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

Primary Purpose

Gastroparesis, Diabetes Mellitus

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
5% dextrose in water
TZP-101
TZP-101
TZP-101
TZP-101
TZP-101
Sponsored by
Tranzyme, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gastroparesis focused on measuring delayed gastric emptying, symptomatic gastroparesis, diabetes mellitus

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • California Pacific Medical Center
  • Central Indiana Gastroenterology Group
  • Kansas University Medical Center
  • University of Louisville
  • Massachusetts General Hospital
  • Wake Forest University Health Sciences
  • Aarhus University Hospital
  • Amrita Institute of Medical Sciences Research Center (AIMS)
  • Haukeland University Hospital
  • Karolinska University Hospital
  • Manchester Royal Infirmary
  • Royal Hallamshire Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Placebo Comparator

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

1

2

3

4

5

6

Arm Description

40 micrograms/kg

80 micrograms/kg

160 micrograms/kg

320 microgram/kg

600 microgram/kg

Outcomes

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.

Secondary Outcome Measures

Cumulative GSA score after each dosing event and after all dosing events

Full Information

First Posted
January 28, 2008
Last Updated
December 5, 2012
Sponsor
Tranzyme, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT00612014
Brief Title
Safety and Efficacy of IV Infusion of Investigational Agent (TZP-101) in Patients With Severe Diabetic Gastroparesis
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 Type
Interventional

2. Study Status

Record Verification Date
December 2012
Overall Recruitment Status
Completed
Study Start Date
October 2007 (undefined)
Primary Completion Date
February 2009 (Actual)
Study Completion Date
March 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Tranzyme, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. 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.
Detailed Description
Subjects are randomized according to an adaptive randomization procedure.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gastroparesis, Diabetes Mellitus
Keywords
delayed gastric emptying, symptomatic gastroparesis, diabetes mellitus

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
78 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Placebo Comparator
Arm Title
2
Arm Type
Experimental
Arm Description
40 micrograms/kg
Arm Title
3
Arm Type
Experimental
Arm Description
80 micrograms/kg
Arm Title
4
Arm Type
Experimental
Arm Description
160 micrograms/kg
Arm Title
5
Arm Type
Experimental
Arm Description
320 microgram/kg
Arm Title
6
Arm Type
Experimental
Arm Description
600 microgram/kg
Intervention Type
Drug
Intervention Name(s)
5% dextrose in water
Other Intervention Name(s)
D5W
Intervention Description
60 ml IV infusion over 30 minutes
Intervention Type
Drug
Intervention Name(s)
TZP-101
Intervention Description
40 micrograms/kg iv 2ml/minute for 30 minutes 1 infusion/day for 4 consecutive days
Intervention Type
Drug
Intervention Name(s)
TZP-101
Intervention Description
80 micrograms/kg iv 2ml/minute for 30 minutes 1 infusion/day for 4 consecutive days
Intervention Type
Drug
Intervention Name(s)
TZP-101
Intervention Description
160 micrograms/kg iv 2ml/minute for 30 minutes 1 infusion/day for 4 consecutive days
Intervention Type
Drug
Intervention Name(s)
TZP-101
Intervention Description
320 micrograms/kg iv 2ml/minute for 30 minutes 1 infusion/day for 4 consecutive days
Intervention Type
Drug
Intervention Name(s)
TZP-101
Intervention Description
600 micrograms/kg iv 2ml/minute for 30 minutes 1 infusion/day for 4 consecutive days
Primary Outcome Measure Information:
Title
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 Measure Information:
Title
Cumulative GSA score after each dosing event and after all dosing events
Time Frame
every 30 minutes for 4 hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
California Pacific Medical Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
Central Indiana Gastroenterology Group
City
Anderson
State/Province
Indiana
ZIP/Postal Code
46016-4346
Country
United States
Facility Name
Kansas University Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
University of Louisville
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Wake Forest University Health Sciences
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Facility Name
Aarhus University Hospital
City
Aarhus
Country
Denmark
Facility Name
Amrita Institute of Medical Sciences Research Center (AIMS)
City
Cochin
State/Province
Kerala
ZIP/Postal Code
682026
Country
India
Facility Name
Haukeland University Hospital
City
Bergen
Country
Norway
Facility Name
Karolinska University Hospital
City
Stockholm
Country
Sweden
Facility Name
Manchester Royal Infirmary
City
Manchester
ZIP/Postal Code
M139WL
Country
United Kingdom
Facility Name
Royal Hallamshire Hospital
City
Sheffield
ZIP/Postal Code
S102JF
Country
United Kingdom

12. IPD Sharing Statement

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

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