Delving into the Latest Updates on SB-773812 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

+ [1]

Target

5-HT2A receptor x 5-HT2C receptor x 5-HT6 receptor x D2 receptor x D3 receptor

Action

antagonists

Mechanism

5-HT2A receptor antagonists(Serotonin 2a (5-HT2a) receptor antagonists), 5-HT2C receptor antagonists(Serotonin 2c (5-HT2c) receptor antagonists), 5-HT6 receptor antagonists(Serotonin 6 (5-HT6) receptor antagonists)

+ [2]

Therapeutic Areas

Other Diseases

Active Indication-

Inactive Indication

Schizophrenia

Originator Organization

GSK Plc

Active Organization-

Inactive Organization

GSK Plc

License Organization-

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

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Study to compare PK of a new 120mg tablet with two 60mg tablets. This is required because we plan to have only single tablets administered in the later phase clinical trials but we have not had a 120mg strength before. As this is a new previously untested strength we need to ensure that the PK is similar to that achieved using 2x60mg before we start a large manufacturing campaign and before we administer to a large number of patients. The study is planned to consist of a single part, with two dosing periods, periods 1 and 2 consisting of 18 subjects. There will be 20 days washout between each dose. Initially 4 subjects will be given a single oral dose of 120 mg SB-773812 and 2 will be given placebo. If 120mg SB-773812 is well tolerated in the first four volunteers, the remaining 12 subjects will be dosed. If the 120mg single oral dose in the first 4 subjects is poorly tolerated, the study will be stopped. Subjects will return to the centre for follow-up 14 to 21 days after the final dose.It is expected that the total duration of the study should be approximately 11 weeks.

Start Date24 May 2007

Sponsor / Collaborator

GSK Plc

NCT00411866

/ CompletedPhase 1

Open Label Study in Healthy Volunteers to Investigate the Effect of Ketoconazole 400mg on Pharmacokinetics of SB-773812 20mg

The purposes of this study are to determine if there is a difference in how SB-773812 is distributed through the bloodstream before and after multiple doses of ketoconazole have been given and to determine if there is a difference in how safe and well tolerated SB-773812 is when given on its own and given with ketoconazole.

Start Date13 Oct 2006

Sponsor / Collaborator

GSK Plc

NCT00259870

/ CompletedPhase 2

A Multi Centre, Double-Blind, Double-Dummy, Placebo-Controlled, Randomised, Adaptive, Dose-Range Study To Evaluate the Safety and Efficacy of SB-773812 Administered Once Daily for 12 Weeks in Adults With Schizophrenia

This is a two part study designed to evaluate the safety and efficacy of SB-773812 in the treatment of acute schizophrenia. Subjects with acute schizophrenia will be randomized in an adaptive design study to receive placebo, SB-773812 60mg or olanzapine 15mg for 12 weeks in Part A. An interim analysis will be conducted to assess the efficacy and safety of the SB-773812 60mg dose compared with placebo. Based on these data, up to two further doses of SB-773812 will be added to the randomization for Part B.

Start Date01 Sep 2005

Sponsor / Collaborator

GSK Plc

100 Clinical Results associated with SB-773812

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100 Translational Medicine associated with SB-773812

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100 Patents (Medical) associated with SB-773812

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2

Literatures (Medical) associated with SB-773812

03 Jun 2017·Expert Opinion on Investigational DrugsQ2 · MEDICINE

Investigational dopamine antagonists for the treatment of schizophrenia

Q2 · MEDICINE

Review

Author: Masand, Prakash S. ; Wang, Sheng-Min ; Patkar, Ashwin A. ; Jun, Tae-Youn ; Pae, Chi-Un ; Lee, Soo-Jung ; Han, Changsu

INTRODUCTIONSchizophrenia is a debilitating illness with a chronic impact on social function and daily living. Although various antipsychotics are available, there are still many challenges and unmet needs. Thus, many compounds with diverse mechanisms have been investigated, but all approved antipsychotics still require interactions with dopamine D₂ receptors. Areas covered: We searched for investigational drugs using the key words 'dopamine' and 'schizophrenia' in American and European clinical trial registers (clinicaltrials.gov; clinicaltrialsregister.eu). Published articles were searched in PubMed, Embase, Medline, PsycINFO, Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Web of Science and the Cochrane Central Register of Controlled Trials Library. Expert opinion: The prospect of developing a dopamine antagonist is hopeful. Brexpiprazole and cariprazine, which were agents listed as 'investigational dopamine antagonists,' just received FDA approval. Novel agents such as BL 1020, ITI-007, and JNJ-37822681 have solid published data available, and agents such as L-THP, Lu AF35700, S33138, and SB-773812 are under vigorous investigation. However, the expected benefits of the newly developed antagonists may not be great because they offer little enhanced efficacy for negative symptoms, cognition and functional outcomes.

01 Apr 2011·Journal of Nuclear Medicine

Contribution of SPECT Measurements of D₂and 5-HT_2AOccupancy to the Clinical Development of the Antipsychotic SB-773812

Article

Author: Bullich, Santiago ; Burgess, Clare ; Nucci, Gianluca ; Gray, Frank ; Merlo-Pich, Emilio ; Catafau, Ana M.

The aim of this study was to assess human striatal dopamine receptor 2 (D(2)) and cortical 5-hydroxytryptamine receptor 2A (5-HT(2A)) occupancy of SB-773812 to demonstrate brain penetration and binding to the target receptors and assess the pharmacokinetics-receptor occupancy relationship over time to aid dose selection and dosage regimen, in preparation for the phase II trials.METHODSD(2) and 5-HT(2A) occupancy were measured over time (both at the time of maximum [T(max); 6 ± 2 h] and at the time of minimum [T(trough); 24 ± 4 h] plasma concentration after dosing) by means of (123)I-iodobenzamide and (123)I-4-amino-N-[1-[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl]5-iodo-2-methoxybenzamide ((123)I-R91150) SPECT in 3 studies. Study A consisted of SB-773812 single doses in healthy volunteers-D(2) occupancy measured at 48 (n = 9) and 56 mg (n = 9) and 5-HT(2A) occupancy at 56 mg (n = 9); study B consisted of D(2) and 5-HT(2A) occupancy measured in 12 stabilized-schizophrenia patients on stable doses (16-18 d of 56 mg/d) after washout of previous medication; and study C included D(2) occupancy measured in a double-blind study of patients with acutely exacerbated schizophrenia (n = 10) on stable doses (18-21 d) of SB-773812 (100 mg/d; n = 7) or risperidone (6 mg/d; n = 3).RESULTSStudy A showed less than 30% D(2) occupancy at T(max), maintained at T(trough). 5-HT(2A) occupancy was 74%-97% and also maintained over time. Study B revealed that 8 of the 12 schizophrenia patients showed more than 40% D(2) occupancy. 5-HT(2A) occupancy ranged from 91% to 100%. In study C, SB-773812-induced D(2) occupancy was 60.3% ± 13.3% at T(max) and 55.1% ± 4.9% at T(trough). The pharmacokinetics-receptor occupancy relationship was assessed in each study and strengthened, combining all data to yield a concentration associated with 50% occupancy (EC(50)) of 92.7 ± 13.5 ng/mL for D(2) and 2.11 ± 0.50 ng/mL for 5-HT(2A).CONCLUSIONIn all subjects, SB-773812 showed penetration into the brain, reaching its target receptors. In patients with schizophrenia, D(2) occupancy levels induced by a single dose were maintained over time, indicating that once-daily dosing regimens are appropriate. Pharmacokinetics-receptor occupancy analysis provided guidance for the selection of a clinically effective dose, supporting progression in phase II.

100 Deals associated with SB-773812

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External Link

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Schizophrenia	Phase 2	Russia	GSK Plc	01 Sep 2005
Schizophrenia	Phase 2	Czechia	GSK Plc	01 Sep 2005
Schizophrenia	Phase 2	India	GSK Plc	01 Sep 2005
Schizophrenia	Phase 2	Peru	GSK Plc	01 Sep 2005
Schizophrenia	Phase 2	Costa Rica	GSK Plc	01 Sep 2005
Schizophrenia	Phase 2	Belgium	GSK Plc	01 Sep 2005
Schizophrenia	Phase 2	United States	GSK Plc	01 Sep 2005