E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with type 2 Diabetes Mellitus with insufficient glycaemic control. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045242 |
E.1.2 | Term | Type II 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 objective of the study is to investigate the efficacy, safety and tolerability of BI 1356 (5 mg / once daily) compared to placebo given for 24 weeks as initial combination therapy with pioglitazone 30 mg in patients with type 2 diabetes mellitus with insufficient glycaemic control. |
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E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. All patients must sign an informed consent consistent with ICH-GCP (International Conference on Harmonization – Good Clinical Practice) guidelines prior to participation in the trial (Obtain written informed consent for enrolment into the trial prior to making any changes in medication or performing any procedures necessary to meet entry criteria). 2. Patients with a diagnosis of type 2 diabetes mellitus prior to informed consent and treatment naïve or previously treated with any oral hypoglycaemic agent. 3. Glycosylated haemoglobin A1 (HbA1c) at Visit 1a (Screening) For patients undergoing wash out of previous medication: HbA1c 7.0-9.0%. For patients not undergoing wash out of previous medication: HbA1c 7.5-10.0%. 4. Glycosylated haemoglobin A1 (HbA1c) 7.5-10.0% at Visit 2 (Start of Run-in) . 5. Male and female patients aged 18 and < 80 years at Visit 1a (Screening). 6. Body Mass Index (BMI) 40 kg/m2 at Visit 1a (Screening). |
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E.4 | Principal exclusion criteria |
1. Myocardial infarction, stroke or TIA within 6 months prior to informed consent. 2. Impaired hepatic function, defined by serum levels of either ALT (SGPT), AST (SGOT), or alkaline phosphatase (ALP) above 3 x upper limit of normal (ULN) as determined at Visit 1a. 3. Known hypersensitivity or allergy to the investigational product or its excipients), hypersensitivity or allergy to hydrochloride of pioglitazone or its excipients (carmellose calcium, hyprolose, lactose monohydrate, magnesium stearate). 4. Treatment with injectable GLP-1 analogue/agonist within 3 months prior to Informed Consent. 5. Treatment with insulin within 3 months prior to informed consent. 6. Treatment with anti-obesity drugs (e.g. sibutramine, orlistat, riminibant) 3 months prior to informed consent. 7. Alcohol or drug abuse within the 3 months prior to informed consent that would interfere with trial participation. 8. Participation in another trial with an investigational drug within 2 months prior to informed consent. 9. Pre-menopausal women (last menstruation 1 year prior to signing 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 transdermal patch, intra uterine devices/systems (IUDs/IUSs), oral, implantable or injectable contraceptives, sexual abstinence and vasectomised partner. No exception will be made. 10. Treatment with systemic steroids or change in the dosage of thyroid hormone within six weeks prior to informed consent. 11. Fasting blood glucose > 240 mg/dl (=13.3 mmol/L) at screening . 12. Heart failure NYHA class III-IV (Class III: patients with marked limitation of activity; they are comfortable only at rest; Class IV: patients who should be at complete rest, confined to bed or chair; any physical activity brings on discomfort and symptoms occur at rest) or history of heart failure prior to this study. 13. Diabetic ketoacidosis within 6 months prior to informed consent. 14. Hemodialysis patients, due to limited experience with TZDs. 15. Any other clinical condition which, in the opinion of the investigator, would not allow safe completion of the protocol and safe administration of BI 1356 and pioglitazone. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint for this study will be the change from baseline in HbA1c (HbA1c after 24 weeks of treatment). |
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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 | No |
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 | No |
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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | Information not present in EudraCT |
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 | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 72 |
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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Patients who complete the 24 week treatment period of this trial will be given the option of participating in an open-label extension trial. This extension study will be conducted under a separate protocol and patients will need to provide consent again for participation. |
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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 | |
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 | 6 |