Effects of Nateglinide on Postprandial Glucose Excursion by Restoring Early Phase Insulin Secretion

Study Overview
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Brief Summary
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A 3-week, multi-center, open-label, randomized, active-control, parallel-group study to compare effects of Nateglinide and Acarbose on postprandial glucose fluctuation in Chinese drug-naive patients type 2 diabetes mellitus (T2DM). In this study, participants in different groups took Nateglinide at a dose of 120 mg orally three times daily for up to 3 weeks or Acarbose at a dose of 50 mg three times daily for up to 3 weeks, respectively.

Official Title
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A 3-week, Multi-center, Open-label, Randomized, Active-control, Parallel-group Study to Compare Effects of Nateglinide and Acarbose on Postprandial Glucose Fluctuation in Chinese Drug-naive Patients Type 2 Diabetes Mellitus

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Nateglinide
* Drug: Acarbose


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Patients must give written informed consent before any assessment is performed. Male, non-fertile female or female of childbearing potential using a medically approved birth control method based on local regulations. Drug naïve type 2 diabetes patients, defined as who neither take consecutive anti-hyperglycemic drug treatment more than 3 months anytime, nor any anti-hyperglycemic drug treatment in 4 weeks prior to visit 1. Age in the range of 18-75 years inclusive. HbA1c in the range of > 6.5 to ≤9.0% at Visit 1. Exclusion criteria Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (>5 mIU/mL). With known hypersensitivity to Nateglinide, Acarbose or any of the excipients. 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 metabolic diabetic complications such as ketoacidosis or hyperosmolar state (coma) within the past 6 months. Torsades de pointes, sustained and clinically relevant ventricular tachycardia or ventricular fibrillation. percutaneous coronary intervention within the past 3 months. any of the following within the past 6 months: myocardial infarction (MI), coronary artery bypass surgery, unstable angina, or stroke. Evidence of significant diabetic complications, e.g., symptomatic autonomic neuropathy or gastroparesis. Acute infections which may affect blood glucose control within 4 weeks prior to visit 1. Congestive heart failure requiring pharmacologic treatment. mg/dL (123μmol/L)

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: Nateglinide<br>Nateglinide tablets, oral administration, three times daily, 120 mg orally 10 minutes immediately before 3 meals three times daily. | Drug: Nateglinide<br>* Nateglinide tablets, oral administration, three times daily, 120 mg orally 10 minutes immediately before 3 meals three times daily.<br>|
| Active Comparator: Acarbose<br>Acarbose tablets, oral administration, three times daily, dosage of 50 mg orally chewing with the first bite of a meal three times daily. | Drug: Acarbose<br>* Acarbose tablets, oral administration, three times daily, dosage of 50 mg orally chewing with the first bite of a meal three times daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Area Under Curve of 0-4 Hours Postprandial Glucose (AUCpp0-4hours) in Standardized Meal Test Using Continuous Glucose Monitoring System (CGMS) | The postprandial glucose area under the curve (AUC)was calculated using values from the 3 time points. Participants were fasting (no calorie intake for at least 8 hours prior to the meal test) and completed the standardized meal test between 7 and 10 AM. 0-4 hours AUC were calculated using trapezoid methods. | 3 weeks (end of study) minus baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Incremental Glucose Peak (IGP) From Baseline | Incremental glucose peak (IGP) was the maximal incremental increase in blood glucose obtained at any point after meal | baseline, 3 weeks (end of study) | 
| Change in Mean Blood Glucose (MBG) | The 24 hour mean blood glucose (MBG) level was calculated as the mean of all the consecutive readings on baseline and end of study(3 weeks later) separately. | baseline and at 3 weeks (end of study) | 
| Change in Standard Deviation (SD) From Baseline of Mean Blood Glucose (MBG) Over 24 Hours. | Change in standard deviation (SD) from baseline of mean blood glucose (MBG) describes the range of blood glucose fluctuation over 24 hours. | baseline, 3 weeks (end of study) | 
| Change in Mean of Daily Difference of Paired Blood Glucose Value (MODD) | The mean of the daily differences (MODD), calculated as the average absolute difference of paired glucose values during two successive 24 hour periods, was used to assess day-to-day glycaemic variability. | baseline, 3 weeks (end of study) | 
| Changes in 24 Hour Glucose Area Under Curve (AUCpp) | Blood samples were collected for measurement of plasma glucose at 30, 60, 90, and 120 minutes following the start of a standardized meal test at Baseline and Week 4. The postprandial glucose area under the curve was calculated using values from the 4 time points. Participants were fasting (no calorie intake for at least 8 hours prior to the meal test) and completed the standardized meal test between 7 and 10 AM. | baseline, end of study (3 weeks) | 
| Change in Glycated Serum Albumin (GSA) Levels From Baseline After Treatment | GSA levels were to be determined by CGMS at 7:00 10:00 am in the 4-hour standardized meal test before treatment after overnight fasting for efficacy assessments | baseline, 3 weeks (end of study) | 
| Change in Insulin Levels (μU/ml) During Standardized Meal Test at Endpoint From Baseline | This outcome measure calculated the change in insulin levels between groups over time at 0, 30 then 120 minutes | baseline, 3 weeks (end of study) | 
| Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) | change in LDL-C at 0, 30 and 120 minutes | baseline, 3 weeks (end of study) | 
| Change of Total Cholesterol in Blood Lipids Levels During Standardized Meal Test at Endpoint From Baseline at Each Time Point | time to change in Total Cholesterol blood lipids level at 0, 30, 120 minutes | baseline, 3 weeks (end of study) | 
| Change in Triglyceride (TG)Levels in Blood Lipid Levels During Standardized Meal Test at Endpoint | TG change in blood lipids level from baseline to endpoint | baseline, 3 weeks (end of study) | 
| Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) at the End of the Study | Blood samples were collected for measurement of HDL-C prior to (fasting) and 120 minutes following the start of a standardized meal test at Baseline and Week 3. Participants were fasting (no calorie intake for at least 8 hours prior to the meal test) and completed the standardized meal test between 7 and 10 AM. HDL-C was assessed at each study site using the same method and same reference value. | baseline, 3 weeks (end of study) | 
| Change in Mean Amplitude of Glycaemic Excursion (MAGE) | mean amplitude of glycaemic excursion (MAGE) is an average of the amplitudes of all glycemic excursions greater than a prespecified threshold size | baseline, 3 weeks (end of study) | 
| The Percent of 24 Hour Hypoglycemic Measurements | Measures/compares changes in percentage of hypoglycemia(<3.9mmol/l or <70 mg/dl) in glucose measurements in 24hours by continuous glucose monitoring system (CGMS) at endpoint from baseline between groups. Reported values are percent change of the base absolute values [100% * ((X-Y)/Y)] | baseline, 3 weeks (end of study) | 
| Change in Percent of 24 Hour Hyperglycemic Measurements | Measures/compares changes in percentage of hyperglycemia (>7.8mmol/l or 140 mg/dl) in glucose measurements in 24 hours by continuous glucose monitoring system (CGMS) at endpoint from baseline between groups. Reported values are percent change of the base absolute values [100% * ((X-Y)/Y)] | baseline, 3 weeks (end of study) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes Mellitus, Type 2, Nateglinide, Acarbose, glucose fluctuation