Compared with subject areas who went through the down-regulation treatment, subject matter in our study experienced a relatively high serum concentration of subunits from endogenous LH and r-hCG injected. for the geometric imply ratio (GMR) of LZM003 to reference drug fell within predefined margins of 80% ?125%. Results Forty-eight subjects (24 males and 24 females) were enrolled and one subject withdrew for personal reasons. Mean values of main PK parameters were comparable (p 0.05) between LZM003 and the reference drug. The 90% CIs for main PK endpoints GMR of LZM003 to reference drug ranged between 0.9144 and 1.1845, which were within bioequivalence margins of 80?125%. Incidence of AEs was comparable (p 0.05) between the two groups. Neither LZM003 nor reference drug produced anti-drug antibody (ADA) in healthy subjects. Conclusion LZM003 and reference drug were bioequivalent. The PK and security assessments were comparable (p 0.05) between the two formulations in healthy Chinese subjects. Trial Registration Number ChiCTR-IIR-16010158 (http://www.chictr.org.cn). Trial Registration Date December 15, 2016. = AUC0-t (LZM003)/AUC0-t (reference drug) 100%]. Immunogenicity Blood samples (5 mL) for the measurement of anti-drug antibodies (ADAs) were collected at 10 mins pre-dose and at 168 hrs post-dose. After standing for 30 mins at Hexestrol room temperature, the blood samples were centrifuged (1500 g, Hexestrol 15 mins) at 2~8 C to separate Hexestrol the serum and the serum was frozen immediately below ?60 C. The serum ADAs were analyzed by Bioanalytical Department, WuXi AppTec Co. Ltd, Shanghai. ADAs Hexestrol were measured using a validated electrochemiluminescent (ECL) immunoassay method with an MSD plate reader (MESO QuickPlex SQ 120). The ECL values correspondingly reflected the levels of anti-LZM003 or anti-reference drug antibodies in samples. The immunoreaction-specific inhibition assay and titer test would be run to further confirm and measure the intensity of positive ADAs. Security Assessments Safety profiles were investigated by vital indicators, physical examinations, 12-lead ECG, clinical lab tests (hematology, serum biochemistry, coagulation function, hormones and routine urinalysis), adverse events (AEs) reporting, local tolerability and immunogenicity (ADAs and NAbs). AEs were categorized and outlined according to System Organ Class (SOC) and Favored Term (PT) in the Medical Dictionary for Regulatory Activities (MedDRA, version 20.0). The severities of AEs were graded by Common Terminology Criteria for Adverse Events (CTCAE, version 4.03). All AEs were followed up until solved, stable, or subject(s) withdrew from your trial or out of contact. Analysis Sets The following analysis sets were employed: Full analysis set (FAS) for demographic and characteristic analysis that included randomized subjects receiving LZM003 and reference drug. Safety set (SS) for security analysis that included subjects from FAS who experienced post-medication safety profiles. The analysis was based on their groups and medication cycles. Pharmacokinetic analysis set (PKAS) for PK analysis that included subjects from your FAS who were admittable for the calculation of Cmax, AUC0-t, AUC0- and the drug absorption, distribution, metabolism and removal and drug immunogenicity were not adversely affected. Bioequivalence analysis set (BEAS) for bioequivalence analysis that included subjects from PKAS who were admittable to evaluate primary PK parameters in both cycles. Anti-drug antibody analysis set (ADA-AS) for immunogenicity analysis that included subjects enrolled, received drugs and experienced immunogenicity data. Statistical Analysis All statistical analyses were performed using SAS Enterprise Guideline 7.1 (SAS Institute Inc., USA). The sample size for this study was determined using a 90% power analysis performed on the basis of previous pharmacokinetic studies, which revealed 28% of %CV for Cmax.4,21 The significance CD276 level of the two one-sided values between groups for continuous measurements and discrete measurements, separately. Hexestrol Descriptive statistics such as mean and standard deviation, minimum, median, maximum, geometric mean and CV% were offered for PK parameters. An analysis of variance (ANOVA) model with treatment groups, period, sequence and treatment effects as fixed effects and subjects within sequence effect as a random effect was applied to the log-transformed.
