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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00612014
Recruitment Status : Completed
First Posted : February 11, 2008
Last Update Posted : December 7, 2012
Information provided by (Responsible Party):
Tranzyme, Inc.

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 Phase 2

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

Study Type : Interventional  (Clinical Trial)
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 : October 2007
Actual Primary Completion Date : February 2009
Actual Study Completion Date : March 2009

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Placebo Comparator: 1 Drug: 5% dextrose in water
60 ml IV infusion over 30 minutes
Other Name: 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

Primary Outcome Measures :
  1. 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 :
  1. Cumulative GSA score after each dosing event and after all dosing events [ Time Frame: every 30 minutes for 4 hours ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00612014

United States, California
California Pacific Medical Center
San Francisco, California, United States, 94115
United States, Indiana
Central Indiana Gastroenterology Group
Anderson, Indiana, United States, 46016-4346
United States, Kansas
Kansas University Medical Center
Kansas City, Kansas, United States, 66160
United States, Kentucky
University of Louisville
Louisville, Kentucky, United States, 40202
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, North Carolina
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States, 27157
Aarhus University Hospital
Aarhus, Denmark
Amrita Institute of Medical Sciences Research Center (AIMS)
Cochin, Kerala, India, 682026
Haukeland University Hospital
Bergen, Norway
Karolinska University Hospital
Stockholm, Sweden
United Kingdom
Manchester Royal Infirmary
Manchester, United Kingdom, M139WL
Royal Hallamshire Hospital
Sheffield, United Kingdom, S102JF
Sponsors and Collaborators
Tranzyme, Inc.

Responsible Party: Tranzyme, Inc. Identifier: NCT00612014     History of Changes
Other Study ID Numbers: TZP-101-CL-G004
First Posted: February 11, 2008    Key Record Dates
Last Update Posted: December 7, 2012
Last Verified: December 2012

Keywords provided by Tranzyme, Inc.:
delayed gastric emptying
symptomatic gastroparesis
diabetes mellitus

Additional relevant MeSH terms:
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Stomach Diseases
Gastrointestinal Diseases
Digestive System Diseases
Neurologic Manifestations
Signs and Symptoms