PMID- 28864922
OWN - NLM
STAT- MEDLINE
DCOM- 20171120
LR  - 20181113
IS  - 1432-0843 (Electronic)
IS  - 0344-5704 (Print)
IS  - 0344-5704 (Linking)
VI  - 80
IP  - 4
DP  - 2017 Oct
TI  - A phase I, randomized, single-dose study evaluating the pharmacokinetic 
      equivalence of biosimilar ABP 215 and bevacizumab in healthy adult men.
PG  - 755-763
LID - 10.1007/s00280-017-3416-4 [doi]
AB  - PURPOSE: This study compared the pharmacokinetic (PK) profiles of the proposed 
      biosimilar ABP 215 with bevacizumab in healthy males. METHODS: In this 
      randomized, single-blind, single-dose, three-arm, parallel-group study, healthy 
      subjects were randomized to receive ABP 215 (n = 68), bevacizumab (US) (n = 67), 
      or bevacizumab (EU) (n = 67) 3 mg/kg intravenously. Primary endpoints were area 
      under the serum concentration-time curve from time 0 extrapolated to infinity 
      (AUC(inf)) and the maximum observed concentration (C (max)). Secondary endpoints 
      included safety and immunogenicity. RESULTS: AUC(inf) and C (max) were similar 
      across the three groups. Geometric means ratio (GMR) for C (max) and AUC(inf), 
      respectively, was 0.98 and 0.99 for ABP 215 versus bevacizumab (US); 1.03 and 
      0.96 for ABP 215 versus bevacizumab (EU); and 1.05 and 0.97 for bevacizumab (US) 
      versus bevacizumab (EU). The 90% confidence intervals for the GMRs of AUC(inf) 
      and C (max) were within the prespecified standard PK bioequivalence criteria of 
      0.80 to 1.25. The incidence of adverse events (AEs) was 47.1, 32.8, and 61.2% in 
      the ABP 215, bevacizumab (US) and bevacizumab (EU) groups, respectively. When 
      analyzed by investigational site, the incidence and severity of AEs were 
      comparable in the ABP 215 and bevacizumab groups. There were no AEs leading to 
      study discontinuation. No binding or neutralizing anti-drug anti-bodies was 
      detected. CONCLUSIONS: This study demonstrated the PK similarity of ABP 215 to 
      both bevacizumab (US) and bevacizumab (EU), and of bevacizumab (US) to 
      bevacizumab (EU). Safety and tolerability were comparable between treatments and 
      no subject developed binding or neutralizing anti-drug anti-bodies.
FAU - Markus, Richard
AU  - Markus R
AD  - Biosimilars Development, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA, 
      91320, USA.
FAU - Chow, Vincent
AU  - Chow V
AD  - Biosimilars Development, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA, 
      91320, USA.
FAU - Pan, Zhiying
AU  - Pan Z
AD  - Biosimilars Development, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA, 
      91320, USA.
FAU - Hanes, Vladimir
AU  - Hanes V
AD  - Biosimilars Development, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA, 
      91320, USA. vhanes@amgen.com.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20170901
PL  - Germany
TA  - Cancer Chemother Pharmacol
JT  - Cancer chemotherapy and pharmacology
JID - 7806519
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Biosimilar Pharmaceuticals)
RN  - 2S9ZZM9Q9V (Bevacizumab)
SB  - IM
EIN - Cancer Chemother Pharmacol. 2017 Nov 20;:. PMID: 29159475
MH  - Administration, Intravenous
MH  - Adult
MH  - Angiogenesis Inhibitors/*administration & dosage/pharmacokinetics
MH  - Area Under Curve
MH  - Bevacizumab/*administration & dosage/adverse effects/pharmacokinetics
MH  - Biosimilar Pharmaceuticals/*administration & dosage/adverse 
      effects/pharmacokinetics
MH  - Humans
MH  - Male
MH  - Single-Blind Method
MH  - Therapeutic Equivalency
MH  - Young Adult
PMC - PMC5696486
OTO - NOTNLM
OT  - ABP 215
OT  - Bevacizumab
OT  - Biosimilar
OT  - Immunogenicity
OT  - Pharmacokinetics
COIS- CONFLICT OF INTEREST: Richard Markus, Vincent Chow, Zhiying Pan, and Vladimir 
      Hanes are employees and stockholders of Amgen Inc. ETHICAL APPROVAL: All 
      procedures performed in studies involving human participants were in accordance 
      with the ethical standards of the institutional and/or national research 
      committee and with the 1964 Helsinki declaration and its later amendments or 
      comparable ethical standards. FUNDING: This study was funded by Amgen Inc., 
      Thousand Oaks, CA.
EDAT- 2017/09/03 06:00
MHDA- 2017/11/29 06:00
PMCR- 2017/09/01
CRDT- 2017/09/03 06:00
PHST- 2017/06/21 00:00 [received]
PHST- 2017/08/03 00:00 [accepted]
PHST- 2017/09/03 06:00 [pubmed]
PHST- 2017/11/29 06:00 [medline]
PHST- 2017/09/03 06:00 [entrez]
PHST- 2017/09/01 00:00 [pmc-release]
AID - 10.1007/s00280-017-3416-4 [pii]
AID - 3416 [pii]
AID - 10.1007/s00280-017-3416-4 [doi]
PST - ppublish
SO  - Cancer Chemother Pharmacol. 2017 Oct;80(4):755-763. doi: 
      10.1007/s00280-017-3416-4. Epub 2017 Sep 1.