Delving into the Latest Updates on Trimebutine 3-thiocarbamoylbenzenesulfonate with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

GIC-1001, TB-905-02

Target

Opioid receptors

Mechanism

Opioid receptors agonists(Opioid receptors agonists)

Therapeutic Areas

NeoplasmsNervous System DiseasesDigestive System Disorders

Active Indication-

Inactive Indication

AnalgesiaColonic DiseasesIrritable Bowel Syndrome+ [3]

Originator Organization

Gicare Pharma, Inc.

Active Organization-

Inactive Organization

Gicare Pharma, Inc.

Algorithme Pharma, Inc.

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC29H36N2O8S2

InChIKeyACKBGPXURGPUEW-UHFFFAOYSA-N

CAS Registry1456509-46-8

This study evaluates colonic analgesia by comparing two novel formulations, GIC-1001 and GIC-1002 with placebo using a barostat distender. The healthy male and female volunteers randomized to one of 5 possible treatments will be exposed to rectal distension following a 3-day treatment TID. The barostat methodology is a well-established and validated way to assess visceral pain. Visceral pain will be evaluated during exposure to varying distender pressures using a visual analog scale.

Start Date01 Oct 2014

Sponsor / Collaborator

Gicare Pharma, Inc.

[+1]

NCT01926444 / CompletedPhase 2

A Randomized, Double-Blind, Placebo-Controlled, Phase 2a Proof-of-Concept Study of GIC-1001 for the Management of Visceral Pain in Subjects Undergoing Sedation-Free, Full Colonoscopy

GIC-1001 is a novel, orally-administered, colonic analgesic drug developed as an alternative to i.v. sedation during full colonoscopy. It will be evaluated for efficacy and safety in a multi-center, randomized, double-blind, placebo controlled, dose-ranging, proof of concept Phase 2a trial. Up to 240 patients will receive one of 3 doses of GIC-1001 or its matching placebo. A pharmacokinetic evaluation will be carried out on a subset of patients (N: 24).

Start Date01 Jul 2013

Sponsor / Collaborator

Gicare Pharma, Inc.

[+2]

NCT01738425 / CompletedPhase 1

A Double-Blind, Placebo Controlled, Phase I Study to Assess Safety, Tolerability and Pharmacokinetics of Single and Multiple Ascending Oral Doses of GIC-1001 in Normal Healthy Volunteers

The objectives of this single center, randomized, double-blinded, placebo-controlled Phase I clinical study are to evaluate the safety and tolerability of five (5) single and four (4) multiple increasing oral doses of GIC-1001 compared to placebo, and to evaluate the pharmacokinetics of GIC-1001 following single and multiple-dose administration in 80 healthy, 18-50 years old male and female subjects. Moreover, the effect of food on the pharmacokinetics of GIC-1001 in healthy subjects will be assessed. This study is designed with an integrated, adaptive approach which allows the evaluation of single and multiples doses of GIC-1001 in a progressive, overlapped fashion.

Start Date01 Nov 2012

Sponsor / Collaborator

Gicare Pharma, Inc.

100 Clinical Results associated with Trimebutine 3-thiocarbamoylbenzenesulfonate

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100 Translational Medicine associated with Trimebutine 3-thiocarbamoylbenzenesulfonate

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100 Patents (Medical) associated with Trimebutine 3-thiocarbamoylbenzenesulfonate

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2

Literatures (Medical) associated with Trimebutine 3-thiocarbamoylbenzenesulfonate

01 May 2015·BioanalysisQ4 · MEDICINE

Discovery of A Novel Trimebutine Metabolite and its Impact on N -Desmethyltrimebutine Quantification by LC–MS/MS

Q4 · MEDICINE

Article

Author: Garofolo, Fabio ; Montpetit, Hélène ; Furtado, Milton ; Colin, Patrick ; Ranger, Maxime

Hélène Montpetit has a Bachelor of Science in Biochemistry from the University du Québec at Montreal. For the past 15 years, she has worked in the bioanalysis field in CROs environment as well as in a big Pharma. She currently holds a position as scientific reviewer in the method development group at Algorithme Pharma. Background: A failure in incurred sample reanalysis (ISR) for N-desmethyltrimebutine (NDMT), during the analysis of a trimebutine-containing drug GIC-1001 Phase I study, led to the discovery of a never-before reported metabolite of trimebutine. Results: A positive bias for NDMT during the ISR and post-reconstitution stability evaluations indicated the presence of an unstable metabolite of NDMT. Precursor ion scans performed on freshly extracted samples enabled the identification of this metabolite to be the NDMT glucuronide conjugate and its fragmentation pattern suggested that the glucuronide moiety was attached at the N-terminal of NDMT. Conclusions: An acidification step was introduced in the extraction procedure to completely hydrolyze the glucuronide and measure the total NDMT in plasma, rendering this method a successful fit-for-purpose assay.

01 Nov 2014·Clinical therapeuticsQ4 · MEDICINE

Safety, Tolerability and Pharmacokinetics of Trimebutine 3-Thiocarbamoylbenzenesulfonate (GIC-1001) in a Randomized Phase I Integrated Design Study: Single and Multiple Ascending Doses and Effect of Food in Healthy Volunteers

Q4 · MEDICINE

Article

Author: Iovu Niculita, Mirela ; Lefebvre, Marc ; Ranger, Maxime ; Massicotte, Julie ; Telmat, Ariles ; Colin, Patrick ; Paquette, Jean-Michel ; Rufiange, Marianne

PURPOSE:

Trimebutine 3-thiocarbamoylbenzenesulfonate (GIC-1001) is a new drug intended to be used for the management of visceral pain in patients undergoing sedation-free, full colonoscopy. The objectives of this Phase I, single-center, randomized, double-blinded, placebo-controlled, integrated study were to evaluate the safety and pharmacokinetics of GIC-1001 after single ascending doses (SAD) and multiple ascending doses (MAD) and to evaluate the influence of food on the pharmacokinetics in healthy volunteers.

METHODS:

GIC-1001 or placebo was orally administered to 80 healthy male and female subjects (non- or ex-smokers) aged 18 to 50 years with a body mass index between 18.5 and 30 kg/m(2). The SAD portion of the study consisted of 5 cohorts with dose levels of 125 to 1000 mg. The MAD portion included 4 cohorts in which subjects received TID doses of 125 to 500 mg over 7 days (19 consecutive doses). Subjects were randomized (6:2) to receive GIC-1001 or placebo. The third portion of the study included a single 375-mg dose of GIC-1001 in a randomized, 2-period, crossover design to assess the influence of food (n = 8 subjects). Safety was evaluated by using adverse events (AEs), vital signs, ECGs, physical examination, cardiac monitoring, and laboratory test results. The analytes were assayed by using validated HPLC-MS/MS methods. Pharmacokinetic parameters were evaluated by using a noncompartmental analysis, and regression models were used to assess dose linearity. To evaluate the effect of food, 90% CIs of the ratio of geometric least squares means from ln-transformed pharmacokinetic parameters were calculated.

FINDINGS:

The most frequently reported drug-related AEs were of nervous system and gastrointestinal origin. The most common AEs included headache, somnolence, and nausea. After single-dose administration, Tmax of trimebutine ranged from 1.0 to 1.5 hours. Cmax and AUCT were linear (nonlinearity P ≥ 0.05) and proportional (P < 0.05) over the studied dose range. Food increased the Cmax and AUC of trimebutine; the ratio of geometric least squares means (90% CI) were 140% (84-234) and 174% (138-221), respectively. In the MAD study portion, the Tmax of trimebutine ranged from 0.5 to 2 hours and AUCτ increased from 38 to 170 ng · h/mL. AUCτ and Cmax were linear and proportional over the studied dose range.

IMPLICATIONS:

GIC-1001 was well tolerated, and its safety profile was similar to that of placebo. Pharmacokinetics of GIC-1001 and its metabolites were mainly linear and proportional over the studied dose ranges. Steady state was generally considered to be reached after 3 days. Food consumption affected the pharmacokinetic profile of the analytes differently. (ClinicalTrials.gov identifier: NCT01738425.).

100 Deals associated with Trimebutine 3-thiocarbamoylbenzenesulfonate

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Colonic Diseases	Phase 2	US	Gicare Pharma, Inc.	01 Jul 2013
Colonic Diseases	Phase 2	CA	Gicare Pharma, Inc.	01 Jul 2013
Neoplasms	Phase 2	US	Gicare Pharma, Inc.	01 Jul 2013
Neoplasms	Phase 2	CA	Gicare Pharma, Inc.	01 Jul 2013
Visceral Pain	Phase 2	US	Gicare Pharma, Inc.	01 Jul 2013
Visceral Pain	Phase 2	CA	Gicare Pharma, Inc.	01 Jul 2013
Pain, Procedural	Phase 2	US	Gicare Pharma, Inc.	-
Pain, Procedural	Phase 2	CA	Gicare Pharma, Inc.	-
Analgesia	Phase 1	CA	Gicare Pharma, Inc.	01 Oct 2014
Analgesia	Phase 1	CA	Algorithme Pharma, Inc.	01 Oct 2014

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01926444 (CTgov)	Phase 2	Colonic Diseases \| Neoplasms \| Visceral Pain	308	GIC-1001 (GIC-1001 Low Dose)	ttfofltrmn(ddemfzdenp) = byvzkehvwd jqohpkoxei (nrmdocwkam, lxxtcioava - mjxwgmfjua) View more	-	08 May 2019
				GIC-1001 (GIC-1001 Mid-dose)	ttfofltrmn(ddemfzdenp) = tiilubhlgm jqohpkoxei (nrmdocwkam, mivecpeadx - uootupvnje) View more