PMID- 23512638
OWN - NLM
STAT- MEDLINE
DCOM- 20130916
LR  - 20221207
IS  - 1179-1918 (Electronic)
IS  - 1173-2563 (Linking)
VI  - 33
IP  - 4
DP  - 2013 Apr
TI  - Comparison of the pharmacokinetics of subcutaneous ustekinumab between Chinese 
      and non-Chinese healthy male subjects across two Phase 1 studies.
PG  - 291-301
LID - 10.1007/s40261-013-0072-2 [doi]
AB  - BACKGROUND AND OBJECTIVE: Ustekinumab, a human immunoglobulin G1 kappa (IgG1kappa) 
      monoclonal antibody against interleukin-12/23p40, has been reported to be 
      significantly efficacious in treating patients with moderate-to-severe plaque 
      psoriasis. Although the efficacy and safety of ustekinumab have been previously 
      studied in Asian patients with psoriasis, the pharmacokinetics of ustekinumab has 
      not been reported for Asian patients. The objective of this analysis was to 
      compare the pharmacokinetics of ustekinumab in Chinese and non-Chinese subjects. 
      SUBJECTS AND METHODS: Two Phase 1, open-label, single-period, 
      inpatient/outpatient studies were conducted to evaluate the pharmacokinetics of 
      ustekinumab following a single subcutaneous (SC) injection. In Study 1, 
      non-Chinese healthy male subjects (n = 31) received a single SC injection of 
      ustekinumab 90 mg. In Study 2, Chinese healthy male subjects (n = 24) were 
      randomized (1:1) to receive a single SC injection of ustekinumab 45 mg or 90 mg. 
      Serum ustekinumab concentrations were measured using validated immunoassays. The 
      pharmacokinetic parameters were calculated using non-compartmental analyses. 
      After data collection, a linear mixed model approach was used to compare the 
      log-transformed maximum observed serum concentration (Cmax) and area under the 
      serum concentration-time curves (AUCs) generated from the 90-mg dose groups in 
      the two studies. The ratios of the geometric means of the Cmax and AUCs in 
      Chinese subjects (Test) to those in non-Chinese subjects (Reference) along with 
      the 90 % confidence intervals (CIs) were calculated. RESULTS: The mean body 
      weight was 80.3 kg in non-Chinese (Caucasian: 77.4 %; black: 12.9 %; Asian: 0.0 
      %; other: 9.7 %) and 65.7 kg in Chinese subjects, with an overall mean of 74 kg. 
      Across studies and dose groups, the median time corresponding to the Cmax (tmax) 
      was 4.0-8.5 days, the mean terminal half-life (t(1/2)) was approximately 3 weeks, and 
      the mean apparent volume of distribution based on the terminal phase (Vz/F) was 
      80.3-97.3 mL/kg. In the 90-mg groups, mean exposure parameters of ustekinumab 
      were 1.1- to 1.3-fold higher in Chinese versus non-Chinese subjects. However, 
      exposure parameters were not significantly different between the two study 
      populations when individual parameters were adjusted to a subject weighing 74 kg: 
      the 90 % CIs of the geometric mean ratios (Chinese versus non-Chinese) for 
      weight-adjusted Cmax, AUC from time zero to time of last measurable concentration 
      (AUClast), and AUC from time zero to infinity (AUCinfinity) were (0.76-1.09), 
      (0.85-1.16) and (0.88-1.22), respectively. Ustekinumab was generally well 
      tolerated, with no unexpected adverse events; one subject (non-Chinese) developed 
      anti-drug antibodies to ustekinumab. CONCLUSION: The pharmacokinetics of 
      ustekinumab were comparable between Chinese and non-Chinese healthy male subjects 
      when exposure parameters were adjusted by subject body weight. CLINICAL TRIAL 
      REGISTRATION: Study 1, conducted with non-Chinese subjects (March-July 2006), was 
      completed before the 7th revision of the Declaration of Helsinki and was 
      therefore exempt from registration under the existing guidelines. The clinical 
      trial registration number for Study 2, conducted with Chinese subjects (October 
      2009-June 2010), is NCT01081704.
FAU - Zhu, Yaowei
AU  - Zhu Y
AD  - Pharmacokinetics & Pharmacodynamics, Biologics Clinical Pharmacology, Janssen 
      Research & Development, LLC, Welsh & McKean Roads, Spring House, PA 19477, USA. 
      yzhu8@its.jnj.com
FAU - Wang, Qingmin
AU  - Wang Q
FAU - Frederick, Bart
AU  - Frederick B
FAU - Bouman-Thio, Esther
AU  - Bouman-Thio E
FAU - Marini, Joseph C
AU  - Marini JC
FAU - Keen, Monica
AU  - Keen M
FAU - Petty, Kevin J
AU  - Petty KJ
FAU - Davis, Hugh M
AU  - Davis HM
FAU - Zhou, Honghui
AU  - Zhou H
LA  - eng
SI  - ClinicalTrials.gov/NCT01081704
PT  - Clinical Trial, Phase I
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - New Zealand
TA  - Clin Drug Investig
JT  - Clinical drug investigation
JID - 9504817
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Dermatologic Agents)
RN  - FU77B4U5Z0 (Ustekinumab)
SB  - IM
MH  - Adult
MH  - Antibodies, Monoclonal, Humanized/administration & dosage/*pharmacokinetics
MH  - Area Under Curve
MH  - Asian People
MH  - Black People
MH  - Dermatologic Agents/administration & dosage/*pharmacokinetics
MH  - Humans
MH  - Injections, Subcutaneous
MH  - Male
MH  - Ustekinumab
MH  - White People
MH  - Young Adult
EDAT- 2013/03/21 06:00
MHDA- 2013/09/17 06:00
CRDT- 2013/03/21 06:00
PHST- 2013/03/21 06:00 [entrez]
PHST- 2013/03/21 06:00 [pubmed]
PHST- 2013/09/17 06:00 [medline]
AID - 10.1007/s40261-013-0072-2 [doi]
PST - ppublish
SO  - Clin Drug Investig. 2013 Apr;33(4):291-301. doi: 10.1007/s40261-013-0072-2.