Delving into the Latest Updates on AZD-1981 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

CRTH2 x Prostanoid receptor

Mechanism

CRTH2 antagonists(Prostaglandin D2 receptor 2 antagonists), Prostanoid receptor antagonists

Therapeutic Areas

Immune System DiseasesRespiratory DiseasesSkin and Musculoskeletal Diseases+ [2]

Active Indication-

Inactive Indication

AsthmaChronic UrticariaContraception+ [2]

Originator Organization

AstraZeneca PLC

Active Organization-

Inactive Organization

AstraZeneca PLC

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC19H17ClN2O3S

InChIKeyJWYIGNODXSRKGP-UHFFFAOYSA-N

CAS Registry802904-66-1

The investigators are recruiting for a chronic hives study. This research is being done to test whether an investigational drug called AstraZeneca drug (AZD)1981 may be helpful for treating people with Chronic Idiopathic Urticaria who continue to have symptoms despite taking antihistamines. The word "investigational" means that AZD1981 is not approved for marketing by the Food and Drug Administration (FDA). The FDA is allowing the use of AZD1981 in this study.
People with chronic hives lasting for at least 6 months and without a known cause may join. The study involves 6 visits over 8 weeks. Approximately 48 participants expected to take part in this study at the Johns Hopkins Asthma and Allergy Clinic. All participants will be treated with the study medication and/or placebo for 8 weeks.
The results of this trial may have a benefit others with Chronic Idiopathic Urticaria who don't respond well to antihistamines by generating experience and data to support the design of a larger, multicenter trial investigating the efficacy of AZD1981 in treating antihistamine refractory CIU.

Start Date01 Jan 2014

Sponsor / Collaborator

The Johns Hopkins University

[+1]

JPRN-jRCT2080221485 / Unknown statusPhase 2

A Double-blind, Placebo-controlled, Randomised, Parallel-group, Phase II, Multi-centre Study to Assess the Efficacy, Safety and Tolerability of 4 Twice Daily Doses and 2 Once Daily Doses of AZD1981 Given as Tablets During 12 Weeks in Asthmatic Patients

Start Date20 Jun 2011

Sponsor / Collaborator

AstraZeneca PLC

NCT01311635 / CompletedPhase 1

A Phase I, Open Label, Randomised, 4-way Crossover Study to Investigate the Relative Bioavailability of Single Dose AZD1981 Via 3 Different Tablets in Healthy Men and Healthy Women of Non-childbearing Potential

The purpose of this study is to study the relative bioavailability of AZD1981 when using a new tablet compared to the current tablet.

Start Date01 Apr 2011

Sponsor / Collaborator

AstraZeneca PLC

100 Clinical Results associated with AZD-1981

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100 Translational Medicine associated with AZD-1981

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100 Patents (Medical) associated with AZD-1981

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11

Literatures (Medical) associated with AZD-1981

01 Jul 2022·Clinical & Experimental AllergyQ2 · MEDICINE

Efficacy of an oral CRTH2 antagonist (AZD1981) in the treatment of chronic rhinosinusitis with nasal polyps in adults: A randomized controlled clinical trial

Q2 · MEDICINE

Article

Author: Price, Caroline P. E. ; Tan, Bruce K. ; Grammer, Leslie C. ; Peters, Anju T. ; Stevens, Whitney W. ; Vu, Thanh‐Huyen T. ; Schleimer, Robert P. ; Kern, Robert C. ; Cousens, Leslie ; Suh, Lydia A. ; Conley, David ; Kato, Atsushi ; Smith, Stephanie S. ; Guo, Amina ; Erickson, Kristin A. ; Welch, Kevin C.

AbstractBackgroundChronic rhinosinusitis with nasal polyps (CRSwNP) is a type 2 inflammatory disease of the upper airways. AZD1981 is a selective antagonist of chemoattractant receptor‐homologous molecule expressed on T helper type 2 and other type 2 cells, including innate lymphoid cells type 2, eosinophils, and basophils.ObjectiveTo evaluate the efficacy of AZD1981 in reducing nasal polyp size when added to intranasal corticosteroids in adult patients with CRSwNP.MethodsEighty‐one subjects (18–70 years of age) with CRSwNP were recruited and screened for trial eligibility from allergy and otolaryngology clinics from a single tertiary care site between June 2016 and August 2019. Eligible patients were randomized in a double‐blind fashion to receive either AZD1981 (n = 22) or placebo (n = 21) orally three times a day for 12 weeks, added to intranasal corticosteroids. The primary endpoint was a change in nasal polyp score (NPS) at 12 weeks. Secondary endpoints included improvement in sinus computed tomography using Lund Mackay scoring, symptoms using visual analog scale, quality of life using Sino Nasal Outcome Test‐22, and the Brief Smell Identification Test.ResultsForty‐three patients met the inclusion criteria and were enrolled. At 12 weeks, there was no difference in NPS change in the AZD1981 arm (mean 0, standard error 0.34, n = 15) compared with placebo (mean 0.20, standard error 0.36, n = 17); mean difference −0.20 (95% confidence interval: −1.21, 0.81; p = .69). No significant differences were observed for Lund Mackay score, symptoms, quality of life, or smell test. AZD1981 was well tolerated except for one case of hypersensitivity reaction.ConclusionIn patients with CRSwNP, the addition of AZD1981 to intranasal corticosteroids did not change nasal polyp size, radiographic scores, symptoms, or disease‐specific quality of life.

01 Jan 2019·International Archives of Allergy and Immunology

Effects of an Oral CRTh2 Antagonist (AZD1981) on Eosinophil Activity and Symptoms in Chronic Spontaneous Urticaria

Article

Author: Vonakis, Becky Marie ; Chichester, Kris ; Devine, Kelly ; Sterba, Patricia Meghan ; Oliver, Eric Tyrell ; Saini, Sarbjit Singh ; Wegner, Craig

Background: Approximately 50% of patients with chronic spontaneous urticaria (CSU) experience symptoms that are not fully controlled by antihistamines, indicating an unmet clinical need. Objective: To evaluate the effects of the selective CRTh2 antagonist AZD1981 on symptoms and targeted leukocytes in adults with persistent CSU despite treatment with H1-antihistamines. Methods: We performed a single-center, randomized, placebo-controlled study involving adult CSU subjects with symptoms despite daily antihistamines. The subjects underwent a 2-week placebo run-in and 4 weeks of double-blinded therapy with either AZD1981 40 mg TID or placebo, followed by a 2-week placebo washout. The primary objective was to assess the effect of AZD1981 on CSU signs and symptoms. Secondary objectives included the effects of AZD1981 on prostaglandin D2 (PGD2)-induced eosinophil shape change, circulating leukocyte subsets, CRTh2 expression on blood leukocytes, and total blood leukocyte histamine content. Results: Twenty-eight subjects were randomized to AZD1981 or placebo, with 26 subjects completing the study. The urticaria activity scores declined during the treatment phase in both groups, and they were significantly reduced in the AZD1981 group at the end of washout. AZD1981 treatment increased circulating eosinophils and significantly impaired PGD2-mediated eosinophil shape change. CRTh2 surface expression rose significantly on blood basophils during active treatment. No serious adverse events were observed. Conclusions: This is the first study to examine the efficacy of a CRTh2 antagonist in antihistamine-refractory CSU. AZD1981 treatment was well tolerated, effectively inhibited PGD2-mediated eosinophil shape change, shifted numbers of circulating eosinophils, and reduced weekly itch scores more than hives during treatment and into washout. Further studies are needed to determine whether inhibition of the PGD2/CRTh2 pathway will be an effective treatment for CSU.

01 Dec 2017·Clinical and Translational AllergyQ2 · MEDICINE

Looking forward to new targeted treatments for chronic spontaneous urticaria

Q2 · MEDICINE

ReviewOA

Author: Grattan, Clive ; Metz, Martin ; Maurer, Marcus ; Kocatürk, Emek

The introduction of omalizumab to the management of chronic spontaneous urticaria (CSU) has markedly improved the therapeutic possibilities for both, patients and physicians dealing with this disabling disease. But there is still a hard core of patients who do not tolerate or benefit from existing therapies and who require effective treatment. Novel approaches include the use of currently available drugs off-licence, investigational drugs currently undergoing clinical trials and exploring the potential for therapies directed at pathophysiological targets in CSU. Off-licence uses of currently available drugs include rituximab and tumour necrosis factor inhibitors. Ligelizumab (anti-IgE), canakinumab (anti-IL-1), AZD1981 (a PGD2 receptor antagonist) and GSK 2646264 (a selective Syk inhibitor) are currently in clinical trials for CSU. Examples of drugs that could target potential pathophysiological targets in CSU include substance P antagonists, designed ankyrin repeat proteins, C5a/C5a receptor inhibitors, anti-IL-4, anti-IL-5 and anti-IL-13 and drugs that target inhibitory mast cell receptors. Other mediators and receptors of likely pathogenic relevance should be explored in skin profiling and functional proof of concept studies. The exploration of novel therapeutic targets for their role and relevance in CSU should help to achieve a better understanding of its etiopathogenesis.

100 Deals associated with AZD-1981

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB11946

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Chronic Urticaria	Phase 2	US	AstraZeneca PLC	01 Jan 2014
Asthma	Phase 2	AR	AstraZeneca PLC	01 Sep 2008
Asthma	Phase 2	CR	AstraZeneca PLC	01 Sep 2008
Asthma	Phase 2	BR	AstraZeneca PLC	01 Sep 2008
Asthma	Phase 2	PL	AstraZeneca PLC	01 Sep 2008
Pulmonary Disease, Chronic Obstructive	Phase 2	BG	AstraZeneca PLC	01 May 2008
Pulmonary Disease, Chronic Obstructive	Phase 2	PL	AstraZeneca PLC	01 May 2008
Pulmonary Disease, Chronic Obstructive	Phase 2	DK	AstraZeneca PLC	01 May 2008
Pulmonary Disease, Chronic Obstructive	Phase 2	SK	AstraZeneca PLC	01 May 2008
Pulmonary Disease, Chronic Obstructive	Discovery	SE	AstraZeneca PLC	01 May 2008

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02031679 (CTgov)	Phase 2	Chronic Urticaria	38	AZD1981 (AZD1981)	butpbmfzlh(baxjyaejew) = fefyphtjeq ycadrwypwf (vpmjkwwoll, jztjyxhqpy - fabzcrjpae) View more	-	12 Jul 2017
				Placebo (Placebo)	butpbmfzlh(baxjyaejew) = mjhtgeppir ycadrwypwf (vpmjkwwoll, rqtqrqcwzr - nhzvhrjyks) View more
NCT00766415 (Biopsy \| D9831C00002, CTgov)	Phase 2	Pulmonary Disease, Chronic Obstructive	52	AZD1981 (AZD1981)	rxmupcpfsd(byameapzgy) = sonwmzxmmr qerpypnnkp (tvgjbujbix, zrlyhbfjiu - qetdhccqrn) View more	-	28 Feb 2014
				Placebo (Placebo)	rxmupcpfsd(byameapzgy) = sxtdaawilv qerpypnnkp (tvgjbujbix, lporuzbiwl - rncnzcdgwc) View more
NCT00758589 (OLIVE, CTgov)	Phase 2	Asthma	368	Placebo	stvrdaizza(cpzoyuksxu) = hrxdgukusn rudgrhdyjh (ujrijressi, ugvmevlvua - vvluhjwgjh) View more	-	13 Dec 2013
NCT00690482 (Columbus, CTgov)	Phase 2	Pulmonary Disease, Chronic Obstructive	118	AZD1981 (AZD1981)	(vjjwkirrtk) = kpzyvxggys ukwjxrxayr (vfylicmbyh, elbsbkncsi - kyyivyceni) View more	-	06 Dec 2013
				Placebo (Placebo)	(vjjwkirrtk) = ljrvocdgfl ukwjxrxayr (vfylicmbyh, lpwvnsfxjk - zkyrzzdukt) View more