Diabetes Mellitus, Type 2
Conditions
Keywords
rosiglitazone, Avandia, type 2 diabetes mellitus, diabetes
Brief summary
This study was designed to compare the efficacy and safety of BRL49653C versus placebo with concomitant use of sulfonyl urea (SU).
Interventions
DRUGRosiglitazone (BRL49653C)
study drug
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with type 2 diabetes mellitus managed by SU will be candidate for this study. These candidates will be checked up on their clinical laboratory data, and must have adequate blood, liver and kidney function.
Exclusion criteria
* Patient with serious cardiovascular disease or serious hepatic disease will not be eligible.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Glycosylated Hemoglobin (HbA1c) After 16 Weeks of Treatment in Rosiglitazone Group and Placebo Group | Baseline (Day 0) and Week 16 | Baseline value was value on Day 0. Change from Baseline was defined as value at Week 16 minus Baseline value. The full analysis set used which was defined as remaining after participant who infringed on the following events were excluded from the randomized participants, who did not take the investigational drug during or after the treatment period (amount of investigational drug taken was zero tablets) and who were not measured for HbA1c even once as the observation period Baseline value or in the treatment period (after the investigational drug was prescribed), or for whom the above were unavailable (including cases that the above were considered missing measurements due to a defective sample). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline After 16 Weeks of Treatment in Fasting Insulin | Baseline (Day 0) and Week 16 | Baseline value was value on Day 0. Change from Baseline was defined as value at Week 16 minus Baseline value. |
| Change From Baseline After 16 Weeks of Treatment in Fasting Proinsulin | Baseline (Day 0) and Week 16 | Baseline value was value on Day 0. Change from Baseline was defined as value at Week 16 minus Baseline value. |
| Change From Baseline After 16 Weeks of Treatment in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) | Baseline (Day 0) and Week 16 | Baseline value was value on Day 0. Change from Baseline was defined as value at Week 16 minus Baseline value. |
| Change From Baseline After 16 Weeks of Treatment in Fasting Plasma Glucose (FPG) | Baseline (Day 0) and Week 16 | Baseline value was value on Day 0. Change from Baseline was defined as value at Week 16 minus Baseline value. |
| Change From Baseline After 16 Weeks of Treatment in Adiponectin | Baseline (Day 0) and Week 16 | Baseline value was value on Day 0. Change from Baseline was defined as value at Week 16 minus Baseline value. |
| Change From Baseline After 16 Weeks of Treatment in Leptin and High Sensitivity C-reactive Protein (Hs-CRP) | Baseline (Day 0) and Week 16 | Baseline value was value on Day 0. Change from Baseline was defined as value at Week 16 minus Baseline value. |
| Percentage of Participants With Changes in HbA1c and FPG Meeting Specified Criteria After 16 Weeks of Treatment | Up to Week 16 | The specified criteria for HbA1c was, if the decrease from the observation period Baseline value meets the following conditions: 1) decrease from the observation period Baseline value is 0.7% or more; 2) fell below 6.5%; 3) satisfied either 1 or 2 noted above. And for FPG was, if the decrease from the observation period Baseline value meets the following conditions: 1) decrease of 30 mg per decilliter or more from the observation period Baseline value; 2) fell below 126 mg per deciliter; 3) satisfied either 1 or 2 noted above. |
| Change From Baseline After 16 Weeks of Treatment in Homeostasis Model Assessment of Beta-cell Function (HOMA-beta) | Baseline (Day 0) and Week 16 | Baseline value was value on Day 0. Change from Baseline was defined as value at Week 16 minus Baseline value. |
Countries
Japan
Participant flow
Recruitment details
From 19 April 2006 to 28 March 2007, total of 149 participants were randomized at 22 centers in Japan.
Pre-assignment details
Out of 172 participants given consent to participate in the study, 23 participants were withdrawn from the study before randomization.
Participants by arm
| Arm | Count |
|---|---|
| Rosiglitazone 4 mg Orally Once Daily Participants in this arm were randomized to receive rosiglitazone (BRL49653C) 4 mg tablets orally once daily before or after breakfast for 16 weeks. Participants also received either of concomitant medication (sulphonylureas) glibenclamide (1.25 to 5 mg), gliclazide (40 to 80 mg) or glimepiride (1 to 3 mg) per day during study. | 74 |
| Placebo Participants in this arm were randomized to receive rosiglitazone placebo tablets orally once daily before or after breakfast for 16 weeks. Participants also received either of concomitant medication (sulphonylureas) glibenclamide (1.25 to 5 mg), gliclazide (40 to 80 mg) or glimepiride (1 to 3 mg) per day during study. | 75 |
| Total | 149 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 2 |
Baseline characteristics
| Characteristic | Placebo | Total | Rosiglitazone 4 mg Orally Once Daily |
|---|---|---|---|
| Age, Continuous | 61.6 Years STANDARD_DEVIATION 9.8 | 60.8 Years STANDARD_DEVIATION 9.32 | 60.1 Years STANDARD_DEVIATION 8.81 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 75 Participants | 149 Participants | 74 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 28 Participants | 55 Participants | 27 Participants |
| Sex: Female, Male Male | 47 Participants | 94 Participants | 47 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 74 | 0 / 75 |
| other Total, other adverse events | 61 / 74 | 53 / 75 |
| serious Total, serious adverse events | 1 / 74 | 1 / 75 |
Outcome results
Primary
Change From Baseline in Glycosylated Hemoglobin (HbA1c) After 16 Weeks of Treatment in Rosiglitazone Group and Placebo Group
Baseline value was value on Day 0. Change from Baseline was defined as value at Week 16 minus Baseline value. The full analysis set used which was defined as remaining after participant who infringed on the following events were excluded from the randomized participants, who did not take the investigational drug during or after the treatment period (amount of investigational drug taken was zero tablets) and who were not measured for HbA1c even once as the observation period Baseline value or in the treatment period (after the investigational drug was prescribed), or for whom the above were unavailable (including cases that the above were considered missing measurements due to a defective sample).
Time frame: Baseline (Day 0) and Week 16
Population: Full analysis set used.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rosiglitazone 4 mg Orally Once Daily | Change From Baseline in Glycosylated Hemoglobin (HbA1c) After 16 Weeks of Treatment in Rosiglitazone Group and Placebo Group | -0.62 Percentage of Glycosylated Hemoglobin | Standard Deviation 0.074 |
| Placebo | Change From Baseline in Glycosylated Hemoglobin (HbA1c) After 16 Weeks of Treatment in Rosiglitazone Group and Placebo Group | 0.19 Percentage of Glycosylated Hemoglobin | Standard Deviation 0.073 |
p-value: <0.00195% CI: [-1.01, -0.61]ANCOVA
Secondary
Change From Baseline After 16 Weeks of Treatment in Adiponectin
Baseline value was value on Day 0. Change from Baseline was defined as value at Week 16 minus Baseline value.
Time frame: Baseline (Day 0) and Week 16
Population: Full analysis set used. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rosiglitazone 4 mg Orally Once Daily | Change From Baseline After 16 Weeks of Treatment in Adiponectin | 9.19 Micrograms per millilliter | Standard Deviation 7.03 |
| Placebo | Change From Baseline After 16 Weeks of Treatment in Adiponectin | 0.98 Micrograms per millilliter | Standard Deviation 2.301 |
p-value: <0.00195% CI: [6.52, 9.91]Unpaired t-test
Secondary
Change From Baseline After 16 Weeks of Treatment in Fasting Insulin
Baseline value was value on Day 0. Change from Baseline was defined as value at Week 16 minus Baseline value.
Time frame: Baseline (Day 0) and Week 16
Population: Full analysis set used. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rosiglitazone 4 mg Orally Once Daily | Change From Baseline After 16 Weeks of Treatment in Fasting Insulin | -0.479 Microunits per millilliter | Standard Deviation 3.2699 |
| Placebo | Change From Baseline After 16 Weeks of Treatment in Fasting Insulin | -1.197 Microunits per millilliter | Standard Deviation 6.1434 |
p-value: 0.37795% CI: [-0.883, 2.319]Unpaired t-test
Secondary
Change From Baseline After 16 Weeks of Treatment in Fasting Plasma Glucose (FPG)
Baseline value was value on Day 0. Change from Baseline was defined as value at Week 16 minus Baseline value.
Time frame: Baseline (Day 0) and Week 16
Population: Full analysis set used.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rosiglitazone 4 mg Orally Once Daily | Change From Baseline After 16 Weeks of Treatment in Fasting Plasma Glucose (FPG) | -15.9 Mg per decilliter | Standard Deviation 28.91 |
| Placebo | Change From Baseline After 16 Weeks of Treatment in Fasting Plasma Glucose (FPG) | 6.2 Mg per decilliter | Standard Deviation 32.69 |
p-value: <0.00195% CI: [-32.1, -12.1]Unpaired t-test
Secondary
Change From Baseline After 16 Weeks of Treatment in Fasting Proinsulin
Baseline value was value on Day 0. Change from Baseline was defined as value at Week 16 minus Baseline value.
Time frame: Baseline (Day 0) and Week 16
Population: Full analysis set used. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rosiglitazone 4 mg Orally Once Daily | Change From Baseline After 16 Weeks of Treatment in Fasting Proinsulin | -1.64 Picomoles per millilliter | Standard Deviation 13.63 |
| Placebo | Change From Baseline After 16 Weeks of Treatment in Fasting Proinsulin | 0.40 Picomoles per millilliter | Standard Deviation 11.666 |
p-value: 0.3395% CI: [-6.18, 2.09]Unpaired t-test
Secondary
Change From Baseline After 16 Weeks of Treatment in Homeostasis Model Assessment of Beta-cell Function (HOMA-beta)
Baseline value was value on Day 0. Change from Baseline was defined as value at Week 16 minus Baseline value.
Time frame: Baseline (Day 0) and Week 16
Population: Full analysis set used. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rosiglitazone 4 mg Orally Once Daily | Change From Baseline After 16 Weeks of Treatment in Homeostasis Model Assessment of Beta-cell Function (HOMA-beta) | 3.776 Percentage of normal beta cells function | Standard Deviation 18.7875 |
| Placebo | Change From Baseline After 16 Weeks of Treatment in Homeostasis Model Assessment of Beta-cell Function (HOMA-beta) | -4.444 Percentage of normal beta cells function | Standard Deviation 24.0408 |
p-value: 0.02295% CI: [1.191, 15.248]Unpaired t-test
Secondary
Change From Baseline After 16 Weeks of Treatment in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)
Baseline value was value on Day 0. Change from Baseline was defined as value at Week 16 minus Baseline value.
Time frame: Baseline (Day 0) and Week 16
Population: Full analysis set used. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rosiglitazone 4 mg Orally Once Daily | Change From Baseline After 16 Weeks of Treatment in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) | -0.496 MilliUnit per liter*millimoles per liter | Standard Deviation 1.5562 |
| Placebo | Change From Baseline After 16 Weeks of Treatment in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) | -0.486 MilliUnit per liter*millimoles per liter | Standard Deviation 3.7556 |
p-value: 0.98395% CI: [-0.945, 0.925]Unpaired t-test
Secondary
Change From Baseline After 16 Weeks of Treatment in Leptin and High Sensitivity C-reactive Protein (Hs-CRP)
Baseline value was value on Day 0. Change from Baseline was defined as value at Week 16 minus Baseline value.
Time frame: Baseline (Day 0) and Week 16
Population: Full analysis set used. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rosiglitazone 4 mg Orally Once Daily | Change From Baseline After 16 Weeks of Treatment in Leptin and High Sensitivity C-reactive Protein (Hs-CRP) | Leptin | 0.59 Nanograms per millilliter | Standard Deviation 2.751 |
| Rosiglitazone 4 mg Orally Once Daily | Change From Baseline After 16 Weeks of Treatment in Leptin and High Sensitivity C-reactive Protein (Hs-CRP) | Hs-CRP | -189.1 Nanograms per millilliter | Standard Deviation 5376.91 |
| Placebo | Change From Baseline After 16 Weeks of Treatment in Leptin and High Sensitivity C-reactive Protein (Hs-CRP) | Leptin | -0.07 Nanograms per millilliter | Standard Deviation 1.332 |
| Placebo | Change From Baseline After 16 Weeks of Treatment in Leptin and High Sensitivity C-reactive Protein (Hs-CRP) | Hs-CRP | 699.7 Nanograms per millilliter | Standard Deviation 4349.58 |
p-value: 0.06995% CI: [-0.05, 1.35]Unpaired t-test
p-value: 0.27195% CI: [-2477.7, 700.1]Unpaired t-test
Secondary
Percentage of Participants With Changes in HbA1c and FPG Meeting Specified Criteria After 16 Weeks of Treatment
The specified criteria for HbA1c was, if the decrease from the observation period Baseline value meets the following conditions: 1) decrease from the observation period Baseline value is 0.7% or more; 2) fell below 6.5%; 3) satisfied either 1 or 2 noted above. And for FPG was, if the decrease from the observation period Baseline value meets the following conditions: 1) decrease of 30 mg per decilliter or more from the observation period Baseline value; 2) fell below 126 mg per deciliter; 3) satisfied either 1 or 2 noted above.
Time frame: Up to Week 16
Population: Full analysis set used.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rosiglitazone 4 mg Orally Once Daily | Percentage of Participants With Changes in HbA1c and FPG Meeting Specified Criteria After 16 Weeks of Treatment | HbA1c, fell below 6.5% | 6.8 Percentage of participants |
| Rosiglitazone 4 mg Orally Once Daily | Percentage of Participants With Changes in HbA1c and FPG Meeting Specified Criteria After 16 Weeks of Treatment | FPG, decrease of 30 milligrams per decilliter | 31.1 Percentage of participants |
| Rosiglitazone 4 mg Orally Once Daily | Percentage of Participants With Changes in HbA1c and FPG Meeting Specified Criteria After 16 Weeks of Treatment | HbA1c, decrease by 0.7% | 44.6 Percentage of participants |
| Rosiglitazone 4 mg Orally Once Daily | Percentage of Participants With Changes in HbA1c and FPG Meeting Specified Criteria After 16 Weeks of Treatment | HbA1c, satisfied either 1 or 2 | 44.6 Percentage of participants |
| Rosiglitazone 4 mg Orally Once Daily | Percentage of Participants With Changes in HbA1c and FPG Meeting Specified Criteria After 16 Weeks of Treatment | FPG, satisfied either 1 or 2 | 35.1 Percentage of participants |
| Rosiglitazone 4 mg Orally Once Daily | Percentage of Participants With Changes in HbA1c and FPG Meeting Specified Criteria After 16 Weeks of Treatment | FPG, fell below 126 milligrams per deciliter | 16.2 Percentage of participants |
| Placebo | Percentage of Participants With Changes in HbA1c and FPG Meeting Specified Criteria After 16 Weeks of Treatment | FPG, satisfied either 1 or 2 | 14.7 Percentage of participants |
| Placebo | Percentage of Participants With Changes in HbA1c and FPG Meeting Specified Criteria After 16 Weeks of Treatment | HbA1c, decrease by 0.7% | 4.0 Percentage of participants |
| Placebo | Percentage of Participants With Changes in HbA1c and FPG Meeting Specified Criteria After 16 Weeks of Treatment | HbA1c, fell below 6.5% | 0.0 Percentage of participants |
| Placebo | Percentage of Participants With Changes in HbA1c and FPG Meeting Specified Criteria After 16 Weeks of Treatment | HbA1c, satisfied either 1 or 2 | 4.0 Percentage of participants |
| Placebo | Percentage of Participants With Changes in HbA1c and FPG Meeting Specified Criteria After 16 Weeks of Treatment | FPG, decrease of 30 milligrams per decilliter | 8.0 Percentage of participants |
| Placebo | Percentage of Participants With Changes in HbA1c and FPG Meeting Specified Criteria After 16 Weeks of Treatment | FPG, fell below 126 milligrams per deciliter | 9.3 Percentage of participants |
95% CI: [27.1, 54.1]
95% CI: [-0.3, 13.8]
95% CI: [27.1, 54.1]
95% CI: [9.5, 36.6]
95% CI: [-5.1, 18.9]
95% CI: [5.6, 35.3]