Percent change from baseline (adjusted mean *)
4.4%
4.6%
3.3%
6.4%
Adjusted for baseline, pooled center and pooled center by treatment interaction
† p<0.05 versus placebo
Table 7. Lipids in a 26-Week, Placebo-Controlled, Monotherapy, Dose-Ranging Study
Placebo
Pioglitazone 15 mg Once Daily
Pioglitazone 30 mg Once Daily
Pioglitazone 45 mg Once Daily
Triglycerides (mg/dL)
N=79
N=79
N=84
N=77
Baseline (mean)
263
284
261
260
Percent change from baseline (adjusted mean *)
4.8%
-9%†
-9.6%†
-9.3%†
HDL Cholesterol (mg/dL)
N=79
N=79
N=83
N=77
Baseline (mean)
42
40
41
41
Percent change from baseline (adjusted mean *)
8.1%
14.1%†
12.2%
19.1%†
LDL Cholesterol (mg/dL)
N=65
N=63
N=74
N=62
Baseline (mean)
139
132
136
127
Percent change from baseline (adjusted mean *)
4.8%
7.2%
5.2%
6%
Total Cholesterol (mg/dL)
N=79
N=79
N=84
N=77
Baseline (mean)
225
220
223
214
Percent change from baseline (adjusted mean *)
4.4%
4.6%
3.3%
6.4%
In the two other monotherapy studies (16 weeks and 24 weeks) and in combination therapy studies with sulfonylurea (16 weeks and 24 weeks), metformin (16 weeks and 24 weeks) or insulin (16 weeks and 24 weeks), the lipid results were generally consistent with the data above.
12.3 PharmacokineticsAbsorption and Bioavailability
Alogliptin and Pioglitazone
In bioequivalence studies of OSENI, the AUC and maximum concentration (Cmax ) of both the alogliptin and the pioglitazone component following a single dose of the combination tablet (12.5 mg/15 mg or 25 mg/45 mg) were bioequivalent to alogliptin (12.5 mg or 25 mg) concomitantly administered with pioglitazone (15 mg or 45 mg respectively) tablets under fasted conditions in healthy subjects.
Administration of OSENI 25 mg/45 mg with food resulted in no significant change in overall exposure of alogliptin or pioglitazone. OSENI may therefore be administered with or without food.
Alogliptin
The absolute bioavailability of alogliptin is approximately 100%. Administration of alogliptin with a high-fat meal results in no significant change in total and peak exposure to alogliptin. Alogliptin may therefore be administered with or without food.
Pioglitazone
Following oral administration of pioglitazone hydrochloride, peak concentrations of pioglitazone were observed within two hours. Food slightly delays the time to peak serum concentration (Tmax ) to three to four hours but does not alter the extent of absorption (AUC).
advertisementDistribution
Alogliptin
Following a single, 12.5 mg intravenous infusion of alogliptin to healthy subjects, the volume of distribution during the terminal phase was 417 L, indicating that the drug is we
