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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10051153 |
E.1.2 | Term | Diabetic gastroparesis |
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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 symptomatic diabetic gastroparesis. |
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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): o Confirmed delayed gastric emptying (properly conducted gastric emptying assessment within prior 6 months acceptable) o 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). o AND a 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 o AND it is confirmed by endoscopy that there are no obstructive lesions in the esophagus or stomach (endoscopy within 3 prior months acceptable) • Subject has never had a gastrectomy, nor major abdominal surgery or any evidence of bowel obstruction within previous 12 months • Dosage of any concomitant medications has been stable for at least 3 weeks • HbA1c level is ≤ 12.5% • Subject has a BMI < 35 • Subject body weight is ≤ 110 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. If male, using a highly effective form of contraception (i.e. condom with spermicidal foam/gel/film/cream/suppository) for the duration of the study, and for 3 months after the last dose of the study drug. |
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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 o 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 o 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 | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 8 |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial months | 18 |
E.8.9.2 | In all countries concerned by the trial days | 0 |