E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with type 2 diabetes mellitus. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045242 |
E.1.2 | Term | Type II 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 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 and sitagliptin (100 mg once daily) given for 24 weeks as monotherapy in patients with T2DM with insufficient glycaemic control.
For the open-label part of the study the objective is to estimate the efficacy and safety of BI 10773 when given for 24 weeks in patients with T2DM with very poor glycaemic control. (Irish sites will not contribute to the open-label part of the study.) |
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E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Irish sites will not be participating in the Body Composition substudy.
Body composition substudy (optional) - Revised Protocol, Version 2.0, Date: 04 November 2010.
2 subparts 1) Whole body Dual Energy X-ray Absorptiometry (DXA) scan and 2) Magnetic Resonance Imaging (MRI) Scan
Endpoints for 1) Whole Body Scan using DXA: changes from baseline to week 24 in trunk fat, limb fat, fat free mass and total fat mass
Endpoints for 2) MRI: Changes in abdominal visceral adipose tissue (VAT) from baseline to week 24; Changes in abdominal subcutaneous adipose tissue (SAT) from baseline to week 24; changes in VAT/SAT ratio from baseline to week 24 |
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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 drug-naïve, defined as absence of any oral or injectable anti-diabetes therapy for 12 weeks prior to randomisation or start of active open-label treatment (25 mg BI 10773) (active open-label treatment is not applicable for Ireland)
3. HbA1c
- ≥ 7.0% and <= 10.0% at Visit 1 (screening) in order to be eligible for randomised treatment
- > 10.0% at visit 1 (screening) in order to be eligible for the open-label BI 10773 arm. In Ireland, patients must not be enrolled into the open label BI 10773 arm.
4. Age >= 20 (Japan)
Age >= 18 (countries other than Japan)
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 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. Acute coronary syndrome (non-STEMI, STEMI and unstable angina pectoris), stroke or TIA within 3 months prior to informed consent
3. 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) during screening and/or run-in phase
4. Impaired renal function, defined as eGFR<50 ml/min (moderate to severe renal impairment; MDRD formula)
5. Bariatric surgery within the past two years and other gastrointestinal surgeries that induce chronic malabsorption
6. Medical history of cancer (except for basal cell carcinoma) and/or treatment for cancer within the last 5 years
7. Contraindications to sitagliptin according to the local label
8. Blood dyscrasias or any disorders causing haemolysis or unstable Red Blood Cell (e.g. malaria, babesiosis, haemolytic anaemia)
9. Treatment with any anti-diabetes drug within 12 weeks prior to randomisation or start of active open-label treatment (25 mg BI 10773) (active open-label treatment is not applicable for Ireland)
10. Treatment with anti-obesity drugs 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
11. 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 T2DM.
12. 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 study 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 by local authorities), double barrier method and vasectomised partner
13. 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
14. Intake of an investigational drug in another trial within 30 days prior to intake of study medication in this trial
15. Any other clinical condition that would jeopardize patients safety while participating in this clinical trial
Ireland only
16. Known hypersensitivity or allergy to the investigational product, sitagliptin or their excipients
17. Lactose intolerance
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint in this study is the change from baseline in HbA1c after 24 weeks of treatment (%). Throughout the study protocol, the term "baseline" refers to the last observation prior to the administration of any (open-label 25 mg BI 10773 or 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 | No |
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 | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 28 |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 10 |
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 | 7 |
E.8.9.2 | In all countries concerned by the trial days | 10 |