OBJECTIVE: The dipeptidyl peptidase-4 inhibitor alogliptin, under development for treatment of Type 2 diabetes, primarily is excreted renally. This study investigated (1) the effect of food on alogliptin pharmacokinetics and tolerability and (2) pharmacokinetic interactions between alogliptin and metformin or cimetidine and tolerability of alogliptin when administered with either drug. METHODS: This randomized, open-label, two-phase, crossover study recruited healthy adults. In the single-dose phase, 36 subjects received an oral dose of alogliptin 100 mg under fed or fasted conditions. In the multiple-dose phase, subjects in one arm (n = 17) received 6 days each of alogliptin 100 mg once daily (q.d.), metformin 1,000 mg twice daily (b.i.d), and alogliptin q.d. + metformin b.i.d; subjects in the other arm (n = 18) received 6 days each of alogliptin 100 mg q.d., cimetidine 400 mg q.d., and alogliptin q.d. + cimetidine b.i.d. Pharmacokinetic parameters were determined after the last dose in each period. Tolerability was assessed through adverse events and clinical findings. RESULTS: Food had no effect on alogliptin area under the concentration-time curve (AUC) from 0 h to infinity and a small, clinically insignificant effect on maximum plasma concentration (C(max)) (fed/fasted least squares (LS) geometric mean ratio, 0.856; 90% confidence interval (CI), 0.798 - 0.917). Metformin and cimetidine did not affect alogliptin pharmacokinetics. Alogliptin had no effect on metformin C(max) and a small, clinically insignificant effect on AUC over the dosing interval ((alogliptin + metformin)/metformin LS geometric mean ratio, 1.19; 90% CI, 1.095 - 1.291). Alogliptin did not affect cimetidine pharmacokinetics. Alogliptin tolerability was similar under all conditions. CONCLUSION:Alogliptin can be administered without regard to meals and with metformin or cimetidine without the need for dose adjustment.
RCT Entities:
OBJECTIVE: The dipeptidyl peptidase-4 inhibitor alogliptin, under development for treatment of Type 2 diabetes, primarily is excreted renally. This study investigated (1) the effect of food on alogliptin pharmacokinetics and tolerability and (2) pharmacokinetic interactions between alogliptin and metformin or cimetidine and tolerability of alogliptin when administered with either drug. METHODS: This randomized, open-label, two-phase, crossover study recruited healthy adults. In the single-dose phase, 36 subjects received an oral dose of alogliptin 100 mg under fed or fasted conditions. In the multiple-dose phase, subjects in one arm (n = 17) received 6 days each of alogliptin 100 mg once daily (q.d.), metformin 1,000 mg twice daily (b.i.d), and alogliptin q.d. + metformin b.i.d; subjects in the other arm (n = 18) received 6 days each of alogliptin 100 mg q.d., cimetidine 400 mg q.d., and alogliptin q.d. + cimetidine b.i.d. Pharmacokinetic parameters were determined after the last dose in each period. Tolerability was assessed through adverse events and clinical findings. RESULTS: Food had no effect on alogliptin area under the concentration-time curve (AUC) from 0 h to infinity and a small, clinically insignificant effect on maximum plasma concentration (C(max)) (fed/fasted least squares (LS) geometric mean ratio, 0.856; 90% confidence interval (CI), 0.798 - 0.917). Metformin and cimetidine did not affect alogliptin pharmacokinetics. Alogliptin had no effect on metformin C(max) and a small, clinically insignificant effect on AUC over the dosing interval ((alogliptin + metformin)/metformin LS geometric mean ratio, 1.19; 90% CI, 1.095 - 1.291). Alogliptin did not affect cimetidine pharmacokinetics. Alogliptin tolerability was similar under all conditions. CONCLUSION:Alogliptin can be administered without regard to meals and with metformin or cimetidine without the need for dose adjustment.