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 | 15.1 |
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 | 100000004861 |
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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 safety and efficacy of BI10773 (10 mg q.d. and 25mg q.d.) compared to placebo added to a multiple daily injections (MDI) insulin regimen alone or with metformin in patients with T2DM. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Diagnosis of T2DM prior to informed consent.
2. Male and female patients on diet and exercise regimen who are pre-treated with multiple daily injections (MDI) of insulin alone or in combination with immediate or extended release metformin. Insulin therapy must include both basal and prandial insulin. Any type of basal and any type of prandial insulin are allowed. Pre-mixed insulin preparations are not allowed.
3. Total prescribed insulin dose must be >60 IU/day at Visit 1 (screening) and should not be changed within 12 weeks prior to randomization by more than 10% from the baseline value at randomization (Visit 3).
4. Patients not taking metformin
or
Patients on stable metformin therapy:
• Daily dose ≥1500 mg/day or maximum tolerated dose (must be documented) or maximum dose according to the local label.
• The metformin dose has to be unchanged for 12 weeks before the randomization (Visit 3).
5. HbA1c ≥7.5% and ≤10% at Visit 1 (screening).
6. Age ≥18 years at Visit 1 (screening).
7. Body mass index (BMI) ≥30 and ≤45 kg/m² at Visit 1 (screening).
8. 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 hyperglycemia with a glucose level >240 mg/dl (>13.3 mmol/l) after an overnight fast during placebo run-in and confirmed by second measurement (not on the same day).
2. Any other antidiabetic drug within 12 weeks prior to randomization except those mentioned in inclusion criterion 2.
3. Acute coronary syndrome (non-STEMI, STEMI and unstable angina pectoris), stroke or transient ischemic attack (TIA) within 3 months prior to informed consent.
4. Indication of liver disease, defined by serum levels of either alanine transaminase (ALT, SGPT), aspartate transaminase (AST, SGOT), or alkaline phosphatase above 3 times upper limit of normal (ULN) as determined during screening or run-in period.
5. Impaired renal function, defined as GFR <60 ml/min (MDRD formula) as determined during screening and/or run-in period.
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) or treatment for cancer within the last 5 years.
8. Known blood dyscrasias or any disorders causing hemolysis or unstable red blood cell (e.g. malaria, babesiosis, hemolytic anemia).
9. Any contraindications to metformin according to the local label for those patients who entered the study with metformin therapy.
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 vasectomized 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; or participating in another trial (involving an investigational drug and/or follow-up) after discontinuing medication in this trial.
15. 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 primary endpoint in this study is the change from baseline in HbA1c after 18 weeks of treatment. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Change from baseline in insulin dose after 52 weeks of treatment
Change from baseline in body weight after 52 weeks of treatment
Change from baseline in HbA1c after 52 weeks of treatment
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E.5.2.1 | 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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 46 |
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 |
Belgium |
Bulgaria |
Colombia |
Czech Republic |
Finland |
France |
Germany |
Guatemala |
Mexico |
Peru |
Russian Federation |
Spain |
Ukraine |
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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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 | 2 |
E.8.9.1 | In the Member State concerned days | 21 |
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 | 21 |