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

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

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

Official Title
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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

Conditions
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Gastroparesis, Diabetes Mellitus

Intervention / Treatment
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* Drug: 5% dextrose in water
* Drug: TZP-101
* Drug: TZP-101
* Drug: TZP-101
* Drug: TZP-101
* Drug: TZP-101


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 1<br> | Drug: 5% dextrose in water<br>* 60 ml IV infusion over 30 minutes<br>* Other names: D5W;|
| Experimental: 2<br>40 micrograms/kg | Drug: TZP-101<br>* 40 micrograms/kg iv 2ml/minute for 30 minutes 1 infusion/day for 4 consecutive days<br>|
| Experimental: 3<br>80 micrograms/kg | Drug: TZP-101<br>* 80 micrograms/kg iv 2ml/minute for 30 minutes 1 infusion/day for 4 consecutive days<br>|
| Experimental: 4<br>160 micrograms/kg | Drug: TZP-101<br>* 160 micrograms/kg iv 2ml/minute for 30 minutes 1 infusion/day for 4 consecutive days<br>|
| Experimental: 5<br>320 microgram/kg | Drug: TZP-101<br>* 320 micrograms/kg iv 2ml/minute for 30 minutes 1 infusion/day for 4 consecutive days<br>|
| Experimental: 6<br>600 microgram/kg | Drug: TZP-101<br>* 600 micrograms/kg iv 2ml/minute for 30 minutes 1 infusion/day for 4 consecutive days<br>|

What is the study measuring?
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Primary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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delayed gastric emptying, symptomatic gastroparesis, diabetes mellitus