E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
TZP-101 will be developed as a first-in class therapy for the treatment of gastric dysmotility. |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The objective of this study is to evaluate safety and efficacy of various doses of TZP- 101 in subjects with severe gastroparesis due to diabetes mellitus. |
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E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Subject (male or female) is 18-80 years old •Subject has type 1 or type 2 diabetes mellitus •Subject has documented diagnosis of gastroparesis (all of the following apply): - Confirmed delayed gastric emptying (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 a post-prandial fullness/early satiety subscale score of ≥ 3.0 - AND it is confirmed by endoscope that there are no obstructive lesions in the esophagus or stomach (endoscopy within prior 3 months acceptable) •Subject is currently on or has had standard gastroparesis therapy •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 •Albumin level ≥ 2.0 gms/dL •HbA1c level is ≤ 12.5% •Subject has a BMI < 35 •Subject body weight is ≤ 110 kg •Subject uses adequate contraception
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E.4 | Principal 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
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in the mean GCSI post-prandial fullness/early satiety subscale score across the four days of dosing. Baseline is the mean of the four GCSI post-prandial fullness/early satiety subscale scores (24 hour recall version) across the four days prior to admission for dosing.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 9 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Please refer to the protocol |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 18 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 18 |