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

NCT00131664 | Completed Phase 3 Results DMC

• 1 other identifier: AVM103436
• Study Type: interventional
• Target: 391
• Locations: 1 country
• Sites: 1

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.

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• Mean Change From Baseline in A1C at Month 6

  Change from baseline was calculated as the Month 6 value minus the baseline value, with last on-treatment observation carried forward (LOCF) from Month 2 for withdrawn subjects or missing values.

  Baseline and Month 6

Secondary Outcomes (17)

• Mean Change From Baseline in A1C at Month 4

  Baseline and Month 4

• Mean Change From Baseline in A1C at Month 12

  Baseline and Month 12

• Number of Subjects Achieving A1C Target at Month 4

  Month 4

• Number of Subjects Achieving A1C Target at Month 6

  Month 6

• Number of Subjects Achieving A1C Target at Month 12

  Month 12

Study Arms (3)

Avandamet

ACTIVE COMPARATOR

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

Drug: Avandamet

Avandia and Amaryl

ACTIVE COMPARATOR

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

Drug: Avandia and Amaryl

Metformin

ACTIVE COMPARATOR

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

Drug: Metformin

Interventions

Avandamet 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.

Also known as: rosiglitazone maleate and metformin hydrochloride, Avandamet 2 mg / 500 mg, Avandamet 4 mg / 500 mg, Avandamet 4 mg / 1000 mg

Avandamet

Avandia and Amaryl 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.

Also known as: 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

Avandia and Amaryl

Metformin 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

Also known as: Metformin 500 mg, Metformin 850 mg

Metformin

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Type 2 diabetes patients
• years old
• Type 2 diabetes mellitus (DM) drug naïve or on submaximal oral monotherapy \< 3 years
• A1C criteria at screening:
• % for drug naïve patients after failure of diet control and life-style modification
• % 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
• Signed informed consent

You may not qualify if:

• Type 1 diabetes
• Subjects currently treated with insulin
• Subject treated for previous 3 month with any thiazolidinedione (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 (Alanine Aminotransferase (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

Sponsors & Collaborators

• Canadian Heart Research Centre: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

Canadian Heart Research Centre

Toronto, Ontario, m5b 2p9, Canada

Location

Related Links

• coordinating centre web site

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

rosiglitazone-metformin combination; Rosiglitazone; Metformin; glimepiride

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Biguanides; Guanidines; Amidines

Limitations and Caveats

The LOCF used in the ITT population for withdrawn subjects or missing values was analyzed as per protocol. The 3 treatment groups used throughout the results section were the numbers where the patients were originally randomized to.

Results Point of Contact

• Title: Dr. Robert Josse
• Organization: Dr. Anatoly Langer, Chair CHRC, Canadian Heart Research Centre

langera@chrc.net

416-977-8010

Study Officials

• robert josse, md

  University of Toronto

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chair, Steering Committe

Study Record Dates

• First Submitted: August 17, 2005
• First Posted: August 19, 2005
• Study Start: September 1, 2005
• Primary Completion: January 1, 2008
• Study Completion: January 1, 2008
• Last Updated: April 17, 2013
• Results First Posted: April 17, 2013

Record last verified: 2013-04

Locations

CA (1)