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 | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10067585 |
E.1.2 | Term | Type 2 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 |
To investigate the long-term safety and tolerability of BI 10773 (10 and 25 mg once daily) |
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E.2.2 | Secondary objectives of the trial |
To assess the efficacy of BI 10773 (10 and 25 mg once daily) and for patients from 1245.20 of sitagliptin (100 mg once daily) for a minimum 76 weeks (incl. 24 weeks of preceding trial) compared to: • placebo as monotherapy (patients rolled over from trial 1245.20) • or placebo on a background of pioglitazone (patients rolled over from trial 1245.19) • or placebo on a background of metformin with or without sulfonylurea (patients rolled over from trial 1245.23) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Patients completing the entire treatment period of the preceding double-blind trial 1245.19, 1245.20 or 1245.23 with or without rescue therapy. 2) 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) Patient who meet one or more of the withdrawal criteria of the treatment period of the previous trial 1245.19, 1245.20 or 1245.23. 2) 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 last visit of preceding trial. 3) Impaired renal function defined as GFR<30 ml/min (severe renal impairment, MDRD formula) as determined during last visit of preceding trial. 4) Contraindications to sitagliptin, pioglitazone, metformin or sulfonylurea according to local label, which started during trial participation in 1245.19, 1245.20 or 1245.23 5) 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. 6) 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. 7) Participation in another trial with an investigational drug within 30 days prior to informed consent (except 1245.19, 1245.20 and 1245.23). 8) Any other clinical condition that would jeopardize patient's safety while participating in this clinical trial. |
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E.5 End points |
E.5.1 | Primary end point(s) |
No primary endpoints defined in the protocol.
Endpoint(s) of safety: • Adverse events • Hypoglycaemic events • Protocol-specified significant adverse events • Cardiovascular events (Clinical Event Committee adjudication results) • Changes from baseline in clinical laboratory values • Changes from baseline of GFR • Changes from baseline of albumin/creatinine ratio • Use of rescue therapy
Endpoints of efficacy (only applicable as secondary endpoints) The secondary efficacy endpoints in this study are: 1) The change from baseline in HbA1c after 52, 76 weeks of treatment and to end of treatment (EoT). Change from baseline in HbA1c by visit over time. 2) Body weight and waist circumference: Change from baseline to week 52, 76 and EoT. Change from baseline in body weight and waist circumference by visit over time. 3) Fasting plasma glucose (FPG): Change from baseline in fasting plasma glucose (FPG) after 52, 76 weeks of treatment and to EoT; Change from baseline in FPG by visit over time.
Other exploratory efficacy endpoints are the following: • Composite endpoint of the following conditions at week 52, 76 and EoT (all three fulfilled) - Change from baseline HbA1c of more than 0.5%, i.e. < -0.5%; - Change from baseline in SBP of more than 3 mmHg, i.e., < -3 mmHg; - Percentage change from baseline in weight of more than 2%, i.e., < -2%. • Systolic and diastolic blood pressure (SBP and DBP): Change from baseline to week 52, 76 and EoT. Change from baseline in SBP and DBP by visit over time.
The term "baseline" refers to the baseline values from the preceding trial, meaning the last evaluation before randomisation into the preceding trial. |
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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 | 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) | 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 | No |
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 |
Pts are rand. in the preceding trials. No new rand. will be done as pts stay on treatment in 1245.31 |
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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 | 17 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 80 |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |