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

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

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

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus; Gastroparesis
• Intervention / Treatment: Drug: 5% dextrose in water; Drug: TZP-101; Drug: TZP-101; Drug: TZP-101; Drug: TZP-101; Drug: TZP-101

Detailed Description

Subjects are randomized according to an adaptive randomization procedure.

• Study Type: Interventional
• Enrollment (Actual): 78
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

6

Arms and Interventions

Participant Group / 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; Drug: TZP-101; 80 micrograms/kg iv 2ml/minute for 30 minutes 1 infusion/day for 4 consecutive days; Drug: TZP-101; 160 micrograms/kg iv 2ml/minute for 30 minutes 1 infusion/day for 4 consecutive days; Drug: TZP-101; 320 micrograms/kg iv 2ml/minute for 30 minutes 1 infusion/day for 4 consecutive days; Drug: TZP-101; 600 micrograms/kg iv 2ml/minute for 30 minutes 1 infusion/day for 4 consecutive days
EXPERIMENTAL: 3; 80 micrograms/kg	Drug: TZP-101; 40 micrograms/kg iv 2ml/minute for 30 minutes 1 infusion/day for 4 consecutive days; Drug: TZP-101; 80 micrograms/kg iv 2ml/minute for 30 minutes 1 infusion/day for 4 consecutive days; Drug: TZP-101; 160 micrograms/kg iv 2ml/minute for 30 minutes 1 infusion/day for 4 consecutive days; Drug: TZP-101; 320 micrograms/kg iv 2ml/minute for 30 minutes 1 infusion/day for 4 consecutive days; Drug: TZP-101; 600 micrograms/kg iv 2ml/minute for 30 minutes 1 infusion/day for 4 consecutive days
EXPERIMENTAL: 4; 160 micrograms/kg	Drug: TZP-101; 40 micrograms/kg iv 2ml/minute for 30 minutes 1 infusion/day for 4 consecutive days; Drug: TZP-101; 80 micrograms/kg iv 2ml/minute for 30 minutes 1 infusion/day for 4 consecutive days; Drug: TZP-101; 160 micrograms/kg iv 2ml/minute for 30 minutes 1 infusion/day for 4 consecutive days; Drug: TZP-101; 320 micrograms/kg iv 2ml/minute for 30 minutes 1 infusion/day for 4 consecutive days; Drug: TZP-101; 600 micrograms/kg iv 2ml/minute for 30 minutes 1 infusion/day for 4 consecutive days
EXPERIMENTAL: 5; 320 microgram/kg	Drug: TZP-101; 40 micrograms/kg iv 2ml/minute for 30 minutes 1 infusion/day for 4 consecutive days; Drug: TZP-101; 80 micrograms/kg iv 2ml/minute for 30 minutes 1 infusion/day for 4 consecutive days; Drug: TZP-101; 160 micrograms/kg iv 2ml/minute for 30 minutes 1 infusion/day for 4 consecutive days; Drug: TZP-101; 320 micrograms/kg iv 2ml/minute for 30 minutes 1 infusion/day for 4 consecutive days; Drug: TZP-101; 600 micrograms/kg iv 2ml/minute for 30 minutes 1 infusion/day for 4 consecutive days
EXPERIMENTAL: 6; 600 microgram/kg	Drug: TZP-101; 40 micrograms/kg iv 2ml/minute for 30 minutes 1 infusion/day for 4 consecutive days; Drug: TZP-101; 80 micrograms/kg iv 2ml/minute for 30 minutes 1 infusion/day for 4 consecutive days; Drug: TZP-101; 160 micrograms/kg iv 2ml/minute for 30 minutes 1 infusion/day for 4 consecutive days; Drug: TZP-101; 320 micrograms/kg iv 2ml/minute for 30 minutes 1 infusion/day for 4 consecutive days; Drug: TZP-101; 600 micrograms/kg iv 2ml/minute for 30 minutes 1 infusion/day for 4 consecutive days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
Cumulative GSA score after each dosing event and after all dosing events	every 30 minutes for 4 hours

Collaborators and Investigators

• Sponsor: Tranzyme, Inc.

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (ACTUAL): February 1, 2009
• Study Completion (ACTUAL): March 1, 2009

Study Registration Dates

• First Submitted: January 28, 2008
• First Submitted That Met QC Criteria: February 8, 2008
• First Posted (ESTIMATE): February 11, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): December 7, 2012
• Last Update Submitted That Met QC Criteria: December 5, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Keywords: diabetes mellitus; delayed gastric emptying; symptomatic gastroparesis
• Additional Relevant MeSH Terms: Digestive System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Neurologic Manifestations; Endocrine System Diseases; Gastrointestinal Diseases; Stomach Diseases; Paralysis; Diabetes Mellitus; Gastroparesis
• Other Study ID Numbers: TZP-101-CL-G004; 2007-003279-38