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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Tranzyme, Inc.
ClinicalTrials.gov Identifier:
NCT00612014
First received: January 28, 2008
Last updated: December 5, 2012
Last verified: December 2012
  Purpose

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


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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Tranzyme, Inc.:

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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Cumulative GSA score after each dosing event and after all dosing events [ Time Frame: every 30 minutes for 4 hours ] [ Designated as safety issue: No ]

Enrollment: 78
Study Start Date: October 2007
Study Completion Date: March 2009
Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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


Detailed Description:

Subjects are randomized according to an adaptive randomization procedure.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00612014

Locations
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
Denmark
Aarhus University Hospital
Aarhus, Denmark
India
Amrita Institute of Medical Sciences Research Center (AIMS)
Cochin, Kerala, India, 682026
Norway
Haukeland University Hospital
Bergen, Norway
Sweden
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.
  More Information

No publications provided

Responsible Party: Tranzyme, Inc.
ClinicalTrials.gov Identifier: NCT00612014     History of Changes
Other Study ID Numbers: TZP-101-CL-G004, 2007-003279-38
Study First Received: January 28, 2008
Last Updated: December 5, 2012
Health Authority: United States: Food and Drug Administration
Denmark: Danish Medicines Agency
Sweden: Medical Products Agency
Norway: Norwegian Medicines Agency

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

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

ClinicalTrials.gov processed this record on September 29, 2014