PMID- 27016000
OWN - NLM
STAT- MEDLINE
DCOM- 20171120
LR  - 20210109
IS  - 1365-2125 (Electronic)
IS  - 0306-5251 (Print)
IS  - 0306-5251 (Linking)
VI  - 82
IP  - 1
DP  - 2016 Jul
TI  - Pharmacokinetics and pharmacodynamics of multiple doses of BG00010, a 
      neurotrophic factor with anti-hyperalgesic effects, in patients with sciatica.
PG  - 108-17
LID - 10.1111/bcp.12941 [doi]
AB  - AIMS: BG00010 is a protein in the glial cell line-derived neurotrophic factor 
      (GDNF) family. It is a selective ligand for the GDNF family receptor alpha-3 
      (GFRalpha3) co-receptor that normalizes cellular changes resulting from damage or 
      disease, and potentially alleviates neuropathic pain. The main objectives of this 
      study were to evaluate the pharmacokinetic and safety profiles and to determine 
      the effects on pain of ascending doses of intravenous injections of BG00010 in 
      patients with sciatica. METHODS: This was a randomized, blinded, 
      placebo-controlled multiple-dose study in subjects with sciatica. In Part I (16 
      patients), four IV dose levels were examined (50, 150, 400, 800 mug kg(-1) ) and 
      in Part II (12 patients), three dose levels were examined (400, 600 and 
      1200 mug kg(-1) ). Safety and efficacy assessments were used as endpoints. 
      RESULTS: The BG00010 concentration-time data indicated relatively low 
      inter-patient variability and there was a dose-dependent (not dose-proportional) 
      increase in serum exposure from 150 to 1200 mug kg(-1) . The effective half-life 
      was between 40 and 60 h. The most frequently occurring adverse events (AEs) 
      reported by patients receiving BG00010 were headache (67-83%), feeling hot 
      (50-100%), and pruritus (42-67%). Most AEs were mild; no serious AEs or AEs 
      leading to discontinuation occurred. Higher dose regimens of BG00010 resulted in 
      greater pain reduction than placebo or lower dose regimens, although a clear 
      dose-response relationship was not seen. CONCLUSIONS: The pharmacokinetic profile 
      of BG00010 was characterized by low intra-patient variability. These data from a 
      small sample suggest that BG00010 may have a benefit for patients with sciatica.
CI  - (c) 2016 The British Pharmacological Society.
FAU - Okkerse, Pieter
AU  - Okkerse P
AUID- ORCID: 0000-0002-0193-4732
AD  - Centre for Human Drug Research (CHDR), Leiden, The Netherlands.
FAU - Hay, Justin L
AU  - Hay JL
AD  - Centre for Human Drug Research (CHDR), Leiden, The Netherlands.
FAU - Versage, Eve
AU  - Versage E
AD  - Biogen, Cambridge, MA, USA.
FAU - Tang, Yongqiang
AU  - Tang Y
AD  - Biogen, Cambridge, MA, USA.
FAU - Galluppi, Gerald
AU  - Galluppi G
AD  - Biogen, Cambridge, MA, USA.
FAU - Ravina, Bernard
AU  - Ravina B
AD  - Biogen, Cambridge, MA, USA.
FAU - Verma, Ajay
AU  - Verma A
AD  - Biogen, Cambridge, MA, USA.
FAU - Williams, Leslie
AU  - Williams L
AD  - Biogen, Cambridge, MA, USA.
FAU - Aycardi, Ernesto
AU  - Aycardi E
AD  - Biogen, Cambridge, MA, USA.
FAU - Groeneveld, Geert Jan
AU  - Groeneveld GJ
AD  - Centre for Human Drug Research (CHDR), Leiden, The Netherlands.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20160513
PL  - England
TA  - Br J Clin Pharmacol
JT  - British journal of clinical pharmacology
JID - 7503323
RN  - 0 (ARTN protein, human)
RN  - 0 (Analgesics)
RN  - 0 (Nerve Tissue Proteins)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Analgesics/*administration & dosage/pharmacokinetics/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Half-Life
MH  - Humans
MH  - Hyperalgesia/*drug therapy
MH  - Injections, Intravenous
MH  - Male
MH  - Middle Aged
MH  - Nerve Tissue Proteins/*administration & dosage/pharmacokinetics/pharmacology
MH  - Sciatica/*drug therapy
MH  - Treatment Outcome
MH  - Young Adult
PMC - PMC4917813
OTO - NOTNLM
OT  - BG00010
OT  - neublastin
OT  - pharmacodynamics
OT  - pharmacokinetics
OT  - sciatica
EDAT- 2016/03/27 06:00
MHDA- 2017/11/29 06:00
PMCR- 2017/07/01
CRDT- 2016/03/27 06:00
PHST- 2015/10/30 00:00 [received]
PHST- 2016/03/10 00:00 [revised]
PHST- 2016/03/13 00:00 [accepted]
PHST- 2016/03/27 06:00 [entrez]
PHST- 2016/03/27 06:00 [pubmed]
PHST- 2017/11/29 06:00 [medline]
PHST- 2017/07/01 00:00 [pmc-release]
AID - BCP12941 [pii]
AID - 10.1111/bcp.12941 [doi]
PST - ppublish
SO  - Br J Clin Pharmacol. 2016 Jul;82(1):108-17. doi: 10.1111/bcp.12941. Epub 2016 May 
      13.