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 | 13.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067585 |
E.1.2 | Term | Type 2 diabetes mellitus |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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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 main objective of the current study is to investigate the efficacy, safety and tolerability of BI 10773 (10 and 25 mg/once daily) compared to placebo given for 24 weeks as add-on therapy to pioglitazone alone or in combination with metformin in patients with type 2 diabetes mellitus with insufficient glycaemic control. The study is designed to show superiority over placebo. |
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E.2.2 | Secondary objectives of the trial |
The key secondary endpoint is:
• change from baseline after 24 weeks in the fasting plasma glucose (FPG)
Other exploratory efficacy endpoints are the following:
• HbA1c: Occurrence of treat to target efficacy response, that is an HbA1c of < 7.0% after 24 weeks of treatment; Occurrence of relative efficacy response (HbA1c lowering by a least 0.5% after 24 weeks of treatment; Change from baseline in HbA1c by visit over time
• Fasting plasma glucose (FPG): Change from baseline in FPG by visit over time
• Body weight and waist circumference: change from baseline to week 24
• Systolic and diastolic blood pressure (SBP and DBP): change from baseline to week 24
• Composite endpoint of the following conditions at week 24 (change from baseline): - HbA1c reduction of > 0.5% or HbA1c < 7% - change in systolic blood pressure (SBP) > 3 mmHg - body weight reduction of > 2%
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Diagnosis of type 2 diabetes mellitus prior to informed consent
2. Male and female patients on diet and exercise regimen who are pre-treated with pioglitazone alone or in combination with metformin (see below for minimum doses). The treatment regimen should be unchanged for 12 weeks prior to randomisation.
Minimum dose for pioglitazone: ≥ 30 mg/day or maximum tolerated dose or maximum dose according to the local label
Minimum dose for metformin: ≥ 1500 mg/day or maximum tolerated dose or maximum dose according to the local label
3. HbA1c of ≥ 7.0% and < 10.0% at Visit 1 (screening)
4. Age >/= 18
5. BMI </= 45 kg/m2 (Body Mass Index) at Visit 1 (screening)
6. Signed and dated written informed consent by date of Visit 1 in accordance with Good Clinical Practice (GCP) and local legislation
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E.4 | Principal exclusion criteria |
1. Uncontrolled hyperglycaemia with a glucose level > 240 mg/dl (> 13.3 mmol/l) after an overnight fast during placebo run-in and confirmed by a second measurement (not on the same day)
2. Any other antidiabetic medication within 12 weeks prior to randomisation, except those defined as the permitted background therapy via inclusion criteria no. 2
3. Acute coronary syndrome (non-STEMI, STEMI and unstable angina pectoris), stroke or transient ischaemic attack (TIA) within 3 months prior to informed consent 4. Indication of liver disease, defined by serum levels of either ALT (SGPT), AST (SGOT), or alkaline phosphatase above 3 x upper limit of normal (ULN) as determined during screening or during the placebo run-in period (i.e. at a visit prior to the randomisation visit, Visit 3)
5. Impaired renal function, defined as eGFR (estimated Glomerular Filtration Rate) < 30 ml/min (severe renal impairment, MDRD [Modification of Diet in Renal Disease] formula) as determined during screening or during the placebo run-in period (i.e. at a visit prior to the randomisation visit, Visit 3)
6. Bariatric surgery within the past two years and other gastrointestinal surgeries that induce chronic malabsorption
7. Medical history of cancer (except for basal cell carcinoma) and/or treatment for cancer within the last 5 years
8. Blood dyscrasias or any disorders causing haemolysis or unstable red blood cells (e.g. malaria, babesiosis, haemolytic anaemia)
9. Contraindications to pioglitazone according to the local label
10. Contraindication to pioglitazone in combination with metformin (relevant only for those patients who enter the study with this background therapy) according to the local label
11. Treatment with anti-obesity drugs (e.g. sibutramine, orlistat) 3 months prior to informed consent or any other treatment at the time of screening (i.e. surgery, aggressive diet regimen etc.) leading to unstable body weight
12. Current treatment with systemic steroids at time of informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent or any other uncontrolled endocrine disorder except T2D
13. Pre-menopausal women (last menstruation 1 year prior to informed consent) who: - are nursing or pregnant or - are of child bearing potential and are not practicing an acceptable method of birth control, or do not plan to continue using this method throughout the trial and do not agree to submit to periodic pregnancy testing during participation in the trial. Acceptable methods of birth control include tubal ligation, transdermal patch, intra uterine devices/systems (IUDs/IUSs), oral, implantable or injectable contraceptives, sexual abstinence (if acceptable to local authorities), double barrier method and vasectomised partner
14. Alcohol or drug abuse within the 3 months prior to informed consent that would interfere with trial participation or any ongoing condition leading to a decreased compliance to study procedures or study drug intake
15. Participation in another trial with an investigational drug within 30 days prior to informed consent
16. Any other clinical condition that would jeopardise patient safety while participating in this clinical trial
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint in this trial is the change from baseline in HbA1c after 24 weeks of treatment. Throughout the trial protocol, the term "baseline" refers to the last observation prior to the administration of any randomised study medication. |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Yes |
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) | 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 | 5 |
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 | 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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Defined in the protocol - Section 8.6 - last patient out. |
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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 | 4 |
E.8.9.1 | In the Member State concerned days | 15 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 15 |