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Blood samples for PK and PD analyses were taken pre-dose and 1, 4, 12, 24, 48 and 72 h post-dose and then at Days 7, 14, 21 and 28. Median (range) baseline TGA peak level (a key coagulation-related clinical biomarker) of 9.20 (4.9-45.3) nmol in Chinese participants with severe haemophilia was similar to that seen in non-Asian patients with haemophilia ( I n i = 26).[7] The treatment-related trends in all PD endpoints were similar to those seen in healthy White participants[6] and non-Asian participants with severe haemophilia following administration of a single 300 mg dose of marstacimab.[7] No participants had positive ADAs at baseline. For severe haemophilia A or B (factor VIII [FVIII] or IX [FIX] activity levels <1% of normal [<1 IU/dL]), the main prophylaxis treatment is standard clotting factor concentrates (CFCs). Samples were collected at baseline (pre-dose on Day 1); 1, 4 and 12 h post-dose on Day 1; 24 h post-dose (Day 2); 48 h post-dose (Day 3); 72 h post-dose (Day 4); and at Days 7, 14, 21 and 28. [Extracted from the article]

This was an open‐label, randomized study in healthy Chinese participants to assess the bioequivalence of 2 fluconazole 150‐mg capsules under fasted and fed conditions. The study consisted of 2 treatment periods, separated by a 14‐day washout period. Thirty‐six participants were enrolled, with 18 participants each in the fasted and fed groups. In each treatment period, participants received a single oral dose of the test or reference fluconazole 150‐mg capsule. After washout, participants received the alternate treatment. Blood samples for pharmacokinetic analysis were collected from 1 hour before dosing to 72 hours after dosing. The median plasma concentration–time profiles were similar for both treatments under fasted and fed conditions. Bioequivalence of fluconazole between the 2 capsules was demonstrated as 90% confidence intervals of the geometric mean ratios for the maximum plasma concentration and area under the plasma concentration–time curve from time 0 to 72 hours after dosing under fasted and fed conditions were within the acceptable range of 80%–125%. Overall, 7 participants reported at least 1 treatment‐emergent adverse event; all were mild in severity. No serious adverse events or deaths were reported. The test fluconazole capsule was bioequivalent to the reference capsule, and a single dose was well tolerated. Clinicaltrials.gov ID: NCT03621072 [ABSTRACT FROM AUTHOR]

Azithromycin (Zithromax) is an azalide antibiotic that binds to the 50S ribosomal subunit of the susceptible organism and thereby interferes with its protein synthesis. An open‐label, randomized, single‐dose, 3‐way crossover bioequivalence study was conducted to compare the rate and extent of absorption of the azithromycin 250‐mg tablet manufactured at Pfizer Dalian (China) and that at Pfizer Barceloneta (United States) under fasted and fed conditions in healthy Chinese subjects. This study aimed to support a generic consistency evaluation program, initiated by the National Medical Products Administration, for evaluating the quality and efficacy of the products manufactured in China. In the study, the within‐subject standard deviation for area under the serum concentration–time profile from time 0 to 72 hours after dosing in the fasted condition was <0.294, and the 90%CI for the ratio was within 80% to 125%; the within‐subject SDs for serum peak concentration in the fasted condition, area under the serum concentration–time profile from time 0 to 72 hours after dosing in the fed condition, and serum peak concentration in the fed condition, were all >0.294, with the upper confidence bounds being <0.00, and the point estimates of the ratios being within 80% to 125%. The results support the bioequivalence between azithromycin tablets manufactured in China and the United States in fasted and fed conditions, with both tablets showing an acceptable safety/tolerability profile in the studied population. [ABSTRACT FROM AUTHOR]

Abstract: A robust and validated high performance liquid chromatography tandem mass spectrometry (LC–MS/MS) method has been developed for simultaneous determination of F351 (5-methyl-1-(4-hydroxylphenyl)-2-(1H)-pyridone) and three major metabolites in human urine sample. This assay method has also been validated in terms of selectivity, linearity, lower limit of quantification (LLOQ), accuracy, precision, stability, matrix effect and recovery. Chromatography was carried out on an XTerra RP 18 column and mass spectrometric analysis was performed using an API 4000 mass spectrometer coupled with electro-spray ionization (ESI) source in the positive ion mode. The MRM transitions of m/z 202→109, 232→93, 282→202 and 378→202 were used to quantify F351 and three metabolites, respectively. Retention times for F351 and three metabolites were 2.54, 1.38, 1.53 and 1.34min, respectively. The assay was validated from 20 to 4000ng/mL for F351 and M1, from 80 to16,000ng/mL for M2 and M3. Intra- and inter-day precision for all analytes was <6.3%, method accuracy was between −11.2 and 0.3%. This assay was used to support a clinical study where multiple oral doses were administered to healthy subjects to investigate the pharmacokinetics, safety, and tolerability of F351. [Copyright &y& Elsevier]