A Randomised, Double-blind, Placebo-controlled 4-period Cross-over Study to Assess the Efficacy and Safety of Repeat Dose Intranasal GSK1004723 (1000µg), Oral GSK835726 (10mg) and Cetirizine (10mg) in the Environmental Challenge Chamber in Subjects With Seasonal Allergic Rhinitis

This is a randomised, double-blind, placebo-controlled 4-period cross-over study to assess the efficacy and safety of repeat dose intranasal GSK1004723 (1000µg), oral GSK835726 (10mg) and cetirizine (10mg) in the environmental challenge chamber in subjects with seasonal allergic rhinitis.

Start Date01 Jun 2009

Sponsor / Collaborator

GSK Plc

EUCTR2008-001567-10-DE / Not yet recruitingNot Applicable

A randomised, double-blind, placebo-controlled, 3-period crossover study to assess the efficacy and safety of single dose intranasal GSK1004723 compared with placebo in an allergen challenge chamber in male subjects with seasonal allergic rhinitis

Start Date25 Jun 2008

Sponsor / Collaborator

GlaxoSmithKline Research & Development Ltd.

NCT00824356 / CompletedPhase 2

A Randomised, Double-Blind, Placebo-Controlled, 3-Period Crossover Study to Assess the Efficacy and Safety of Single Dose Intranasal GSK1004723 Compared With Placebo in an Allergen Challenge Chamber in Male Subjects With Seasonal Allergic Rhinitis

This is a placebo-controlled, 3-period crossover study to assess the efficacy and safety of two single doses of an intranasal anti-histamine GSK1004723 compared with placebo in an allergen challenge chamber in male subjects with seasonal allergic

Start Date01 Jun 2008

Sponsor / Collaborator

GSK Plc

100 Clinical Results associated with GSK-1004723

100 Translational Medicine associated with GSK-1004723

100 Patents (Medical) associated with GSK-1004723

Literatures (Medical) associated with GSK-1004723

01 Jan 2012·International Archives of Allergy and Immunology

The Efficacy and Tolerability of Two Novel H1/H3 Receptor Antagonists in Seasonal Allergic Rhinitis

Review

Author: Watson, Joanna ; McQuade, Barbara ; Daley-Yates, Peter ; Oliver, Amanda ; Ambery, Claire ; Sweeney, Lisa

Background: A therapeutic role for histamine H3 receptor antagonism in allergic rhinitis has been proposed and may be complimentary to the well-known benefits of H1 receptor antagonism. Combined H1/H3 blockade has therefore been investigated as a novel therapeutic approach that may enhance symptom relief, particularly nasal blockage. Methods: Two novel H1/H3 dual receptor antagonists were investigated in phase I and II safety and efficacy studies. One molecule (GSK1004723) was designed for intranasal administration as a suspension or solution and the other molecule (GSK835726) for oral administration. In phase I and II studies, both molecules were compared with an active control and/or placebo in randomised studies. In phase II studies, efficacy was assessed in an environmental allergen challenge chamber (ECC). Subjects with seasonal allergic rhinitis were exposed to allergen to induce symptoms. Efficacy and safety was measured over 4, 7 and 20–24 h post-dose. The endpoints included total nasal symptom score and nasal blockage. Results: Intranasal suspension of GSK1004723 and oral GSK835726 were well tolerated. Single-dose intranasal suspensions of GSK1004723 (220, 1,100 µg) failed to demonstrate clinically significant attenuation of symptoms of allergic rhinitis induced in the ECC. Single (10, 50, 100 mg) and 3-day repeat (10 mg) dose oral GSK835726 demonstrated clinically significant attenuation of symptoms in the ECC comparable to cetirizine 10 mg. Three-day repeat dosing of the intranasal solution GSK1004723 1,000 µg also demonstrated a statistically significant attenuation of nasal symptoms, but was less than seen with cetirizine and GSK835726 and caused initial nasal discomfort. Conclusions: Combined H1/H3 antagonism did not show differentiation from H1 antagonism in reducing total nasal symptom score or nasal blockage.

01 Nov 2011·British Journal of PharmacologyQ2 · MEDICINE

Pharmacological characterization of GSK1004723, a novel, long‐acting antagonist at histamine H₁and H₃receptors

Q2 · MEDICINE

Article

Author: Saunders, K. A. ; Ford, A. J. ; Hodgson, S. T. ; Clark, K. L. ; Slack, R. J. ; Luttmann, M. A. ; Connor, H. E. ; Hall, D. A. ; Russell, L. J. ; Browning, C.

BACKGROUND AND PURPOSEPreclinical pharmacological characterization of GSK1004723, a novel, dual histamine H1and H3receptor antagonist.EXPERIMENTAL APPROACHGSK1004723 was characterizedin vitroandin vivousing methods that included radioligand binding, intracellular calcium mobilization, cAMP production, GTPγS binding, superfused human bronchus and guinea pig whole body plethysmography.KEY RESULTSIn cell membranes over‐expressing human recombinant H1and H3receptors, GSK1004723 displayed high affinity, competitive binding (H1pKi = 10.2; H3pKi = 10.6). In addition, GSK1004723 demonstrated slow dissociation from both receptors with at1/2of 1.2 and 1.5 h for H1and H3respectively. GSK1004723 specifically antagonized H1receptor mediated increases in intracellular calcium and H3receptor mediated increases in GTPγS binding. The antagonism exerted was retained after cell washing, consistent with slow dissociation from H1and H3receptors. Duration of action was further evaluated using superfused human bronchus preparations. GSK1004723 (100 nmol·L−1) reversed an established contractile response to histamine. When GSK1004723 was removed from the perfusate, only 20% recovery of the histamine response was observed over 10 h. Moreover, 21 h post‐exposure to GSK1004723 there remained almost complete antagonism of responses to histamine.In vivopharmacology was studied in conscious guinea pigs in which nasal congestion induced by intranasal histamine was measured indirectly (plethysmography). GSK1004723 (0.1 and 1 mg·mL−1intranasal) antagonized the histamine‐induced response with a duration of up to 72 h.CONCLUSIONS AND IMPLICATIONSGSK1004723 is a potent and selective histamine H1and H3receptor antagonist with a long duration of action and represents a potential novel therapy for allergic rhinitis.

100 Deals associated with GSK-1004723

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Indication	Highest Phase	Country/Location	Organization	Date
Rhinitis, Allergic, Seasonal	Phase 2	DE	GSK Plc	01 Jun 2008

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00972504 (CTgov)	Phase 2	Rhinitis, Allergic, Seasonal	54	placebo	ohligdeuqr(sjksytqfam) = oidlnitjvf jctyvosnri (asiooucyfb, ubngppaygz - ccgqgsqrcx) View more	-	02 Aug 2017

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