Body Weight Effects on Glucophage's Efficacy in Chinese Diagnosed T2DM Patients

Type 2 Diabetes Mellitus Clinical Trial

Official title:

The Relationship Between Baseline Body Weight and Glycemic Control Following Metformin Extended-Release Tablets (Glucophage XR) Monotherapy in Chinese Patients With Newly Diagnosed Type 2 Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00778622
• Other study ID #: CV138-097
• Status: Completed
• Phase: Phase 4
• First received: October 22, 2008
• Last updated: August 19, 2013
• Start date: November 2009
• Est. completion date: March 2011

Study information

• Verified date: August 2013
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to investigate the effect of the baseline body mass index (BMI) on the response to Glucophage XR monotherapy in glycemic control in Chinese patients with newly diagnosed type 2 diabetes

Recruitment information / eligibility

• Status: Completed
• Enrollment: 371
• Est. completion date: March 2011
• Est. primary completion date: March 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 17 Years to 79 Years

Eligibility

Inclusion Criteria:

• Signed Written Informed Consent

• Age= 17 and <80 years,

• Newly diagnosed T2DM (defined as T2DM diagnosed within 6 months prior to enrollment)

• Oral antidiabetic agents naïve (defined as without receiving any anti-diabetic medication therapy before, or having received anti-diabetic medication = 14 days but not received any antidiabetic medication within the last 1 month prior to enrollment)

• HbA1c = 7.0% and =10.0%

Exclusion Criteria:

• Women of child bearing potential

• body mass index (BMI)=35 Kg/m2 or BMI <18.5 Kg/m2

• Hemoglobin A1c (HbA1c)>10.0% or <7.0%

• Active liver disease and/or significant abnormal liver function

• Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma

• Congestive heart failure defined as New York Heart Association (NYHA) class III or IV and /or left ventricular ejection fraction =40%

• Significant cardiovascular history with the past 6 months

• Severe retinopathy, persistent uncontrolled hypertension (SBP=180mmHg, or DBP=105mmHg)

• Severe chronic gastrointestinal disease

• History of alcohol abuse or illegal drug abuse within the past 12 months

• Diagnosed anemia

• Creatine kinase =3 X ULN

• Serum creatinine =1.5 mg/dL(133µmol/L) [males], =1.4 mg/dL(124 µmol/L)[females]

• Alanine amino transferase (ALT) and/or aspartate amino transferase (AST)> 1.5 X ULN and/or total bilirubin > 2 X ULN

• Hemoglobin <12g/dL [males], <11g/dL [females]

• Allergies and Adverse Drug Reactions

• Prohibited Treatments and/or Therapies

• Prisoners or subjects who are involuntarily incarcerated

• Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness

• Subjects decline to participate

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Body Weight
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Metformin XR
Tablets, Oral, 500mg tid, 1500 mg/day, 16 weeks

Locations

Country	Name	City	State
China	Local Institution	Beijing	Beijing
China	Local Institution	Beijing	Beijing
China	Local Institution	Beijing	Beijing
China	Local Institution	Beijing	Beijing
China	Local Institution	Beijing	Beijing
China	Local Institution	Beijing	Beijing
China	Local Institution	Beijing	Beijing
China	Local Institution	Guangdong	Guangdong
China	Local Institution	Guangdong Province	Guangdong
China	Local Institution	Guangdong Province	Guangdong
China	Local Institution	Shanghai	Shanghai
China	Local Institution	Shanghai	Shanghai
China	Local Institution	Shanghai	Shanghai
China	Local Institution	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Participants With Episodes of Lactic Acidosis or Hypoglycemia From Day 1 to Week 16 - Safety Population	Day 1 was first day of treatment. Lactic acidosis defined as elevated blood lactate levels (>5 mmol/L), decreased blood pH, electrolyte disturbances with an increased anion gap, and increased lactate/pyruvate ratio. Hypoglycemia (low levels of blood glucose) was reported as an adverse event. Safety population included participants who had enrolled in the study and took at least 1 dose of glucophage extended release (glucophage XR). If a subject experienced more than one adverse event, the subject was counted once at the highest severity.	Day 1 to Week 16	Yes
Other	Number of Participants With Clinically Significant Changes From Baseline at Week 16 in the Hematology Laboratory Test Profile - Safety Population	Hematology profile = hematocrit, hemoglobin, red blood cell count (RBC), white blood cell count(WBC), lymphocytes, monocytes, basophils, eosinophils, neutrophils, platelet count. Baseline: value obtained at screening or last value obtained before treatment. LLN=lower limit of normal; ULN=upper limit of normal; preRX=pretreatment. Hemoglobin (g/dL): >3 g/dL decrease from preRX; hematocrit (%): <0.75*preRX; RBC (*10^6 c/uL): <0.75*preRX; platelet count (*10^9 c/uL): <0.67*LLN or >1.5*ULN, of if preRX	Baseline to Week 16	Yes
Other	Number of Participants Who Had Abnormal Increase From Baseline at Week 16 in Kidney or Liver Function Serum Chemistry Values - Safety Population	Baseline defined as value obtained either in screening visit or last value obtained before glucophage XR treatment given on Day 1. Serum chemistries evaluating kidney or liver function: blood urea nitrogen(BUN), serum creatinine (SCr), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), total bilirubin (BR), uric acid (UA). Abnormal increase in kidney and liver function tests defined as 1.25 - less than, equal to (<=)2.6 times (x) upper limit of normal (ULN)in ALT, AST, total BR, UA; abnormal increase defined as 1.25 to <= 5.1 x ULN in BUN. Safety population included participants who enrolled in the study and took at least 1 dose of Glucophage XR.	Baseline to Week 16	Yes
Other	Number of Participants With Clinically Significant Changes From Baseline at Week 16 in Urinalysis - Safety Population	Urinalysis included pH and specific gravity. Baseline defined as values obtained at screening visit. Clinically significant: outside the reference range (low/high)and judged to be significant by the investigator: Specific gravity 1.003 - 1.035; ph 5 - 8. Safety population included participants who enrolled in the study and took at least 1 dose of Glucophage XR.	Baseline to Week 16	Yes
Other	Mean Change From Baseline at Week at Week 16 in ECG Parameter Heart Rate (HR) - Safety Population	Baseline was defined as ECG obtained at the screening visit. ECG was 12-lead. Heart rate (HR) was measured in beats per minute (beats/min). Safety population included participants who enrolled in the study and took at least 1 dose of Glucophage XR.	Baseline to Week 16	Yes
Other	Mean Change From Baseline at Week 16 in Diastolic and Systolic Blood Pressure - Safety Population	Baseline was defined as the value obtained at screening or value obtained on Day 1 before treatment. Diastolic and systolic blood pressure was measured in millimeters of mercury (mm Hg). Safety population included participants who enrolled in the study and took at least 1 dose of Glucophage XR.	Baseline to Week 16	Yes
Other	Number of Participants Who Had a Normal Electrocardiogram (ECG) at Baseline and an ECG at Week 16 (or Termination Visit) Which Was Considered to be Abnormal With Clinical Significance - Safety Population	Baseline was defined as ECG obtained at the screening visit. A judgment of clinical significance was at the discretion of the investigator. Safety population included participants who enrolled in the study and took at least 1 dose of Glucophage XR.	Baseline to Week 16	Yes
Primary	Mean Change From Baseline at Week 16 (95% Confidence Interval) in Glycosated Hemoglobin A1c (HbA1c) (Last Observation Carried Forward) - Full Analysis Set (FAS)	Baseline for HbA1c is defined as that value obtained at screening visit. HbA1c was measured as a percent (%) of hemoglobin; normal range was 4.7 to 6.4% and values were obtained through a central laboratory. The Last Observation Carried Forward (LOCF) data set includes data recorded at a given visit or, if no observation is recorded at that visit, data carried forward from the previous visit.	Baseline to Week 16	No
Secondary	Mean Change From Baseline at Week 16 (95% Confidence Interval) of Fasting Plasma Glucose (FPG) - Full Analysis Set	Baseline was defined as the value obtained at the screening visit. FPG was measured in millimoles/Liter (mmol/L) and obtained through local laboratories.	Baseline to Week 16	No
Secondary	Mean Change From Baseline at Week 16 (95% Confidence Interval) in Fasting Total Cholesterol (TC) - Full Analysis Set	For fasting total cholesterol (TC), baseline is defined as Day 1 (first day of treatment). Total cholesterol was measured in millimoles per liter (mmol/L) and obtained through local laboratories.	Baseline to Week 16	No
Secondary	Mean Change From Baseline at Week 16 (95% Confidence Interval) in Fasting Low-density Lipoprotein Cholesterol (LDL-C) - Full Analysis Set	Baseline was defined as values obtained on Day 1. Low-density lipoprotein cholesterol (LDL-C) was measured in millimoles per liter (mmol/L) and obtained through local laboratories.	Baseline to Week 16	No
Secondary	Mean Change From Baseline at Week 16 (95% Confidence Interval) in Fasting High-density Lipoprotein Cholesterol (HDL-C) - Full Analysis Set	Baseline was defined as value obtained on Day 1 (first day of treatment). High-density lipoprotein cholesterol (HDL-C) was measured in millimoles per liter (mmol/L) and obtained through local laboratories.	Baseline to Week 16	No
Secondary	Mean Change From Baseline at Week 16 (95% Confidence Interval) in Fasting Triglycerides (TG) - Full Analysis Set	Baseline was defined as value obtained on Day 1 (first day of treatment). Triglycerides (TG) were measured in millimoles per liter (mmol/L)and values obtained through local laboratories.	Baseline to Week 16	No
Secondary	Mean Change From Baseline at Week 16 (95% Confidence Interval) in C-Reactive Protein (CRP) - Full Analysis Set	Baseline was defined as value obtained on Day 1 (first day of treatment). C-Reactive Protein (CRP) was measured in milligrams/liter (mg/L) and values were obtained through a central laboratory; normal was less than 5.0 mg/L.	Baseline to Week 16	No
Secondary	Mean Change From Baseline at Week 16 (95% Confidence Interval) in Plasminogen Activator Inhibitor-1 (PAI-1) - Full Analysis Set	Baseline was defined as value obtained on Day 1 (first day of treatment). PAI-1 (activity) was measured in units/milliliter (U/mL)and values obtained through a central laboratory; normal was less than 25.00 U/mL.	Baseline to Week 16	No
Secondary	Mean Change From Baseline at Week 16 (95% Confidence Interval) in Adiponectin - Full Analysis Set	Baseline was defined as value obtained on Day 1 (first day of treatment). Adiponectin was measured in milligrams/liter (mg/L) and values obtained through a central laboratory; normal range was 1.20 to 20.00 mg/L.	Baseline to Week 16	No

External Links

•   BMS Clinical Trials Disclosure
•   For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm
•   Investigator Inquiry form