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

Phase 2

Completed

• Conditions: Gastroparesis; Diabetes Mellitus
• Interventions: Drug: 5% dextrose in water; Drug: TZP-101

• Registration Number: NCT00612014
• Lead Sponsor: 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.

Detailed Description

Subjects are randomized according to an adaptive randomization procedure.

Study Timeline

• Study Start: 2007-10
• Study First Submitted: 2008-01-28
• Study First Submitted QC: 2008-02-08
• Study First Posted: 2008-02-11
• Primary Completion: 2009-02
• Study Completion: 2009-03
• Status Verified: 2012-12
• Disposition First Submitted: 2012-12-05
• Disposition First Submitted QC: 2012-12-05
• Last Update Submitted: 2012-12-05
• Disposition First Posted: 2012-12-07
• Last Update Posted: 2012-12-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 78

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	5% dextrose in water	-
2	TZP-101	40 micrograms/kg
4	TZP-101	160 micrograms/kg
3	TZP-101	80 micrograms/kg
5	TZP-101	320 microgram/kg
6	TZP-101	600 microgram/kg

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Cumulative GSA score after each dosing event and after all dosing events	every 30 minutes for 4 hours

Trial Locations

Locations (12)

Wake Forest University Health Sciences; 🇺🇸 Winston-Salem, North Carolina, United States

Kansas University Medical Center; 🇺🇸 Kansas City, Kansas, United States

University of Louisville; 🇺🇸 Louisville, Kentucky, United States

California Pacific Medical Center; 🇺🇸 San Francisco, California, United States

Manchester Royal Infirmary; 🇬🇧 Manchester, United Kingdom

Central Indiana Gastroenterology Group; 🇺🇸 Anderson, Indiana, United States

Karolinska University Hospital; 🇸🇪 Stockholm, Sweden

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Aarhus University Hospital; 🇩🇰 Aarhus, Denmark

Haukeland University Hospital; 🇳🇴 Bergen, Norway

Royal Hallamshire Hospital; 🇬🇧 Sheffield, United Kingdom

Amrita Institute of Medical Sciences Research Center (AIMS); 🇮🇳 Cochin, Kerala, India