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 | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012601 |
E.1.2 | Term | 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 determine the efficacy, with respect to glycemic control, of multiple doses and regimens of RO5073031 which, when added to metformin, are safe and tolerable compared with placebo in patients with type 2 diabetes. |
|
E.2.2 | Secondary objectives of the trial |
-To compare the effects of RO5073031 with placebo, when both are added to metformin, on body weight and additional parameters of glycemic and lipid control; -To investigate, by a population analysis approach, the pharmacokinetics and the exposure-response relationship of RO5073031 in the target population, including the influence of covariates. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Type 2 diabetes mellitus patients treated with individual maximum tolerated daily dose of metformin monotherapy (metformin daily dose ≥ 1.5 g, maximum not higher than recommended in the label) for at least 3 months prior to screening. -Males, postmenopausal women (defined as more than two years after the cessation of menses) or surgically sterilized women. -Age 18 to 75 years at the time of the screening examination. -HbA1c ≥ 7.0 % and ≤ 9.5 % at screening. -Fasting plasma glucose (FPG) > 126 mg/dL (7.0 mmol/L) and ≤ 240 mg/dL (13.3 mmol/L) at screening. -BMI > 25 kg/m2 and ≤ 45 kg/m2 at screening -Stable weight ± 10% for at least 3 months before screening. -Patients able and willing to give written informed consent and to comply with the requirements of the study (patients that cannot follow blood glucose selfmonitoring and study requirements independently from another person cannot be included). |
|
E.4 | Principal exclusion criteria |
-Type 1 diabetes mellitus patients -Known hypersensitivity to RO5073031 or any of its components. -Known contraindications to metformin, i.e. -Congestive heart failure requiring pharmacologic treatment; -Clinically significant respiratory insufficiency. -History of ketoacidosis or lactic acidosis. -Treatment with any anti-hyperglycemic medication other than metformin monotherapy during the last 3 months (except insulin use in acute situations or during surgery for up to 7 days). -Any previous exposure to GLP-1, GLP-1 analogues or exenatide before the study. -Systemic use of corticosteroids in the last 3 months. -Use of weight lowering medications (orlistat, sibutramine, rimonabant, phentermine) in the last 3 months. -Patients receiving ACE inhibitors, beta-blockers, thiazide diuretics, thyroid hormones, and/or lipid lowering medications who are not on a stable dose for more than 6 weeks prior to the start of the study. -Impaired liver function (ALAT or ASAT or total bilirubin or alkaline phosphatase > 2.5x ULN) at screening. -Renal disease or renal dysfunction (as suggested by serum creatinine levels ≥ 1.5 mg/dL [males], ≥ 1.4 mg/dl [females]) at screening. -Uncontrolled hypertension (SBP > 160 mmHg and/or DBP > 100 mmHg, despite treatment) at the time of the screening examination. -Myocardial infarction or stroke within 6 months prior to the screening examination. -Known hemoglobinopathy. -Known proliferative diabetic retinopathy. -Clinically significant GI disease including inflammatory bowel disease, irritable bowel syndrome, celiac disease, dyspepsia, apparent diabetic gastroparesis, diabetic diarrhoea, or surgery of the gastro-intestinal tract (except appendectomy / cholecystectomy). -Any abnormality in clinical laboratory tests or ECG, which precludes safe involvement in the study as judged by the investigator. -Pregnant or lactating women or women of childbearing potential. -Participation in an investigational drug study within 90 days [3 months] (or treatment with any investigational agent within five half-lives of that investigational drug, whichever is longer) prior to screening. -Serious illness, such as active cancer, major active infection, severe psychiatric disorders at the time of the screening examination. -Alcohol or drug abuse. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
EFFICACY / PHARMACODYNAMIC: Absolute change from baseline in HbA1c at the end of the treatment period. |
|
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 | 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 | 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.8.3 |
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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 13 |
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 | 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 | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 9 |