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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00778622
First received: October 22, 2008
Last updated: August 19, 2013
Last verified: August 2013
  Purpose

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


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: Metformin XR
Phase 4

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

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Mean Change From Baseline at Week 16 (95% Confidence Interval) in Glycosated Hemoglobin A1c (HbA1c) (Last Observation Carried Forward) - Full Analysis Set (FAS) [ Time Frame: Baseline to Week 16 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Mean Change From Baseline at Week 16 (95% Confidence Interval) of Fasting Plasma Glucose (FPG) - Full Analysis Set [ Time Frame: Baseline to Week 16 ] [ Designated as safety issue: No ]
    Baseline was defined as the value obtained at the screening visit. FPG was measured in millimoles/Liter (mmol/L) and obtained through local laboratories.

  • Mean Change From Baseline at Week 16 (95% Confidence Interval) in Fasting Total Cholesterol (TC) - Full Analysis Set [ Time Frame: Baseline to Week 16 ] [ Designated as safety issue: No ]
    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.

  • Mean Change From Baseline at Week 16 (95% Confidence Interval) in Fasting Low-density Lipoprotein Cholesterol (LDL-C) - Full Analysis Set [ Time Frame: Baseline to Week 16 ] [ Designated as safety issue: No ]
    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.

  • Mean Change From Baseline at Week 16 (95% Confidence Interval) in Fasting High-density Lipoprotein Cholesterol (HDL-C) - Full Analysis Set [ Time Frame: Baseline to Week 16 ] [ Designated as safety issue: No ]
    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.

  • Mean Change From Baseline at Week 16 (95% Confidence Interval) in Fasting Triglycerides (TG) - Full Analysis Set [ Time Frame: Baseline to Week 16 ] [ Designated as safety issue: No ]
    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.

  • Mean Change From Baseline at Week 16 (95% Confidence Interval) in C-Reactive Protein (CRP) - Full Analysis Set [ Time Frame: Baseline to Week 16 ] [ Designated as safety issue: No ]
    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.

  • Mean Change From Baseline at Week 16 (95% Confidence Interval) in Plasminogen Activator Inhibitor-1 (PAI-1) - Full Analysis Set [ Time Frame: Baseline to Week 16 ] [ Designated as safety issue: No ]
    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.

  • Mean Change From Baseline at Week 16 (95% Confidence Interval) in Adiponectin - Full Analysis Set [ Time Frame: Baseline to Week 16 ] [ Designated as safety issue: No ]
    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.


Other Outcome Measures:
  • Number of Participants With Episodes of Lactic Acidosis or Hypoglycemia From Day 1 to Week 16 - Safety Population [ Time Frame: Day 1 to Week 16 ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With Clinically Significant Changes From Baseline at Week 16 in the Hematology Laboratory Test Profile - Safety Population [ Time Frame: Baseline to Week 16 ] [ Designated as safety issue: Yes ]
    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<LLN, use 0.5*preRX and <100,000/mm^3; WBC (*10^3 c/uL): <0.75*LLN or >1.25*ULN, or if preRX <LLN, use <0.8*preRX or >ULN, or if preRX>ULN, use >1.2*preRX or <LLN; neutrophils+bands (*10^3 c/uL): if value <1.0*10^3 c/uL; eosinophils (*10^3 c/uL): if value >0.750*10^3 c/uL; basophils (*10^3 c/uL): if value >400/mm^3; monocytes (*10^3 c/uL): if value >2000/mm^3; lymphocytes (*10^3 c/uL): if value <0.750*10^3 c/uL or if value >7.50*10^3 c/uL.

  • Number of Participants Who Had Abnormal Increase From Baseline at Week 16 in Kidney or Liver Function Serum Chemistry Values - Safety Population [ Time Frame: Baseline to Week 16 ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With Clinically Significant Changes From Baseline at Week 16 in Urinalysis - Safety Population [ Time Frame: Baseline to Week 16 ] [ Designated as safety issue: Yes ]
    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.

  • Mean Change From Baseline at Week at Week 16 in ECG Parameter Heart Rate (HR) - Safety Population [ Time Frame: Baseline to Week 16 ] [ Designated as safety issue: Yes ]
    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.

  • Mean Change From Baseline at Week 16 in Diastolic and Systolic Blood Pressure - Safety Population [ Time Frame: Baseline to Week 16 ] [ Designated as safety issue: Yes ]
    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.

  • 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 [ Time Frame: Baseline to Week 16 ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 371
Study Start Date: November 2009
Study Completion Date: March 2011
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A1
Normal Weight by Body Weight Index
Drug: Metformin XR
Tablets, Oral, 500mg tid, 1500 mg/day, 16 weeks
Experimental: A2
Overweight by Body Weight Index
Drug: Metformin XR
Tablets, Oral, 500mg tid, 1500 mg/day, 16 weeks
Experimental: A3
Obese by Body Weight Index
Drug: Metformin XR
Tablets, Oral, 500mg tid, 1500 mg/day, 16 weeks

  Eligibility

Ages Eligible for Study:   17 Years to 79 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00778622

Locations
China, Beijing
Local Institution
Beijing, Beijing, China, 100044
Local Institution
Beijing, Beijing, China, 100034
Local Institution
Beijing, Beijing, China, 100730
Local Institution
Beijing, Beijing, China, 100028
Local Institution
Beijing, Beijing, China, 101100
Local Institution
Beijing, Beijing, China, 200016
Local Institution
Beijing, Beijing, China, 100088
China, Guangdong
Local Institution
Guangdong, Guangdong, China, 510180
Local Institution
Guangdong Province, Guangdong, China, 510180
Local Institution
Guangdong Province, Guangdong, China, 528000
China, Shanghai
Local Institution
Shanghai, Shanghai, China, 200003
Local Institution
Shanghai, Shanghai, China, 201100
Local Institution
Shanghai, Shanghai, China, 201200
Local Institution
Shanghai, Shanghai, China, 200092
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided by Bristol-Myers Squibb

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00778622     History of Changes
Other Study ID Numbers: CV138-097
Study First Received: October 22, 2008
Results First Received: June 14, 2013
Last Updated: August 19, 2013
Health Authority: China: Food and Drug Administration

Additional relevant MeSH terms:
Body Weight
Diabetes Mellitus
Diabetes Mellitus, Type 2
Signs and Symptoms
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 19, 2014