Pharmacokinetics and safety profile of DA-3803, a proposed biosimilar of recombinant human chorionic gonadotropin, in healthy subjects

Yu Jung Cha, Kyoung Ah Kim, Tae Young Oh, Ji-Young Park

Research output: Contribution to journalArticle

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, twoperiod, 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 (Cmax) 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 Cmax 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 Cmax, 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 Cmax 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.

Original languageEnglish
Pages (from-to)199-205
Number of pages7
JournalBioDrugs
Volume29
Issue number3
DOIs
Publication statusPublished - 2015 Jun 3

Fingerprint

Biosimilar Pharmaceuticals
Chorionic Gonadotropin
Area Under Curve
Healthy Volunteers
Pharmacokinetics
Safety
Pharmaceutical Preparations
Confidence Intervals
Single-Blind Method
Subcutaneous Injections
Cross-Over Studies
Infertility
Therapeutics

ASJC Scopus subject areas

  • Biotechnology
  • Pharmacology
  • Pharmacology (medical)

Cite this

Pharmacokinetics and safety profile of DA-3803, a proposed biosimilar of recombinant human chorionic gonadotropin, in healthy subjects. / Cha, Yu Jung; Kim, Kyoung Ah; Oh, Tae Young; Park, Ji-Young.

In: BioDrugs, Vol. 29, No. 3, 03.06.2015, p. 199-205.

Research output: Contribution to journalArticle

@article{c6cfcd7615fe4ec18bc194644cc8bb8c,
title = "Pharmacokinetics and safety profile of DA-3803, a proposed biosimilar of recombinant human chorionic gonadotropin, in healthy subjects",
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{\circledR}, reference). Methods: A single-blind, randomized, single-dose, twoperiod, 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 (Cmax) 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 Cmax 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 Cmax, 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{\circledR} was safe and well-tolerated. A comparative pharmacokinetics study showed that DA-3803 was bioequivalent to Ovidrel{\circledR} in the Cmax 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.",
author = "Cha, {Yu Jung} and Kim, {Kyoung Ah} and Oh, {Tae Young} and Ji-Young Park",
year = "2015",
month = "6",
day = "3",
doi = "10.1007/s40259-015-0128-3",
language = "English",
volume = "29",
pages = "199--205",
journal = "BioDrugs",
issn = "1173-8804",
publisher = "Adis International Ltd",
number = "3",

}

TY - JOUR

T1 - Pharmacokinetics and safety profile of DA-3803, a proposed biosimilar of recombinant human chorionic gonadotropin, in healthy subjects

AU - Cha, Yu Jung

AU - Kim, Kyoung Ah

AU - Oh, Tae Young

AU - Park, Ji-Young

PY - 2015/6/3

Y1 - 2015/6/3

N2 - 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, twoperiod, 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 (Cmax) 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 Cmax 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 Cmax, 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 Cmax 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.

AB - 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, twoperiod, 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 (Cmax) 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 Cmax 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 Cmax, 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 Cmax 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.

UR - http://www.scopus.com/inward/record.url?scp=84934444778&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84934444778&partnerID=8YFLogxK

U2 - 10.1007/s40259-015-0128-3

DO - 10.1007/s40259-015-0128-3

M3 - Article

VL - 29

SP - 199

EP - 205

JO - BioDrugs

JF - BioDrugs

SN - 1173-8804

IS - 3

ER -