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 | 10.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10067585 |
E.1.2 | Term | <Manually entered code. Term in E.1.1> |
|
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 efficacy of AVE0010 on glycemic control in comparison to placebo as an add-on treatment to basal insulin in Type 2 Diabetes patients treated with basal insulin in terms of absolute HbA1c reduction over a period of 24 weeks. |
|
E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are:
To assess the effects of AVE0010 on • Body weight, • 2-hour postprandial plasma glucose after standardized meal challenge test, • Percentage of patients reaching HbA1c <7%, • Percentage of patients reaching HbA1c ≤6.5%, • Fasting Plasma Glucose (FPG), • Change in 7-point Self Monitored Plasma Glucose (SMPG) profiles, • Change in basal insulin and total insulin doses.
To assess AVE0010 safety and tolerability.
To assess AVE0010 PK.
To assess anti-AVE0010 antibody development. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients meeting all of the following inclusion criteria will be screened: • Patients with type 2 diabetes mellitus, as defined by Fasting plasma glucose ≥ 7 mmol/L (126 mg/dL) or 2 hours postprandial plasma glucose ≥ 11.1 mmol/L (200 mg/dL) and diagnosed for at least 1 year at the time of the screening visit, insufficiently controlled with basal insulin, i.e. the clinical need of treatment intensification with a short-acting insulin or the inability to increase the baseline basal insulin dose due to hypoglycemia. • Written informed consent obtained. |
|
E.4 | Principal exclusion criteria |
Patients presenting with any of the following criteria will not be included in the study: • Exclusion criteria related to study methodology - HbA1c <7.0 % or HbA1c >10 % at screening. - At the time of screening age <legal age of majority. - Women of childbearing potential with no effective contraceptive method (Women of childbearing potential (pre-menopausal, not surgically sterile women for at least 3 months prior to the time of screening) must have a confirmed negative serum β-hCG pregnancy test at screening visit. They must use an effective contraceptive method throughout the study, and agree to repeat serum β-hCG pregnancy test at designated visits). - Type 1 diabetes mellitus. - Treatment with basal insulin for less than 3 months prior to screening or insulin regimen changed during the last 3 months prior to screening. - During the last 2 month prior to screening dose of basal insulin <30 U/day and/or dose not stable (± 20 %). - If treatment with metformin: no stable dose of at least 1.5 g/day (except for South Korea: at least 1.0g/day) for at least 3 months prior to screening visit. - Fasting Plasma Glucose at screening >250 mg/dL (>13.9 mmol/l). - History of hypoglycemia unawareness. - Body Mass Index (BMI) ≤20 kg/m². - Weight change of more than 5 kg during the 3 months preceding the screening visit. - History of unexplained pancreatitis, 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 myocardial infarction, 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 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 the normal laboratory range, − Amylase and/or lipase: >3 times the upper limit of the normal laboratory range, − 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 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 inappropriate for this study for any reason. - Use of other oral or injectable antidiabetic or hypoglycemic agents other than metformin or basal insulin within 3 months prior to the time of screening. - Use of systemic glucocorticoids (excluding topical application or inhaled forms) for one 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 or participation in a previous study with AVE0010.
• Exclusion criteria related to background therapy (i.e. metformin). - Renal impairment defined with Creatinine >1.4 mg/dL in women and Creatinine >1.5 mg/dL in men (applicable only for patients with metformin treatment).
• Exclusion criteria related to AVE0010 - End-stage renal disease defined by a serum Creatinine clearance of <15 mL/min and/or patients on dialysis, if no treatment with metformin - 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. - Allergic reaction to any GLP-1 agonist in the past or to metacresol.
• Additional Exclusion criteria at the end of the run-in phase: - Patient with any AE, which, by the judgment of the investigator would preclude the inclusion in the study. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Absolute change of HbA1c from baseline to week 24. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
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) | 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 | 32 |
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 |
|
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
| |
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 | 32 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 32 |