E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Type II Diabetes Mellitus |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10063624 |
E.1.2 | Term | Type II diabetes mellitus inadequate control |
E.1.2 | System Organ Class | 100000004861 |
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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 |
Efficacy:
To evaluate the effect of aleglitazar on whole body insulin sensitivity compared with placebo after 16 weeks of treatment in patients with T2D inadequately controlled with metformin monotherapy, as assessed by hyperinsulinemic-euglycemic clamp. |
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E.2.2 | Secondary objectives of the trial |
Efficacy:
To evaluate the effect of aleglitazar compared to placebo on hepatic insulin sensitivity, on beta cell function, on parameters of diabetes control, on the lipid profile, on 24-hour blood pressure, on hepatic fat content, on fat distribution and content in the abdominal region, on total body fat content, and on the markers of insulin sensitivity and cardiovascular risk in patients with T2D inadequately controlled with metformin monotherapy
Safety:
To assess the safety and tolerability of aleglitazar versus placebo, focusing on selected adverse events relevant to PPAR activation or of other interest, cardiovascular events, other adverse events, and serious adverse events |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Adult patients with type 2 diabetes, 30-70 years of age, treated with stable metformin therapy for at least 12 weeks
• HbA1c ≥ 6.5% and ≤ 9% and fasting plasma glucose ≤ 13.3 mmol/L (≤ 240 mg/dL)
• Overweight (BMI ≥ 25) |
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E.4 | Principal exclusion criteria |
• Type 1 diabetes
• Previous treatment with a thiazolidinedione or dual PPAR agonist; prior intolerance to fibrate
• Treatment with any anti-diabetes medication other than stable dose metformin within the last 12 week
• Treatment any body weight lowering or lipoprotein-modifying therapy (eg, fibrates) within 12 weeks with the exception of statin therapy
• History of bariatric surgery
• Anaemia
• Estimated glomerular filtration rate <60mL/min/1.73m2
• Symptomatic congestive heart failure classified as NYHA class II-IV |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Change in whole-body insulin sensitivity |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• Change in liver insulin sensitivity
• Change in parameters of beta cell function
• Change in parameters of diabetes control (HbA1c, Fasting plasma glucose)
• Change in the lipid profile parameters
• Change in 24-hour blood pressure
• Change in fat content in the liver
• Change in fat content and distribution in the abdominal region
• Change in markers of insulin sensitivity and cardiovascular risk |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
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) | 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.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 20 |