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

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ClinicalTrials.gov Identifier: NCT00386100
Recruitment Status : Completed
First Posted : October 11, 2006
Results First Posted : April 5, 2011
Last Update Posted : November 23, 2016
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Diabetes Mellitus, Type 2
Interventions: Drug: Avandamet 6 mg/1500 mg (ttd)
Drug: Avandamet 4 mg/1000 mg (ttd)
Drug: Avandamet 2 mg/500 mg (ttd)
Drug: Avandamet 8 mg/ 2000 mg (ttd)
Drug: Metformin 500 mg (ttd)
Drug: Metformin 1000 mg (ttd)
Drug: Metformin 1500 mg (ttd)
Drug: Metformin 2000 mg (ttd)

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Metformin Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
Avandamet Beginning dose of Avandamet (AVM) 4 mg/500 mg once a day. Dose could be increased up to a maximum dose of 8 mg/2000 mg.

Participant Flow:   Overall Study
    Metformin   Avandamet
STARTED   340   348 
COMPLETED   186   217 
NOT COMPLETED   154   131 
Did not receive study medication                6                4 
Adverse Event                15                25 
Death                0                1 
Insufficient therapeutic effect                30                6 
Lost to Follow-up                29                29 
Non-compliance                18                19 
Protocol Violation                5                3 
Withdrawal by Subject                32                31 
Bone mass density (BMD) loss >6%                4                4 
BMD <2.5                1                0 
Consecutive elevated Hba1C                1                0 
Visit 11 DXA showed excessive bone loss                0                1 
Laboratory findings                1                0 
Participant's concern due to CPK levels                1                0 
Participant moving out of state                2                0 
Excessive bone loss vs. baseline value                0                1 
Didn't meet entry criteria                1                1 
Participant's PCP wanted to stop drug                1                0 
Osteoporosis findings on Visit 2 DXA                0                1 
Bad metabolic control & patient security                1                0 
Bone loss by DXA bone scan                1                0 
DBP 93 mmHg at randomization                1                0 
7.6% bone loss                1                0 
Osteoporosis                0                1 
Positive pregnancy test                1                3 
Out of country for 5 months                1                0 
Hb1Ac >8%                0                1 
Participant randomized in error                1                0 



  Baseline Characteristics

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
Metformin Beginning dose of Metformin (MET) 500 milligrams (mg) once a day. Dose could be increased up to a maximum dose of MET 2000 mg.
Avandamet Beginning dose of Avandamet (AVM) 4 mg/500 mg once a day. Dose could be increased up to a maximum dose of 8 mg/2000 mg.
Total Total of all reporting groups

Baseline Measures
   Metformin   Avandamet   Total 
Overall Participants Analyzed 
[Units: Participants]
 334   344   678 
Age [1] 
[Units: Years]
Mean (Standard Deviation)
 50.7  (10.49)   51.5  (10.52)   51.1  (10.50) 
[1] The Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication, was used for all baseline characteristics.
Gender 
[Units: Participants]
     
Female   158   160   318 
Male   176   184   360 
Race/Ethnicity, Customized 
[Units: Participants]
     
African America/African   13   17   30 
American Indian or Alaskan Native   3   7   10 
Asian – Central/South Asian   23   22   45 
Asian – East Asian   44   51   95 
Asian – Japanese   0   1   1 
Asian – South East Asian   48   48   96 
White – Arabic/North African   4   3   7 
White – White/Caucasian/European   185   183   368 
Mixed Race   5   5   10 
Not Specified   9   7   16 
Duration of Diabetes [1] 
[Units: Years]
Mean (Standard Deviation)
 2.570  (3.2671)   2.293  (3.0774)   2.429  (3.1729) 
[1] The Safety Population, comprised of all participants who were randomized and received at least one dose of the study medication, was used for all baseline characteristics.


  Outcome Measures

1.  Primary:   Change From Baseline in HbA1c at Week 80   [ Time Frame: Baseline and Week 80 ]

2.  Secondary:   Mean Change From Baseline in HbA1c at Week 80   [ Time Frame: Baseline and Week 80 ]

3.  Secondary:   Number of Participants Achieving HbA1c <=6.5% and <7% at Week 80   [ Time Frame: Week 80 ]

4.  Secondary:   Change in Fasting Plasma Glucose (FPG) From Baseline at Week 80   [ Time Frame: Baseline and Week 80 ]

5.  Secondary:   Change From Baseline in FPG at Week 80   [ Time Frame: Baseline and Week 80 ]

6.  Secondary:   Number of Participants Achieving FPG <=6 mmol/L (110 mg/dL) and <=7 mmol/L (126 mg/dL) at Week 80   [ Time Frame: Week 80 ]

7.  Secondary:   Number of Participants Achieving Treatment Failure   [ Time Frame: Randomization to treatment failure (up to Week 80) ]

8.  Secondary:   Percent Change From Baseline in Total Cholesterol, Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein (HDL) Cholesterol, and Triglycerides at Week 80   [ Time Frame: Baseline and Week 80 ]

9.  Secondary:   Percent Change From Baseline in Adiponectin at Week 80 (United States [US] and Mexico Subset of Participants )   [ Time Frame: Baseline and Week 80 ]

10.  Secondary:   Percent Change From Baseline in C-reactive Protein (CRP) at Week 80 (US and Mexico Subset of Participants)   [ Time Frame: Baseline and Week 80 ]

11.  Secondary:   Percent Change in Free Fatty Acids (FFA) From Baseline at Week 80 (US and Mexico Subset of Participants).   [ Time Frame: Baseline and Week 80 ]

12.  Secondary:   Change in Fasting Insulin From Baseline at Week 80 (US and Mexico Subset of Participants)   [ Time Frame: Baseline and Week 80 ]

13.  Secondary:   Change in C-peptide From Baseline at Week 80 (US and Mexico Subset of Participants)   [ Time Frame: Baseline and Week 80 ]

14.  Secondary:   Percent Change From Baseline in in HOMA-S and HOMA-B to Week 80 (US and Mexico Subset of Participants)   [ Time Frame: Baseline and Week 80 ]

15.  Secondary:   Slope of Delta-cell Function as Estimated by the Ratio deltaI/deltaG   [ Time Frame: Baseline and Week 80 ]

16.  Secondary:   Number of Participants at Final Dose Level   [ Time Frame: Baseline to Week 80 or withdrawal ]

17.  Secondary:   Percent Change From Baseline in Lumbar Spine Bone Mass Density (BMD) at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)   [ Time Frame: Baseline and Weeks 20, 56, and 80 ]

18.  Secondary:   Percent Change From Baseline in Total Hip BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)   [ Time Frame: Baseline and Weeks 20, 56, and 80 ]

19.  Secondary:   Percent Change From Baseline in Trochanter BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)   [ Time Frame: Baseline and Weeks 20, 56, and 80 ]

20.  Secondary:   Percent Change From Baseline in Femoral Neck BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)   [ Time Frame: Baseline and Weeks 20, 56, and 80 ]

21.  Secondary:   Percent Change From Baseline in Distal Radius BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)   [ Time Frame: Baseline and Weeks 20, 56, and 80 ]

22.  Secondary:   Percent Change From Baseline in Total Body BMD at Weeks 20, 56, and 80 (Bone Sub-study Subset of Participants)   [ Time Frame: Baseline and Weeks 20, 56, and 80 ]

23.  Secondary:   Percent Change From Baseline in Serum Calcium at Weeks 12, 32, 56, and 80   [ Time Frame: Baseline and Weeks 12, 32, 56, and 80 ]

24.  Secondary:   Percent Change From Baseline in Intact Parathyroid Hormone at Week 80   [ Time Frame: Baseline and Week 80 ]

25.  Secondary:   Percent Change From Baseline in 25-hydroxy Vitamin D at Week 80   [ Time Frame: Baseline and Week 80 ]

26.  Secondary:   Percent Change From Baseline in Estradiol at Weeks 20, 56, and 80   [ Time Frame: Baseline and Weeks 20, 56, and 80 ]

27.  Secondary:   Percent Change From Baseline in C-terminal Telopeptide (CTX) at Weeks 20, 56, and 80   [ Time Frame: Baseline and Weeks 20, 56, and 80 ]

28.  Secondary:   Percent Change From Baseline in Procollagen Type-1 N-propeptide (P1NP) at Weeks 20, 56, and 80   [ Time Frame: Baseline and Weeks 20, 56, and 80 ]

29.  Secondary:   Percent Change From Baseline in Bone Alkaline Phosphatase (BSAP) at Weeks 20, 56, and 80   [ Time Frame: Baseline and Weeks 20, 56, and 80 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

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
Ten participants who started the study and were randomized did not receive any study medication (6 participants in the metformin arm and 4 participants in the avandamet arm). These participants are not included in any of the analysis populations.


  More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
phone: 866-435-7343


Publications:

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00386100     History of Changes
Other Study ID Numbers: AVT105913
First Submitted: October 9, 2006
First Posted: October 11, 2006
Results First Submitted: July 8, 2010
Results First Posted: April 5, 2011
Last Update Posted: November 23, 2016