E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 | LLT |
E.1.2 | Classification code | 10012601 |
E.1.2 | Term | 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 the study is to evaluate the tolerability of different doses of RO5073031 (30 mg and 40 mg weekly) when administered following injection of 20 mg weekly for 4 weeks to diabetic patients treated with a stable dose of metformin monotherapy. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are: - To investigate the glycemic response in the different treatment groups, evaluating 24-hour blood glucose concentrations (based on 7-point sampling profile) and additional parameters of glycemic control. - To investigate the effects of different doses of RO5073031 on body weight. - 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.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Able and willing to give written informed consent and to comply with the requirements of the study protocol (patients must be able to perform self-monitoring of blood glucose and/or comply with protocol requirements independently from another person to be included in the study). - Type 2 diabetes mellitus patients treated with stable metformin monotherapy (at any dose, but not higher than recommended in the label) for at least 3 months prior to screening. - Age 18 to 75 years at the time of screening. - 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. - If receiving ACE inhibitors, angiotensin II antagonists, beta blockers, thiazide diuretics, thyroid hormones and/or lipid lowering medications, the dose(s) must have been stable for at least 6 weeks prior to screening. - Males, postmenopausal women (defined as more than one year after the cessation of menses and documented by FSH > 50 UI/L) or surgically sterilized women (by means of hysterectomy, bilateral oopherectomies or tubal ligations). |
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E.4 | Principal exclusion criteria |
- Known hypersensitivity to RO5073031 or any of the components of its formulation. - Type 1 diabetes mellitus patients. - Clinically significant GI disease including inflammatory bowel disease, irritable bowel syndrome, celiac disease, dyspepsia, apparent diabetic gastroparesis, diabetic diarrhea or surgery of the gastrointestinal tract (except appendicectomy/cholecystectomy). - Uncontrolled hypertension (SBP > 160 mmHg and/or DBP > 100 mmHg, despite treatment) at the time of screening. - Myocardial infarction or stroke within 6 months prior to screening. - Known proliferative diabetic retinopathy. - Known haemoglobinopathy or chronic anemias. - Evidence of serious concomitant disease, such as active cancer, major active infection or severe psychiatric disorders, at the time of screening. - Any new conditions diagnosed at screening requiring treatment longer than 10 days or chronic therapies that can not be stabilized during the screening period. - Contraindications to metformin, i.e. - Congestive heart failure requiring pharmacologic treatment - Clinically significant respiratory insufficiency. - History of ketoacidosis or lactic acidosis. - Any previous exposure to GLP-1, GLP-1 analogues or exenatide. - Treatment with any anti-hyperglycemic medication other than metformin monotherapy within 3 months prior to screening (except insulin use for up to 7 days in acute situations). - Systemic (oral or parental) use of corticosteroids within 6 weeks prior to screening. - Use of weight lowering medications (orlistat, sibutramine, rimonabant, phentermine) within 3 months prior to screening. - Impaired liver function (ALT, AST, 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 (133 umol/L) [males], ≥1.4 mg/dL (124 umol/L) [females]) at screening. - Any abnormalities in clinical laboratory tests or ECG, which preclude safe involvement in the study as judged by the Investigator. - Participation in an investigational drug study within 90 days (or five half-lives, whichever is longer) prior to screening. - Pregnant women, lactating women or women of childbearing potential. - Alcohol or drug abuse.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of the study is the proportion of patients withdrawn because of GI adverse events by treatment groups. |
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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 | Yes |
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) | 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 | 8 |
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 | 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
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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 |