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

This study has been completed.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
Dr. Anatoly Langer, Canadian Heart Research Centre
ClinicalTrials.gov Identifier:
NCT00131664
First received: August 17, 2005
Last updated: April 15, 2013
Last verified: April 2013
Results First Received: January 28, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Type 2 Diabetes Mellitus
Interventions: Drug: Avandamet
Drug: Avandia and Amaryl
Drug: Metformin

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
391 patients were randomized from 49 Canadian sites of General Practitioners and Community Endocrinologists during an 8 month recruitment period.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
This open-label, prospective, randomized multi-centre study included naïve or recently treated type 2 diabetes mellitus (T2DM) patients. Recently treated patients (up to 3 years on single therapy of a low to moderate dose of Glyburide or Amaryl™ or Metformin) entered the study after a 2-week wash-out period.

Reporting Groups
  Description
Avandia and Amaryl Avandia™ + Amaryl™ Arm: at month 2 initial dose of 4 mg + 1 mg once daily (OD) was titrated up to 8 mg + 1 mg OD; at month 4 it was further titrated up to 8 mg + 2 mg OD.
Avandamet Avandamet™ Arm: at month 2 the initial dose of 2 mg / 500 mg twice daily (BID) was titrated up to 4 mg / 500 mg BID; at month 4 it was be further titrated up to 4 mg / 1000 mg BID.
Metformin Metformin Arm: initial dose of 500 mg twice daily (BID) was titrated up to 850 mg BID at month 2. At month 4, it was further titrated up to 1000 mg BID.
Avandia, Amaryl and Metformin Avandia™ + Amaryl™ Arm: At month 6, if patients not achieving A1C target of less than 7 received additional specified drug therapy. Metformin was added and titrated up to 1000 mg twice daily (BID) maximum dose for an additional 6 months.
Avandamet and Amaryl Avandamet™ Arm: At month 6, if patients not achieving A1C target of less than 7 received additional specified drug therapy. Amaryl™ was added and titrated up to 4 mg once daily maximum dose for an additional 6 months
Metformin and Amaryl Metformin Arm: At month 6, if patients not achieving A1C target of less than 7 received additional specified drug therapy. Amaryl™ was added and titrated up to 4 mg once daily maximum dose for an additional 6 months.

Participant Flow for 2 periods

Period 1:   First Period (First 6 Months)
    Avandia and Amaryl     Avandamet     Metformin     Avandia, Amaryl and Metformin     Avandamet and Amaryl     Metformin and Amaryl  
STARTED     136     135     120     0     0     0  
COMPLETED     111     117     104     0     0     0  
NOT COMPLETED     25     18     16     0     0     0  
Lost to Follow-up                 7                 3                 3                 0                 0                 0  
Death                 0                 1                 0                 0                 0                 0  
Protocol Violation                 2                 2                 1                 0                 0                 0  
Withdrawal by Subject                 4                 6                 2                 0                 0                 0  
Adverse Event                 9                 4                 5                 0                 0                 0  
Clinically significant lab abnormalities                 1                 2                 0                 0                 0                 0  
Administrative reasons                 2                 0                 5                 0                 0                 0  

Period 2:   Second Period (Additional Drug Added)
    Avandia and Amaryl     Avandamet     Metformin     Avandia, Amaryl and Metformin     Avandamet and Amaryl     Metformin and Amaryl  
STARTED     90 [1]   101 [2]   79 [3]   21     16     25  
COMPLETED     81     97     76     19     15     22  
NOT COMPLETED     9     4     3     2     1     3  
Lost to Follow-up                 3                 0                 2                 1                 0                 2  
Protocol Violation                 0                 1                 1                 0                 0                 0  
Withdrawal by Subject                 2                 0                 0                 0                 0                 0  
Adverse Event                 0                 1                 0                 0                 0                 1  
Clinically significant lab abnormalities                 0                 0                 0                 1                 0                 0  
Administrative reasons                 4                 2                 0                 0                 1                 0  
[1] 21 had added Metformin at Month 6
[2] 16 had added Amaryl at Month 6
[3] 25 had added Amaryl at Month 6



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Avandia and Amaryl 4 mg + 1 mg once daily titration up to 8 mg + 2 mg once daily over 6 months
Avandamet 2 mg / 500 mg twice daily titration up to 4 mg / 1000 mg twice daily over 6 months
Metformin 500 mg twice daily titration up to 1000 mg twice daily over 6 months
Total Total of all reporting groups

Baseline Measures
    Avandia and Amaryl     Avandamet     Metformin     Total  
Number of Participants  
[units: participants]
  136     135     120     391  
Age  
[units: years]
Mean ± Standard Deviation
  54.3  ± 10.1     53.7  ± 11.6     56.0  ± 10.1     54.6  ± 10.7  
Gender  
[units: participants]
       
Female     48     59     57     164  
Male     88     76     63     227  
Region of Enrollment  
[units: participants]
       
Canada     136     135     120     391  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Mean Change From Baseline in A1C at Month 6   [ Time Frame: Baseline and Month 6 ]

2.  Secondary:   Mean Change From Baseline in A1C at Month 4   [ Time Frame: Baseline and Month 4 ]

3.  Secondary:   Mean Change From Baseline in A1C at Month 12   [ Time Frame: Baseline and Month 12 ]

4.  Secondary:   Number of Subjects Achieving A1C Target at Month 4   [ Time Frame: Month 4 ]

5.  Secondary:   Number of Subjects Achieving A1C Target at Month 6   [ Time Frame: Month 6 ]

6.  Secondary:   Number of Subjects Achieving A1C Target at Month 12   [ Time Frame: Month 12 ]

7.  Secondary:   Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Month 4   [ Time Frame: Baseline and Month 4 ]

8.  Secondary:   Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Month 6   [ Time Frame: Baseline and Month 6 ]

9.  Secondary:   Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Month 12   [ Time Frame: Baseline and Month 12 ]

10.  Secondary:   Number of Subjects Achieving FPG Target at Month 4   [ Time Frame: Month 4 ]

11.  Secondary:   Number of Subjects Achieving FPG Target at Month 6   [ Time Frame: Month 6 ]

12.  Secondary:   Number of Subjects Achieving FPG Target at Month 12   [ Time Frame: Month 12 ]

13.  Secondary:   Mean Change From Baseline in 5 Year UKPDS Risk Scores at Month 6   [ Time Frame: Baseline and Month 6 ]

14.  Secondary:   Mean Change From Baseline in 5 Year UKPDS Risk Scores at Month 12   [ Time Frame: Baseline and Month 12 ]

15.  Secondary:   Mean Change From Baseline in C-reactive Protein (CRP) at Month 6   [ Time Frame: Baseline and Month 6 ]

16.  Secondary:   Mean Change From Baseline in C-reactive Protein (CRP) at Month 12   [ Time Frame: Baseline and Month 12 ]

17.  Secondary:   Mean Change From Baseline in Adiponectin at Month 6   [ Time Frame: Baseline and Month 6 ]

18.  Secondary:   Mean Change From Baseline in Adiponectin at Month 12   [ Time Frame: Baseline and Month 12 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Dr. Robert Josse
Organization: Dr. Anatoly Langer, Chair CHRC, Canadian Heart Research Centre
phone: 416-977-8010
e-mail: langera@chrc.net


No publications provided


Responsible Party: Dr. Anatoly Langer, Canadian Heart Research Centre
ClinicalTrials.gov Identifier: NCT00131664     History of Changes
Other Study ID Numbers: AVM103436
Study First Received: August 17, 2005
Results First Received: January 28, 2012
Last Updated: April 15, 2013
Health Authority: Canada: Health Canada