TZP-102(TZP-102) - 药物靶点：GHSR_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

GHSR

作用机制

GHSR激动剂(促生长激素释放激素受体激动剂)

治疗领域

神经系统疾病内分泌与代谢疾病免疫系统疾病+ [1]

在研适应症-

非在研适应症

糖尿病1型糖尿病2型糖尿病+ [2]

原研机构

OCERA Therapeutics LLC

在研机构-

非在研机构

Tranzyme

OCERA Therapeutics LLC

最高研发阶段终止临床2/3期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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关联

9

项与 TZP-102 相关的临床试验

EUCTR2012-002576-14-PL / Not yet recruitingN/A

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Evaluation of the Efficacy and Safety of TZP-102 Given Orally Three Times a Day for the Treatment of Symptoms Associated with Diabetic Gastroparesis

开始日期2012-08-23

申办/合作机构

Tranzyme

NCT01664637 / Terminated临床2期

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Evaluation of the Efficacy and Safety of TZP-102 Given Orally Three Times a Day for the Treatment of Symptoms Associated With Diabetic Gastroparesis

The purpose of this study is to test the safety and effectiveness of 10 mg TZP-102 given prior to meals three times a day compared to placebo (capsule that looks like active study drug but contains no active drug), administered for 12 weeks, in diabetic subjects with symptoms associated with gastroparesis.

开始日期2012-08-01

申办/合作机构

Tranzyme

EUCTR2011-002594-33-BE / Not yet recruiting临床2期

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Evaluation of the Efficacy and Safety of Once-Daily Administrations of TZP 102 for the Treatment of Symptoms Associated with Diabetic Gastroparesis

开始日期2012-01-30

申办/合作机构

Tranzyme

100 项与 TZP-102 相关的临床结果

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100 项与 TZP-102 相关的转化医学

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100 项与 TZP-102 相关的专利（医药）

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8

项与 TZP-102 相关的文献（医药）

2015-04-01·European Journal of Pharmacology3区 · 医学

Analysis of the ghrelin receptor-independent vascular actions of ulimorelin

3区 · 医学

Article

作者: Furness, John B ; Broad, John ; Brock, James A ; Callaghan, Brid ; Sanger, Gareth J

Ulimorelin (TZP101) is a ghrelin receptor agonist that stimulates intestinal motility, but also reduces blood pressure in rodents and humans and dilates blood vessels. It has been proposed as a treatment for intestinal motility disorders. Here we investigated the mechanisms through which ulimorelin affects vascular diameter. Actions of ulimorelin on wall tension of rodent arteries were investigated and compared with other ghrelin receptor agonists. Saphenous, mesenteric and basilar arteries were obtained from Sprague-Dawley rats (male, 8 weeks) and saphenous arteries were obtained from wild type or ghrelin receptor null mice. These were mounted in myography chambers to record artery wall tension. Ulimorelin (0.03-30µM) inhibited phenylephrine-induced contractions of rat saphenous (IC50=0.6µM; Imax=66±5%; n=3-6) and mesenteric arteries (IC50=5µM, Imax=113±16%; n=3-4), but not those contracted by U46619, ET-1 or 60mM [K(+)]. Relaxation of phenylephrine-constricted arteries was not observed with ghrelin receptor agonists TZP102, capromorelin or AZP-531. In rat saphenous and basilar arteries, ulimorelin (10-100µM) and TZP102 (10-100µM) constricted arteries (EC50=9.9µM; Emax=50±7% and EC50=8µM; Emax=99±16% respectively), an effect not attenuated by the ghrelin receptor antagonist YIL 781 3µM or mimicked by capromorelin or AZP-531. In mesenteric arteries, ulimorelin, 1-10µM, caused a surmountable rightward shift in the response to phenylephrine (0.01-1000µM; pA2=5.7; n=3-4). Ulimorelin had similar actions in mouse saphenous artery from both wild type and ghrelin receptor null mice. We conclude that ulimorelin causes vasorelaxation through competitive antagonist action at α1-adrenoceptors and a constrictor action not mediated via the ghrelin receptor.

2015-02-01·Current Gastroenterology Reports

Therapeutic Applications of Ghrelin Agonists in the Treatment of Gastroparesis

Review

作者: Andrea Shin ; John M. Wo

There remains an unmet need for effective pharmacologic treatments for gastroparesis. Ghrelin is the endogenous ligand for the growth hormone secretagogue receptor and has been shown to regulate energy homeostasis and exert prokinetic effects on gastrointestinal motility. In recent years, several ghrelin receptor agonists have been studied in clinical trials of patients with diabetic gastroparesis. The intravenous macrocyclic peptidomimetic, TZP-101, initially suggested improvement in gastroparesis symptoms with intravenous administration when compared to placebo. However, in subsequent studies of oral preparations, TZP-102 failed to confirm these results. Another ghrelin receptor agonist, RM-131, was recently shown to significantly accelerate gastric emptying (GE) in patients with type 1 and type 2 diabetes and delayed GE. RM-131 reduced total Gastroparesis Cardinal Symptom Index-Daily Diary (GCSI-DD) and composite scores among type 1 diabetics. Continued development of ghrelin agonists should be explored in attempts to expand therapeutic options for the treatment of gastroparesis.

2013-11-01·Neurogastroenterology & Motility3区 · 医学

Phase 2b, randomized, double‐blind 12‐week studies of TZP‐102, a ghrelin receptor agonist for diabetic gastroparesis

3区 · 医学

Article

作者: Ejskjaer, N. ; McCallum, R. W. ; Quinn, J. ; Cosentino, C. ; Bhandari, B. R. ; Esfandyari, T. ; Rousseau, F. ; Helton, N. ; Mondou, E. ; Lembo, A.

AbstractBackgroundTZP‐102, a potent, oral, ghrelin receptor agonist, improved diabetic gastroparesis symptoms in Phase 2a.MethodsPatients with type 1 or 2 diabetes, delayed gastric half‐emptying (T1/2), and ≥3 months gastroparesis symptoms randomized 1 : 1 : 1 to double‐blind placebo, 10‐mg, or 20‐mg TZP‐102 once daily for 12 weeks (Study TZP‐102‐CL‐G003). Study TZP‐102‐CL‐G004 patients randomized 1 : 1 to 10‐mg TZP‐102:placebo three‐times‐daily. Primary endpoint was change‐from‐baseline through Weeks 11–12 in Daily Diary of Gastroparesis Symptoms Questionnaire (GSDD) via electronic Patient Recorded Outcome device: worst severity of nausea, early satiety, bloating, and upper abdominal pain in 24 h (0 = none‐to‐5 = very severe). GSDD Composite Score for eligibility was ≥2.5 (Day‐14‐to‐baseline). Patient Overall Treatment Evaluation (OTE) provided an anchor‐based minimal clinically important difference (MCID) for GSDD Composite Score.Key ResultsStudy TZP‐102‐CL‐G003 enrolled 201 outpatients: females 72%; Caucasians 87%; type 2 diabetes 61%; insulin‐dependent 65%; age mean ± SD 53 ± 11.3 years; HbA1c 7.8 ± 1.5%; GCSI 3.4 ± 0.7; GSDD Composite 3.6 ± 0.6; gastric T1/2 131 ± 32 min; n = 69 (10‐mg), n = 66 (20‐mg), n = 66 (placebo). Primary endpoint (GSDD): significant improvement in all arms, although not for TZP‐102 vs placebo: mean change‐from‐baseline −1.7, −1.4, −1.5 (10‐mg, 20‐mg, placebo); Gastroparesis Cardinal Symptom Index −1.8, −1.6, −1.5, respectively. The OTE (all patients) at Week‐12 was: Patient 3.7 ± 3.2 and Physician 3.6 ± 3.0 with median score for both of 5.0 = important on scale of improvement; individual MCID was 1.61 and 0.94 for group analyses, greater than expected. Study TZP‐102‐CL‐G004 with similar demographic/disease characteristics was prematurely terminated for efficacy futility (n = 64 with Week‐4 assessments).Conclusions & InferencesEfficacy of TZP‐102 was not demonstrated compared with placebo in diabetic gastroparesis; however, there was substantial symptom improvement in all arms (ClinicalTrials.gov NCT01452815/NCT01664637).

100 项与 TZP-102 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB16129

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
糖尿病性胃轻瘫	临床3期	瑞典	OCERA Therapeutics LLC	-
糖尿病性胃轻瘫	临床3期	德国	OCERA Therapeutics LLC	-
糖尿病性胃轻瘫	临床3期	德国	OCERA Therapeutics LLC	-
糖尿病性胃轻瘫	临床3期	瑞典	OCERA Therapeutics LLC	-
糖尿病性胃轻瘫	临床3期	丹麦	OCERA Therapeutics LLC	-
糖尿病性胃轻瘫	临床3期	挪威	OCERA Therapeutics LLC	-
糖尿病性胃轻瘫	临床3期	挪威	OCERA Therapeutics LLC	-
糖尿病性胃轻瘫	临床3期	美国	OCERA Therapeutics LLC	-
糖尿病性胃轻瘫	临床3期	美国	OCERA Therapeutics LLC	-
糖尿病性胃轻瘫	临床3期	丹麦	OCERA Therapeutics LLC	-