Avandia™ + Amaryl™ or Avandamet™ Compared With Metformin (AVALANCHE™ Study) - Full Text View

Sponsors and Collaborators:	Canadian Heart Research Centre GlaxoSmithKline
Information provided by:	Canadian Heart Research Centre
ClinicalTrials.gov Identifier:	NCT00131664

Purpose

The incidence of type 2 diabetes is on the increase. According to recent Canadian Diabetes Association guidelines glucose control, based on the A1C measurement, needs to be achieved within a 6-12 month period of time after the initial diagnosis of type 2 diabetes. The guidelines on the use of antihyperglycemic agents identify the potential benefits of sub-maximal oral combination therapy in order to achieve more rapid and improved glycemic control compared with higher dose monotherapy. Furthermore, many patients on prolonged oral antihyperglycemic monotherapy who then start on combination therapy may not achieve the required target glycemic control. Indeed early initiation of combination therapies may be necessary to achieve and maintain glycemic targets because of the progressive deterioration of pancreatic β cell function and glycemic control.

Condition	Intervention	Phase
Type 2 Diabetes Mellitus	Drug: Avandia, Amaryl, Avandamet, Metformin	Phase III

MedlinePlus related topics: Diabetes

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

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Avandia™ + Amaryl™ or Avandamet™ Compared With Metformin: A 48-Week Randomized, Open-Label, Multicentre Phase IIIB Study to Compare the Effectiveness of Combination Therapy to Monotherapy in Type 2 Diabetes Mellitus Patients

Further study details as provided by Canadian Heart Research Centre:

Primary Outcome Measures:

The mean change in A1C from baseline to 6 months post-randomization [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

The mean change from baseline in A1C to 4, and 12 months post-randomization, [ Time Frame: 4 - 12 months ] [ Designated as safety issue: No ]
% of patients achieving A1C < 7% and a FPG < 7 mmol/L at 4, 6 and 12 months, [ Time Frame: 4, 6 and 12 months ] [ Designated as safety issue: No ]
change in FPG to month 4, 6, 12, [ Time Frame: 4, 6 and 12 months ] [ Designated as safety issue: No ]
change in QoL/HE evaluation to month 6 and 12, [ Time Frame: 6 and 12 months ] [ Designated as safety issue: No ]
change in insulin sensitivity as measured by IS (Isotechnika) breath test and HOMA-S 6 and 12 month; [ Time Frame: 6 and 12 months ] [ Designated as safety issue: No ]
'homeostasis model assessment' (HOMA) (ref. 1, 2), [ Time Frame: 12months ] [ Designated as safety issue: No ]
change in mean risk-engine score to month 6 and 12, [ Time Frame: 6 and 12 months ] [ Designated as safety issue: No ]
change in CV biomarkers from baseline to month 6 and 12. [ Time Frame: 6 and 12 months ] [ Designated as safety issue: No ]

Enrollment:	391
Study Start Date:	September 2005
Study Completion Date:	January 2008
Primary Completion Date:	January 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator Avandamet 2mg/500mg BID titration up to 4mg/1000mg BID over 6 months	Drug: Avandia, Amaryl, Avandamet, Metformin Avandamet 2/500mg BID to 4mg/1000mg BID;Avandia+Amaryl 4mg+1mg OD up to 8mg+2mg OD over 6 months or Metformin 500mg BID up to 1000mg over 6 months
2: Active Comparator Avandia + Amaryl 4mg + 1mg OD titration up to 8mg +2mf OD over 6 months	Drug: Avandia, Amaryl, Avandamet, Metformin Avandamet 2/500mg BID to 4mg/1000mg BID;Avandia+Amaryl 4mg+1mg OD up to 8mg+2mg OD over 6 months or Metformin 500mg BID up to 1000mg over 6 months
3: Active Comparator Metformin 500mg BID titration up to 1000mg BID over 6 months	Drug: Avandia, Amaryl, Avandamet, Metformin Avandamet 2/500mg BID to 4mg/1000mg BID;Avandia+Amaryl 4mg+1mg OD up to 8mg+2mg OD over 6 months or Metformin 500mg BID up to 1000mg over 6 months

Detailed Description:

AvandametTM combines two oral antihyperglycemic agents, rosiglitazone maleate and metformin hydrochloride, with different but complementary mechanisms of action to improve glycemic control while reducing circulating insulin levels in patients with type 2 diabetes. AvandiaTM and AmarylTM combine two antidiabetic agents, rosiglitazone maleate and glimepiride. Glimepiride is an effective antihyperglycemic agent which has a low incidence of hypoglycemia, symptomatic hypoglycemia, severe hypoglycemia, and confirmed hypoglycemia. Subjects in this study who are inadequately controlled on diet, exercise and a submaximal dose of metformin or SU will be randomized to either a combination of metformin plus rosiglitazone (AvandametTM) or a combination of AvandiaTM + AmarylTM or a Metformin monotherapy arm. As per the Canadian Diabetes Association guidelines, their fasting plasma glucose and A1C to be 7 (mmol/L/%) or less throughout the study. If the subject does not achieve the target then either AvandametTM or AvandiaTM and AmarylTM or Metformin will be up-titrated in an effort to reach this CDA recommended target. This study will attempt to demonstrate that the either combination arm of rosiglitazone plus metformin (AvandametTM) or the other combination arm of AvandiaTM + AmarylTM will provide greater glycemic control while avoiding the side-effects associated with the use of maximal dose metformin.

Eligibility

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

Criteria

Inclusion Criteria:

Type 2 diabetes patients
18 - 75 years old
Type 2 DM drug naïve or on submaximal oral monotherapy < 3 years
A1C criteria at screening:
1. 7.1-10% for drug naïve patients after failure of diet control and life-style modification
2. 7.1 - 9% on single therapy (e.g. not more 10 mg of Glyburide or 4 mg of Amaryl™ or 1000mg of Metformin) who will start after 2 weeks wash-out. During wash out the following will be done: i) diet and life style modification ii) ACE, aspirin (80 mg), and statin if appropriate
Signed informed consent

Exclusion Criteria:

Type 1 diabetes
Subjects currently treated with insulin
Subject treated for previous 3 month with any TZD
Evidence of clinically significant concomitant illnesses which are not controlled by medication and/or may limit participation in the study as judged by the investigator
Subjects who have hypersensitivity to any components of study drugs
Participation in a clinical trial and/or intake of an investigational drug within 30 days prior to screening.
Pregnant or nursing females
Females of childbearing potential who are not on adequate birth control
Liver enzymes (ALT > 2.5 times upper limit of normal)
Renal impairment: serum creatinine ≥136umol/L (males) and ≥124 umol/L (females)
Congestive Heart Failure (CHF class III/IV)
Weight >160 kg

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00131664

Locations

Canada, Ontario
Canadian Heart Research Centre
toronto, Ontario, Canada, m5b 2p9

Sponsors and Collaborators

Canadian Heart Research Centre

GlaxoSmithKline

Investigators

Principal Investigator:

robert josse, md

University of Toronto

More Information

coordinating centre web site This link exits the ClinicalTrials.gov site

Responsible Party:	Canadian Heart Research Centre ( Dr. Anatoly Langer, Chair CHRC )
Study ID Numbers:	AVM103436
Study First Received:	August 17, 2005
Last Updated:	May 9, 2008
ClinicalTrials.gov Identifier:	NCT00131664
Health Authority:	Canada: Health Canada

Study placed in the following topic categories:

Glimepiride
Metabolic Diseases
Metformin
Diabetes Mellitus, Type 2
Diabetes Mellitus

Endocrine System Diseases
Endocrinopathy
Metabolic disorder
Glucose Metabolism Disorders
Rosiglitazone

Additional relevant MeSH terms:

Hypoglycemic Agents
Immunologic Factors
Therapeutic Uses
Physiological Effects of Drugs

Cardiovascular Agents
Anti-Arrhythmia Agents
Immunosuppressive Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009