E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
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 demonstrate the efficacy of LAF237 in patients with type 2 diabetes with HbA1c 9- 11% by testing the hypothesis that the HbA1c reduction with LAF237 50 mg BID is superior to that with LAF 237 50 mg OD after 12 weeks of treatment. |
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E.2.2 | Secondary objectives of the trial |
1 To explore the efficacy of LAF237 in patients with type 2 diabetes with HbA1c 9-11% by testing the hypothesis that the HbA1c reduction with LAF237 50 mg BID is superior to that with pioglitazone 30 mg OD after 12 weeks of treatment.
2.To explore the efficacy of LAF237 in patients with type 2 diabetes with HbA1c 9-11% by testing the hypothesis that the responder rates (defined as reduction in HbA1c ≥ 0,5% ≥ 0.7% and ≥ 1% respectively) with LAF237 50 mg BID are superior to those with LAF 237 50 OD or pioglitazone 30 mg OD after 12 weeks of treatment.
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1.Drug nave patients with type 2 diabetes (drug naïve patients are defined as patients who have had no treatment with oral antidiabetic agents for at least 12 weeks prior to study entry (visit 1) and no treatment with oral antidiabetic agents for > 3 consecutive months at any time in the past). 2. Body mass index (BMI) in the range of 22-45 kg/m2 inclusive at visit 1. 3. HbA1c in the range of 9.0 to 11.0 % inclusive at visit 1. 4. Fasting C-peptide > 0.6 ng/ml (0.2 nmol/l) at visit 1. 5 Age ≥ 18 year 6.Male, non-fertile female (i.e., post menopausal, post hysterectomy, or sterilized by tubal ligation) or female of childbearing potential using a non-hormonal medically approved birth control method (e.g., IUD, double-barrier contraception). Females using hormonal contraceptives must use a non-hormonal medically approved birth control method in addition during the full course of the study. A female of childbearing potential must be willing to use the same method(s) of contraception during the entire study. |
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E.4 | Principal exclusion criteria |
1. Pregnant or lactating female. 2. A history of: Type 1 diabetes, diabetes that is a result of pancreatic injury, or secondary forms of diabetes, e.g., Cushing’s syndrome and acromegaly. Acute diabetic complication 3. Liver disease such as cirrhosis or chronic active hepatitis. 4. Congestive heart failure. 5. Acute infections which may affect blood glucose control within 4 weeks prior to visit 1. 6. Acromegaly or treatment with growth hormone or similar drugs. 7. Any of the following ECG abnormalities: 12. Investigational drug treatment within 4 weeks prior to visit 1 unless local health authority guidelines mandate a longer period. 13. Treatment with any drug with a known and frequent toxicity to a major organ system within the past 3 months (i.e., cytostatic drugs). 14. Any of the following significant laboratory abnormalities: ALT, AST greater than 2.5 times the upper limit of the normal range at visit 1. Direct bilirubin greater than 1.3 times the upper limit of the normal range at visit 1. Serum creatinine levels > 2.5 mg/dl (220 mol/l) at visit 1. Clinically significant abnormal TSH at visit 1. Clinically significant laboratory abnormalities, confirmed by repeat measurement, that may interfere with the assessment of safety and/or efficacy of the study drug, other than hyperglycemia, hyperinsulinemia, and glycosuria at visit 1. Fasting triglycerides 700 mg/dl (>7.9 mmol/l) at visit 1. Positive GAD antibodies at visit 1 (GAD antibodies will be tested in patients < 30 years.). 15. Evidence of significant diabetic complications, e.g., symptomatic autonomic neuropathy or gastroparesis. 16. Known sensitivity to any of the test drugs. 17. Further contraindications and warnings according to the country specific label for pioglitazone not listed in the other exclusion criteria. 18. History of active substance abuse (including alcohol) within the past 2 years. 19. Concurrent medical condition that may interfere with the interpretation of efficacy and safety data during the study. 20. Donation of one unit (500 ml) or more of blood, significant blood loss equaling to at least one unit of blood within 2 weeks or a blood transfusion within 8 weeks prior to visit 1. 21. Potentially unreliable patients, and those judged by the investigator to be unsuitable for the study.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable is change from baseline in HbA1c at Week 12 or at the final visit with HbA1c measurement for those patients who do not have a Week 12 HbA1c measurement (the last observation carried forward (LOCF) approach). Baseline is the measurement obtained on the day of randomization (Day 1, Visit 2), or the screening measurement (Week -2, Visit 1) if Day 1 measurement is missing. |
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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 | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Yes |
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 | 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.8.1.7.1 | 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 | No |
E.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
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 | |
E.8.9.1 | In the Member State concerned months | 12 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 12 |