OBJECTIVE: The primary objective was to demonstrate bioequivalence between the estrogen components ofActivelle (1 mg estradiol (E2) + 0.5 mg norethisterone acetate (NETA)) and the combined phase of Novofem (1 mg E2 + 1 mg NETA) and between the NETA components of the combined phase of Novofem (1 mg E2 + 1 mg NETA) and Trisequens (2 mg E2 + 1 mg NETA). SUBJECTS, MATERIALS AND METHODS: The study design was double-blind, randomized, three-way, balanced six-sequence cross-over. The washout period was 14 days between treatments. Single doses of the above-described tablets were administered in the morning following an overnight fast to 24 healthy postmenopausal or bilaterally oophorectomized women. Plasma concentration profiles of E2, estrone (E1; pharmacologically active metabolite of E2) and norethindrone (NET: NET was determined since NETA is very rapidly metabolized to NET) were measured over 72 h, and 36 h, respectively. For the two former substances a baseline correction was performed by subtracting the mean of two predose measurements from the concentrations measured after dosing. RESULTS: One subject dropped out of the study, completing only one treatment sequence; therefore, the results are based on 23 subjects. The baseline-corrected E2 and E1 AUC0-t (Novofem)/AUC0-t (Activelle) ratios were 105% and 100%, respectively; and the Cmax ratios 100% and 105%, respectively. Identical median tmax was observed for E2 (6 h) and for E1 (5 h). The NET AUC0-t (Novofem)/AUC0-t (Trisequens) ratio was 95%, and the corresponding Cmax ratio 98%. The median tmax for Novofem was 0.75 h and for Trisequens 1.0 h. CONCLUSION: Bioequivalence was demonstrated for E2, E1 and NET in accordance with the study objectives.
RCT Entities:
OBJECTIVE: The primary objective was to demonstrate bioequivalence between the estrogen components ofActivelle (1 mg estradiol (E2) + 0.5 mg norethisterone acetate (NETA)) and the combined phase of Novofem (1 mg E2 + 1 mg NETA) and between the NETA components of the combined phase of Novofem (1 mg E2 + 1 mg NETA) and Trisequens (2 mg E2 + 1 mg NETA). SUBJECTS, MATERIALS AND METHODS: The study design was double-blind, randomized, three-way, balanced six-sequence cross-over. The washout period was 14 days between treatments. Single doses of the above-described tablets were administered in the morning following an overnight fast to 24 healthy postmenopausal or bilaterally oophorectomized women. Plasma concentration profiles of E2, estrone (E1; pharmacologically active metabolite of E2) and norethindrone (NET: NET was determined since NETA is very rapidly metabolized to NET) were measured over 72 h, and 36 h, respectively. For the two former substances a baseline correction was performed by subtracting the mean of two predose measurements from the concentrations measured after dosing. RESULTS: One subject dropped out of the study, completing only one treatment sequence; therefore, the results are based on 23 subjects. The baseline-corrected E2 and E1 AUC0-t (Novofem)/AUC0-t (Activelle) ratios were 105% and 100%, respectively; and the Cmax ratios 100% and 105%, respectively. Identical median tmax was observed for E2 (6 h) and for E1 (5 h). The NET AUC0-t (Novofem)/AUC0-t (Trisequens) ratio was 95%, and the corresponding Cmax ratio 98%. The median tmax for Novofem was 0.75 h and for Trisequens 1.0 h. CONCLUSION: Bioequivalence was demonstrated for E2, E1 and NET in accordance with the study objectives.