Trial Outcomes & Findings for Avandia™ + Amaryl™ or Avandamet™ Compared With Metformin (AVALANCHE™ Study) (NCT NCT00131664)
NCT ID: NCT00131664
Last Updated: 2013-04-17
Results Overview
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the Month 6 value minus the baseline value, with last on-treatment observation carried forward (LOCF) from Month 2 for withdrawn subjects or missing values.
COMPLETED
PHASE3
391 participants
Baseline and Month 6
2013-04-17
Participant Flow
391 patients were randomized from 49 Canadian sites of General Practitioners and Community Endocrinologists during an 8 month recruitment period.
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.
Participant milestones
| Measure |
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.
|
|---|---|---|---|---|---|---|
|
First Period (First 6 Months)
STARTED
|
136
|
135
|
120
|
0
|
0
|
0
|
|
First Period (First 6 Months)
COMPLETED
|
111
|
117
|
104
|
0
|
0
|
0
|
|
First Period (First 6 Months)
NOT COMPLETED
|
25
|
18
|
16
|
0
|
0
|
0
|
|
Second Period (Additional Drug Added)
STARTED
|
90
|
101
|
79
|
21
|
16
|
25
|
|
Second Period (Additional Drug Added)
COMPLETED
|
81
|
97
|
76
|
19
|
15
|
22
|
|
Second Period (Additional Drug Added)
NOT COMPLETED
|
9
|
4
|
3
|
2
|
1
|
3
|
Reasons for withdrawal
| Measure |
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.
|
|---|---|---|---|---|---|---|
|
First Period (First 6 Months)
Lost to Follow-up
|
7
|
3
|
3
|
0
|
0
|
0
|
|
First Period (First 6 Months)
Death
|
0
|
1
|
0
|
0
|
0
|
0
|
|
First Period (First 6 Months)
Protocol Violation
|
2
|
2
|
1
|
0
|
0
|
0
|
|
First Period (First 6 Months)
Withdrawal by Subject
|
4
|
6
|
2
|
0
|
0
|
0
|
|
First Period (First 6 Months)
Adverse Event
|
9
|
4
|
5
|
0
|
0
|
0
|
|
First Period (First 6 Months)
Clinically significant lab abnormalities
|
1
|
2
|
0
|
0
|
0
|
0
|
|
First Period (First 6 Months)
Administrative reasons
|
2
|
0
|
5
|
0
|
0
|
0
|
|
Second Period (Additional Drug Added)
Lost to Follow-up
|
3
|
0
|
2
|
1
|
0
|
2
|
|
Second Period (Additional Drug Added)
Protocol Violation
|
0
|
1
|
1
|
0
|
0
|
0
|
|
Second Period (Additional Drug Added)
Withdrawal by Subject
|
2
|
0
|
0
|
0
|
0
|
0
|
|
Second Period (Additional Drug Added)
Adverse Event
|
0
|
1
|
0
|
0
|
0
|
1
|
|
Second Period (Additional Drug Added)
Clinically significant lab abnormalities
|
0
|
0
|
0
|
1
|
0
|
0
|
|
Second Period (Additional Drug Added)
Administrative reasons
|
4
|
2
|
0
|
0
|
1
|
0
|
Baseline Characteristics
Avandia™ + Amaryl™ or Avandamet™ Compared With Metformin (AVALANCHE™ Study)
Baseline characteristics by cohort
| Measure |
Avandia and Amaryl
n=136 Participants
4 mg + 1 mg once daily titration up to 8 mg + 2 mg once daily over 6 months
|
Avandamet
n=135 Participants
2 mg / 500 mg twice daily titration up to 4 mg / 1000 mg twice daily over 6 months
|
Metformin
n=120 Participants
500 mg twice daily titration up to 1000 mg twice daily over 6 months
|
Total
n=391 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age Continuous
|
54.3 years
STANDARD_DEVIATION 10.1 • n=5 Participants
|
53.7 years
STANDARD_DEVIATION 11.6 • n=7 Participants
|
56.0 years
STANDARD_DEVIATION 10.1 • n=5 Participants
|
54.6 years
STANDARD_DEVIATION 10.7 • n=4 Participants
|
|
Sex: Female, Male
Female
|
48 Participants
n=5 Participants
|
59 Participants
n=7 Participants
|
57 Participants
n=5 Participants
|
164 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
88 Participants
n=5 Participants
|
76 Participants
n=7 Participants
|
63 Participants
n=5 Participants
|
227 Participants
n=4 Participants
|
|
Region of Enrollment
Canada
|
136 participants
n=5 Participants
|
135 participants
n=7 Participants
|
120 participants
n=5 Participants
|
391 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline and Month 6Population: Intent-to-Treat (ITT) population: all randomized subjects who took at least one dose of study medication and had at least one valid observation. For withdrawn subjects or missing values, the last on-treatment observation was carried forward (LOCF). Only subjects with a value at baseline and at Month 6 were analyzed.
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.
Outcome measures
| Measure |
Avandia and Amaryl
n=125 Participants
4 mg + 1 mg once daily titration up to 8 mg + 2 mg once daily over 6 months
|
Avandamet
n=128 Participants
2 mg / 500 mg twice daily titration up to 4 mg / 1000 mg twice daily over 6 months
|
Metformin
n=115 Participants
500 mg twice daily titration up to 1000 mg twice daily over 6 months
|
|---|---|---|---|
|
Mean Change From Baseline in A1C at Month 6
Baseline
|
8.14 percent
Standard Error 0.095
|
7.96 percent
Standard Error 0.076
|
7.90 percent
Standard Error 0.085
|
|
Mean Change From Baseline in A1C at Month 6
Change from baseline
|
-1.61 percent
Standard Error 0.108
|
-1.39 percent
Standard Error 0.081
|
-1.02 percent
Standard Error 0.092
|
SECONDARY outcome
Timeframe: Baseline and Month 4Population: Intent-to-Treat (ITT) population: all randomized subjects who took at least one dose of study medication and had at least one valid observation. For withdrawn subjects or missing values, the last on-treatment observation was carried forward (LOCF). Only subjects with values at baseline and Month 4 were analyzed.
Change from baseline was calculated as the Month 4 value minus the baseline value, with last on-treatment observation carried forward (LOCF) from Month 2 for withdrawn subjects or missing values.
Outcome measures
| Measure |
Avandia and Amaryl
n=125 Participants
4 mg + 1 mg once daily titration up to 8 mg + 2 mg once daily over 6 months
|
Avandamet
n=128 Participants
2 mg / 500 mg twice daily titration up to 4 mg / 1000 mg twice daily over 6 months
|
Metformin
n=115 Participants
500 mg twice daily titration up to 1000 mg twice daily over 6 months
|
|---|---|---|---|
|
Mean Change From Baseline in A1C at Month 4
|
-1.44 percent
Standard Error 0.099
|
-1.28 percent
Standard Error 0.083
|
-0.94 percent
Standard Error 0.097
|
SECONDARY outcome
Timeframe: Baseline and Month 12Population: Intent-to-Treat (ITT) population: all randomized subjects who took at least one dose of study medication and had at least one valid observation. For withdrawn subjects or missing values, the last on-treatment observation was carried forward (LOCF). Only subjects with values at baseline and Month 12 were analyzed.
Change from baseline was calculated as the Month 12 value minus the baseline value, with last on-treatment observation carried forward (LOCF) from Month 2 for withdrawn subjects or missing values.
Outcome measures
| Measure |
Avandia and Amaryl
n=131 Participants
4 mg + 1 mg once daily titration up to 8 mg + 2 mg once daily over 6 months
|
Avandamet
n=131 Participants
2 mg / 500 mg twice daily titration up to 4 mg / 1000 mg twice daily over 6 months
|
Metformin
n=116 Participants
500 mg twice daily titration up to 1000 mg twice daily over 6 months
|
|---|---|---|---|
|
Mean Change From Baseline in A1C at Month 12
|
-1.50 percent
Standard Error 0.115
|
-1.56 percent
Standard Error 0.086
|
-1.14 percent
Standard Error 0.111
|
SECONDARY outcome
Timeframe: Month 4Population: Intent-to-Treat (ITT) population: all randomized subjects who took at least one dose of study medication and had at least one valid observation. For withdrawn subjects or missing values, the last on-treatment observation was carried forward (LOCF). Only subjects with values at baseline and Month 4 were analyzed.
A1C responders were described as subjects having achieved A1C less than 7 percent at Month 4, with LOCF from Month 2.
Outcome measures
| Measure |
Avandia and Amaryl
n=125 Participants
4 mg + 1 mg once daily titration up to 8 mg + 2 mg once daily over 6 months
|
Avandamet
n=128 Participants
2 mg / 500 mg twice daily titration up to 4 mg / 1000 mg twice daily over 6 months
|
Metformin
n=115 Participants
500 mg twice daily titration up to 1000 mg twice daily over 6 months
|
|---|---|---|---|
|
Number of Subjects Achieving A1C Target at Month 4
|
83 participants
|
96 participants
|
69 participants
|
SECONDARY outcome
Timeframe: Month 6Population: Intent-to-Treat (ITT) population: all randomized subjects who took at least one dose of study medication and had at least one valid observation. For withdrawn subjects or missing values, the last on-treatment observation was carried forward (LOCF). Only subjects with values at baseline Month 6 were analyzed.
A1C responders were described as subjects having achieved A1C less than 7 percent at Month 6, with LOCF from Month 2.
Outcome measures
| Measure |
Avandia and Amaryl
n=125 Participants
4 mg + 1 mg once daily titration up to 8 mg + 2 mg once daily over 6 months
|
Avandamet
n=128 Participants
2 mg / 500 mg twice daily titration up to 4 mg / 1000 mg twice daily over 6 months
|
Metformin
n=115 Participants
500 mg twice daily titration up to 1000 mg twice daily over 6 months
|
|---|---|---|---|
|
Number of Subjects Achieving A1C Target at Month 6
|
94 participants
|
98 participants
|
69 participants
|
SECONDARY outcome
Timeframe: Month 12Population: Intent-to-Treat (ITT) population: all randomized subjects who took at least one dose of study medication and had at least one valid observation. For withdrawn subjects or missing values, the last on-treatment observation was carried forward (LOCF). Only subjects with values at baseline and Month 12 were analyzed.
A1C responders were described as subjects having achieved A1C less than 7 percent at Month 12 with LOCF from Month 2.
Outcome measures
| Measure |
Avandia and Amaryl
n=131 Participants
4 mg + 1 mg once daily titration up to 8 mg + 2 mg once daily over 6 months
|
Avandamet
n=131 Participants
2 mg / 500 mg twice daily titration up to 4 mg / 1000 mg twice daily over 6 months
|
Metformin
n=116 Participants
500 mg twice daily titration up to 1000 mg twice daily over 6 months
|
|---|---|---|---|
|
Number of Subjects Achieving A1C Target at Month 12
|
95 participants
|
111 participants
|
82 participants
|
SECONDARY outcome
Timeframe: Baseline and Month 4Population: Intent-to-Treat (ITT) population: all randomized subjects who took at least one dose of study medication and had at least one valid observation. For withdrawn subjects or missing values, the last on-treatment observation was carried forward (LOCF). Only subjects with values at baseline and Month 4 were analyzed.
Change from baseline was calculated as the Month 4 value minus the baseline value, with last on-treatment observation carried forward (LOCF) from Month 2 for withdrawn subjects or missing values.
Outcome measures
| Measure |
Avandia and Amaryl
n=124 Participants
4 mg + 1 mg once daily titration up to 8 mg + 2 mg once daily over 6 months
|
Avandamet
n=127 Participants
2 mg / 500 mg twice daily titration up to 4 mg / 1000 mg twice daily over 6 months
|
Metformin
n=115 Participants
500 mg twice daily titration up to 1000 mg twice daily over 6 months
|
|---|---|---|---|
|
Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Month 4
|
-2.86 millimoles per litre (mmol/L)
Standard Error 0.247
|
-2.33 millimoles per litre (mmol/L)
Standard Error 0.181
|
-1.75 millimoles per litre (mmol/L)
Standard Error 0.204
|
SECONDARY outcome
Timeframe: Baseline and Month 6Population: Intent-to-Treat (ITT) population: all randomized subjects who took at least one dose of study medication and had at least one valid observation. For withdrawn subjects or missing values, the last on-treatment observation was carried forward (LOCF). Only subjects with values at baseline and Month 6 were analyzed.
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.
Outcome measures
| Measure |
Avandia and Amaryl
n=124 Participants
4 mg + 1 mg once daily titration up to 8 mg + 2 mg once daily over 6 months
|
Avandamet
n=127 Participants
2 mg / 500 mg twice daily titration up to 4 mg / 1000 mg twice daily over 6 months
|
Metformin
n=115 Participants
500 mg twice daily titration up to 1000 mg twice daily over 6 months
|
|---|---|---|---|
|
Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Month 6
|
-2.98 millimoles per litre (mmol/L)
Standard Error 0.259
|
-2.55 millimoles per litre (mmol/L)
Standard Error 0.200
|
-1.86 millimoles per litre (mmol/L)
Standard Error 0.192
|
SECONDARY outcome
Timeframe: Baseline and Month 12Population: Intent-to-Treat (ITT) population: all randomized subjects who took at least one dose of study medication and had at least one valid observation. For withdrawn subjects or missing values, the last on-treatment observation was carried forward (LOCF). Only subjects with values at baseline and Month 6 were analyzed.
Change from baseline was calculated as the Month 12 value minus the baseline value, with LOCF from Month 2 for withdrawn subjects or missing values.
Outcome measures
| Measure |
Avandia and Amaryl
n=130 Participants
4 mg + 1 mg once daily titration up to 8 mg + 2 mg once daily over 6 months
|
Avandamet
n=130 Participants
2 mg / 500 mg twice daily titration up to 4 mg / 1000 mg twice daily over 6 months
|
Metformin
n=116 Participants
500 mg twice daily titration up to 1000 mg twice daily over 6 months
|
|---|---|---|---|
|
Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Month 12
|
-2.71 millimoles per litre (mmol/L)
Standard Error 0.274
|
-2.76 millimoles per litre (mmol/L)
Standard Error 0.225
|
-2.12 millimoles per litre (mmol/L)
Standard Error 0.231
|
SECONDARY outcome
Timeframe: Month 4Population: Intent-to-Treat (ITT) population: all randomized subjects who took at least one dose of study medication and had at least one valid observation. For withdrawn subjects or missing values, the last on-treatment observation was carried forward (LOCF). Only subjects with values at baseline and Month 4 were analyzed.
FPG responders were described as subjects having achieved FPG less than 7 mmol/L at Month 4 with LOCF from Month 2.
Outcome measures
| Measure |
Avandia and Amaryl
n=124 Participants
4 mg + 1 mg once daily titration up to 8 mg + 2 mg once daily over 6 months
|
Avandamet
n=127 Participants
2 mg / 500 mg twice daily titration up to 4 mg / 1000 mg twice daily over 6 months
|
Metformin
n=115 Participants
500 mg twice daily titration up to 1000 mg twice daily over 6 months
|
|---|---|---|---|
|
Number of Subjects Achieving FPG Target at Month 4
|
58 participants
|
65 participants
|
38 participants
|
SECONDARY outcome
Timeframe: Month 6Population: Intent-to-Treat (ITT) population: all randomized subjects who took at least one dose of study medication and had at least one valid observation. For withdrawn subjects or missing values, the last on-treatment observation was carried forward (LOCF). Only subjects with values at baseline and Month 6 were analyzed.
FPG responders were described as subjects having achieved FPG less than 7 mmol/L at Month 6 with LOCF from Month 2.
Outcome measures
| Measure |
Avandia and Amaryl
n=124 Participants
4 mg + 1 mg once daily titration up to 8 mg + 2 mg once daily over 6 months
|
Avandamet
n=127 Participants
2 mg / 500 mg twice daily titration up to 4 mg / 1000 mg twice daily over 6 months
|
Metformin
n=115 Participants
500 mg twice daily titration up to 1000 mg twice daily over 6 months
|
|---|---|---|---|
|
Number of Subjects Achieving FPG Target at Month 6
|
61 participants
|
76 participants
|
43 participants
|
SECONDARY outcome
Timeframe: Month 12Population: Intent-to-Treat (ITT) population: all randomized subjects who took at least one dose of study medication and had at least one valid observation. For withdrawn subjects or missing values, the last on-treatment observation was carried forward (LOCF). Only subjects with values at baseline and Month 6 were analyzed.
FPG responders were described as subjects having achieved FPG less than 7 mmol/L at Month 12 with LOCF from Month 2.
Outcome measures
| Measure |
Avandia and Amaryl
n=130 Participants
4 mg + 1 mg once daily titration up to 8 mg + 2 mg once daily over 6 months
|
Avandamet
n=130 Participants
2 mg / 500 mg twice daily titration up to 4 mg / 1000 mg twice daily over 6 months
|
Metformin
n=116 Participants
500 mg twice daily titration up to 1000 mg twice daily over 6 months
|
|---|---|---|---|
|
Number of Subjects Achieving FPG Target at Month 12
|
64 participants
|
86 participants
|
51 participants
|
SECONDARY outcome
Timeframe: Baseline and Month 6Population: Intent-to-Treat (ITT) population: all randomized subjects who took at least one dose of study medication and had at least one valid observation. For withdrawn subjects or missing values, the last on-treatment observation was carried forward (LOCF). Only subjects with values at baseline and Month 6 were analyzed.
Change from baseline was calculated as the Month 6 value minus the baseline value, with LOCF from Month 2. The UKPDS (United Kingdom Prospective Diabetes Study) risk engine calculated was based on 5 years risk using gender, race, age at diagnosis of diabetes, duration of diabetes, smoking status, A1C, systolic blood pressure and total cholesterol to high-density lipoprotein (HDL) ratio at a specified visit. The UKPDS cardiovascular disease (CVD) risk engine is used to estimate the risk of having coronary heart disease in type II diabetes according to the UKPDS model. The possible risk scores can range from 0 to 100% and hence lower scores would predict a person is less likely to have an event.
Outcome measures
| Measure |
Avandia and Amaryl
n=111 Participants
4 mg + 1 mg once daily titration up to 8 mg + 2 mg once daily over 6 months
|
Avandamet
n=116 Participants
2 mg / 500 mg twice daily titration up to 4 mg / 1000 mg twice daily over 6 months
|
Metformin
n=99 Participants
500 mg twice daily titration up to 1000 mg twice daily over 6 months
|
|---|---|---|---|
|
Mean Change From Baseline in 5 Year UKPDS Risk Scores at Month 6
|
-1.09 percent
Standard Error 0.246
|
-1.05 percent
Standard Error 0.169
|
-1.54 percent
Standard Error 0.234
|
SECONDARY outcome
Timeframe: Baseline and Month 12Population: Intent-to-Treat (ITT) population: all randomized subjects who took at least one dose of study medication and had at least one valid observation. For withdrawn subjects or missing values, the last on-treatment observation was carried forward (LOCF). Only subjects with values at baseline and Month 12 were analyzed.
Change from baseline was calculated as the Month 12 value minus the baseline value, with LOCF from Month 2. The UKPDS (U.K. Prospective Diabetes Study) risk engine calculated was based on 5 years risk using gender, race, age at diagnosis of diabetes, duration of diabetes, smoking status, A1C, systolic blood pressure and total cholesterol to HDL ratio at a specified visit. The UKPDS cardiovascular disease (CVD) risk engine is used to estimate the risk of having coronary heart disease in type II diabetes according to the UKPDS model. The possible risk scores can range from 0 to 100% and hence lower scores would predict a person is less likely to have an event.
Outcome measures
| Measure |
Avandia and Amaryl
n=122 Participants
4 mg + 1 mg once daily titration up to 8 mg + 2 mg once daily over 6 months
|
Avandamet
n=124 Participants
2 mg / 500 mg twice daily titration up to 4 mg / 1000 mg twice daily over 6 months
|
Metformin
n=104 Participants
500 mg twice daily titration up to 1000 mg twice daily over 6 months
|
|---|---|---|---|
|
Mean Change From Baseline in 5 Year UKPDS Risk Scores at Month 12
|
-0.72 percent
Standard Error 0.392
|
-0.62 percent
Standard Error 0.252
|
-1.11 percent
Standard Error 0.234
|
SECONDARY outcome
Timeframe: Baseline and Month 6Population: All Primary and secondary endpoints were calculated on the Intent to Treat (ITT) population where each patient had at least one dose of the medication and at least one valid observation. Missing values were carried forward (using Last Observation Carried Forward method) except for the calculation of the composite variables.
Change from baseline was calculated as the Month 6 value minus the baseline value. LOCF was not used for this analysis. CRP was only done at baseline, months 6 and 8. The test was optional and performed only by participating sites.
Outcome measures
| Measure |
Avandia and Amaryl
n=24 Participants
4 mg + 1 mg once daily titration up to 8 mg + 2 mg once daily over 6 months
|
Avandamet
n=28 Participants
2 mg / 500 mg twice daily titration up to 4 mg / 1000 mg twice daily over 6 months
|
Metformin
n=22 Participants
500 mg twice daily titration up to 1000 mg twice daily over 6 months
|
|---|---|---|---|
|
Mean Change From Baseline in C-reactive Protein (CRP) at Month 6
|
-1.20 milligram per decilitre (mg/dL)
Standard Error 0.419
|
-1.68 milligram per decilitre (mg/dL)
Standard Error 0.640
|
-1.25 milligram per decilitre (mg/dL)
Standard Error 0.804
|
SECONDARY outcome
Timeframe: Baseline and Month 12Population: Intent-to-Treat (ITT) population: all randomized subjects who took at least one dose of study medication and had at least one valid observation. For withdrawn subjects or missing values, the last on-treatment observation was carried forward (LOCF). Only subjects with values at baseline and Month 12 were analyzed.
Change from baseline was calculated as the Month 12 value minus the baseline value, with LOCF from Month 6. CRP was only done at baseline, months 6 and 12. The test was optional and performed only by participating sites.
Outcome measures
| Measure |
Avandia and Amaryl
n=32 Participants
4 mg + 1 mg once daily titration up to 8 mg + 2 mg once daily over 6 months
|
Avandamet
n=30 Participants
2 mg / 500 mg twice daily titration up to 4 mg / 1000 mg twice daily over 6 months
|
Metformin
n=25 Participants
500 mg twice daily titration up to 1000 mg twice daily over 6 months
|
|---|---|---|---|
|
Mean Change From Baseline in C-reactive Protein (CRP) at Month 12
|
-0.40 mg/dL
Standard Deviation 0.323
|
-1.52 mg/dL
Standard Deviation 0.642
|
-1.52 mg/dL
Standard Deviation 0.817
|
SECONDARY outcome
Timeframe: Baseline and Month 6Population: Intent-to-Treat (ITT) population: all randomized subjects who took at least one dose of study medication and had at least one valid observation. For withdrawn subjects or missing values, the last on-treatment observation was carried forward (LOCF). Only subjects with values at baseline and Month 6 were analyzed.
Change from baseline was calculated as the Month 6 value minus the baseline value. LOCF was not used for this analysis. Adiponectin was only done at baseline, months 6 and 12. The test was optional and performed only by participating sites.
Outcome measures
| Measure |
Avandia and Amaryl
n=25 Participants
4 mg + 1 mg once daily titration up to 8 mg + 2 mg once daily over 6 months
|
Avandamet
n=23 Participants
2 mg / 500 mg twice daily titration up to 4 mg / 1000 mg twice daily over 6 months
|
Metformin
n=22 Participants
500 mg twice daily titration up to 1000 mg twice daily over 6 months
|
|---|---|---|---|
|
Mean Change From Baseline in Adiponectin at Month 6
|
5.73 microgram per millilitre (µg/mL)
Standard Error 0.869
|
6.37 microgram per millilitre (µg/mL)
Standard Error 1.453
|
0.23 microgram per millilitre (µg/mL)
Standard Error 0.299
|
SECONDARY outcome
Timeframe: Baseline and Month 12Population: Intent-to-Treat (ITT) population: all randomized subjects who took at least one dose of study medication and had at least one valid observation. For withdrawn subjects or missing values, the last on-treatment observation was carried forward (LOCF). Only subjects with values at baseline and Month 12 were analyzed.
Change from baseline was calculated as the Month 12 value minus the baseline value, with LOCF from Month 6. Adiponectin was only done at baseline, months 6 and 12. The test was optional and performed only by participating sites.
Outcome measures
| Measure |
Avandia and Amaryl
n=31 Participants
4 mg + 1 mg once daily titration up to 8 mg + 2 mg once daily over 6 months
|
Avandamet
n=27 Participants
2 mg / 500 mg twice daily titration up to 4 mg / 1000 mg twice daily over 6 months
|
Metformin
n=24 Participants
500 mg twice daily titration up to 1000 mg twice daily over 6 months
|
|---|---|---|---|
|
Mean Change From Baseline in Adiponectin at Month 12
|
4.95 µg/mL
Standard Error 0.902
|
8.21 µg/mL
Standard Error 1.804
|
1.453 µg/mL
Standard Error 0.371
|
Adverse Events
Avandia and Amaryl
Avandamet
Metformin
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Avandia and Amaryl
n=136 participants at risk
Avandia™ + Amaryl™ Arm: at month 2 initial dose of 4 mg +1 mg OD was titrated up to 8 mg + 1 mg OD; at month 4 it was further titrated up to 8 mg / 2 mg OD. At month 6, patients not achieving target received additional specified drug therapy: Metformin was added and titrated up to 1000 mg BID maximum dose for an additional 6 months.
|
Avandamet
n=117 participants at risk；n=135 participants at risk
Avandamet™ Arm: at month 2 the initial dose of 2 mg / 500 mg 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. At month 6, patients not achieving target received additional specified drug therapy Amaryl™ was added and titrated up to 4 mg OD maximum dose for an additional 6 months
|
Metformin
n=104 participants at risk；n=120 participants at risk
Metformin Arm: initial dose of 500 mg BID was titrated up to 850 mg BID at month 2. At month 4, it was further titrated up to 1000 mg BID. At month 6 (visit 6), patients not achieving target received additional specified drug therapy: Amaryl™ was added and titrated up to 4 mg OD maximum dose for an additional 6 months.
|
|---|---|---|---|
|
Musculoskeletal and connective tissue disorders
Fracture
|
1.5%
2/136 • Number of events 2
|
2.6%
3/117 • Number of events 3
|
0.00%
0/104
|
Additional Information
Dr. Robert Josse
Dr. Anatoly Langer, Chair CHRC, Canadian Heart Research Centre
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place