Efficacy and Safety of Treatment With Balaglitazone in Type 2 Diabetes Patients on Stable Insulin Therapy

Study Overview
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Brief Summary
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Type 2 diabetes mellitus is a metabolic disorder that is primarily characterized by insulin resistance, relative insulin deficiency, and hyperglycemia. People with type 2 diabetes are at high risk of many serious diabetic complications, including cardiovascular disease, blindness, nerve damage and kidney damage. Balaglitazone is a thiazolidinedione derivative that is being developed as an oral anti-diabetic drug to improve blood glucose control in patients with type 2 diabetes. The purpose of this study is to assess if additional treatment with balaglitazone in patients with type 2 diabetes on stable insulin treatment will improve blood glucose control and decrease the daily insulin dose compared to placebo, but with less impact on weight gain and oedema than pioglitazone (Actos®) 45 mg.

Official Title
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A Randomized, Double-blind, Parallel-group, Placebo and Active Comparator (Pioglitazone)-Controlled Clinical Study to Determine the Efficacy and Safety of Balaglitazone in Patients With Type 2 Diabetes on Stable Insulin Therapy

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Balaglitazone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetes mellitus, being diagnosed according to the 1999 WHO criteria for at least 3 months Age ≥ 18 years BMI ≥ 25.0 kg/m2 HbA1c ≥ 7.0 % Treatment with insulin with stable dose of at least 30 U/day (± 4 U/day), for at least 75 days Exclusion Criteria: Prior or current use of any PPAR-γ agonist Recent use (< 3 months) of an investigational drug Pre-existing medical condition judged to preclude safe participation in the study Contraindication/intolerance to study medication Use of any drug which in the Investigator's opinion could interfere with the glucose level (e.g. systemic corticosteroids) Diagnosed or receiving medication for heart failure, NYHA I to IV Hospitalisation for a major CV event in the last 3 months, scheduled major CV intervention Uncontrolled treated/untreated systolic blood pressure >180 mmHg and/or diastolic blood pressure > 95 mmHg Known diabetic macular oedema Hematuria Serum creatinine >130 μmol/l ALT, AST, total bilirubin or alkaline phosphatase ≥ 2.5 times the upper limit of normal 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 Pregnancy, breast feeding or planning pregnancy or not using adequate contraceptive methods (adequate contraceptive measures are an intrauterine device or oral contraceptives) Mental incapacity, unwillingness, or language barrier precluding adequate understanding or cooperation Abuse of alcohol or drugs, or presence of any condition that in the Investigators opinion may lead to poor adherence to study protocols Cancer or any clinically significant disease or disorder, except for conditions associated to the type 2 diabetes, which in the Investigator's opinion could interfere with the results of the trial

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Balaglitazone 10 mg per day<br> | Drug: Balaglitazone<br>* One arm balaglitazone 10mg, one arm balaglitazone 20mg, one arm placebo, one arm pioglitazone (Actos®) 45mg, orally taken once daily.<br>|
| Experimental: Balaglitazone 20 mg per day<br> | Drug: Balaglitazone<br>* One arm balaglitazone 10mg, one arm balaglitazone 20mg, one arm placebo, one arm pioglitazone (Actos®) 45mg, orally taken once daily.<br>|
| Active Comparator: Pioglitazone 45 mg per day<br> | Drug: Balaglitazone<br>* One arm balaglitazone 10mg, one arm balaglitazone 20mg, one arm placebo, one arm pioglitazone (Actos®) 45mg, orally taken once daily.<br>|
| Placebo Comparator: Placebo<br> | Drug: Balaglitazone<br>* One arm balaglitazone 10mg, one arm balaglitazone 20mg, one arm placebo, one arm pioglitazone (Actos®) 45mg, orally taken once daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HbA1c, fasting plasma glucose and 7-point plasma glucose profiles, weight gain, lower leg oedema and safety parameters. |  | baseline, 4, 8, 12, 17, 21 and 26 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Waist and hip circumferences, plasmaNT-proBNP, ECG, body composition as measured by DXA, blood lipid profiles, plasma insulin |  | baseline and 26 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HbA1c, Type 2 diabetes mellitus on Stable insulin therapy, Balaglitazone, Pioglitazone (Actos®), Weight gain, Oedema, Fasting blood glucose