GLYBURIDE AND METFORMIN HYDROCHLORIDE
-
glyburide and
metformin hydrochloride tablet, film coated
Med Health Pharma LLC.
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Subject Groups: Metformin Dosea
(number of subjects) | Cmaxb (mcg/mL) | Tmaxc
(hrs) | Renal Clearance (mL/min) |
---|---|---|---|
a All doses given fasting except the first 18 doses of the multiple-dose studies b Peak plasma concentration c Time to peak plasma concentration d SD=single dose e Combined results (average means) of 5 studies: mean age 32 years (range 23 to 59 years) f Kinetic study done following dose 19, given fasting g Elderly subjects, mean age 71 years (range 65 to 81 years) h CLcr=creatinine clearance normalized to body surface area of 1.73 m2 |
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Healthy, nondiabetic adults: 500 mg SDd (24) 850 mg SD (74)e 850 mg t.i.d. for 19 dosesf (9) |
1.03 (±0.33) 1.6 (±0.38) 2.01 (±0.42) |
2.75 (±0.81) 2.64 (±0.82) 1.79 (±0.94) |
600 (±132) 552 (±139) 642 (±173) |
Adults with type 2 diabetes: 850 mg SD (23) 850 mg t.i.d. for 19 dosesf (9) |
1.48 (±0.5) 1.9 (±0.62) |
3.32 (±1.08) 2.01 (±1.22) |
491 (±138) 550 (±160) |
Elderlyg, healthy nondiabetic adults: 850 mg SD (12) |
2.45 (±0.7) |
2.71 (±1.05) |
412 (±98) |
Renal-impaired adults: 850 mg SD Mild (CLcrh 61-90 mL/min) (5) Moderate (CLcr 31-60 mL/min) (4) Severe (CLcr 10-30 mL/min) (6) |
1.86 (±0.52) 4.12 (±1.83) 3.93 (±0.92) |
3.2 (±0.45) 3.75 (±0.5) 4.01 (±1.1) |
384 (±122) 108 (±57) 130 (±90) |
Placebo | Glyburide 2.5 mg tablets | Metformin 500 mg tablets | Glyburide and Metformin Hydrochloride 1.25 mg/250 mg tablets | Glyburide and Metformin Hydrochloride 2.5 mg/500 mg tablets |
|
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a p<0.001 b p<0.05 c p=NS |
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Mean Final Dose | 0 mg | 5.3 mg | 1317 mg | 2.78 mg/557 mg | 4.1 mg/824 mg |
Hemoglobin A1c
| N=147 | N=142 | N=141 | N=149 | N=152 |
Baseline Mean (%) | 8.14 | 8.14 | 8.23 | 8.22 | 8.2 |
Mean Change from Baseline | -0.21 | -1.24 | -1.03 | -1.48 | -1.53 |
Difference from Placebo | -1.02 | -0.82 | -1.26a
| -1.31a
|
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Difference from Glyburide | -0.24b
| -0.29b
|
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Difference from Metformin | -0.44b
| -0.49b
|
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Fasting Plasma Glucose
| N=159 | N=158 | N=156 | N=153 | N=154 |
Baseline Mean FPG (mg/dL) | 177.2 | 178.9 | 175.1 | 178 | 176.6 |
Mean Change from Baseline | 4.6 | -35.7 | -21.2 | -41.5 | -40.1 |
Difference from Placebo | -40.3 | -25.8 | -46.1a
| -44.7a
|
|
Difference from Glyburide | -5.8c
| -4.5c
|
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Difference from Metformin | -20.3c
| -18.9c
|
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Body Weight Mean Change from Baseline | -0.7 kg | +1.7 kg | -0.6 kg | +1.4 kg | +1.9 kg |
Final HbA1c
Distribution (%) | N=147 | N=142 | N=141 | N=149 | N=152 |
<7% | 19.7% | 59.9% | 50.4% | 66.4% | 71.7% |
≥7% and <8% | 37.4% | 26.1% | 29.8% | 25.5% | 19.1% |
≥8% | 42.9% | 14.1% | 19.9% | 8.1% | 9.2% |
Glyburide 5 mg tablets | Metformin 500 mg tablets | Glyburide and Metformin Hydrochloride 2.5 mg/500 mg tablets | Glyburide and Metformin Hydrochloride 5 mg/500 mg tablets |
|
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a p<0.001
|
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Mean Final Dose | 20 mg | 1840 mg | 8.8 mg/1760 mg | 17 mg/1740 mg |
Hemoglobin A1c
| N=158 | N=142 | N=154 | N=159 |
Baseline Mean (%) | 9.63 | 9.51 | 9.43 | 9.44 |
Final Mean | 9.61 | 9.82 | 7.92 | 7.91 |
Difference from Glyburide | -1.69a
| -1.7a
|
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Difference from Metformin | -1.9a
| -1.91a
|
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Fasting Plasma Glucose | N=163 | N=152 | N=160 | N=160 |
Baseline Mean (mg/dL) | 218.4 | 213.4 | 212.2 | 210.2 |
Final Mean | 221 | 233.8 | 169.6 | 161.1 |
Difference from Glyburide | -51.3a
| -59.9a
|
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Difference from Metformin | -64.2a
| -72.7a
|
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Body Weight Mean Change from Baseline | +0.43 kg | -2.76 kg | +0.75 kg | +0.47 kg |
Final HbA1c Distribution (%) | N=158 | N=142 | N=154 | N=159 |
<7% | 2.5% | 2.8% | 24.7% | 22.6% |
≥7% and <8% | 9.5% | 11.3% | 33.1% | 37.1% |
≥8% | 88% | 85.9% | 42.2% | 40.3% |
Placebo + Glyburide and Metformin Hydrochloride | Rosiglitazone + Glyburide and Metformin Hydrochloride |
|
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a Adjusted for the baseline mean difference b p<0.001 |
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Mean Final Dose Glyburide and Metformin Hydrochloride Rosiglitazone |
10 mg/1992 mg 0 mg |
9.6 mg/1914 mg 7.4 mg |
Hemoglobin A1c
| N=178 | N=177 |
Baseline Mean (%) | 8.09 | 8.14 |
Final Mean | 8.21 | 7.23 |
Difference from Placeboa
| | -1.02b
|
Fasting Plasma Glucose | N=181 | N=176 |
Baseline Mean (mg/dL) | 173.1 | 178.4 |
Final Mean | 181.4 | 136.3 |
Difference from Placeboa
| | -48.5b
|
Body Weight Mean Change from Baseline | +0.03 kg | +3.03 kg |
Final HbA1c Distribution (%) | N=178 | N=177 |
<7% | 13.5% | 42.4% |
≥7% and <8% | 32% | 38.4% |
≥8% | 54.5% | 19.2% |
There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with glyburide and metformin hydrochloride or any other antidiabetic drug.
Glyburide 2.5 mg tablets | Metformin 500 mg tablets | Glyburide and Metformin Hydrochloride 12.5 mg/250 mg tablets |
|
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Mean Final Dose
| 6.5 mg | 1500 mg | 3.1 mg/623 mg |
Hemoglobin A1c
| N=49 | N=54 | N=57 |
Baseline Mean (%) | 7.7 | 7.99 | 7.85 |
Mean Change from Baseline | -0.96 | -0.48 | -0.8 |
Difference from Metformin Difference from Glyburide | -0.32 +0.16 |
Adverse Event
| Number (%) of Patients
|
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Placebo
N=161 | Glyburide
N=324 | Metformin
N=312 | Glyburide and
Metformin Hydrochloride N=642 |
|
Upper respiratory infection | 22 (13.7) | 57 (17.6) | 51 (16.3) | 111 (17.3) |
Diarrhea | 9 (5.6) | 20 (6.2) | 64 (20.5) | 109 (17) |
Headache | 17 (10.6) | 37 (11.4) | 29 (9.3) | 57 (8.9) |
Nausea/vomiting | 10 (6.2) | 17 (5.2) | 38 (12.2) | 49 (7.6) |
Abdominal pain | 6 (3.7) | 10 (3.1) | 25 (8) | 44 (6.9) |
Dizziness | 7 (4.3) | 18 (5.6) | 12 (3.8) | 35 (5.5) |
Variable | Placebo N=161 | Glyburide Tablets N=160 | Metformin Tablets N=159 | Glyburide and Metformin Hydrochloride 1.25 mg/250 mg Tablets N=158 | Glyburide and Metformin Hydrochloride 2.5 mg/500 mg Tablets N=162 |
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Mean Final Dose | 0 mg | 5.3 mg | 1317 mg | 2.78 mg/557 mg | 4.1 mg/824 mg |
Number (%) of patients with symptoms of hypoglycemia | 5 (3.1) | 34 (21.3) | 5 (3.1) | 18 (11.4) | 61 (37.7) |
Number (%) of patients with gastrointestinal adverse events | 39 (24.2) | 38 (23.8) | 69 (43.3) | 50 (31.6) | 62 (38.3) |
GLYBURIDE AND METFORMIN HYDROCHLORIDE
glyburide and metformin hydrochloride tablet, film coated |
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Marketing Information | |||
Marketing Category | Application Number or Monograph Citation | Marketing Start Date | Marketing End Date |
ANDA | ANDA077870 | 06/01/2011 |
GLYBURIDE AND METFORMIN HYDROCHLORIDE
glyburide and metformin hydrochloride tablet, film coated |
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Marketing Information | |||
Marketing Category | Application Number or Monograph Citation | Marketing Start Date | Marketing End Date |
ANDA | ANDA077870 | 06/01/2011 |
GLYBURIDE AND METFORMIN HYDROCHLORIDE
glyburide and metformin hydrochloride tablet, film coated |
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Marketing Information | |||
Marketing Category | Application Number or Monograph Citation | Marketing Start Date | Marketing End Date |
ANDA | ANDA077870 | 06/01/2011 |
Labeler - Med Health Pharma LLC. (962603812) |
Establishment | |||
Name | Address | ID/FEI | Operations |
Med Health Pharma LLC. | 962603812 | repack |
Revised: 06/2011 Med Health Pharma LLC.