A clinical study to study the effects of the drug TZP-101 in patients with severe gastroparesis (delayed gastric emptying)due to Diabetes Mellitus

Phase 2

• Conditions: Severe gastroparesis due to Diabetes Mellitus

• Registration Number: CTRI/2008/091/000254
• Lead Sponsor: Tranzyme Inc

Brief Summary

This is a multicenter, randomized, double-Blind, placebo-Controlled, parallel group, dose-Ranging study to assess the efficacy and safety of TZP-101 in subjects with severe gastroparesis due to diabetes mellitus. TZP-101 will be administered as a 40/80/160/320/600 micrograms/kg, 30 Minute I.V. Infusion once daily for 4 days. Upto 100 patients (The sample size will be determined by adaptive randomization) will be enrolled in the study that will be conducted in approximately 15 centers in US and Europe and 3 centers in India. In India, upto 30 patients will be enrolled. Recruitment in India is expected to start by end of November 2008. Primary Outcome Measures: Change from baseline in the mean Gastroparesis Cardinal Symptom Index score (24 hour recall version) across the four days of dosing. Baseline is the average of the scores collected across the 4 days just prior to admission for dosing. [ Time Frame: after 4 dosing days ] Secondary Outcome Measures: Cumulative GSA score after each dosing event and after all dosing events [ Time Frame: every 30 minutes for 4 hours on each of the 4 dosing days] Change from baseline in mean GCSI total score (Time Frame: after 4 dosing days) Change from baseline in the mean of any of the four GCSI post-prandial fullness/early satiety subscale score items (stomach fullness, not able to finish a normal-sized meal,feeling excessively full after meals, loss of appetite) across the four days of dosing Change from baseline gastric emptying rate. (Time Frame: After 4 dosing days).study terminated

Detailed Description

Not available

Study Timeline

• Study Start: 2005-10-21
• Last Update Posted: 2012-12-12

Recruitment & Eligibility

• Status: Other
• Sex: All
• Target Recruitment: 78

Inclusion Criteria

• Subjects who meet all of the following inclusion criteria may be enrolled in the study: 1.
• Subject (male or female) is 18-80 years old 2.
• Subject has type 1 or type 2 diabetes mellitus 3.
• Subject has documented diagnosis of gastroparesis (all of the following apply): a) Confirmed delayed gastric emptying (see Appendix IV; also, properly conducted gastric emptying assessment within prior 6 months acceptable) b) AND a minimum 3 month history of relevant symptoms for gastroparesis (chronic post-prandial fullness, bloating, epigastric discomfort, early satiety, belching after meal, post-prandial nausea, vomiting).
• c) AND a Gastroparesis Cardinal Symptom Index (GCSI) total score of ≥ 2.66 and a post-prandial fullness/early satiety subscale score of ≥ 3.00 d) AND it is confirmed by endoscopy that there are no obstructive lesions in the esophagus or stomach (endoscopy within 3 prior months acceptable) 4.
• Subject has never had a gastrectomy, nor major abdominal surgery or any evidence of bowel obstruction within previous 12 months 5.
• Dosage of any concomitant medications has been stable for at least 3 weeks 6.
• HbA1c level is ≤ 12.5% 7.
• Subject has a BMI < 35 8.
• Subject body weight is ≤ 110 kg 9.
• Subject uses adequate contraception.

Exclusion Criteria

• Subjects who meet none of the following exclusion criteria may be enrolled in the study: 1.
• Subject has acute severe gastroenteritis 2.
• Subject has a gastric pacemaker 3.
• Subject has daily persistent severe vomiting 5.
• Subject has pronounced dehydration 6.
• Subject has had diabetic ketoacidosis in last 4 weeks 7.
• Subject has a history of eating disorders (anorexia nervosa, binge eating, bulimia) 8.
• Subject has a marked baseline prolongation of QT/QTc interval (repeated demonstration of a QTc interval >450 ms for male / >470 ms for female) 9.
• Subject has a history of additional risk factors for Torsades de Pointes (heart failure, chronic hypokalemia, family history of Long QT Syndrome) 10.
• Subject requires use of concomitant medication that prolongs the QT interval 11.
• Subject has history of cardiovascular ischemia in previous 12 months or acute myocardial infarction (MI) or unstable angina 12.
• Subject requires use of concomitant medication that is known to interact with isoenzyme CYP3A4 and the combination with an CYP3A4 inhibitor is known to introduce a clinically significant drug interaction 13.
• Subject has a history of psychiatric disorder or cognitive impairment that would interfere with participation in the study 14.
• Subject has a history of alcoholism 15.
• Subject is taking regular daily narcotics 16.
• Subject has a known history of Hep B, Hep C or HIV 17.
• Subject has severely impaired renal function (creatinine clearance < 30 mL/min) 18.
• Subject has severe impairment of liver function, defined as albumin level ≤ 2.5 gm/dL and/or prothrombin time >6 seconds over control (INR > 2.3) 19.
• Subject has participated in an investigational study within 30 days prior to or received TZP-101 within 90 days prior to study initiation 20.
• Subject is pregnant or is breast-feeding.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Change from baseline in the mean Gastroparesis Cardinal Symptom Index score (24 hour recall version) across the four days of dosing. Baseline is the average of the scores collected across the 4 days just prior to admission for dosing.	Time Frame: after 4 dosing days

Secondary Outcome Measures

Name	Time	Method
Cumulative Gastroparesis Symptoms Assessment (GSA) score after each dosing event and after all dosing events	Time Frame: every 30 minutes for 4 hours
Change from baseline in mean GCSI total score	Time Frame: after 4 dosing days
Change from baseline in the mean of any of the four GCSI post-prandial fullness/early satiety subscale score items (stomach fullness, not able to finish a normal-sized meal,feeling excessively full after meals, loss of appetite) across the four days of dosing	Each of the 4 dosing days
Change from baseline gastric emptying rate	Time Frame: After 4 dosing days

Trial Locations

Locations (1)

Amrita Institute of Medical Sciences and Research Center; 🇮🇳 Ernakulam, KERALA, India

Amrita Institute of Medical Sciences and Research Center

🇮🇳Ernakulam, KERALA, India

DrV Balakrishnan

Principal investigator

04844001225

vbalakrishnan@aims.amrita.edu