OBJECTIVE: To assess the steady-state galantamine (GAL) bioavailability of the extended-release 24-mg qd capsule (GAL-ER) with and without food and to evaluate the relative bioavailability of GAL-ER with the immediate-release 12-mg bid tablet (GAL-IR) at steady state. METHODS: This was a single-center, open-label, randomized, 3-way crossover study in 24 healthy volunteers (12 males and 12 females) aged 18 to 45 years. After 7 days of GAL-ER 8 mg qd each morning and 7 days of GAL-ER 16 mg qd each morning, subjects received the following treatments in randomized, crossover order (7 days each): GAL-ER 24 mg qd each morning (fasted before Day 7 morning dose), GAL-ER 24 mg qd each morning (fed before Day 7 morning dose), and GAL-IR 12 mg bid (fasted before Day 7). Pharmacokinetic parameters of GAL at steady state were determined after morning intake on Day 7 of each treatment week. Safety evaluations included adverse event (AE) reporting, physical examination, clinical laboratory tests, vital signs, and electrocardiography. RESULTS: The treatment ratios of area under the plasma concentration-time curve of GAL from time 0-24 h post-dosing (AUC24 h), peak plasma concentration (Cmax), and pre-dose plasma concentration (Cmin) for GAL-ER fed/fasting were 105%, 112%, and 103%, respectively. The treatment ratios and 90% confidence intervals for all above mentioned pharmacokinetic parameters demonstrated bioequivalence (with the range of 80-125%), indicating that food had no effect on GAL-ER bioavailability. As anticipated, GAL-ER (fasting) had mean AUC24 h similar to GAL-IR (fasting), with lower Cmax (63 ng/mL vs 84 ng/mL) and longer time to reach Cmax (4.4 h vs 1.2 h). The treatment ratios and 90% confidence intervals for both AUC24 h and Cmin demonstrated bioequivalence (within the range of 80-125%). The treatment ratio for Cmax was 75.7%, indicating a 24% lower Cmax for GAL-ER than for GAL-IR. In this study, GAL-ER was safe and well tolerated with or without food and was comparable to the GAL-IR formulation. CONCLUSION: Food had no effect on the GAL bioavailability of GAL-ER at steady state. GAL-ER was bioequivalent to GAL-IR with respect to AUC24 h and Cmin.
RCT Entities:
OBJECTIVE: To assess the steady-state galantamine (GAL) bioavailability of the extended-release 24-mg qd capsule (GAL-ER) with and without food and to evaluate the relative bioavailability of GAL-ER with the immediate-release 12-mg bid tablet (GAL-IR) at steady state. METHODS: This was a single-center, open-label, randomized, 3-way crossover study in 24 healthy volunteers (12 males and 12 females) aged 18 to 45 years. After 7 days of GAL-ER 8 mg qd each morning and 7 days of GAL-ER 16 mg qd each morning, subjects received the following treatments in randomized, crossover order (7 days each): GAL-ER 24 mg qd each morning (fasted before Day 7 morning dose), GAL-ER 24 mg qd each morning (fed before Day 7 morning dose), and GAL-IR 12 mg bid (fasted before Day 7). Pharmacokinetic parameters of GAL at steady state were determined after morning intake on Day 7 of each treatment week. Safety evaluations included adverse event (AE) reporting, physical examination, clinical laboratory tests, vital signs, and electrocardiography. RESULTS: The treatment ratios of area under the plasma concentration-time curve of GAL from time 0-24 h post-dosing (AUC24 h), peak plasma concentration (Cmax), and pre-dose plasma concentration (Cmin) for GAL-ER fed/fasting were 105%, 112%, and 103%, respectively. The treatment ratios and 90% confidence intervals for all above mentioned pharmacokinetic parameters demonstrated bioequivalence (with the range of 80-125%), indicating that food had no effect on GAL-ER bioavailability. As anticipated, GAL-ER (fasting) had mean AUC24 h similar to GAL-IR (fasting), with lower Cmax (63 ng/mL vs 84 ng/mL) and longer time to reach Cmax (4.4 h vs 1.2 h). The treatment ratios and 90% confidence intervals for both AUC24 h and Cmin demonstrated bioequivalence (within the range of 80-125%). The treatment ratio for Cmax was 75.7%, indicating a 24% lower Cmax for GAL-ER than for GAL-IR. In this study, GAL-ER was safe and well tolerated with or without food and was comparable to the GAL-IR formulation. CONCLUSION: Food had no effect on the GAL bioavailability of GAL-ER at steady state. GAL-ER was bioequivalent to GAL-IR with respect to AUC24 h and Cmin.