Delving into the Latest Updates on TZP-102 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

TZP 102

Target

GHSR

Mechanism

GHSR agonists(Ghrelin/growth hormone secretagogue receptor agonists)

Therapeutic Areas

Nervous System DiseasesEndocrinology and Metabolic DiseaseImmune System Diseases+ [2]

Active Indication-

Inactive Indication

Diabetes MellitusDiabetes Mellitus, Type 1Diabetes Mellitus, Type 2+ [2]

Originator Organization

OCERA Therapeutics LLC

Active Organization-

Inactive Organization

Tranzyme

OCERA Therapeutics LLC

Drug Highest PhaseDiscontinuedPhase 2/3

First Approval Date-

Regulation-

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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.

Start Date01 Aug 2012

Sponsor / Collaborator

Tranzyme

EUCTR2011-002594-33-BE

/ Not yet recruitingPhase 2

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

Start Date30 Jan 2012

Sponsor / Collaborator

Tranzyme

100 Clinical Results associated with TZP-102

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100 Translational Medicine associated with TZP-102

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100 Patents (Medical) associated with TZP-102

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7

Literatures (Medical) associated with TZP-102

01 Feb 2015·Current gastroenterology reports

Therapeutic Applications of Ghrelin Agonists in the Treatment of Gastroparesis

Review

Author: 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.

01 Nov 2013·Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility SocietyQ3 · MEDICINE

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

Q3 · MEDICINE

Article

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

Abstract:

Background:

TZP‐102, a potent, oral, ghrelin receptor agonist, improved diabetic gastroparesis symptoms in Phase 2a.

Methods:

Patients 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 Results:

Study 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 & Inferences:

Efficacy 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).

01 Jun 2013·Expert opinion on pharmacotherapyQ3 · MEDICINE

Pathophysiology and pharmacotherapy of gastroparesis: current and future perspectives

Q3 · MEDICINE

Review

Author: Karen L Jones ; Julie E Stevens ; Michael Horowitz ; Christopher K Rayner

INTRODUCTION:

Gastroparesis is an important clinical disorder characterised by delayed gastric emptying in the absence of mechanical outlet obstruction. Idiopathic, diabetes and postsurgical causes represent the most common aetiologies. The condition commonly manifests as upper gastrointestinal symptoms, including nausea, vomiting, postprandial fullness, early satiety, abdominal pain and bloating.

AREAS COVERED:

This paper provides a review of the prevalence, pathophysiology and clinical features associated with gastroparesis, with a particular focus on current pharmacological management options and novel and emerging therapies. A literature search was undertaken using the search terms: gastroparesis, diabetic gastroparesis, idiopathic gastroparesis, gastric emptying, prokinetic, metoclopramide, domperidone, erythromycin, motilin, alemcinal, KC11458, mitemcinal, ghrelin, TZP-101, TZP-102, RM-131, tegaserod, prucalopride, naronapride, velusetrag, levosulpiride, itopride, botulinum toxin, gastric electrical stimulation, Enterra.

EXPERT OPINION:

Strategies for the management of gastroparesis include correction of malnutrition, dehydration and electrolyte imbalance, relief of symptoms by appropriate use of prokinetic and antiemetic agents and, in patients with gastroparesis associated with diabetes or critical illness-induced hyperglycaemia, optimisation of glycaemic control. Conventional prokinetic agents form the mainstay of treatment. While novel pharmacotherapies are in development, compelling evidence for their efficacy, particularly in symptom relief, remains to be established.

100 Deals associated with TZP-102

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External Link

KEGG	Wiki	ATC	Drug Bank
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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Diabetic Gastroparesis	Phase 3	US	OCERA Therapeutics LLC	-
Diabetic Gastroparesis	Phase 3	BE	OCERA Therapeutics LLC	-
Diabetic Gastroparesis	Phase 3	DK	OCERA Therapeutics LLC	-
Diabetic Gastroparesis	Phase 3	FI	OCERA Therapeutics LLC	-
Diabetic Gastroparesis	Phase 3	DE	OCERA Therapeutics LLC	-
Diabetic Gastroparesis	Phase 3	NO	OCERA Therapeutics LLC	-
Diabetic Gastroparesis	Phase 3	PL	OCERA Therapeutics LLC	-
Diabetic Gastroparesis	Phase 3	SE	OCERA Therapeutics LLC	-
Diabetes Mellitus, Type 1	Phase 2	US	Tranzyme	01 Sep 2011
Diabetes Mellitus, Type 1	Phase 2	BE	Tranzyme	01 Sep 2011