Health Condition 1: null- Severe gastroparesis due to Diabetes Mellitus
Conditions
Interventions
Intervention1: TZP-101: 40/80/160/320/600 micrograms/kg iv 2ml/minute for 30 minutes
1 infusion/day for 4 consecutive days
Control Intervention1: Placebo - 5% dextrose in water: 60 ml IV infusion ov
Sponsors
Tranzyme Inc
Eligibility
Inclusion criteria
Inclusion criteria: Subjects who meet all of the following inclusion criteria may be enrolled in the study: 1. Subject (male or female) is 18-80 years old 2. Subject has type 1 or type 2 diabetes mellitus 3. Subject has documented diagnosis of gastroparesis (all of the following apply): a) Confirmed delayed gastric emptying (see Appendix IV; also, properly conducted gastric emptying assessment within prior 6 months acceptable) b) AND a minimum 3 month history of relevant symptoms for gastroparesis (chronic post-prandial fullness, bloating, epigastric discomfort, early satiety, belching after meal, post-prandial nausea, vomiting). c) AND a Gastroparesis Cardinal Symptom Index (GCSI) total score of ≥ 2.66 and a post-prandial fullness/early satiety subscale score of ≥ 3.00 d) AND it is confirmed by endoscopy that there are no obstructive lesions in the esophagus or stomach (endoscopy within 3 prior months acceptable) 4. Subject has never had a gastrectomy, nor major abdominal surgery or any evidence of bowel obstruction within previous 12 months 5. Dosage of any concomitant medications has been stable for at least 3 weeks 6. HbA1c level is ≤ 12.5% 7. Subject has a BMI 8. Subject body weight is ≤ 110 kg 9. Subject uses adequate contraception
Exclusion criteria
Exclusion criteria: Subjects who meet none of the following exclusion criteria may be enrolled in the study: 1. Subject has acute severe gastroenteritis 2. Subject has a gastric pacemaker 3. Subject is on chronic parenteral feeding 4. Subject has daily persistent severe vomiting 5. Subject has pronounced dehydration 6. Subject has had diabetic ketoacidosis in last 4 weeks 7. Subject has a history of eating disorders (anorexia nervosa, binge eating, bulimia) 8. Subject has a marked baseline prolongation of QT/QTc interval (repeated demonstration of a QTc interval >450 ms for male / >470 ms for female) 9. Subject has a history of additional risk factors for Torsades de Pointes (heart failure, chronic hypokalemia, family history of Long QT Syndrome) 10. Subject requires use of concomitant medication that prolongs the QT interval 11. Subject has history of cardiovascular ischemia in previous 12 months or acute myocardial infarction (MI) or unstable angina 12. 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 13. Subject has a history of psychiatric disorder or cognitive impairment that would interfere with participation in the study 14. Subject has a history of alcoholism 15. Subject is taking regular daily narcotics 16. Subject has a known history of Hep B, Hep C or HIV 17. Subject has severely impaired renal function (creatinine clearance 18. 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) 19. Subject has participated in an investigational study within 30 days prior to or received TZP-101 within 90 days prior to study initiation 20. Subject is pregnant or is breast-feeding
Design outcomes
Primary
| 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.Timepoint: Time Frame: after 4 dosing days | — |
Secondary
| Measure | Time frame |
|---|---|
| Change from baseline gastric emptying rateTimepoint: Time Frame: After 4 dosing days;Change from baseline in mean GCSI total scoreTimepoint: Time Frame: after 4 dosing days;Change from baseline in the mean of any of the four GCSI post-prandial fullness/early satiety subscale score items (stomach fullness, not able to finish a normal-sized meal,feeling excessively full after meals, loss of appetite) across the four days of dosingTimepoint: Each of the 4 dosing days;Cumulative Gastroparesis Symptoms Assessment (GSA) score after each dosing event and after all dosing eventsTimepoint: Time Frame: every 30 minutes for 4 hours | — |
Countries
Denmark, India, Norway, Sweden, United Kingdom, United States of America
Contacts
Public ContactCapt A Venkat Rao Retd
QED Pharmaceutical Services, Pvt. Ltd., Hyderabad
Outcome results
None listed