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

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01030952
• Other study ID #: CDJN608ACN07
• Status: Completed
• Phase: Phase 4
• First received: December 11, 2009
• Last updated: September 18, 2012
• Start date: December 2009
• Est. completion date: February 2011

Study information

• Verified date: September 2012
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 103
• Est. completion date: February 2011
• Est. primary completion date: February 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion criteria

1. Patients must give written informed consent before any assessment is performed.

2. Male, non-fertile female or female of childbearing potential using a medically approved birth control method based on local regulations.

3. 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.

4. Age in the range of 18-75 years inclusive.

5. HbA1c in the range of > 6.5 to =9.0% at Visit 1.

Exclusion criteria

1. 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).

2. With known hypersensitivity to Nateglinide, Acarbose or any of the excipients.

3. A history of,

1. type 1 diabetes, diabetes that is a result of pancreatic injury, or secondary forms of diabetes, e.g., Cushing's syndrome and acromegaly.

2. acute metabolic diabetic complications such as ketoacidosis or hyperosmolar state (coma) within the past 6 months.

3. Torsades de pointes, sustained and clinically relevant ventricular tachycardia or ventricular fibrillation.

4. percutaneous coronary intervention within the past 3 months.

5. any of the following within the past 6 months: myocardial infarction (MI), coronary artery bypass surgery, unstable angina, or stroke.

4. Evidence of significant diabetic complications, e.g., symptomatic autonomic neuropathy or gastroparesis.

5. Acute infections which may affect blood glucose control within 4 weeks prior to visit 1.

6. Congestive heart failure requiring pharmacologic treatment. mg/dL (123µmol/L)

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• Nateglinide
Nateglinide tablets, oral administration, three times daily, 120 mg orally 10 minutes immediately before 3 meals three times daily.
• Acarbose
Acarbose tablets, oral administration, three times daily, dosage of 50 mg orally chewing with the first bite of a meal three times daily.

Locations

Country	Name	City	State
China	Sir Run Run Shaw Hospital, 3 East Qingchun Road	Hangzhou
China	Shanghai Sixth People's Hospital, 600 Xuanshan Road	Shanghai
China	Shanghai Tongji Hospital, 389 Xinchun Road	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

China, 

References & Publications (1)

Gao HW, Xie C, Wang HN, Lin YJ, Hong TP. Beneficial metabolic effects of nateglinide versus acarbose in patients with newly-diagnosed type 2 diabetes. Acta Pharmacol Sin. 2007 Apr;28(4):534-9. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No