E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Balaglitazone is being developed as an oral anti-diabetic drug to improve glycaemic control in patients with type 2 diabetes |
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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 |
To compare, in type 2 diabetes patients on stable insulin therapy, the efficacy of balaglitazone 10 mg and 20 mg against placebo on absolute change in HbA1c from baseline to end of trial.
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E.2.2 | Secondary objectives of the trial |
To assess and compare the effect of balaglitazone against pioglitazone 45 mg or placebo on various pharmacodynamic measurements in patients with type 2 diabetes on stable insulin therapy from baseline to end of trial. The secondary outcome measures include changes in;
1. Fasting plasma glucose, 4- and 7-point plasma glucose profiles 2. Percentage/proportion of patients achieving an HbA1c <7.0% or <6.5% 3. Blood lipid profile (TG, TC, LDL-C, HDL-C, LDL/HDL) 4. Body weight gain 5. Waist and hip circumferences 6. Plasma volume and plasma NT-proBNP 7. Frequency of lower leg oedema by clinical assessment or by water displacement 8. Change in body composition, as measured by DXA, as a measure of changes in fat tissue mass and Lean tissue mass, i.e. fluid retention 9. Daily dose of insulin
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Type 2 diabetes mellitus, being diagnosed according to the 1999 WHO criteria for at least 3 months 2. Age ≥ 18 years 3. BMI ≥ 25.0 kg/m2 4. HbA1c ≥ 7.0 % 5. Treatment with insulin on stable dose of at least 30 U/day (± 4 U/day), for at least 75 days (insulin adjustments are during a previous and resolved short trem acute disease are permitted).
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E.4 | Principal exclusion criteria |
1. Prior or current use of PPAR-γ agonist 2. Hospitalisation for a major CV event in the last 3 months, scheduled major CV intervention 3. Diagnosed or receiving medication for heart failure, NYHA I to IV 4. Uncontrolled treated/untreated systolic > 180 mmHg and/or diastolic blood pressure > 95 mmHg 5. Serum creatinine > 130 μmol/L 6. ALT, AST, total bilirubin or alkaline phosphatase ≥ 2.5 times the upper limit of normal 7. Haemoglobin significantly (in the Investigators opinion, but not more than 1 mmol/L) below the lower limit of normal or haemoglobinopathy interfering with valid HbA1c assay 8. Hematuria, defined as any, even trace of, hematuri on a urinary dipstick at the screening or randomisation visit 9. Contraindication/intolerance to study medication 10. Pre-existing medical condition judged to preclude safe participation in the study 11. Abuse of alcohol or drugs, or presence of any condition that in the Investigators opinion may lead to poor adherence to study protocol 12. Recent use (< 3 months) of an investigational drug 13. Pregnancy, breast feeding or planning pregnancy or not using adequate contraceptive methods (adequate contraceptive measures are an intrauterine device or oral contraceptives). 14. Mental incapacity, unwillingness, or language barrier precluding adequate understanding or cooperation 15. Use of any drug which in the Investigator’s opinion could interfere with the glucose level (e.g. systemic corticosteroids). 16. Any cancer history or currently diagnosed/treated cancer 17. Diagnosis of clinically significant disease/disorder which in the Investigator’s opinion could interfere with the results of the trial 18. Known Diabetic macular oedema 19. Planned surgery
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E.5 End points |
E.5.1 | Primary end point(s) |
To compare, in type 2 diabetes patients on stable insulin therapy, the efficacy of balaglitazone 10 mg and 20 mg against placebo on absolute change in HbA1c from baseline to end of 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 | No |
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 | 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) | 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 | 22 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
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 |