (p = 1.1 × 10−4, odds ratio = 5.28); viral load copies were also significantly different between both groups, being 25% higher in the case group. Melting curve analysis showed clear amplification among positive samples. Phylogenetic inferences and genetic diversity analyses showed that the Ad36 E1a gene exhibits low genetic variability and differentiation with strong gene flow due to an expanding process. Our results suggest that the phenomenon of infectobesity by Ad36 might not be a low‐risk factor, as has been previously argued by other authors.

01 Jun 2023·Journal of Clinical Sleep Medicine

Effects of atomoxetine plus a hypnotic on obstructive sleep apnea severity in patients with a moderately collapsible pharyngeal airway

Article

Author: Warren-McCormick, Jennifer ; Rucosky, Gregg ; Eves, Erica ; Corser, Bruce

STUDY OBJECTIVESPharmacotherapy for obstructive sleep apnea (OSA) regained consideration after the discovery that atomoxetine and oxybutynin greatly reduced OSA severity. However, atomoxetine and oxybutynin reduced the arousal threshold and may therefore be poorly tolerated in patients with OSA and disturbed sleep. As a result, we tested the combination of atomoxetine plus 2 hypnotics in patients with OSA. The effects of atomoxetine plus: (1) trazodone (Ato-Trazo) and (2) lemborexant vs placebo on apnea-hypopnea index, hypoxic burden, arousal threshold, and total sleep time were assessed. Drug safety was also ascertained, together with the effect of the combinations on other OSA traits, self-reported sleep quality, and next-day alertness.METHODSFollowing a baseline study, 15 patients with mild-to-severe OSA with moderate upper airway collapsibility were administered Ato-Trazo, atomoxetine and lemborexant, and matching placebo according to a double-blind, randomized, crossover design. Apnea-hypopnea index and other objective outcomes were calculated from 3 clinical, in-laboratory polysomnograms.RESULTSAto-Trazo significantly reduced apnea-hypopnea index from a median [interquartile range] of 18.2 [11.8 to 31.3] on placebo to 7.4 [5.4 to 16.1] events/h, P = .024, and hypoxic burden from 46.3 [25.1 to 88.3] on placebo to 18.7 [14.9 to 43.5], P = .003. This effect was likely driven by an increase in polysomnography-estimated pharyngeal muscle activity during the events (P = .029). Atomoxetine and lemborexant had smaller statistically insignificant effects. Contrary to atomoxetine and oxybutynin, Ato-Trazo and atomoxetine and lemborexant did not reduce the arousal threshold. Both combinations had no effect on total sleep time but worsened self-reported sleep quality.CONCLUSIONSAto-Trazo has the potential to become a useful drug combination, however, longer trials are needed to determine the best dosage and the subgroup of patients who may benefit most from this combination.CLINICAL TRIAL REGISTRATIONRegistry: ClinicalTrials.gov; Name: Crossover Trial of AD182 and AD504 in Obstructive Sleep Apnea; URL: https://clinicaltrials.gov/ct2/show/NCT04645524; Identifier: NCT04645524.CITATIONCorser B, Eves E, Warren-McCormick J, Rucosky G. Effects of atomoxetine plus a hypnotic on obstructive sleep apnea severity in patients with a moderately collapsible pharyngeal airway. J Clin Sleep Med. 2023;19(6):1035-1042.

100 Deals associated with Atomoxetine Hydrochloride/Oxybutynin

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Sleep Apnea, Central	Phase 2	Australia	Apnimed, Inc.	02 Dec 2020
Sleep Apnea, Central	Phase 2	United States	Apnimed, Inc.	02 Dec 2020
Sleep Apnea, Obstructive	Phase 2	United States	Apnimed, Inc.	07 Mar 2019

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04445688 (CTgov)	Phase 2	Sleep Apnea, Obstructive	62	AD036 (AD036)	zcmaqjpftj(gjwbyuchdv) = grmzlrnohz fuhexjhukl (yeqdrchxmn, biqvnukjgd - pjdotvjoob) View more	-	21 Aug 2023
				Atomoxetine (Atomoxetine)	zcmaqjpftj(gjwbyuchdv) = bjapxposae fuhexjhukl (yeqdrchxmn, slhogttldl - avgosdakwm) View more
NCT03845023 (CTgov)	Phase 2	Sleep Apnea, Obstructive	140	Placebo (Placebo)	xjikippwto(nslyknehxt) = hyvfbdtsso jezzhfptmo (oznaezyfpz, jwzvzzmcbp - hkprfjsmdd) View more	-	17 Jan 2023
				AD036 (AD036 Dose 1)	xjikippwto(nslyknehxt) = vzatlhsejv jezzhfptmo (oznaezyfpz, rmqzhsyxgz - xefzlxshlb) View more