A Type 2 Diabetes Study of the Longer-Term Glycemic Effect of AVANDAMET vs. Metformin - Full Text View

Sponsored by:	GlaxoSmithKline
Information provided by:	GlaxoSmithKline
ClinicalTrials.gov Identifier:	NCT00386100

Purpose

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).

Condition	Intervention	Phase
Non-Insulin-Dependent Diabetes Mellitus Type 2 Diabetes Mellitus	Drug: Rosiglitazone maleate/metformin hydrochloride (AVANDAMET)	Phase IV

MedlinePlus related topics: Diabetes

Drug Information available for: Metformin Metformin hydrochloride Rosiglitazone Rosiglitazone Maleate Avandamet

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double-Blind, Parallel Assignment, Safety/Efficacy Study
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.

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:

Mean change in HbA1c from baseline to week 80.

Secondary Outcome Measures:

Time from randomization to treatment failure (i.e., HbA1c 7% after week 32 or withdrawal due to ITE). Change in FFA, fasting insulin, C-peptide, HOMA-S and HOMA-B from baseline to week 80 (subset of subjects).
Rate of change (i.e. slope) in -cell function as estimated by the ratio I/G over 80 weeks of treatment (subset of subjects). Proportion of subjects with HbA1c 6.5% and >6.5%, and <7% and 7% at week 32 and at week 80.
Change in adiponectin and C-reactive protein from baseline to week 56 and week 80. Change in total cholesterol, LDL-cholesterol, non-HDL-cholesterol, HDL-cholesterol and triglycerides from baseline to week 80.
Mean change in FPG from baseline to week 80. Change from baseline in HbA1c and FPG by visit (over time). Proportion of subjects achieving recommended glycemic targets. Evaluation of adverse events/safety and tolerability over 80 weeks of treatment. [ Time Frame: 80 weeks ]
Change in HbA1c from baseline to week 80 based on last observation carried forward (LOCF) from week 32. Proportion of subjects achieving HbA1c 6.5% and <7% at week 80.
Change in FPG from baseline to week 80. Proportion of subjects achieving FPG 100 mg/dL (5.56 mmol/L), <110mg/dL (6.1 mmol/L) and 126 mg/dL (7 mmol/L) at week 80. Change from baseline in HbA1c and FPG at each visit.

Estimated Enrollment:	588
Study Start Date:	October 2006
Estimated Study Completion Date:	August 2009
Estimated Primary Completion Date:	August 2009 (Final data collection date for primary outcome measure)

Eligibility

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

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).

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00386100

Show 117 Study Locations

Sponsors and Collaborators

GlaxoSmithKline

Investigators

Study Director:

GSK Clinical Trials, MD

GlaxoSmithKline

More Information

Responsible Party:	GSK ( Study Director )
Study ID Numbers:	AVT105913
Study First Received:	October 9, 2006
Last Updated:	January 8, 2009
ClinicalTrials.gov Identifier:	NCT00386100
Health Authority:	United States: Food and Drug Administration; Canada: Health Canada

Keywords provided by GlaxoSmithKline:

Type 2 diabetes mellitus
Hyperglycemia
HbA1c
Drug-naive

Study placed in the following topic categories:

Metabolic Diseases
Hyperglycemia
Metformin
Diabetes Mellitus, Type 2
Diabetes Mellitus

Endocrine System Diseases
Endocrinopathy
Metabolic disorder
Glucose Metabolism Disorders
Rosiglitazone

Additional relevant MeSH terms:

Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009