Delving into the Latest Updates on AZD-3199 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

β2-adrenergic receptor

Mechanism

β2-adrenergic receptor agonists(Beta-2 adrenergic receptor agonists)

Therapeutic Areas

Immune System DiseasesRespiratory Diseases

Active Indication-

Inactive Indication

Airway ObstructionAsthmaPulmonary Disease, Chronic Obstructive

Originator Organization

AstraZeneca Pharmaceuticals Co. Ltd.

Active Organization-

Inactive Organization

AstraZeneca PLC

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

Login to view timeline

Structure

Molecular FormulaC32H42N4O4S

InChIKeyZVULMJYRVAVKCP-UHFFFAOYSA-N

CAS Registry925243-19-2

View All Structures (2)

A Randomised, Double-blind, Double-dummy, Placebo-controlled, Multicentre, 6-way Crossover, Single-dose, Phase IIa Study to Evaluate the Pharmacokinetics and Pharmacodynamics of Different Dry Powder Inhalation Formulations of AZD3199 Administered Via Single Inhalation Device Compared to AZD3199 Administered Via Turbuhaler™ Inhaler in Patients With Asthma

The purpose of this study is to evaluate the pharmacokinetics and pharmacodynamics of single doses of three different dry powder inhalation formulations of AZD3199 administered via Single Inhalation Device (SID) compared to AZD3199 administered via Turbuhaler™ Inhaler and compared to placebo in patients with persistent asthma.

Start Date01 May 2011

Sponsor / Collaborator

AstraZeneca PLC

NCT01222442 / CompletedPhase 1

A Single-centre, Randomised, Double-blind, Double-dummy, Placebo Controlled, 4-way Crossover Phase I Study to Investigate the Effect of 2 Single Doses (400 μg and 1200 µg) of Inhaled AZD3199 on QT/QTc Interval, Compared to Placebo, Using Moxifloxacin (Avelox®) as a Positive Control, in Healthy Male Volunteers

The purpose of this research study is to evaluate the effect of AZD3199 on the electrical activity of the heart. The effect of AZD3199 will be compared to a licensed antibiotic (moxifloxacin). Moxifloxacin effects on the electrical activity of the heart are well known. Safety and tolerability of AZD3199 and how much AZD3199 enters the blood circulation will also be assessed.

Start Date01 Nov 2010

Sponsor / Collaborator

AstraZeneca PLC

EUCTR2009-011265-82-BG / Not yet recruitingNot Applicable

A 4-week, phase-II, double-blind, placebo-controlled, randomized, parallel group, multi-centre study to assess the efficacy and tolerability/safety of inhaled AZD3199 once daily compared to 9 µg formoterol bid and placebo in patients with moderate to severe COPD - GLAD

Start Date17 Jul 2009

Sponsor / Collaborator

AstraZeneca AB

100 Clinical Results associated with AZD-3199

Login to view more data

100 Translational Medicine associated with AZD-3199

Login to view more data

100 Patents (Medical) associated with AZD-3199

Login to view more data

6

Literatures (Medical) associated with AZD-3199

01 Nov 2016·Journal of Pharmaceutical SciencesQ3 · MEDICINE

Lung Retention by Lysosomal Trapping of Inhaled Drugs Can Be Predicted In Vitro With Lung Slices

Q3 · MEDICINE

Article

Author: Erica Bäckström ; Margareta Hammarlund-Udenaes ; Elin Boger ; Markus Fridén ; Anders Lundqvist

Modulating and optimizing the local pharmacokinetics of inhaled drugs by chemical design or formulation is challenged by the lack of predictive in vitro systems and in vivo techniques providing a detailed description of drug location in the lung. The present study investigated whether a new experimental setup of freshly prepared agarose-filled lung slices can be used to estimate lung retention in vitro, by comparing with in vivo lung retention after intratracheal instillation. Slices preloaded with inhaled β-adrenergic compounds (salbutamol, formoterol, salmeterol, indacaterol or AZD3199) were incubated in a large volume of buffer (w/wo monensin to assess the role of lysosomal trapping), and the amount remaining in slices at different time points was determined with liquid chromatography-tandem mass spectrometry. The in vitro lung retention closely matched the in vivo lung retention (half-lives within 3-fold for 4/5 compounds), and monensin shortened the half-lives for all compounds. The results suggest that freshly prepared rat lungs slices can be used to predict lung retention and that slow kinetics of lysosomal trapping is a key mechanism by which retention in the lung and the effect duration of inhaled β-adrenergic bronchodilators are prolonged.

10 Apr 2014·ACS Medicinal Chemistry LettersQ3 · MEDICINE

Discovery of AZD3199, An Inhaled Ultralong Acting β₂ Receptor Agonist with Rapid Onset of Action

Q3 · MEDICINE

Article

Author: Young, Alan ; Ingall, Anthony ; Bonnert, Roger ; Flaherty, Alice ; Mullen, Alex ; Fisher, Adrian ; Alcaraz, Lilian ; Stocks, Michael J. ; Lawson, Mandy ; Humphries, Alexander ; Dixon, John ; Paine, Stuart ; Cook, Anthony ; Nicholls, David ; Jordan, Stephen ; Christie, Jadeen ; Pairaudeau, Garry ; Connolly, Stephen ; Bailey, Andrew ; Cadogan, Elaine

A series of dibasic des-hydroxy β2 receptor agonists has been prepared and evaluated for potential as inhaled ultralong acting bronchodilators. Determination of activities at the human β-adrenoreceptors demonstrated a series of highly potent and selective β2 receptor agonists that were progressed to further study in a guinea pig histamine-induced bronchoconstriction model. Following further assessment by onset studies in guinea pig tracheal rings and human bronchial rings contracted with methacholine (guinea pigs) or carbachol (humans), duration of action studies in guinea pigs after intratracheal (i.t.) administration and further selectivity and safety profiling AZD3199 was shown to have an excellent over all profile and was progressed into clinical evaluation as a new ultralong acting inhaled β2 receptor agonist with rapid onset of action.

01 Oct 2013·Therapeutic Advances in Respiratory DiseaseQ3 · MEDICINE

Comparison of the bronchodilator and systemic effects of AZD3199, an inhaled ultra-long-acting β₂-adrenoceptor agonist, with formoterol in patients with asthma

Q3 · MEDICINE

ArticleOA

Author: Bjermer, Leif ; Bengtsson, Thomas ; Rosenborg, Johan ; Lötvall, Jan

Objectives: Pharmacologically mediated bronchodilation is important in the management of asthma, and is primarily achieved with β2-agonists. Novel compounds should preferably have a longer duration of action and a better systemic side effect profile than established alternatives at comparable peak bronchodilation. This single-dose crossover study was conducted to investigate and compare with formoterol the bronchodilatory and systemic effects, tolerability and safety of AZD3199, a novel ultra-long-acting β2-agonist (uLABA). Methods: Patients with asthma ( n = 37) were randomized to receive AZD3199 (120, 480, 1920 µg), formoterol (9, 36 µg) or placebo inhaled via a Turbuhaler™. Bronchodilation was evaluated by maximum ( Emax) and average 22–26 h ( E22–26) forced expiratory volume in 1 second (FEV1). Serum potassium was evaluated by minimum ( Emin) and 0–4 h average ( Eav) determined from serial measurements. AZD3199 and formoterol were compared on the basis of relative dose potency. Adverse events, clinical laboratory tests and physical examinations were markers for safety and tolerability, with plasma AZD3199 as the indicator of drug exposure. Results: All active treatments dose-dependently increased Emax and AZD3199 (480 and 1920 µg) and formoterol (36 µg) significantly increased E22–26 versus placebo. Relative dose potency between AZD3199 and formoterol was 50-fold on the microgram scale with respect to Emax and 11-fold with respect to E22–26. Small, dose-dependent effects on potassium, heart rate and QTc were seen after administration of AZD3199 compared with placebo. These well-known dose-related class effects of β2-agonists were mild. Notably, serum potassium suppression was less pronounced after AZD3199 compared with formoterol at similar bronchodilation. Overall, AZD3199 was well tolerated. Conclusions: AZD3199 480 µg and 1920 µg produced 24-hour bronchodilation. At comparable peak bronchodilator effect, AZD3199 was associated with a lower level of systemic side effects than formoterol. AZD3199 was well tolerated, with no safety concerns identified to preclude further investigation. ClinicalTrials.gov study identifier: NCT00736489

100 Deals associated with AZD-3199

Login to view more data

R&D Status

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Pulmonary Disease, Chronic Obstructive	Phase 2	CA	AstraZeneca PLC	01 Jun 2009
Pulmonary Disease, Chronic Obstructive	Phase 2	JP	AstraZeneca PLC	01 Jun 2009
Pulmonary Disease, Chronic Obstructive	Phase 2	PL	AstraZeneca PLC	01 Jun 2009
Pulmonary Disease, Chronic Obstructive	Phase 2	RU	AstraZeneca PLC	01 Jun 2009
Pulmonary Disease, Chronic Obstructive	Phase 2	BG	AstraZeneca PLC	01 Jun 2009
Airway Obstruction	Phase 2	SE	AstraZeneca PLC	01 Aug 2008
Airway Obstruction	Phase 2	DK	AstraZeneca PLC	01 Aug 2008
Asthma	Phase 2	DK	AstraZeneca PLC	01 Aug 2008
Asthma	Phase 2	SE	AstraZeneca PLC	01 Aug 2008

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00929708 (GLAD, CTgov)	Phase 2	Pulmonary Disease, Chronic Obstructive	329	AZD3199 (AZD3199 200 Mcg od)	badnuiuduk(vuizrxvuhv) = feoxaxwpbi mfgxlnwhrz (kkcrogsgqw, rmnqlmgkre - viztdgqqvf) View more	-	17 Jan 2014
				AZD3199 (AZD3199 400 Mcg od)	badnuiuduk(vuizrxvuhv) = kulbxtmtrl mfgxlnwhrz (kkcrogsgqw, sepoomokfm - bkirshemxd) View more
NCT00929708 (Pubmed \| Respir Res)	Phase 2	Pulmonary Disease, Chronic Obstructive	329	AZD3199 200 μg	(jgcadcelal) = orridbemym uuzwmnwuau (anhllhhnan ) View more	-	03 Jun 2013
				AZD3199 400 μg	(jgcadcelal) = azfzmsgdmy uuzwmnwuau (anhllhhnan ) View more
ERS2011	Not Applicable	-	-	AZD3199	dgtmftoati(kmoorxqrws) = ibduzieqkq firziddyix (tjlnfaxzjf )	-	01 Sep 2011
				Formoterol	dgtmftoati(kmoorxqrws) = lilhxjgdia firziddyix (tjlnfaxzjf )