Comparison of the Blood Sugar Lowering Effect Between Repaglinide Plus Metformin and Repaglinide Alone in Type 2 Diabetics Not Previously Treated With Oral Sugar-lowering Drugs

Study Overview
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Brief Summary
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This trial is conducted in Asia. The aim of this clinical trial is to investigate the blood sugar lowering effect of repaglinide plus metformin as initial treatment compared to repaglinide alone in Chinese subjects with type 2 diabetes having an HbA1c (glycosylated haemoglobin A1c) over 8.5 % and who never have taken oral sugar-lowering drugs before. The associated unfavourable events including low blood sugar episodes between the two treatments are also compared.

Official Title
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A 16-week, Open-label, Multicentre, Randomised, Parallel Study to Evaluate Efficacy and Safety of Repaglinide and Metformin Combination Therapy Compared to Repaglinide Monotherapy in Chinese OAD Naive Type 2 Diabetic Patients

Conditions
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Diabetes, Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: repaglinide
* Drug: metformin
* Drug: repaglinide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with type 2 diabetes Never taken oral antidiabetic drugs before HbA1c greater than 8.5 % BMI (Body Mass Index) less than or equal to 35 kg/m^2 Exclusion Criteria: Known or suspected allergy to repaglinide, metformin, or any of the excipients in the medications Taken an investigational drug in another clinical trial within 4 weeks prior to this trial Impaired liver function, defined as ASAT (aspartate aminotransferase) or ALAT (alanine aminotransferase) equal to or greater than 2 times upper normal limit Have a clinically significant, active disease of the gastrointestinal, pulmonary, neurological, renal, genitourinary, and haematological systems Severe uncontrolled or untreated hypertension (sitting diastolic blood pressure (BP) equal to or greater than 100 mmHg or systolic BP equal to or greater than 180 mmHg) Impaired renal function Acute or chronic acidosis or if there are plans to have a radiographic material containing iodine Have a clinically significant, active cardiovascular disease, or decompensated heart failure Treatment with systemic corticosteroids within the past two months prior to screening

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Repaglinide + metformin<br>Initial dose of repaglinide 1mg plus metformin 500mg once daily. During the dose titration period of 6 weeks, the dose could be titrated up to repaglinide 4 mg and metformin 500 mg three times daily, according to fasting glucose values. The minimal dose was repaglinide 1 mg plus metformin 500 mg three times daily. | Drug: repaglinide<br>* The dose was started from repaglinide 1 mg plus metformin 500 mg once daily. During the dose titration period, the dose could be titrated up to repaglinide 4 mg and metformin 500mg three times daily, according to fasting glucose. the minimal dose was repaglinide 1 mg plus metformin 500 mg three times daily<br>Drug: metformin<br>* The dose was started from repaglinide 1 mg plus metformin 500 mg once daily. During the dose titration period, the dose could be titrated up to repaglinide 4 mg and metformin 500 mg three times daily, according to fasting glucose. the minimal dose was repaglinide 1 mg plus metformin 500 mg three times daily<br>|
| Active Comparator: Repaglinide<br>Initial dose of repaglinide 1 mg three times daily. During the dose titration period of 6 weeks, the dose of repaglinide could be titrated up to 4 mg three times daily, according to fasting glucose values. The minimal dose was repaglinide 1 mg three times daily. | Drug: repaglinide<br>* The dose was started from repaglinide 1 mg three times daily. During the dose titration period, the dose of repaglinide could be titrated up to 4 mg three times daily, according to fasting glucose.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Glycosylated Haemoglobin A1c (HbA1c) | Calculated as an estimate of the mean change in HbA1c after 16 weeks of treatment. | week -2 (screening), week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Fasting Plasma Glucose | Calculated as an estimate of the mean change in fasting plasma glucose after 16 weeks of treatment. | week 0, week 16 | 
| Change in 2-hour Postprandial Plasma Glucose | Calculated as an estimate of the mean change in 2-hour postprandial plasma glucose following a standard test meal after 16 weeks of treatment | Week 0, week 16 | 
| Change in 7-point Plasma Glucose Profile | Calculated as an estimate of the mean change in 7-point (before breakfast, 2 hours after breakfast, before lunch, 2 hours after lunch, before dinner, 2 hours after dinner, bedtime) plasma glucose profile after 16 weeks of treatment. | Week 0, week 16 | 
| Change in Fasting Serum Insulin | Calculated as an estimate of the mean change in fasting serum insulin after 16 weeks of treatment. | Week 0, week 16 | 
| Change in 2-hour Postprandial Serum Insulin | Calculated as an estimate of the mean change in 2-hour postprandial serum insulin after 16 weeks of treatment. | Week 0, week 16 | 
| Change in Fasting Serum C-peptide | Calculated as an estimate of the mean change in fasting serum C-peptide after 16 weeks of treatment | Week 0, week 16 | 
| Change in 2-hour Postprandial Serum C-peptide | Calculated as an estimate of the mean change in 2-hour postprandial serum C-peptide after 16 weeks of treatment | Week 0, week 16 | 
| Hypoglycaemic Episodes | Number of hypoglycaemic episodes from Week 0 to Week 16, defined as major, minor or symptoms only. Major if unable to treat her/himself. Minor if able to treat her/himself and plasma glucose below 3.1 mmol/L. Symptoms only if able to treat her/himself and no plasma glucose measurement or plasma glucose higher than or equal to 3.1 mmol/L. | Weeks 0-16 | 
| Change in Blood Pressure | Calculated as the mean change in diastolic and systolic blood pressure after 16 weeks of treatment | Week 0, week 16 | 
| Physical Examinations | The number of subjects having a physical examination event that changed from 'Normal' or 'Abnormal, not clinically significant' to 'Abnormal, clinically significant'. Physical examination included cardiovascular system, respiratory system, musculoskeletal system, nervous system and abdomen. | Week -2, week 16 | 
| ECG (ElectroCardioGram) | The number of subjects having a electrocardiogram (ECG) that changed from 'Normal' or 'Abnormal, not clinically significant' to 'Abnormal, clinically significant'. 'Abnormal, Clinically significant' is an abnormality that suggests a disease and/or organ toxicity and is of a severity, which requires active management. | Week -2, week 16 | 
| Biochemistry: Alanine Aminotransferase (ALAT) | The number of subjects having a change in Alanine Aminotransferase (ALAT) from 'Normal' or 'Abnormal, not clinically significant' to 'Abnormal, clinically significant'. 'Abnormal, Clinically significant' is an abnormality that suggests a disease and/or organ toxicity and is of a severity, which requires active management. | Week -2, week 16 | 
| Biochemistry: Alanine Aminotransferase (ASAT) | The number of subjects having a change in Aspartate Aminotransferase (ASAT) from 'Normal' or 'Abnormal, not clinically significant' to 'Abnormal, clinically significant'. 'Abnormal, Clinically significant' is an abnormality that suggests a disease and/or organ toxicity and is of a severity, which requires active management. | Week -2, week 16 | 
| Haematology: Haemoglobin | Haemoglobin was measured. The number of subjects having a change in Haemoglobin measurement from 'Normal' or 'Abnormal, not clinically significant' to 'Abnormal, clinically significant' 'Abnormal, Clinically significant' is an abnormality that suggests a disease and/or organ toxicity and is of a severity, which requires active management. | Week -2, week 16 |