Yu-Jung Cha1, Kyoung-Ah Kim, Tae Young Oh, Ji-Young Park. 1. Department of Clinical Pharmacology and Toxicology, Anam Hospital, Korea University College of Medicine, 126-1, 5-Ga, Anam-dong, Sungbuk-Gu, Seoul, 136-705, Korea.
Abstract
BACKGROUND AND OBJECTIVE:DA-3803 is a proposed biosimilar of recombinant human chorionic gonadotropin (r-hCG), which is a therapeutic protein used to treat infertility. We compared the pharmacokinetics and safety profiles of DA-3803 (test) with those of a conventional formulation (Ovidrel(®), reference). METHODS: A single-blind, randomized, single-dose, two-period, two-sequence, crossover study was conducted in 32 healthy subjects. In each period, 250 μg of r-hCG of the test or reference formulation was administered subcutaneously with a 3-week washout period. Serial blood samples were obtained for pharmacokinetic analysis and blood levels of human chorionic gonadotropin (hCG) were determined. The geometric mean ratios (GMRs) with 90 % confidence intervals (CIs) for the maximum (peak) plasma concentration (C max) and the area under the plasma concentration-time curve (AUC) were estimated. RESULTS: Among the 32 subjects, 27 completed the study. No serious adverse events were observed. The mean concentration-time profiles of the test formulation tended to be higher than those of the reference formulation. The mean C max values of the two products were similar (142 mIU/mL for reference vs. 143 mIU/mL for test), but the mean AUC from time zero to infinity (AUC∞) values of the test drug were approximately 25 % higher than those of the reference drug (9403 mIU·h/mL for reference vs. 11,817 mIU·h/mL for test). The GMR (90 % CI) of the test formulation to the reference formulation for C max, AUC from time zero to the last measurable time (AUClast), and AUC∞ were 1.03 (0.93-1.14), 1.25 (1.18-1.33), and 1.27 (1.19-1.35), respectively. CONCLUSION: A single subcutaneous injection of either DA-3803 or Ovidrel(®) was safe and well-tolerated. A comparative pharmacokinetics study showed that DA-3803 was bioequivalent to Ovidrel(®) in the C max value but non-equivalent in the AUC value. These pharmacokinetic differences may not be expected to affect therapeutic efficacy of these two drugs, but further clinical studies are warranted to confirm their therapeutic equivalence.
RCT Entities:
BACKGROUND AND OBJECTIVE:DA-3803 is a proposed biosimilar of recombinant humanchorionic gonadotropin (r-hCG), which is a therapeutic protein used to treat infertility. We compared the pharmacokinetics and safety profiles of DA-3803 (test) with those of a conventional formulation (Ovidrel(®), reference). METHODS: A single-blind, randomized, single-dose, two-period, two-sequence, crossover study was conducted in 32 healthy subjects. In each period, 250 μg of r-hCG of the test or reference formulation was administered subcutaneously with a 3-week washout period. Serial blood samples were obtained for pharmacokinetic analysis and blood levels of humanchorionic gonadotropin (hCG) were determined. The geometric mean ratios (GMRs) with 90 % confidence intervals (CIs) for the maximum (peak) plasma concentration (C max) and the area under the plasma concentration-time curve (AUC) were estimated. RESULTS: Among the 32 subjects, 27 completed the study. No serious adverse events were observed. The mean concentration-time profiles of the test formulation tended to be higher than those of the reference formulation. The mean C max values of the two products were similar (142 mIU/mL for reference vs. 143 mIU/mL for test), but the mean AUC from time zero to infinity (AUC∞) values of the test drug were approximately 25 % higher than those of the reference drug (9403 mIU·h/mL for reference vs. 11,817 mIU·h/mL for test). The GMR (90 % CI) of the test formulation to the reference formulation for C max, AUC from time zero to the last measurable time (AUClast), and AUC∞ were 1.03 (0.93-1.14), 1.25 (1.18-1.33), and 1.27 (1.19-1.35), respectively. CONCLUSION: A single subcutaneous injection of either DA-3803 or Ovidrel(®) was safe and well-tolerated. A comparative pharmacokinetics study showed that DA-3803 was bioequivalent to Ovidrel(®) in the C max value but non-equivalent in the AUC value. These pharmacokinetic differences may not be expected to affect therapeutic efficacy of these two drugs, but further clinical studies are warranted to confirm their therapeutic equivalence.