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

Sponsor

Tranzyme, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT00612014

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

6.5

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Gastroparesis Diabetes Mellitus	Drug: 5% dextrose in water Drug: TZP-101 Drug: TZP-101 Drug: TZP-101 Drug: TZP-101 Drug: TZP-101	Phase 2

Detailed Description

Subjects are randomized according to an adaptive randomization procedure.

Study Design

Study Type:

Interventional

Actual Enrollment :

78 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

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

Study Start Date :

Oct 1, 2007

Actual Primary Completion Date :

Feb 1, 2009

Actual Study Completion Date :

Mar 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: 1	Drug: 5% dextrose in water 60 ml IV infusion over 30 minutes Other Names: D5W
Experimental: 2 40 micrograms/kg	Drug: TZP-101 40 micrograms/kg iv 2ml/minute for 30 minutes 1 infusion/day for 4 consecutive days
Experimental: 3 80 micrograms/kg	Drug: TZP-101 80 micrograms/kg iv 2ml/minute for 30 minutes 1 infusion/day for 4 consecutive days
Experimental: 4 160 micrograms/kg	Drug: TZP-101 160 micrograms/kg iv 2ml/minute for 30 minutes 1 infusion/day for 4 consecutive days
Experimental: 5 320 microgram/kg	Drug: TZP-101 320 micrograms/kg iv 2ml/minute for 30 minutes 1 infusion/day for 4 consecutive days
Experimental: 6 600 microgram/kg	Drug: TZP-101 600 micrograms/kg iv 2ml/minute for 30 minutes 1 infusion/day for 4 consecutive days

Outcome Measures

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. [after 4 dosing days]

Secondary Outcome Measures

Cumulative GSA score after each dosing event and after all dosing events [every 30 minutes for 4 hours]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	California Pacific Medical Center	San Francisco	California	United States	94115
2	Central Indiana Gastroenterology Group	Anderson	Indiana	United States	46016-4346
3	Kansas University Medical Center	Kansas City	Kansas	United States	66160
4	University of Louisville	Louisville	Kentucky	United States	40202
5	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
6	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
7	Aarhus University Hospital	Aarhus		Denmark
8	Amrita Institute of Medical Sciences Research Center (AIMS)	Cochin	Kerala	India	682026
9	Haukeland University Hospital	Bergen		Norway
10	Karolinska University Hospital	Stockholm		Sweden
11	Manchester Royal Infirmary	Manchester		United Kingdom	M139WL
12	Royal Hallamshire Hospital	Sheffield		United Kingdom	S102JF