E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045242 |
E.1.2 | Term | Type II diabetes mellitus |
|
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 |
To investigate the effects of repeated subcutaneous doses of 20 µg lixisenatide as compared to 1.8 mg liraglutide in reducing postprandial plasma glucose (PPG) assessed as area under the plasma glucose concentration curve (AUC) after a standardized breakfast at the end of a 4-week treatment period in patients with type 2 diabetes |
|
E.2.2 | Secondary objectives of the trial |
• To assess the effects of lixisenatide as compared to liraglutide after a 4-week treatment period in patients with type 2 diabetes: - on the maximum PPG excursion, and on the changes in insulin, pro-insulin, C-peptide and glucagon plasma concentrations following a standardized breakfast - on the 24-h profile of plasma glucose - on HbA1c - on satiety markers (obestatin, PYY-36 and oxyntomodulin) • To assess the clinical and laboratory safety profile of lixisenatide and liraglutide over a 4-week treatment period in patients with type 2 diabetes
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
I 01. Male or female patients with type 2 diabetes mellitus, as defined by WHO (fasting plasma glucose ≥ 7 mmol/L (126mg/dL) or 2 hours postprandial plasma glucose ≥ 11.1 mmol/L (200 mg/dL)), for at least 1 year at the time of screening visit, not adequately controlled by metformin at a dose of at least 1.5 g/day for at least 3 months prior to screening I 02. HbA1c ≥ 6.5% (as recommended by the American Diabetes Association (11)) and HbA1c ≤ 9% at screening I 03. Covered by Health Insurance System where applicable, and/or in compliance with the recommendations of the National (German) Law in force relating to biomedical research I 04. Not under any administrative or legal supervision I 05. Written informed consent obtained |
|
E.4 | Principal exclusion criteria |
E 01. At the time of screening age < 18 year or ≥75 years E 02. Body Mass Index (BMI) : ≤ 20 kg/m² or ≥ 37 kg/m² E 03. History of metabolic acidosis, including diabetic ketoacidosis within 1 year prior to screening E 04. Hemoglobinopathy or hemolytic anemia E 05. History of myocardial infarction, stroke, or heart failure requiring hospitalization within 6 months prior to the time of screening, history or presence of clinically significant diabetic retinopathy, history or presence of macular edema likely to require laser treatment within the study period E 06. Cardiovascular, hepatic, neurological, endocrine disease, active malignant tumor or other major systemic disease or patients with short life expectancy making implementation of the protocol or interpretation of the study results difficult (euthyroid patients on replacement therapy will be included if the dosage of thyroxin is stable for at least three months prior to screening Visit) E 07. Uncontrolled or inadequately controlled hypertension at the time of screening with a resting systolic or diastolic blood pressure > 160 mmHg or > 95 mmHg, respectively E 08. Any clinically significant abnormality identified on physical examination, laboratory tests or vital signs at the time of screening that in the judgment of the investigator or any sub investigator would preclude safe completion of the study E 09. Receipt of blood or plasma products within 3 months prior to the time of screening E 10. Investigator or any sub investigator, pharmacist, study coordinator, other study staff or relative thereof directly involved in the conduct of the protocol E 11. Patients considered by the investigator or any sub investigator as inappropriate for this study for any reason (e.g. impossibility to meet specific protocol requirements, such as scheduled visits, being able to do self-injections, etc) E 12. Use of other oral or injectable antidiabetic or hypoglycemic agents other than metformin (e.g., alpha glucosidase inhibitor, exenatide, DPP-IV inhibitors, insulin, TZD, SU etc.) within 3 months prior to the time of screening E 13. Use of systemic glucocorticoids (excluding topical application or inhaled forms) for one week or more within 3 months prior to the time of screening E 14. Likelihood of requiring treatment during the screening phase and treatment phase with drugs not permitted by the clinical study protocol E 15. Use of any investigational drug within 3 months prior to screening E 16. Pregnant women or breast feeding women E 17. Women of childbearing potential with no effective contraceptive method Female patients of childbearing potential (pre-menopausal, less than two years post-menopausal, not surgically sterile women for at least 3 months prior to the time of screening) must have a confirmed negative blood β-HCG pregnancy test prior to enrollment and Baseline visit, accept to repeat pregnancy test at designated visits and they must use a highly effective method of birth control during the whole study, which is defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly, according to the Note for guidance on non-clinical safety studies for the conduct of human clinical trials for pharmaceuticals (CPMP/ICH/286/95, modification) (12) and according to the following double contraception algorithm [(intra-uterine device or hormonal contraception) plus (spermicide-coated condom or diaphragm)]. E 18. Clinically relevant history of gastrointestinal disease associated with prolonged nausea and vomiting, including, but not limited to gastroparesis and gastroesophageal reflux disease requiring medical treatment, within 6 months prior to the time of screening E 19. Any previous treatment with lixisenatide or liraglutide E 20. Allergic reaction to any GLP-1 agonist in the past (e.g. exenatide) or to metacresol E 21. History of unexplained pancreatits, chronic pancreatitis, pancreatectomy, stomach/gastric surgery, inflammatory bowel disease E 22. Personal or family history of medullary thyroid cancer (MTC) or a genetic condition that predisposes to MTC E 23. Known history of drug or alcohol abuse within 6 months prior to the time of screening E 24. Laboratory findings at the time of screening: - ALT > 3 times the upper limit of the normal laboratory range - Calcitonin ≥ 20pg/mL - Amylase and lipase above 3 times the upper limit - Total bilirubin: > 1.5 times the upper limit of the normal laboratory range (except in case of Gilbert’s syndrome) - Hemoglobin < 11 g/dL and/or neutrophils < 1,500/mm3 and/or platelets < 100,000/mm3 - Positive test for Hepatitis B surface antigen and/or Hepatitis C antibody - Positive reaction to test for anti-HV1 and anti-HV2 antibodies E 25. Renal impairment defined with creatinine clearance 60 mL/min using the Cockcroft- Gault Formula
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
• GLU-AUC0:30-4:30h: area under the plasma glucose concentration time profile calculated using the linear trapezoidal rule from time of standardized breakfast start (30 min after IP injection=T0.5) until 4 hours later (T4.5) |
|
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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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) | Yes |
E.8.2.2 | Placebo | No |
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 | 7 |
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 | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
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
| |
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 | 7 |
E.8.9.1 | In the Member State concerned days | |