Delving into the Latest Updates on Mapracorat with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Mapracorat (USAN)

+ [2]

Target

GR

Mechanism

GR agonists(Glucocorticoid receptor agonists)

Therapeutic Areas

Nervous System DiseasesEye DiseasesOther Diseases+ [3]

Active Indication-

Inactive Indication

CataractConjunctivitis, AllergicCorneal Endothelial Cell Loss+ [7]

Originator Organization

Bayer AG

Active Organization-

Inactive Organization

Bayer AG

Bausch & Lomb, Inc.

Drug Highest PhaseDiscontinuedPhase 3

First Approval Date-

Regulation-

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Structure

Molecular FormulaC25H26F4N2O2

InChIKeyVJGFOYBQOIPQFY-XMMPIXPASA-N

CAS Registry887375-26-0

Evaluation of efficacy and safety of Mapracorat 0.1% ointment and 4 comparator ointments in male and female subjects 18 to 65 years with stable plaque-type psoriasis treated once daily 6 days a week for a maximum of 4 weeks.
Primary objective was to compare the efficacy of all test compounds by measurement of psoriatic infiltrate thickness (PIT) with 20 MHz B mode ultrasound.
Secondary objectives were to assess safety of all test compounds by measurement of the atrophogenic potential on non-lesional skin with 20 MHz B mode ultrasound, to assess the efficacy of all test compounds by measurement of intensity of erythema measured by chromametry, to assess the efficacy of all test compounds by visual assessment of the skin in the test fields using a 5-point score, to assess the safety of all test compounds by visual assessments of formation of teleangiectasia using a 5-point score, to assess the safety of all test compounds by visual assessment of atrophy using a 5-point score, to assess the safety of all test compounds by visual assessment of local tolerability using a 5-point score, to visualize the therapeutic index given by PIT versus non lesional skin thickness.

Start Date11 Feb 2013

Sponsor / Collaborator

Bayer AG

NCT01736462 / CompletedPhase 1

An Open-Label Study to Evaluate 3 Month Corneal Endothelial Cell Density Changes in Healthy Subjects When Mapracorat Ophthalmic Suspension, 3%, is Administered 4 Times Daily for 14 Days

The objective of this study is to evaluate the effect on corneal endothelial cell density (cells/mm²) changes at 3 months when mapracorat ophthalmic suspension, 3% is administered QID (four times daily), for 14 days in healthy subjects with a normal ophthalmic history.

Start Date01 Feb 2013

Sponsor / Collaborator

Bausch & Lomb, Inc.

NCT01591655 / CompletedPhase 3

The Efficacy and Safety of Mapracorat Ophthalmic Suspension, 3% in Subjects for the Treatment of Ocular Inflammation and Pain Following Cataract Surgery.

The objective of this clinical study is to compare the safety and efficacy of mapracorat ophthalmic suspension, 3% with its vehicle for the treatment of postoperative inflammation and pain following cataract surgery. Participants from the United States and Canada will be recruited for this study.

Start Date01 Jul 2012

Sponsor / Collaborator

Bausch & Lomb, Inc.

100 Clinical Results associated with Mapracorat

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100 Translational Medicine associated with Mapracorat

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100 Patents (Medical) associated with Mapracorat

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14

Literatures (Medical) associated with Mapracorat

01 Feb 2017·Veterinary DermatologyQ3 · AGRICULTURAL & FORESTRY SCIENCE

The selective glucocorticoid receptor agonist mapracorat displays a favourable safety–efficacy ratio for the topical treatment of inflammatory skin diseases in dogs

Q3 · AGRICULTURAL & FORESTRY SCIENCE

Article

Author: Schmidt, Bernard H. ; Rossbach, Kristine ; Bäumer, Wolfgang

BackgroundMapracorat is a nonsteroidal Selective Glucocorticoid Receptor Agonist (SEGRA) that is presumed to have a better therapeutic index compared to classical glucocorticoids.ObjectivesTo compare the efficacy and safety of mapracorat with classical glucocorticoids used for the treatment of allergic skin diseases in dogs.AnimalsSix laboratory beagles.MethodsThe effect of mapracorat on lipopolysaccharide‐induced TNFα secretion from canine peripheral blood derived mononuclear cells (PBMC) was tested. In vivo, mapracorat was compared to triamcinolone acetonide using a skin inflammation model. Skin fold thickness was determined after daily administration of mapracorat and triamcinolone acetonide over 14 days.ResultsMapracorat concentration dependently inhibited TNFα secretion from activated canine PBMC with a half maximal inhibitory concentration (IC50) value of approximately 0.2 nmol/L. Intradermal injection of compound 48/80 (50 μg in 50 μL saline) resulted in a clear wheal and flare reaction over the 60 min observation period. Topical pre‐treatment with mapracorat (0.1%) and triamcinolone acetonide (0.015%) led to significant reduction in the wheal and flare responses compared to vehicle (acetone) treated areas. However, once daily topical administration of triamcinolone acetonide significantly reduced skin fold thickness from day 8 to 14, whereas no such reduction was observed for mapracorat.ConclusionThese results demonstrate that mapracorat has comparable anti‐inflammatory efficacy to classical steroidal glucocorticoids under these experimental settings and maintenance of skin fold thickness indicates a better safety profile compared to triamcinolone acetonide at equipotent concentrations. This profile further suggests that SEGRAs show promise in the management of inflammatory and pruritic skin diseases in dogs.

01 Jan 2017·Skin Pharmacology and PhysiologyQ4 · MEDICINE

Comparison of Occlusive and Open Application in a Psoriasis Plaque Test Design, Exemplarily Using Investigations of Mapracorat 0.1% Ointment versus Vehicle and Reference Drugs

Q4 · MEDICINE

Article

Author: Staedtler, Gerald ; Grossmann, Ulrike ; Wigger-Alberti, Walter ; Shakery, Kaweh ; von Mackensen, Yi-Ling ; Hoffman-Wecker, Maciej ; Nkulikiyinka, Richard ; Williams, Ragna

Background/Aims: Psoriasis plaque tests (PPTs) are important tools in the early phases of antipsoriatic drug development. Two distinct PPT design variants (open vs. occluded drug application) are commonly used, but no previous work has aimed to directly compare and contrast their performance. Methods: We compared the antipsoriatic efficacy of mapracorat 0.1% ointment and reference drugs reported in 2 separate studies, representing open and occluded PPT designs. The drug effect size was measured by sonography (mean change in echo-poor band thickness), chromametry, and standardized clinical assessment. Results: Antipsoriatic effects were detectable for the study drugs in both occluded and open PPTs. Differences between the potency of antipsoriatic drugs and vehicle were observable. The total antipsoriatic effect size appeared to be higher in the occluded PPT than the open PPT, despite the shorter treatment duration (2 vs. 4 weeks). Effect dynamics over time revealed greater differences between some study drugs in the open PPT compared to the occluded PPT. Conclusion: Taking the higher technical challenges for the open PPT into account, we recommend the occluded PPT as a standard screening setting in early drug development. In special cases, considering certain drug aspects or study objectives that would require procedural adaptations, an open PPT could be the better-suited design. Finally, both PPT models show clear advantages: classification as phase I studies, small number of psoriatic subjects, relatively short study duration, excellent discrimination between compounds and concentrations, parallel measurement of treatment response, and go/no go decisions very early in clinical development.

29 Jan 2015·Inflammation & Allergy-Drug Targets

Mapracorat, a Novel Non-Steroidal Selective Glucocorticoid Receptor Agonist for the Treatment of Allergic Conjunctivitis

Review

Author: Baiula, Monica ; Spampinato, Santi

Glucocorticoids are used to treat chronic and severe forms of allergic conjunctivitis. Although they exert a rapid and powerful therapeutic activity, relevant side effects may limit their ocular use: increase of intraocular pressure, cataract formation and reduced resistance to infections. New glucocorticoids displaying the same potency of classical glucocorticoids but with fewer adverse effects are needed for the treatment of ocular disorders. Mapracorat (also known as ZK245186 or BOL-303242-X) is a novel non-steroidal selective glucocorticoid receptor agonist that is in the first phases of clinical evaluation (Phase II Clinical trials) for topical treatment of inflammatory skin and ocular disorders. Mapracorat binds selectively to human glucocorticoid receptor and displays powerful anti-inflammatory effects. In experimental models of ocular diseases, mapracorat reduces clinical symptoms, eosinophil recruitment, chemokines and pro-inflammatory cytokines production at ocular level, confirming that it acts preventing both the early and late phase of allergic response. Interestingly, mapracorat induces a lower increase of intraocular pressure in comparison to the classical glucocorticoid dexamethasone. Several clinical trials are ongoing to investigate the efficacy and safety of mapracorat for the treatment of several ocular diseases. Transrepressive mechanisms are thought to account for the majority of mapracorat's antiinflammatory effects; however, the induction of anti-inflammatory proteins likely involved in transactivation events may contribute to mapracorat-mediated anti-inflammatory properties and deserve to be further investigated in suitable in vivo and in vitro models. These observations may influence how novel "differential" ligands are discovered, identified and evaluated.

100 Deals associated with Mapracorat

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External Link

KEGG	Wiki	ATC	Drug Bank
D10136	Mapracorat	-	DB12041

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Plaque psoriasis	Phase 3	DE	Bayer AG	11 Feb 2013
Corneal Endothelial Cell Loss	Phase 3	US	Bausch & Lomb, Inc.	01 Feb 2013
Ophthalmologic surgical procedures	Phase 3	US	Bausch & Lomb, Inc.	01 Jul 2012
Eczema	Phase 3	DE	Bayer AG	01 May 2011
Conjunctivitis, Allergic	Phase 3	US	Bausch & Lomb, Inc.	01 Feb 2011
Pain	Phase 3	US	Bausch & Lomb, Inc.	01 Feb 2011
Cataract	Phase 3	US	Bausch & Lomb, Inc.	01 Nov 2010
Ocular inflammation	Phase 3	US	Bausch & Lomb, Inc.	01 Nov 2010
Dry Eye Syndromes	Phase 3	US	Bausch & Lomb, Inc.	01 Jul 2010
Dermatitis, Atopic	Phase 3	ZA	Bayer AG	15 Jul 2009

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01289431 (CTgov)	Phase 2	Conjunctivitis, Allergic	236	BOL-303242-X (0.3% Once a Day)	jivgpzbaxu(imqkbffaag) = sgbosdqtun jioxpatorx (opxhiadlnk, qyeyutbuct - olhgpqvdwy) View more	-	04 Sep 2020
				BOL-303242-X (2% Once a Day)	jivgpzbaxu(imqkbffaag) = hbypkzxvlf jioxpatorx (opxhiadlnk, jokbbpibuh - oegjdhjboz) View more
NCT01163643 (CTgov)	Phase 2	Dry Eye Syndromes	356	2% BOL-303242-X ophthalmic suspension (2% BOL-303242-X Ophthalmic Suspension)	cmvvgcpntr(oglolanoeu) = sisxrchqzx uknxnkzztn (daozezbtei, teilmewsuy - gkcmzdamqr) View more	-	03 Sep 2020
				2% BOL-303242-X ophthalmic suspension AM (2% BOL-303242-X Ophthalmic Suspension in the Morning)	cmvvgcpntr(oglolanoeu) = xqvdnxysdo uknxnkzztn (daozezbtei, ghuowstpge - ixprwyqbcs) View more
NCT01591161 (CTgov)	Phase 3	Cataract \| Pain \| Ocular inflammation \| Ophthalmologic surgical procedures	369	Mapracorat (Mapracorat)	tmxqoqgbwd(qzkrqtoady) = beaggfeifi zexnkghczh (zclrohwoja, eyqcmxhhzj - odbxkxfusf) View more	-	03 Sep 2020
				Placebo (Vehicle)	tmxqoqgbwd(qzkrqtoady) = eeklfpcnym zexnkghczh (zclrohwoja, pgxhjmigpj - zkkasrgqeq) View more
NCT01591655 (CTgov)	Phase 3	Cataract \| Pain \| Ocular inflammation \| Ophthalmologic surgical procedures	360	Mapracorat (Mapracorat)	gklrnxdhyz(rrjxnoinuv) = qhozvvwuwl xmjuiwmaok (rvlshvoknh, hegzbvboxj - euhwlvmzbs) View more	-	03 Sep 2020
				Vehicle (Vehicle)	gklrnxdhyz(rrjxnoinuv) = tjycsepkvh xmjuiwmaok (rvlshvoknh, gjmnsxebjm - essttpbunk) View more
NCT01230125 (CTgov)	Phase 3	Cataract \| Ocular inflammation	311	Mapracorat (Mapracorat)	emsdtrofro(fymjiarqmr) = aqmzdaxiyi qhnojawavm (cpzdvfcrbt, hvvnxgtzvj - knusgmdzbp) View more	-	03 Sep 2020
				Vehicle (Vehicle)	emsdtrofro(fymjiarqmr) = syrzfqlual qhnojawavm (cpzdvfcrbt, dohgugudkc - czpmcsfftt) View more
NCT01298752 (CTgov)	Phase 3	Cataract \| Pain \| Ocular inflammation	177	Mapracorat (Mapracorat)	ffopsiulvx(qdlbpilddz) = nymlipkvqj nuzivvnsez (jwhtqogsgd, fxvpndjirg - whihjkeoja) View more	-	03 Sep 2020
				Vehicle (Vehicle)	ffopsiulvx(qdlbpilddz) = zdbtnbudrc nuzivvnsez (jwhtqogsgd, vfhjdpyhdo - ehfggeyvbe) View more
NCT00905450 (CTgov)	Phase 2	Cataract \| Inflammation	415	Vehicle for BOL-303242-X	ymvnaahgqk(anjmzzxack) = ydhcqvpymc cpknkuuyqv (oztvobfsjz, bufdujtirs - mydjuolnwc) View more	-	03 Sep 2020
BOL-303242-X (ARVO2010)	Not Applicable	-	-	BOL-303242-X	(yplejmywtl) = lfyuxfmknp hcbohyalid (pszfkdygzf )	-	01 Apr 2010
				Dexamethasone	(yplejmywtl) = pezahiuvcz hcbohyalid (pszfkdygzf )
ARVO2010	Not Applicable	-	-	BOL-303242-X	(ujxgnabjzf) = hwgvnpmsvm wnxdignvgj (crfxuomext )	-	01 Apr 2010