Letrozole is an orally active aromatase inhibitor for the treatment of postmenopausal women with breast cancer. A single-dose, randomized, open-label, two-way crossover study was designed to compare the bioequivalence...Letrozole is an orally active aromatase inhibitor for the treatment of postmenopausal women with breast cancer. A single-dose, randomized, open-label, two-way crossover study was designed to compare the bioequivalence and safety of two formulations of letrozole （2.5 mg/tablet）, including a newly developed generic formulation （test） and a branded formulation （reference） in a group of healthy Chinese postmenopausal women volunteers under fasting conditions. Blood samples were obtained before study drug administration and at 0.25, 0.50, 0.75, 1.00, 1.25, 1.50, 2.00, 2.50, 3.00, 3.50, 4.00, 6.00, 8.00, 12.00, 24.00, 48.00, 72.00, 96.00, 144.00, 192.00 and 240.00 h after drug administration. Letrozole levels in plasma were analyzed using a liquid chromatography-tandem mass spectrometry （LC-MS/MS） method. The safety profile was evaluated by adverse events （AEs） record, and assessed by physical examination, vital signs, spontaneous reporting, and clinical laboratory results. A total of 30 healthy Chinese postmenopausal women were enrolled in this study however, only 29 subjects were included in bioequivalence assessments due to serious adverse events （SAEs） in 1 subject. The 90% CIs for the ln-transformed ratios of C max , AUC 0–t , and AUC 0–∞ were 99.55%–115.17%, 97.35%–103.50%, and 97.29%–103.96%, respectively. All values met the predetermined criteria for assuming bioequivalence. One subject （3.3%） experienced SAE who received the reference formulation and 10 subjects （33.3%） reported a total of 13 mild AEs （4 reported from 4 subjects who received the test formulation, and 9 reported from 6 subjects who received the reference formulation）. In this single-dose （2.5 mg） study, we found that the test and reference formulations of letrozole tablet met the regulatory definition for assuming bioequivalence in healthy Chinese postmenopausal women. Both formulations were generally well tolerated in the population studied. Chinese Clinical Trials registration number： ChiCTR-TRC-11001457.展开更多
文摘Letrozole is an orally active aromatase inhibitor for the treatment of postmenopausal women with breast cancer. A single-dose, randomized, open-label, two-way crossover study was designed to compare the bioequivalence and safety of two formulations of letrozole （2.5 mg/tablet）, including a newly developed generic formulation （test） and a branded formulation （reference） in a group of healthy Chinese postmenopausal women volunteers under fasting conditions. Blood samples were obtained before study drug administration and at 0.25, 0.50, 0.75, 1.00, 1.25, 1.50, 2.00, 2.50, 3.00, 3.50, 4.00, 6.00, 8.00, 12.00, 24.00, 48.00, 72.00, 96.00, 144.00, 192.00 and 240.00 h after drug administration. Letrozole levels in plasma were analyzed using a liquid chromatography-tandem mass spectrometry （LC-MS/MS） method. The safety profile was evaluated by adverse events （AEs） record, and assessed by physical examination, vital signs, spontaneous reporting, and clinical laboratory results. A total of 30 healthy Chinese postmenopausal women were enrolled in this study however, only 29 subjects were included in bioequivalence assessments due to serious adverse events （SAEs） in 1 subject. The 90% CIs for the ln-transformed ratios of C max , AUC 0–t , and AUC 0–∞ were 99.55%–115.17%, 97.35%–103.50%, and 97.29%–103.96%, respectively. All values met the predetermined criteria for assuming bioequivalence. One subject （3.3%） experienced SAE who received the reference formulation and 10 subjects （33.3%） reported a total of 13 mild AEs （4 reported from 4 subjects who received the test formulation, and 9 reported from 6 subjects who received the reference formulation）. In this single-dose （2.5 mg） study, we found that the test and reference formulations of letrozole tablet met the regulatory definition for assuming bioequivalence in healthy Chinese postmenopausal women. Both formulations were generally well tolerated in the population studied. Chinese Clinical Trials registration number： ChiCTR-TRC-11001457.
