E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The purpose of this study is to investigate the pharmacodynamic, safety, tolerability and pharmacokinetics (PK) of AVE0010 in Japanese and Caucasian type 2 diabetic patients in the same study and to assess the treatment by ethnicity interaction between the two populations with regard to AVE0010. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10012613 |
E.1.2 | Term | Diabetes mellitus non-insulin-dependent |
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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 the study is to assess the effects of individually stepwise increasing QD and BID doses of AVE0010 on the increase in plasma glucose concentration induced by a standardized breakfast test meal at the highest tolerated dose of AVE0010 in type 2 diabetic patients. |
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E.2.2 | Secondary objectives of the trial |
The main secondary objective of the study is to assess the treatment by ethnicity interaction of individually increasing QD and BID doses of AVE0010 on the increase in plasma glucose concentration induced by a standardized breakfast test meal between Japanese and Caucasian type 2 diabetic patients at the highest tolerated doses of AVE0010. The other secondary objectives of the study are to assess the effects of individually stepwise increasing QD and BID doses of AVE0010 in Japanese and Caucasian patients on pharmacodynamic, safety, tolerability and pharmacokinetics parameters of AVE0010.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
· Japanese or Caucasian males or females. Female patients must be post-menopausal (i.e. amenorrhea ≥ 12 consecutive months or else follicle stimulating hormone [FSH] and serum estradiol level within post-menopausal range) or surgically sterile for at least 3 months prior to the time of screening. Japanese patients living outside Japan are defined as: 1) having Japanese nationality; 2) parents are both Japanese; 3) living outside Japan for no longer than 5 years · Age 20 – 75 years at the time of screening · Type 2 diabetes mellitus diagnosed for at least one year prior to the time of screening as established in the medical history and defined by American Diabetes Association (ADA) criteria [4] [Appendix A] · Stable type 2 diabetes mellitus treated either with sulfonylurea alone or sulfonylurea and metformin at a stable dose for at least 3 months prior to the time of screening and no other antidiabetic medications for at least 3 months prior to the screening · Body mass index (BMI) ≤ 35 kg/m2 at the time of screening · HbA1c ≥ 7.0% and ≤ 10.0% at the time of screening · Fasting blood glucose at screening between 108-250 mg/dL [6.0-13.9 mmol/L] · Willingness and capability to perform specified self-injections and to otherwise comply with study protocol requirements
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E.4 | Principal exclusion criteria |
Exclusion criteria related to study methodology or general patients characteristics · Type 1 diabetes mellitus · Hospitalized patient at screening · History of chronic pancreatitis, pancreatectomy, stomach/gastric surgery, inflammatory bowel disease or irritable bowel syndrome · History of metabolic acidosis, including diabetic ketoacidosis · Hemoglobinopathy or hemolytic anemia · History of myocardial infarction, stroke, retinopathy requiring laser surgery, or heart failure requiring hospitalization within 6 months prior to the time of screening · History of drug or alcohol abuse within 6 months prior to the time of screening · Cardiovascular, hepatic, neurologic, endocrine, active malignant tumor or other major systemic disease making implementation of the protocol or interpretation of the study results difficult · Presence of any clinically significant abnormality on the ECG performed at the screening visit · Uncontrolled or inadequately controlled hypertension at the time of screening with a resting systolic or diastolic blood pressure > 180 mmHg or > 110 mmHg, respectively · Hypotension at the time of screening with a resting systolic blood pressure < 90 mmHg · Renal or hepatic disease at the time of screening, - Creatinine: > 1.2 times the upper limit of the normal laboratory range - AST, ALT or ALP: > 2 times the upper limit of the normal laboratory range - Total bilirubin: > 1.5 times the upper limit of the normal laboratory range - Positive test for Hepatitis B surface antigen and/or Hepatitis C antibody · 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 subinvestigator would preclude safe completion of the study · Blood or plasma donations of more than 400 mL within 1 year or more than 200 mL within 4 weeks prior to the time of screening, or receipt of blood products within 2 months prior to the time of screening · Body weight at the time of screening < 45 kg · Hemoglobin at the time of screening < 12.5 g/dL · Investigator or any subinvestigator, pharmacist, study coordinator, other study staff or relative thereof directly involved in the conduct of the protocol · Lack of compliance during the run-in period: more than 3 injections missed · Patients living alone (i.e. without any social support in the same house or in the close neighbourhood) or too far from investigational centre (this decision is up to the investigator on the basis if the patient can comply the visit schedule) · Patients considered by the investigator or any subinvestigator as inappropriate for this study for any reason (e.g. impossibility to meet specific protocol requirements, such as scheduled visits and hospitalizations, etc). Exclusion criteria related to concomitant medications · Use of other oral antidiabetic agents other than sulfonylurea or metformin (e.g., alpha glucosidase inhibitor, buformin, thiazolidinedione or quick acting insulinotropic agent, etc) within 3 months prior to the time of screening. · Use of insulin for one week or more within 6 months prior to screening. · Use of drugs affecting insulin secretion, except beta blockers (e.g., phenytoin, diazoxide, somatostatin) within 3 months prior to screening · Use of systemic glucocorticoids (excluding local application or inhaled forms) for one week or more within 3 months prior to the time of screening · Concomitant use of drugs affecting gastrointestinal motility (e.g., including metoclopramide, cisapride, chronic macrolide antibiotics) within 3 months prior to the time of screening. Non-stimulant laxatives are permitted. · Likelihood of requiring treatment during the screening phase and treatment phase with drugs not permitted by the clinical study protocol (see Section 8.9) · Use of any investigational drug within 3 months prior to screening · Any previous use of compounds in this investigational drug class, such as Exendin-4 and GLP-1 analogs Exclusion criteria related to the sanofi-aventis compound · Pregnancy, lactation, women of childbearing potential · Clinically relevant history of gastrointestinal disease associated with prolonged nausea and vomiting, including, but not limited to gastroparesis, within 6 months prior to the time of screening
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary analysis variable is the change from baseline in the area under the concentration time curve [AUC[0.29h-4:30h](h·mg/dl)] for the postprandial changes in plasma glucose determined after a standardized test breakfast on the last day at the highest well tolerated dose in type 2 diabetic patients. |
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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 | No |
E.6.6 | Pharmacokinetic | Yes |
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 | 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 | 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 | 6 |
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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Phone call 72 hours after the last visit of the last patient, as a post treatment follow up |
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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 | |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 7 |