Delving into the Latest Updates on Setipiprant with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Setipiprant (USAN/INN)

Target

CRTH2

Mechanism

CRTH2 antagonists(Prostaglandin D2 receptor 2 antagonists)

Therapeutic Areas

Immune System DiseasesInfectious DiseasesOtorhinolaryngologic Diseases+ [2]

Active Indication-

Inactive Indication

Androgenetic AlopeciaAsthmaRhinitis, Allergic, Seasonal

Originator Organization

Moon Collider Ltd.

Actelion Pharmaceuticals Ltd.

Active Organization-

Inactive Organization

Actelion Pharmaceuticals Ltd.

Moon Collider Ltd.Allergan Ltd. (Ireland)

Drug Highest PhaseDiscontinuedPhase 3

First Approval Date-

Regulation-

Login to view timeline

Structure

Molecular FormulaC24H19FN2O3

InChIKeyIHAXLPDVOWLUOS-UHFFFAOYSA-N

CAS Registry866460-33-5

A Three-part Study to Assess the Tolerability, Safety, Pharmacodynamics, and Pharmacokinetics of Ascending Single Doses (Including Food Interaction) of ACT-453859 in Healthy Male Subjects, of Ascending Multiple Doses of ACT-453859 in Healthy Male and Female Subjects, and of Multiple Doses of Setipiprant (ACT-129968) in Healthy Male and Female Subjects

This is a three-part study to assess the tolerability, safety, pharmacodynamics, and pharmacokinetics of ascending single doses (including food interaction) of ACT-453859 in healthy male subjects, of ascending multiple doses of ACT-453859 in healthy male and female subjects, and of multiple doses of setipiprant (ACT-129968) in healthy male and female subjects.

Start Date01 Dec 2011

Sponsor / Collaborator

Idorsia Pharmaceuticals Ltd.

100 Clinical Results associated with Setipiprant

Login to view more data

100 Translational Medicine associated with Setipiprant

Login to view more data

100 Patents (Medical) associated with Setipiprant

Login to view more data

11

Literatures (Medical) associated with Setipiprant

01 Dec 2017·Allergy, Asthma & Clinical ImmunologyQ4 · MEDICINE

Efficacy and safety of setipiprant in seasonal allergic rhinitis: results from Phase 2 and Phase 3 randomized, double-blind, placebo- and active-referenced studies

Q4 · MEDICINE

ArticleOA

Author: van Bavel, Jay ; Mohar, Dale E ; Andrews, Charles P ; Bourrelly, Denis ; Hampel, Frank C ; Mangialaio, Sara ; Martin, Bruce ; Hmissi, Abdel ; Ratner, Paul ; Dingemanse, Jasper ; Danaietash, Parisa

AbstractBackgroundAntagonism of chemoattractant receptor-homologous molecule on T-helper type-2 cells (CRTH2), a G-protein coupled receptor for prostaglandin D2, could be beneficial for treating allergic disorders. We present findings on the efficacy and safety/tolerability of a CRTH2 antagonist (setipiprant) in participants with seasonal allergic rhinitis (AR) in a real-life setting over 2 weeks.MethodsA Phase 2 trial and a Phase 3 trial were conducted at seven centers in Texas, USA during the Mountain Cedar pollen season. Both were prospective, randomized, double-blind, placebo- and active-referenced (cetirizine) studies. The Phase 2 trial assessed setipiprant 100–1000 mg b.i.d. and 1000 mg o.d. versus placebo in adult and elderly participants. The Phase 3 trial assessed setipiprant 1000 mg b.i.d. in adolescent, adult, and elderly participants. Efficacy was assessed using daytime nasal symptom scores (DNSS), night-time nasal symptom scores (NNSS) and daytime eye symptom scores (DESS).Results579 participants were randomized in the Phase 2 trial (mean age 41.6–43.4 years); 630 were randomized in the Phase 3 trial (mean age 37.5–40.7 years). A statistically significant, dose-related improvement in mean change from baseline DNSS was observed over 2 weeks with setipiprant 1000 mg b.i.d. versus placebo in the Phase 2 trial (−0.15 [95% CI −0.29, −0.01]; p = 0.030). Setipiprant 1000 mg b.i.d. had no significant effect on this endpoint in the Phase 3 trial (−0.02 [95% CI −0.12, 0.07]; p = 0.652). Total and individual NNSS and DESS symptom scores were significantly improved with setipiprant 1000 mg b.i.d. versus placebo in the Phase 2 but not the Phase 3 trial. Setipiprant showed a favorable safety/tolerability profile.ConclusionsThe Phase 2 trial was the first large clinical study to assess a CRTH2 antagonist in seasonal AR in a real-life setting. Setipiprant dose-related efficacy in the Phase 2 trial was not confirmed during Phase 3. Setipiprant was well tolerated in both studies.Trial registrationNCT01241214 and NCT01484119

31 Aug 2017·Physiological Research

Does Inhibition of Aldose Reductase Contribute to the Anti-Inflammatory Action of Setipiprant?

Article

Author: Ballekova, J. ; Soltesova-Prnova, M. ; Stefek, M. ; Majekova, M.

The aim of this study was to investigate aldose reductase inhibitory action of setipiprant as a potential additional mechanism contributing to its anti-inflammatory action. Aldose reductase activity was determined by spectrophotometric measuring of NADPH consumption. Setipiprant was found to inhibit aldose reductase/NADPH-mediated reduction of 4-hydroxynonenal, 4-hydroxynonenal glutathione and prostaglandin H2 substrates, all relevant to the process of inflammation. Molecular modeling simulations into the aldose reductase inhibitor binding site revealed an interaction pattern of setipiprant. Considering multifactorial etiology of inflammatory pathologies, it is suggested that, in addition to the antagonizing prostaglandin D2 receptor, inhibition of aldose reductase may contribute to the reported anti-inflammatory action of setipiprant.

01 Aug 2017·DrugsQ1 · MEDICINE

Targeting the PGD2/CRTH2/DP1 Signaling Pathway in Asthma and Allergic Disease: Current Status and Future Perspectives

Q1 · MEDICINE

Review

Author: Kupczyk, Maciej ; Kuna, Piotr

Prostaglandin D₂ (PGD₂) released by degranulating mast cells is believed to play a key role in orchestrating mechanisms of inflammation in allergies and asthma. The biological effects of PGD₂ are mediated by D-prostanoid (DP1), CRTH2 (DP2), and thromboxane prostanoid (TP) receptors. The CRTH2 receptor is involved in induction of migration and activation of T helper type 2 (Th₂) lymphocytes, eosinophils, and basophils; up-regulation of adhesion molecules; and promotion of pro-inflammatory Th₂-type cytokines (interleukin [IL]-4, 5, 13), whereas the DP receptor is associated with relaxation of smooth muscles, vasodilation, inhibition of cell migration, and apoptosis of eosinophils. A number of CRTH2/PGD₂ receptor antagonists have been investigated in asthma and allergic diseases. The CRTH2 antagonist (OC000459) or dual CRTH2 and TP receptor antagonist (ramatroban) were effective in reducing eosinophilia, nasal mucosal swelling, and clinical symptoms of allergic rhinitis, with the latter drug registered for clinical use in this indication. OC000459 and setipiprant reduced the late but not early phase of response in an allergen challenge in atopic asthmatics. In persistent asthma, some molecules induced limited improvement in lung function, quality of life, and asthma symptoms (OC000459, BI671800), but in other trials with AMG 853 and AZ1981 these findings were not confirmed. The clear discrepancy between animal studies and clinical efficacy of CRTH2 antagonism in allergic rhinitis, and lack of efficacy in a general cohort of asthmatics, highlight the issue of patient phenotyping. There is no doubt that the PGD₂/CATH2/DP1 pathway plays a key role in allergic inflammation and further studies with selective or combined antagonisms in well defined cohorts of patients are needed.

100 Deals associated with Setipiprant

Login to view more data

External Link

KEGG	Wiki	ATC	Drug Bank
D10326	Setipiprant	-	DB12562

R&D Status

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Asthma	Phase 3	US	Actelion Pharmaceuticals Ltd.	-
Asthma	Phase 3	ZA	Actelion Pharmaceuticals Ltd.	-
Asthma	Phase 3	AU	Actelion Pharmaceuticals Ltd.	-
Asthma	Phase 3	SG	Actelion Pharmaceuticals Ltd.	-
Asthma	Phase 3	PL	Actelion Pharmaceuticals Ltd.	-
Asthma	Phase 3	IL	Actelion Pharmaceuticals Ltd.	-
Asthma	Phase 3	SE	Actelion Pharmaceuticals Ltd.	-
Asthma	Phase 3	HU	Actelion Pharmaceuticals Ltd.	-
Rhinitis, Allergic, Seasonal	Phase 3	-	Moon Collider Ltd.	-
Rhinitis, Allergic, Seasonal	Phase 3	US	Actelion Pharmaceuticals Ltd.	-

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02781311 (CTgov)	Phase 2	Androgenetic Alopecia	169	Placebo (Placebo)	jhcvvdnreo(qqdjusonhw) = giipquuvwh vftvjwqrbz (aoumpxugsq, tfmhvalubo - ozheedgxdx) View more	-	05 Apr 2019
				Setipiprant (Setipiprant)	jhcvvdnreo(qqdjusonhw) = qdcttvreco vftvjwqrbz (aoumpxugsq, znesytdlsv - rlnbohgciy) View more
NCT01241214 (Pubmed \| Allergy Asthma Clin Immunol) Manual	Phase 2/3	Rhinitis, Allergic, Seasonal	579	setipiprant	(aulfrndaqb): difference = -0.15 (95% CI, -0.29 to -0.01), P-Value = 0.030	Positive	04 Apr 2017
				Placebo