Last updated: 11/04/2018 05:23:16
A Type 2 Diabetes Study of the Longer-Term Glycemic Effect of AVANDAMET vs. MetforminN/A
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
Official title: A randomized, parallel group, double-blind, multi-center study comparing the efficacy and safety of AVANDAMET and metformin after 80 weeks of treatment.
Trial description: This study will evaluate the longer-term glycemic effect of two medicines approved for initial treatment of type 2 diabetes. The study consists of a 2 week screening period (2 study visits), followed by an 80 week double-blind treatment period (11 study visits). Also, a sub-study was included to look at changes in bone mineral density (BMD) at the lumbar spine.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation:
Randomized
Primary outcomes:
Change from baseline in HbA1c at Week 80
Timeframe: Baseline and Week 80
Secondary outcomes:
Mean change from baseline in HbA1c at Week 80
Timeframe: Baseline and Week 80
Number of participants achieving HbA1c <=6.5% and <7% at Week 80
Timeframe: Week 80
Change in fasting plasma glucose (FPG) from baseline at Week 80
Timeframe: Baseline and Week 80
Change from baseline in FPG at Week 80
Timeframe: Baseline and Week 80
Number of participants achieving FPG <=6 mmol/L (110 mg/dL) and <=7 mmol/L (126 mg/dL) at Week 80
Timeframe: Week 80
Number of Participants Achieving Treatment Failure
Timeframe: Randomization to treatment failure (up to Week 80)
Percent change from baseline in total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides at Week 80
Timeframe: Baseline and Week 80
Percent change from baseline in adiponectin at week 80 (United States [US] and Mexico subset of participants )
Timeframe: Baseline and Week 80
Percent change from baseline in C-reactive protein (CRP) at Week 80 (US and Mexico subset of participants)
Timeframe: Baseline and Week 80
Percent change in free fatty acids (FFA) from baseline at Week 80 (US and Mexico subset of participants).
Timeframe: Baseline and Week 80
Change in fasting insulin from baseline at Week 80 (US and Mexico subset of participants)
Timeframe: Baseline and Week 80
Change in C-peptide from baseline at Week 80 (US and Mexico subset of participants)
Timeframe: Baseline and Week 80
Percent change from baseline in in HOMA-S and HOMA-B to Week 80 (US and Mexico subset of participants)
Timeframe: Baseline and Week 80
Slope of delta-cell function as estimated by the ratio deltaI/deltaG
Timeframe: Baseline and Week 80
Number of participants at final dose level
Timeframe: Baseline to Week 80 or withdrawal
Percent change from baseline in lumbar spine bone mass density (BMD) at Weeks 20, 56, and 80 (bone sub-study subset of participants)
Timeframe: Baseline and Weeks 20, 56, and 80
Percent change from baseline in total hip BMD at Weeks 20, 56, and 80 (bone sub-study subset of participants)
Timeframe: Baseline and Weeks 20, 56, and 80
Percent change from baseline in trochanter BMD at Weeks 20, 56, and 80 (bone sub-study subset of participants)
Timeframe: Baseline and Weeks 20, 56, and 80
Percent change from baseline in femoral neck BMD at Weeks 20, 56, and 80 (bone sub-study subset of participants)
Timeframe: Baseline and Weeks 20, 56, and 80
Percent change from baseline in distal radius BMD at Weeks 20, 56, and 80 (bone sub-study subset of participants)
Timeframe: Baseline and Weeks 20, 56, and 80
Percent change from baseline in total body BMD at Weeks 20, 56, and 80 (bone sub-study subset of participants)
Timeframe: Baseline and Weeks 20, 56, and 80
Percent change from baseline in serum calcium at Weeks 12, 32, 56, and 80
Timeframe: Baseline and Weeks 12, 32, 56, and 80
Percent change from baseline in intact parathyroid hormone at Week 80
Timeframe: Baseline and Week 80
Percent change from baseline in 25-hydroxy vitamin D at Week 80
Timeframe: Baseline and Week 80
Percent change from baseline in estradiol at Weeks 20, 56, and 80
Timeframe: Baseline and Weeks 20, 56, and 80
Percent change from baseline in c-terminal telopeptide (CTX) at Weeks 20, 56, and 80
Timeframe: Baseline and Weeks 20, 56, and 80
Percent change from baseline in procollagen type-1 N-propeptide (P1NP) at Weeks 20, 56, and 80
Timeframe: Baseline and Weeks 20, 56, and 80
Percent change from baseline in bone alkaline phosphatase (BSAP) at Weeks 20, 56, and 80
Timeframe: Baseline and Weeks 20, 56, and 80
Interventions:
Enrollment:
688
Primary completion date:
2009-28-09
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Borges J, Bilezikian J, Jones-Leone A, Acusta A, Ambery P, Nino A, Grosse M, Fitzpatrick L, Cobitz A. A Randomized, Parallel Group, Double-blind, Multicentre Study Comparing the Efficacy and Safety of Avandamet (Rosiglitazone/Metformin) and Metformin on Long-term Glycaemic Control and Bone Mineral Density after 80 Weeks of Treatment in Drug-naïve Type 2 Diabetes Mellitus Patients. . [Diabetes Obes Metab]. 2011;13(11):1036-1046.
Borges J, Bilezikian J, Jones-Leone A, Acusta A, Ambery P, Nino A, Grosse M, Fitzpatrick L, Cobitz A. A Randomized, Parallel Group, Double-blind, Multicentre Study Comparing the Efficacy and Safety of Avandamet (Rosiglitazone/Metformin) and Metformin on Long-term Glycaemic Control and Bone Mineral Density after 80 Weeks of Treatment in Drug-naïve Type 2 Diabetes Mellitus Patients. . [Diabetes Obes Metab]. 2011;Jun 17(.):epub ahead of print.
Medical condition
Diabetes Mellitus, Type 2
Product
metformin, rosiglitazone, rosiglitazone/metformin
Collaborators
Not applicable
Study date(s)
October 2006 to September 2009
Type
Interventional
Phase
4
Participation criteria
Sex
Female & Male
Age
18 - 75 years
Accepts healthy volunteers
No
- The subject provides written informed consent.
- The subject is male or female and 18 to 75 years of age at the time of pre-screening.
- The subject has taken an oral anti-diabetic monotherapy or insulin for more than 14 days in the past 6 months.
- The subject has presence of clinically significant renal or hepatic disease (serum creatinine 1.5 mg/dL (132.6 mol/L) for males and 1.4 mg/dL (123.8 mol/L) for females): ALT, AST, total bilirubin, or alkaline phosphatase >2.5 times the upper limit of the normal (ULN) reference range.
Inclusion and exclusion criteria
Inclusion criteria:
- The subject provides written informed consent.
- The subject is male or female and 18 to 75 years of age at the time of pre-screening.
- The subject has an established clinical diagnosis of type 2 diabetes according to recommended guidelines (e.g., American Diabetes Association, International Diabetes Federation, World Health Organization, Canadian Diabetes Association, or American Association of Clinical Endocrinologists).
- The subject is currently treated with diet and exercise, and has not taken more than 2 weeks of an anti-diabetic monotherapy or insulin in the past 6 months.
- The subject has a BMI >25 kg/m2 at pre-screening.
- The subject has a Quest HbA1c 7.5% to 10.5% at pre-screening.
- The subject has a fasting capillary blood glucose 126 mg/dL (7mmol/L), as measured by the site staff at week 0.
- If the subject is a pre-menopausal female of child-bearing potential, she agrees to practice acceptable contraceptive measures (e.g. oral birth control pills, Norplant, Depo-Provera, an intrauterine device (IUD), a diaphragm with spermicide or a condom with spermicide, or abstinence) at least 1 month before screening, during the study, and for 30 days after the last dose of study medication is taken
- The subject is able and willing to perform self-monitoring of blood glucose as specified in this protocol.
Exclusion criteria:
- The subject has taken an oral anti-diabetic monotherapy or insulin for more than 14 days in the past 6 months.
- The subject has presence of clinically significant renal or hepatic disease (serum creatinine 1.5 mg/dL (132.6 mol/L) for males and 1.4 mg/dL (123.8 mol/L) for females): ALT, AST, total bilirubin, or alkaline phosphatase >2.5 times the upper limit of the normal (ULN) reference range.
- The subject has anemia defined by hemoglobin concentration <11g/dL (110g/L) for males or <10g/dL (100g/L) for females.
- Presence of unstable or severe angina, coronary insufficiency or New York Heart Association (NYHA) class III-IV or any congestive heart failure requiring pharmacologic treatment.
- The subject has systolic blood pressure >160 mmHg or diastolic blood pressure >90 mmHg
- The subject has a chronic disease requiring intermittent or chronic treatment with oral, intravenous, or intra-articular corticosteroids (i.e., only use of topical, inhaled or nasal corticosteroids is permitted).
- The subject has acute or chronic metabolic acidosis or a history of diabetic ketoacidosis.
- The subject has a clinically significant abnormality which in the judgment of the investigator makes the subject unsuitable for inclusion in the study (e.g., physical examination, laboratory tests, or electrocardiogram, etc).
- The subject has used an investigational agent within 30 days or 5 half-lives (whichever was longer) prior to pre-screening.
- The subject is a female who is lactating, pregnant, or planned to become pregnant.
- The subject has a prior history of severe edema or a medically serious fluid related event (e.g., heart failure).
- The subject has a history of macular edema.
- The subject has significant hypersensitivity (e.g., difficulty swallowing, difficulty breathing, and tachycardia or skin reaction) to TZDs, biguanides, or compounds with similar chemical structures.
- The subject has a diagnosis of cancer (other than squamous, basal cell, or cervical cancer in-situ) in the past 3 years and is receiving treatment for cancer.
- The subject has a history or suspicion of drug abuse or alcohol abuse within the last 6 months.
- The subject is known to have severe lactose intolerance.
- The subject is not willing to comply with visits and procedures described in the protocol.
- The subject has a disease that may affect bone turnover including, but not limited to: Paget's disease, hypercalcemia, hypocalcemia, hyperparathyroidism, hyperthyroidism, osteomalacia, metastatic bone disease
- The subject has a weight of greater than 300 lbs (136.4 kg).
- The subject has received treatment with bisphosphonates (≥1 month cumulative treatment within the last 12 months) or fluoride (dose greater than 10mg/day within the previous 5 years).
Trial location(s)
Location
GSK Investigational Site
Excelsior Springs, Missouri, United States, 64024
Status
Study Complete
Location
GSK Investigational Site
Wandsworth, Ohio, United States, 44281
Status
Study Complete
Location
GSK Investigational Site
Oregon City, Oregon, United States, 97045
Status
Study Complete
Location
GSK Investigational Site
Clairton, Pennsylvania, United States, 15205
Status
Study Complete
Location
GSK Investigational Site
Wenatchee, Washington, United States, 98801
Status
Study Complete
Location
GSK Investigational Site
West Chester, Pennsylvania, United States, 19382
Status
Study Complete
Showing 1 - 6 of 112 Results
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Study complete
Actual primary completion date
2009-28-09
Actual study completion date
2009-28-09
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
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