衔接性试验评估与药动学之应用.pptVIP

Japan US/EU Dose 2.5 mg/d 5 mg/d AUC0-24hr (ng.hr/mL) 2.90 ? 1.54 2.52 ? 1.23 Bone mineral density √ √ Risedronate Na Differences in Pharmacokinetics Others include: Alendronate Na Omeprazole + clarithromycin + amoxicillin Clinical pharmacology therapeutics; 2005:78(2)102-13 Pharmacokinetic differences May not always create that necessity : dosage adjustments in some cases might be made without new trials.  However any substantial difference in metabolic pattern : may often indicate a need for a controlled clinical trial. Differences in adverse reactions Japan US/EU Dose 10-40 mg 10-40 mg AUC and Cmax 1 1.3-1.4 Dose 80 mg/day 80 mg /day Nausea 10.4% 5.7% Somnolence 16.9% 6.6% Eletriptan HBr Clinical pharmacology therapeutics; 2005:78(2)102-13 Different dosing recommendations Simply reflected different dose setting in the bridging study. Pramipexole dihydrochloride: smaller initial dose; same maintenance dose Donepezil HCl Leucovorin Ca + tegafur/uracil Clinical pharmacology therapeutics; 2005:78(2)102-13 「銜接性試驗」為可提供與國人相關之 藥動\藥效學或 療效、安全、用法用量等臨床試驗數據， 使國外臨床試驗數據能外推至本國相關族群之試驗， 減少臨床試驗重複執行，以避免研發資源之浪費。 銜接性試驗 (Bridging study) What type of bridging study needed ? A matter of judgment. The Facts There are no predefined statistical criteria for a bridging study for evaluating similarity in 2 populations. Criteria for a successful bridging strategy should be set on a case by-case basis through a consultation with the regulatory authority in a new region. Hints According to ICH E5, locally relevant PK data are an expected part of a complete clinical data package Locally relevant PK data are also needed to evaluate the similarity of PK profiles in the 2 regions and to help determine the appropriate dose in the new region. Request for Bridging study data only those additional data necessary to assess the ability to extrapolate foreign data from the complete clinical data package to the new region. In most cases, a single trial that successfully provide