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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01030952
First received: December 11, 2009
Last updated: September 18, 2012
Last verified: September 2012
History of Changes
  Purpose

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.


Condition Intervention Phase
Diabetes Mellitus, Type 2
 Drug: Nateglinide
Drug: Acarbose
 Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:
  • Change in Area Under Curve of 0-4 Hours Postprandial Glucose (AUCpp0-4hours) in Standardized Meal Test Using Continuous Glucose Monitoring System (CGMS) [ Time Frame: 3 weeks (end of study) minus baseline ] [ Designated as safety issue: No ]

    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.



Secondary Outcome Measures:
  • Change in Incremental Glucose Peak (IGP) From Baseline [ Time Frame: baseline, 3 weeks (end of study) ] [ Designated as safety issue: No ]
    Incremental glucose peak (IGP) was the maximal incremental increase in blood glucose obtained at any point after meal

  • Change in Mean Blood Glucose (MBG) [ Time Frame: baseline and at 3 weeks (end of study) ] [ Designated as safety issue: No ]
    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.

  • Change in Standard Deviation (SD) From Baseline of Mean Blood Glucose (MBG) Over 24 Hours. [ Time Frame: baseline, 3 weeks (end of study) ] [ Designated as safety issue: No ]
    Change in standard deviation (SD) from baseline of mean blood glucose (MBG) describes the range of blood glucose fluctuation over 24 hours.

  • Change in Mean of Daily Difference of Paired Blood Glucose Value (MODD) [ Time Frame: baseline, 3 weeks (end of study) ] [ Designated as safety issue: No ]
    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.

  • Changes in 24 Hour Glucose Area Under Curve (AUCpp) [ Time Frame: baseline, end of study (3 weeks) ] [ Designated as safety issue: No ]
    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.

  • Change in Glycated Serum Albumin (GSA) Levels From Baseline After Treatment [ Time Frame: baseline, 3 weeks (end of study) ] [ Designated as safety issue: No ]
    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

  • Change in Insulin Levels (μU/ml) During Standardized Meal Test at Endpoint From Baseline [ Time Frame: baseline, 3 weeks (end of study) ] [ Designated as safety issue: No ]
    This outcome measure calculated the change in insulin levels between groups over time at 0, 30 then 120 minutes

  • Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) [ Time Frame: baseline, 3 weeks (end of study) ] [ Designated as safety issue: No ]
    change in LDL-C at 0, 30 and 120 minutes

  • Change of Total Cholesterol in Blood Lipids Levels During Standardized Meal Test at Endpoint From Baseline at Each Time Point [ Time Frame: baseline, 3 weeks (end of study) ] [ Designated as safety issue: No ]
    time to change in Total Cholesterol blood lipids level at 0, 30, 120 minutes

  • Change in Triglyceride (TG)Levels in Blood Lipid Levels During Standardized Meal Test at Endpoint [ Time Frame: baseline, 3 weeks (end of study) ] [ Designated as safety issue: No ]
    TG change in blood lipids level from baseline to endpoint

  • Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) at the End of the Study [ Time Frame: baseline, 3 weeks (end of study) ] [ Designated as safety issue: No ]
    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.

  • Change in Mean Amplitude of Glycaemic Excursion (MAGE) [ Time Frame: baseline, 3 weeks (end of study) ] [ Designated as safety issue: No ]
    mean amplitude of glycaemic excursion (MAGE) is an average of the amplitudes of all glycemic excursions greater than a prespecified threshold size

  • The Percent of 24 Hour Hypoglycemic Measurements [ Time Frame: baseline, 3 weeks (end of study) ] [ Designated as safety issue: No ]
    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)]

  • Change in Percent of 24 Hour Hyperglycemic Measurements [ Time Frame: baseline, 3 weeks (end of study) ] [ Designated as safety issue: No ]
    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)]


Enrollment: 103
Study Start Date: December 2009
Study Completion Date: February 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Nateglinide
Nateglinide tablets, oral administration, three times daily, 120 mg orally 10 minutes immediately before 3 meals three times daily.
 Drug: Nateglinide
Nateglinide tablets, oral administration, three times daily, 120 mg orally 10 minutes immediately before 3 meals three times daily.
Active Comparator: Acarbose
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
Acarbose tablets, oral administration, three times daily, dosage of 50 mg orally chewing with the first bite of a meal three times daily.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01030952

Locations
China
Sir Run Run Shaw Hospital, 3 East Qingchun Road
Hangzhou, China, 310016
Shanghai Sixth People's Hospital, 600 Xuanshan Road
Shanghai, China, 200233
Shanghai Tongji Hospital, 389 Xinchun Road
Shanghai, China, 200065
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Publications:

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01030952     History of Changes
Other Study ID Numbers: CDJN608ACN07
Study First Received: December 11, 2009
Results First Received: February 20, 2012
Last Updated: September 18, 2012
Health Authority: China: Food and Drug Administration

Keywords provided by Novartis:
Diabetes Mellitus, Type 2
Nateglinide
Acarbose
glucose fluctuation

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Acarbose
 Nateglinide
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Hypoglycemic Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 23, 2013