2 research outputs found
Pharmacokinetics and pharmacodynamics of multiple doses of BG00010, a neurotrophic factor with anti-hyperalgesic effects, in patients with sciatica
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
(GFRα3) 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 μg kg(-1) ) and in Part II (12
patients), three dose levels were examined (400, 600 and 1200 μg 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 μg 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.TRIAL REGISTRATION: ClinicalTrials.gov NCT00961766 NCT01405833.Perioperative Medicine: Efficacy, Safety and Outcom