E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
patients with type 2 diabetes not adequately controlled with metformin |
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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 | 10045242 |
E.1.2 | Term | Type II diabetes mellitus |
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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 primary objective of this study is to assess the effects of AVE0010 as an add-on treatment to metformin on glycemic control using a two-step dose titration regimen in comparison to placebo in terms of HbA1c reduction (absolute change) over a period of 24 weeks in patients with type 2 diabetes. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are: To assess the effects of AVE0010 on: − Glycemic control in comparison to placebo in terms of HbA1c reduction when it is used in a one-step dose titration regimen, − Percentage of patients reaching HbA1c <7% or HbA1c<6.5%, − Body weight, − Fasting plasma glucose, To assess AVE0010 safety and tolerability, To assess AVE0010 PK and anti-AVE0010 antibody development |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients meeting all the following inclusion criteria will be screened: - Patients with type 2 diabetes mellitus, as defined by WHO (Fasting plasma glucose ≥ 7 mmol/L (126 mg/dL) or 2 hours postprandial plasma glucose ≥ 11.1 mmol/L (200 mg/dL)), diagnosed for at least 1 year at the time of screening visit, insufficiently controlled with metformin at a stable dose of at least 1.5 g/day for at least 3 months prior to screening visit. - Written informed consent obtained. |
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E.4 | Principal exclusion criteria |
- HbA1c < 7% or HbA1c > 10% at screening - At screening age < legal age of majority - Women of childbearing potential with no effective contraceptive method (see protocol) Type 1 diabetes mellitus - Treatment with an antidiabetic pharmacological agent other than metformin within the 3 months preceding the screening - Fasting Plasma Glucose at screening > 250 mg/dL (> 13.9 mmol/L) - Body Mass Index ≤20 kg/m2 - Weight change of more than 5 kg during the 3 months preceding the screening visit - History of unexplained or chronic pancreatitis, pancreatectomy, stomach/gastric surgery, inflammatory bowel disease - History of metabolic acidosis, including diabetic ketoacidosis within 1 year prior to screening - Hemoglobinopathy or hemolytic anemia, receipt of blood or plasma products within 3 months prior to the time of screening - Within the last 6 months prior to screening: history of M.I., stroke, or heart failure requiring hospitalization - Known history of drug or alcohol abuse within 6 months prior to the time of screening - 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, history or presence of clinically significant diabetic retinopathy, history or presence of macular edema likely to require laser treatment within the study period - Uncontrolled or inadequately controlled hypertension at the time of screening with a resting supine systolic or diastolic blood pressure > 180 mmHg or > 95 mmHg, respectively - Laboratory findings at the time of screening: AST, ALT or ALP: > 2 times the upper limit of NR, Amylase and/or lipase > 3 times the upper limit of NR, Total bilirubin: > 1.5 times the upper limit of NR (except in case of Gilberts syndrome), Hb < 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 serum pregnancy test in females of childbearing potential - Any clinically significant abnormality identified on physical examination, laboratory tests, ECG 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 or constrains efficacy assessment - Patients considered by the investigator or any sub-investigator as inappropriatefor this study for any reason likelihood of requiring treatment during the screening phase and treatment phase with drugs not permitted by the clinical study protocol; investigator or any sub-investigator, pharmacist, study coordinator, other study staff or relative thereof directly involved in the conduct of the protocol, etc.) - Use of oral or injectable antidiabetic or hypoglycemic agents other than metformin within 3 months prior to the time of screening - Use of systemic glucocorticoids (excluding topical application or inhaled forms) for 1 week or more within 3 months prior to the time of screening - Use of any investigational drug within 3 months prior to screening - Pregnancy, lactation. - Any previous treatment with AVE0010. Related to the background therapy (i.e. metformin): - Renal impairment defined with serum Creatinine > 1.4 mg/dL in women and serum Creatinine > 1.5 mg/dL in men. Related to AVE0010: - 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 screening - Allergic reaction to any GLP 1agonist in the past (e.g. exenatide, liraglutide) or to metacresol. Additional Exclusion criteria at the end of the run-in phase: - Informed consent withdrawal (patient who is not willing to continue or fails to return). - Lack of compliance during the single-blind place; Patient with any AE, which would preclude inclusion. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Absolute change of HbA1c from baseline to week 24 |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
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 | 8 |
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 | 8 |