Trimebutine 3-thiocarbamoylbenzenesulfonate(Trimebutine 3-thiocarbamoylbenzenesulfonate)

概要

基本信息

药物类型

小分子化药

别名

GIC-1001、TB-905-02

靶点

Opioid receptors

作用机制

Opioid receptors激动剂(阿片样受体激动剂)

治疗领域

肿瘤神经系统疾病消化系统疾病

在研适应症-

非在研适应症

镇痛结肠疾病肠易激综合征+ [3]

原研机构

Gicare Pharma, Inc.

在研机构-

非在研机构

Gicare Pharma, Inc.

Algorithme Pharma, Inc.

最高研发阶段无进展临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构

分子式C29H36N2O8S2

InChIKeyACKBGPXURGPUEW-UHFFFAOYSA-N

CAS号1456509-46-8

关联

3

项与 Trimebutine 3-thiocarbamoylbenzenesulfonate 相关的临床试验

NCT02276768 / Completed临床1期

A Phase 1b Clinical Study on the Analgesic Effect of GIC-1001 and GIC-1002 on Visceral Pain Under Rectal Distension and Rectal Sensory Threshold Using the Barostat Method in Male and Female Healthy Volunteers.

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.

开始日期2014-10-01

申办/合作机构

Gicare Pharma, Inc.

[+1]

NCT01926444 / Completed临床2期

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).

开始日期2013-07-01

申办/合作机构

Gicare Pharma, Inc.

[+2]

NCT01738425 / Completed临床1期

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.

开始日期2012-11-01

申办/合作机构

Gicare Pharma, Inc.

100 项与 Trimebutine 3-thiocarbamoylbenzenesulfonate 相关的临床结果

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100 项与 Trimebutine 3-thiocarbamoylbenzenesulfonate 相关的转化医学

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100 项与 Trimebutine 3-thiocarbamoylbenzenesulfonate 相关的专利（医药）

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2

项与 Trimebutine 3-thiocarbamoylbenzenesulfonate 相关的文献（医药）

2015-05-01·Bioanalysis4区 · 医学

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

4区 · 医学

Article

作者: 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.

2014-11-01·Clinical therapeutics4区 · 医学

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

4区 · 医学

Article

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

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 项与 Trimebutine 3-thiocarbamoylbenzenesulfonate 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
结肠疾病	临床2期	美国	Gicare Pharma, Inc.	2013-07-01
结肠疾病	临床2期	加拿大	Gicare Pharma, Inc.	2013-07-01
肿瘤	临床2期	美国	Gicare Pharma, Inc.	2013-07-01
肿瘤	临床2期	加拿大	Gicare Pharma, Inc.	2013-07-01
内脏疼痛	临床2期	美国	Gicare Pharma, Inc.	2013-07-01
内脏疼痛	临床2期	加拿大	Gicare Pharma, Inc.	2013-07-01
操作性疼痛	临床2期	美国	Gicare Pharma, Inc.	-
操作性疼痛	临床2期	加拿大	Gicare Pharma, Inc.	-
镇痛	临床1期	加拿大	Algorithme Pharma, Inc.	2014-10-01
镇痛	临床1期	加拿大	Gicare Pharma, Inc.	2014-10-01

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT01926444 (CTgov)	临床2期	结肠疾病 \| 肿瘤 \| 内脏疼痛	308	GIC-1001 (GIC-1001 Low Dose)	壓膚築積範鑰憲獵膚構(網築選廠襯衊製醖簾鹽) = 築築鏇鏇齋鬱蓋構襯鑰觸繭鹹壓遞願壓醖鏇顧 (鑰築壓鑰鏇糧範網網鑰, 選壓獵壓遞憲醖獵積選 ~ 廠鏇積遞廠築衊艱積糧) 更多	-	2019-05-08
				GIC-1001 (GIC-1001 Mid-dose)	壓膚築積範鑰憲獵膚構(網築選廠襯衊製醖簾鹽) = 選選鑰壓範夢廠鏇製觸觸繭鹹壓遞願壓醖鏇顧 (鑰築壓鑰鏇糧範網網鑰, 齋繭夢廠鹽繭淵齋簾壓 ~ 醖艱築夢醖淵鏇憲鏇網) 更多