E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Type 1 Diabetes |
Type 1 Diabetes |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067584 |
E.1.2 | Term | Type 1 diabetes mellitus |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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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 present project aims to evaluate the safety and therapeutic effect of the short-acting GLP-1RA exenatide administered three times daily (at meal-times) as add-on therapy to standard basal-plus-prandial insulin regimen in patients with T1D. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria • T1D according to WHO criteria with duration of ≥1 year • Age ≥18 years • BMI >22.0 kg/m2 • HbA1c >7.5% and <10.0% at visit 0 (screening) • Able to count carbohydrates • Able to understand the written patient information and to give informed consent
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E.4 | Principal exclusion criteria |
Exclusion criteria • Insulin pump treatment • Hypoglycaemia unawareness (inability to register low blood glucose) • Diabetic gastroparesis • Compromised kidney function (eGFR <60 ml/min/1.73m2, dialysis or kidney transplantation) • Liver disease with elevated plasma alanine aminotransferase (ALT) > three times the upper limit of normal (measured at visit 0 with the possibility of one repeat analysis within a week, and the last measured value as being conclusive) • History of acute and/or chronic pancreatitis • Subjects with personal or family history of medullary carcinoma or MEN syndrome • Inflammatory bowel disease • Cancer unless in complete remission for >5 years • Proliferative retinopathy • Other concomitant disease or treatment that according to the investigator's assessment makes the patient unsuitable for study participation • Alcohol/drug abuse • Fertile women not using chemical (tablet/pill, depot injection of progesterone, subdermal gestagen implantation, hormonal vaginal ring or transdermal hormonal patch) or mechanical (spirals) contraceptives • Pregnant or nursing women • Known or suspected hypersensitivity to trial product or related products • Receipt of an investigational drug within 30 days prior to visit 0 • Simultaneous participation in any other clinical intervention trial
Withdrawal criteria • In case of pregnancy (or desire for pregnancy), female subjects are withdrawn • Lack of compliance to any of the important study procedures in the discretion of the investigator • Onset of any disorder considered to compromise the safety by participating in the study • Unacceptable adverse effects in the discretion of the investigator • Withdrawal on participants request will be accepted at any time without further justification
Withdrawn patients will not be replaced.
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E.5 End points |
E.5.1 | Primary end point(s) |
Specifically, the primary objective is to determine the effect of exenatide vs. placebo on glycaemic control (HbA1c) over a 26-week treatment period. . |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Week -4 (Screening), 0, 12, 26. |
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E.5.2 | Secondary end point(s) |
Secondary endpoints will include adverse events (including hypoglycaemic episodes) and changes in insulin dosage, body weight, body mass index (BMI), body composition, FPG, PPG, fasting plasma levels of C-peptide, quality of life (QoL), dietary patterns and cardiovascular disease (CVD) risk profile (including biomarkers and cholesterol levels) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Adverse events (including hypoglycaemic episodes) and changes in insulin dosage: Week -4 (screening), 0, 1, 2, 4, 8, 12, 16, 20, 26
Body weight, body mass index (BMI), body composition: Week -4 (screening), 0, 12, 26.
FPG, PPG: Week 0, 4, 12, 26.
Fasting plasma levels of C-peptide: Week -4 (screening), 0, 4, 12, 26
Quality of life (QoL): Week 0, 12, 26.
Dietary patterns: Week 0, 12, 26.
Cardiovascular disease (CVD) risk profile (including biomarkers and cholesterol levels): Week -4 (screening), 0, 4, 12, 26 |
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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 | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
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.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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 | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |