Safety and Efficacy of IV Infusion of Investigational Agent (TZP-101) in Patients With Severe Diabetic Gastroparesis

Diabetes Mellitus Clinical Trial

Official title:

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Dose-ranging Study to Assess the Efficacy and Safety of TZP-101 When Administered as a 30 Minute I.V. Infusion to Subjects With Severe Gastroparesis Due to Diabetes Mellitus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00612014
• Other study ID #: TZP-101-CL-G004
• Secondary ID: 2007-003279-38
• Status: Completed
• Phase: Phase 2
• First received: January 28, 2008
• Last updated: December 5, 2012
• Start date: October 2007
• Est. completion date: March 2009

Study information

• Verified date: December 2012
• Source: Tranzyme, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationDenmark: Danish Medicines AgencySweden: Medical Products AgencyNorway: Norwegian Medicines Agency
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether TZP-101 is effective in the treatment of symptomatic gastroparesis due to diabetes.

Description:

Subjects are randomized according to an adaptive randomization procedure.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 78
• Est. completion date: March 2009
• Est. primary completion date: February 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Subject has type 1 or type 2 diabetes mellitus

• Subject has documented diagnosis of gastroparesis (all of the following apply):

• Confirmed delayed gastric emptying (see Appendix IV; properly conducted gastric emptying assessments within last 6 months acceptable)

• AND a minimum 3 month history of relevant symptoms for gastroparesis (chronic postprandial fullness, bloating, epigastric discomfort, early satiety, belching after meal, postprandial nausea, vomiting).

• AND a mean Gastroparesis Cardinal Symptom Index (GCSI) Score (2 week recall version) of = 2.66

• AND it is confirmed by endoscope that there are no obstructive lesions in the esophagus or stomach (endoscopy within prior 3 months acceptable)

• Subject has never had a gastrectomy, nor major abdominal surgery or any evidence of bowel obstruction within the previous 12 months

• Dosage of any concomitant medications has been stable for at least 3 weeks

• HbA1c level is = 10.0%

• Subject has a BMI < 30

• Subject body weight is = 100 kg

• If female, post-menopausal for the past 12 months, surgically sterile (i.e. tubal ligation, hysterectomy), or using an adequate method of birth control (i.e., oral contraceptives, double barrier method, IUD cover) or sterilized partner

Exclusion Criteria:

• Subject has acute severe gastroenteritis

• Subject has a gastric pacemaker

• Subject is on chronic parenteral feeding

• Subject has daily persistent severe vomiting

• Subject has pronounced dehydration

• Subject has had diabetic ketoacidosis in last 4 weeks

• Subject has a history of eating disorders (anorexia nervosa, binge eating, bulimia)

• Subject has a marked baseline prolongation of QT/QTc interval (repeated demonstration of a QTc interval >450 ms for male / >470 ms for female)

• Subject has a history of additional risk factors for Torsades de Pointes (heart failure, chronic hypokalemia, family history of Long QT Syndrome)

• Subject requires use of concomitant medication that prolongs the QT interval

• List provided to clinical sites

• Subject has history of cardiovascular ischemia in previous 12 months or acute myocardial infarction (MI) or unstable angina

• 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

• List provided to clinical sites

• Subject has a history of psychiatric disorder or cognitive impairment that would interfere with participation in the study

• Subject has a history of alcoholism

• Subject is taking regular daily narcotics

• Subject has a known history of Hep B, Hep C or HIV

• Subject has severely impaired renal function (creatinine clearance < 30 mL/min)

• 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)

• Subject has participated in an investigational study within 30 days prior to or received TZP-101 within 90 days prior to study initiation

• Subject is pregnant or is breast-feeding

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Gastroparesis

Intervention

Drug:
• 5% dextrose in water
60 ml IV infusion over 30 minutes
• TZP-101
40 micrograms/kg iv 2ml/minute for 30 minutes 1 infusion/day for 4 consecutive days
• TZP-101
80 micrograms/kg iv 2ml/minute for 30 minutes 1 infusion/day for 4 consecutive days
• TZP-101
160 micrograms/kg iv 2ml/minute for 30 minutes 1 infusion/day for 4 consecutive days
• TZP-101
320 micrograms/kg iv 2ml/minute for 30 minutes 1 infusion/day for 4 consecutive days
• TZP-101
600 micrograms/kg iv 2ml/minute for 30 minutes 1 infusion/day for 4 consecutive days

Locations

Country	Name	City	State
Denmark	Aarhus University Hospital	Aarhus
India	Amrita Institute of Medical Sciences Research Center (AIMS)	Cochin	Kerala
Norway	Haukeland University Hospital	Bergen
Sweden	Karolinska University Hospital	Stockholm
United Kingdom	Manchester Royal Infirmary	Manchester
United Kingdom	Royal Hallamshire Hospital	Sheffield
United States	Central Indiana Gastroenterology Group	Anderson	Indiana
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Kansas University Medical Center	Kansas City	Kansas
United States	University of Louisville	Louisville	Kentucky
United States	California Pacific Medical Center	San Francisco	California
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Tranzyme, Inc.

Countries where clinical trial is conducted

United States,  Denmark,  India,  Norway,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		after 4 dosing days	No
Secondary	Cumulative GSA score after each dosing event and after all dosing events		every 30 minutes for 4 hours	No