Avandia™ + Amaryl™ or Avandamet™ Compared With Metformin (AVALANCHE™ Study)

NCT ID: NCT00131664

Last Updated: 2013-04-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 391 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-09-30
• Study Completion Date: 2008-01-31

Brief Summary

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.

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 sulfonylurea (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 (CDA) guidelines, their fasting plasma glucose and A1C to be 7 (mmol/L / percent) 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.

Conditions

Type 2 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Avandamet

Avandamet 2 mg / 500 mg twice daily titration up to 4 mg / 1000 mg twice daily over 6 months

Group Type: ACTIVE_COMPARATOR

Avandamet

Intervention Type: DRUG

Avandamet 2 / 500 mg twice daily titration up to 4 mg / 1000 mg twice daily compared to Avandia 4 mg and Amaryl 1 mg once daily over 6 months or compared to Metformin 500 mg twice daily up to 1000 mg over 6 months.

Avandia and Amaryl

Avandia + Amaryl 4 mg + 1 mg once daily titration up to 8 mg + 2 mg once daily over 6 months

Group Type: ACTIVE_COMPARATOR

Avandia and Amaryl

Intervention Type: DRUG

Avandia 4 mg and Amaryl 1 mg once daily compared to Avandamet 2 / 500 mg twice daily titration up to 4 mg / 1000 mg twice daily, or compared to Metformin 500 mg twice daily up to 1000 mg over 6 months.

Metformin

Metformin 500 mg twice daily titration up to 1000 mg twice daily over 6 months

Group Type: ACTIVE_COMPARATOR

Metformin

Intervention Type: DRUG

Metformin 500 mg twice daily up to 1000 mg over 6 months compared to Avandia 4 mg and Amaryl 1 mg once daily or compared to Avandamet 2 / 500 mg twice daily titration up to 4 mg / 1000 mg twice daily

Interventions

Avandamet

Avandamet 2 / 500 mg twice daily titration up to 4 mg / 1000 mg twice daily compared to Avandia 4 mg and Amaryl 1 mg once daily over 6 months or compared to Metformin 500 mg twice daily up to 1000 mg over 6 months.

Intervention Type: DRUG

Avandia and Amaryl

Avandia 4 mg and Amaryl 1 mg once daily compared to Avandamet 2 / 500 mg twice daily titration up to 4 mg / 1000 mg twice daily, or compared to Metformin 500 mg twice daily up to 1000 mg over 6 months.

Intervention Type: DRUG

Metformin

Metformin 500 mg twice daily up to 1000 mg over 6 months compared to Avandia 4 mg and Amaryl 1 mg once daily or compared to Avandamet 2 / 500 mg twice daily titration up to 4 mg / 1000 mg twice daily

Intervention Type: DRUG

Other Intervention Names

rosiglitazone maleate and metformin hydrochloride; Avandamet 2 mg / 500 mg; Avandamet 4 mg / 500 mg; Avandamet 4 mg / 1000 mg; rosiglitazone maleate and glimepiride; Avandia (rosiglitazone maleate) 4 mg; Avandia (rosiglitazone maleate) 8 mg; Amaryl (glimepiride) 1 mg; Amaryl (glimepiride) 2 mg; Amaryl (glimepiride) 4 mg; Metformin 500 mg; Metformin 850 mg

Eligibility Criteria

Inclusion Criteria

1. Type 2 diabetes patients

2. 18 - 75 years old

3. Type 2 diabetes mellitus (DM) drug naïve or on submaximal oral monotherapy < 3 years

4. 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) Angiotensin converting enzyme inhibitor (ACE), aspirin (80 mg), and statin if appropriate

5. Signed informed consent

Exclusion Criteria

1. Type 1 diabetes

2. Subjects currently treated with insulin

3. Subject treated for previous 3 month with any thiazolidinedione (TZD)

4. 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

5. Subjects who have hypersensitivity to any components of study drugs

6. Participation in a clinical trial and/or intake of an investigational drug within 30 days prior to screening.

7. Pregnant or nursing females

8. Females of childbearing potential who are not on adequate birth control

9. Liver enzymes (Alanine Aminotransferase (ALT) > 2.5 times upper limit of normal)

10. Renal impairment: serum creatinine ≥ 136umol/L (males) and ≥ 124 umol/L (females)

11. Congestive Heart Failure (CHF class III/IV)

12. Weight >160 kg

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

Canadian Heart Research Centre

OTHER

Sponsor Role: lead

Responsible Party

Dr. Anatoly Langer

Chair, Steering Committe

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

robert josse, md

Role: PRINCIPAL_INVESTIGATOR

University of Toronto

Locations

Canadian Heart Research Centre

Toronto, Ontario, Canada

Countries

Canada

Related Links

http://www.chrc.net

coordinating centre web site

Other Identifiers

AVM103436

Identifier Type: -

Identifier Source: org_study_id