PMID- 26835603
OWN - NLM
STAT- MEDLINE
DCOM- 20170809
LR  - 20171108
IS  - 1552-4604 (Electronic)
IS  - 0091-2700 (Linking)
VI  - 56
IP  - 10
DP  - 2016 Oct
TI  - A Randomized Trial Evaluating Various Administration Routes of Natalizumab in 
      Multiple Sclerosis.
PG  - 1254-62
LID - 10.1002/jcph.707 [doi]
AB  - The study's primary objective was to compare the pharmacokinetics (PK) and 
      pharmacodynamics (PD) of single subcutaneous (SC) or intramuscular (IM) 300-mg 
      doses of natalizumab with IV 300-mg doses of natalizumab in patients with 
      multiple sclerosis (MS). Secondary objectives included investigation of the 
      safety, tolerability, and immunogenicity of repeated SC and IM natalizumab doses. 
      DELIVER was a 32-week, open-label, multicenter study of natalizumab-naive 
      patients with relapsing-remitting MS (RRMS) or secondary progressive MS (SPMS) 
      randomized to receive 300 mg natalizumab by SC injection, IM injection, or IV 
      infusion. PK and PD were evaluated over 8 weeks after the first natalizumab 
      treatment (Part 1) and over 24 weeks with repeated dosing every 4 weeks, 
      beginning at week 8 (Part 2). Seventy-six patients (24 with RRMS and 52 with 
      SPMS) were enrolled in DELIVER. Following SC or IM administration of natalizumab, 
      peak serum concentrations were approximately 40% of those observed with IV 
      administration and showed no major differences in elimination characteristics. 
      Mean bioavailability relative to IV administration was 57.1% to 71.3% with SC 
      administration and 48.7% with IM administration; mean trough serum concentrations 
      were similar with SC or IV administration and lower with IM administration. 
      Following single or multiple doses of natalizumab, PD response was comparable 
      across administration routes and disease stages. No meaningful differences were 
      observed across administration groups in the incidence or nature of overall 
      adverse events, serious adverse events, administration site reactions, 
      hypersensitivity reactions, or antinatalizumab antibodies. These findings support 
      the comparability of PD measures of natalizumab administered IV, SC, or IM.
CI  - (c) 2016, The American College of Clinical Pharmacology.
FAU - Plavina, Tatiana
AU  - Plavina T
AD  - Biogen, Cambridge, Massachusetts, USA. tatiana.plavina@biogen.com.
FAU - Fox, Edward J
AU  - Fox EJ
AD  - Central Texas Neurology Consultants, Round Rock, Texas, USA.
FAU - Lucas, Nisha
AU  - Lucas N
AD  - Biogen, Cambridge, Massachusetts, USA.
FAU - Muralidharan, Kumar Kandadi
AU  - Muralidharan KK
AD  - Biogen, Cambridge, Massachusetts, USA.
FAU - Mikol, Daniel
AU  - Mikol D
AD  - Biogen, Cambridge, Massachusetts, USA.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20160303
PL  - England
TA  - J Clin Pharmacol
JT  - Journal of clinical pharmacology
JID - 0366372
RN  - 0 (Natalizumab)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Biological Availability
MH  - Drug Administration Schedule
MH  - Female
MH  - Humans
MH  - Injections, Intramuscular
MH  - Injections, Intravenous
MH  - Injections, Subcutaneous
MH  - Male
MH  - Middle Aged
MH  - Multiple Sclerosis/*drug therapy
MH  - Multiple Sclerosis, Chronic Progressive/drug therapy
MH  - Multiple Sclerosis, Relapsing-Remitting/drug therapy
MH  - Natalizumab/*administration & dosage/pharmacokinetics/*therapeutic use
MH  - Patient Safety
MH  - Young Adult
OTO - NOTNLM
OT  - intramuscular
OT  - natalizumab
OT  - relapsing-remitting multiple sclerosis
OT  - secondary progressive multiple sclerosis
OT  - subcutaneous
EDAT- 2016/02/03 06:00
MHDA- 2017/08/10 06:00
CRDT- 2016/02/03 06:00
PHST- 2015/10/07 00:00 [received]
PHST- 2016/01/09 00:00 [accepted]
PHST- 2016/02/03 06:00 [entrez]
PHST- 2016/02/03 06:00 [pubmed]
PHST- 2017/08/10 06:00 [medline]
AID - 10.1002/jcph.707 [doi]
PST - ppublish
SO  - J Clin Pharmacol. 2016 Oct;56(10):1254-62. doi: 10.1002/jcph.707. Epub 2016 Mar 
      3.