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 - Full Text View

Sponsor:	Novo Nordisk
Information provided by:	Novo Nordisk
ClinicalTrials.gov Identifier:	NCT00819741

Purpose

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.

Condition	Intervention	Phase
Diabetes Mellitus, Type 2	Drug: repaglinide Drug: metformin	Phase IV

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	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

Resource links provided by NLM:

Genetics Home Reference related topics: 6q24-related transient neonatal diabetes mellitus

MedlinePlus related topics: Diabetes Diabetes Medicines Diabetes Type 2

Drug Information available for: AG-EE 388 ZW Metformin Metformin hydrochloride

U.S. FDA Resources

Further study details as provided by Novo Nordisk:

Primary Outcome Measures:

Change in Glycosylated Haemoglobin A1c (HbA1c) [ Time Frame: week -2 (screening), week 16 ] [ Designated as safety issue: No ]
Calculated as an estimate of the mean change in HbA1c after 16 weeks of treatment.

Secondary Outcome Measures:

Change in Fasting Plasma Glucose [ Time Frame: week 0, week 16 ] [ Designated as safety issue: No ]
Calculated as an estimate of the mean change in fasting plasma glucose after 16 weeks of treatment.
Change in 2-hour Postprandial Plasma Glucose [ Time Frame: Week 0, week 16 ] [ Designated as safety issue: No ]
Calculated as an estimate of the mean change in 2-hour postprandial plasma glucose following a standard test meal after 16 weeks of treatment
Change in 7-point Plasma Glucose Profile [ Time Frame: Week 0, week 16 ] [ Designated as safety issue: No ]
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.
Change in Fasting Serum Insulin [ Time Frame: Week 0, week 16 ] [ Designated as safety issue: No ]
Calculated as an estimate of the mean change in fasting serum insulin after 16 weeks of treatment.
Change in 2-hour Postprandial Serum Insulin [ Time Frame: Week 0, week 16 ] [ Designated as safety issue: No ]
Calculated as an estimate of the mean change in 2-hour postprandial serum insulin after 16 weeks of treatment.
Change in Fasting Serum C-peptide [ Time Frame: Week 0, week 16 ] [ Designated as safety issue: No ]
Calculated as an estimate of the mean change in fasting serum C-peptide after 16 weeks of treatment
Change in 2-hour Postprandial Serum C-peptide [ Time Frame: Week 0, week 16 ] [ Designated as safety issue: No ]
Calculated as an estimate of the mean change in 2-hour postprandial serum C-peptide after 16 weeks of treatment
Hypoglycaemic Episodes [ Time Frame: Weeks 0-16 ] [ Designated as safety issue: No ]
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.
Change in Blood Pressure [ Time Frame: Week 0, week 16 ] [ Designated as safety issue: No ]
Calculated as the mean change in diastolic and systolic blood pressure after 16 weeks of treatment
Physical Examinations [ Time Frame: Week -2, week 16 ] [ Designated as safety issue: No ]
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.
ECG (ElectroCardioGram) [ Time Frame: Week -2, week 16 ] [ Designated as safety issue: No ]
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.
Biochemistry: Alanine Aminotransferase (ALAT) [ Time Frame: Week -2, week 16 ] [ Designated as safety issue: No ]
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.
Biochemistry: Alanine Aminotransferase (ASAT) [ Time Frame: Week -2, week 16 ] [ Designated as safety issue: No ]
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.
Haematology: Haemoglobin [ Time Frame: Week -2, week 16 ] [ Designated as safety issue: No ]
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.

Enrollment:	433
Study Start Date:	February 2009
Study Completion Date:	November 2009
Primary Completion Date:	November 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Repaglinide + metformin 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 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 Drug: metformin 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
Active Comparator: Repaglinide 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 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.

Arms

Assigned Interventions

Experimental: Repaglinide + metformin

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

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

Drug: metformin

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

Active Comparator: Repaglinide

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

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.

Eligibility

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

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00819741

Locations

China, Shanghai

Shanghai, Shanghai, China, 200025

Sponsors and Collaborators

Novo Nordisk

Investigators

Study Director:

Xiaohui GAO, MS

Novo Nordisk

More Information

Additional Information:

Clinical Trials at Novo Nordisk This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Public Access to Clinical Trials, Novo Nordisk A/S
ClinicalTrials.gov Identifier:	NCT00819741 History of Changes
Other Study ID Numbers:	AGEE-3705
Study First Received:	January 8, 2009
Results First Received:	November 5, 2010
Last Updated:	January 6, 2011
Health Authority:	China: State Food and Drug Administration

Additional relevant MeSH terms:

Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases

Repaglinide
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 09, 2012