E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 | 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 objective of the current study is to investigate the efficacy, safety and tolerability of BI 10773 (10 mg and 25 mg/ once daily) compared to placebo given for 52 weeks as add-on pre-existing antidiabetic therapy in patients with T2DM with insufficient glycaemic control and renal impairment. The study is designed to show superiority of BI 10773 over placebo. |
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E.2.2 | Secondary objectives of the trial |
•HbA1c:
Change from baseline in HbA1c after 52 weeks of treatment
Occurrence of treat to target efficacy response, that is an HbA1c of <7.0% after 24 and 52 weeks of treatment ;
Occurrence of relative efficacy response (HbA1c lowering by a least 0.5% after 24 and 52 weeks of treatment;
Change from baseline in HbA1c by visit over time
•FPG:
Change from baseline in FPG after 24 and 52 weeks of treatment;
Change from baseline in FPG by visit over time
•Body weight and waist circumference: Change from baseline to week 24 and 52
•Systolic and diastolic BP: Change from baseline to week 24 and 52.
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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 and a eGFR of <90 ml/min, as determined during screening and the run-in phase, using the Modification of Diet in Renal Disease (MDRD) equation.
2. Male and female patients on diet and exercise regimen who are pre-treated with any antidiabetic therapy (excluding only SGLT-2 inhibitors) and are on the maximum tolerated dose which has been unchanged for 12 weeks prior to randomisation.
•Metformin therapy should be ≥1500 mg/day or on the maximum tolerated dose or maximum dose according to local labelling
•The prescribed insulin dose should not be changed within the 12 weeks prior to randomisation by +/- 10% from the baseline value at randomisation
•Pioglitazone therapy should be ≥ 30 mg/day or maximum dose according to local labelling
•Sulphonylurea therapy should be ≥ half the recommended maximal dose according to local labelling.
3. HbA1c of ≥7.0% and <=10.0% at Visit 1 (screening).
4. Age ≥18 years.
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. Impaired renal function, defined as eGFR<15 ml/min using the MDRD equation.as determined during screening and/or the run-in phase
3. Renal impairment requiring any form of chronic dialysis.
4. Requiring acute dialysis within three months prior to informed consent.
5. Renal transplant recipient.
6. Acute coronary syndrome (non-STEMI, STEMI and unstable angina pectoris), stroke or Transient Ischemic Attack (TIA) within three months prior to informed consent.
7. Indication of liver disease, defined by serum levels of either Alanine transaminase (ALT) (SGPT), AST (SGOT), or alkaline phosphatase above 3 x upper limit of normal (ULN) as determined during screening and/or the run-in phase.
8. Bariatric surgery within the past two years and other gastrointestinal surgeries that induce chronic malabsorption.
9. Medical history of cancer (except for basal cell carcinoma) and/or treatment for cancer within the last five years.
10. Blood dyscrasias or any disorders causing hemolysis or unstable red blood cell (e.g. malaria, babesiosis, haemolytic anemia).
11. Contraindications to pre-existing background antidiabetic therapy according to the local label.
12. Treatment with anti-obesity drugs three 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.
13. Current treatment with systemic steroids at time of informed consent or change in dosage of thyroid hormones within six weeks prior to informed consent or any other uncontrolled endocrine disorder except T2DM.
14. 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 practising 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.
15.Alcohol or drug abuse within the three 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.
16.Intake of an investigational drug in another trial within 30 days prior to intake of study medication in this trial; or participating in another trial (involving an investigational drug and/or follow-up) after discontinuing medication in this trial.
17.Any other clinical condition that would jeopardize patients safety while participating in this clinical trial.
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E.5 End points |
E.5.1 | Primary end point(s) |
The change from baseline in HbA1c |
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E.5.1.1 | 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 | 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 | 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 | 3 |
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 | 12 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 59 |
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 | No |
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 |
Canada |
France |
Hong Kong |
India |
Israel |
Malaysia |
Netherlands |
Philippines |
Poland |
Portugal |
Russian Federation |
Slovakia |
South Africa |
Spain |
United Kingdom |
United States |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 6 |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial days | 6 |