First-In-Human, Double-Blind, Placebo-Controlled, Randomized, Dose-Escalation Study of BG00010, a Glial Cell Line-Derived Neurotrophic Factor Family Member, in Subjects with Unilateral Sciatica.
<h4>Objective</h4>To evaluate the safety, tolerability, and pharmacokinetics of single doses of BG00010 (neublastin, artemin, enovin) in subjects with unilateral sciatica.<h4>Methods</h4>This was a single-center, blinded, placebo-controlled, randomized Phase 1 sequential-coho...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0125034 |
| _version_ | 1818726721610842112 |
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| author | Paul E Rolan Gilmore O'Neill Eve Versage Jitesh Rana Yongqiang Tang Gerald Galluppi Ernesto Aycardi |
| author_facet | Paul E Rolan Gilmore O'Neill Eve Versage Jitesh Rana Yongqiang Tang Gerald Galluppi Ernesto Aycardi |
| author_sort | Paul E Rolan |
| collection | DOAJ |
| description | <h4>Objective</h4>To evaluate the safety, tolerability, and pharmacokinetics of single doses of BG00010 (neublastin, artemin, enovin) in subjects with unilateral sciatica.<h4>Methods</h4>This was a single-center, blinded, placebo-controlled, randomized Phase 1 sequential-cohort, dose-escalation study (ClinicalTrials.gov identifier NCT00961766; funded by Biogen Idec). Adults with unilateral sciatica were enrolled at The Royal Adelaide Hospital, Australia. Four subjects were assigned to each of eleven cohorts (intravenous BG00010 0.3, 1, 3, 10, 25, 50, 100, 200, 400, or 800 μg/kg, or subcutaneous BG00010 50 μg/kg) and were randomized 3:1 to receive a single dose of BG00010 or placebo. The primary safety and tolerability assessments were: adverse events; clinical laboratory parameters and vital signs; pain as measured by a Likert rating scale; intra-epidermal nerve fiber density; and longitudinal assessment of quantitative sensory test parameters. Blood, serum, and plasma samples were collected for pharmacokinetic and pharmacodynamic assessments. Subjects were blinded to treatment assignment throughout the study. The investigator was blinded to treatment assignment until the Data Safety Review Committee review of unblinded data, which occurred after day 28.<h4>Results</h4>Beyond the planned enrollment of 44 subjects, four additional subjects were enrolled into to the intravenous BG00010 200 μg/kg cohort after one original subject experienced mild generalized pruritus. Therefore, a total of 48 subjects were enrolled between August 2009 and December 2011; all were included in the safety analyses. BG00010 was generally well tolerated: in primary analyses, the most common treatment-emergent adverse events were changes in temperature perception, pruritus, rash, or headache; no trends were observed in clinical laboratory parameters, vital signs, intra-epidermal nerve fiber density, or quantitative sensory testing. BG00010 was not associated with any clear, dose-dependent trends in Likert pain scores. BG00010 was rapidly distributed, with a prolonged terminal elimination phase.<h4>Conclusions</h4>These data support the development of BG00010 for the treatment of neuropathic pain.<h4>Trial registration</h4>ClinicalTrials.gov NCT00961766. |
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| id | doaj.art-ce092cb6e1f94b03a257ac457134d4d5 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-17T22:02:42Z |
| publishDate | 2015-01-01 |
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| spelling | doaj.art-ce092cb6e1f94b03a257ac457134d4d52022-12-21T21:30:56ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01105e012503410.1371/journal.pone.0125034First-In-Human, Double-Blind, Placebo-Controlled, Randomized, Dose-Escalation Study of BG00010, a Glial Cell Line-Derived Neurotrophic Factor Family Member, in Subjects with Unilateral Sciatica.Paul E RolanGilmore O'NeillEve VersageJitesh RanaYongqiang TangGerald GalluppiErnesto Aycardi<h4>Objective</h4>To evaluate the safety, tolerability, and pharmacokinetics of single doses of BG00010 (neublastin, artemin, enovin) in subjects with unilateral sciatica.<h4>Methods</h4>This was a single-center, blinded, placebo-controlled, randomized Phase 1 sequential-cohort, dose-escalation study (ClinicalTrials.gov identifier NCT00961766; funded by Biogen Idec). Adults with unilateral sciatica were enrolled at The Royal Adelaide Hospital, Australia. Four subjects were assigned to each of eleven cohorts (intravenous BG00010 0.3, 1, 3, 10, 25, 50, 100, 200, 400, or 800 μg/kg, or subcutaneous BG00010 50 μg/kg) and were randomized 3:1 to receive a single dose of BG00010 or placebo. The primary safety and tolerability assessments were: adverse events; clinical laboratory parameters and vital signs; pain as measured by a Likert rating scale; intra-epidermal nerve fiber density; and longitudinal assessment of quantitative sensory test parameters. Blood, serum, and plasma samples were collected for pharmacokinetic and pharmacodynamic assessments. Subjects were blinded to treatment assignment throughout the study. The investigator was blinded to treatment assignment until the Data Safety Review Committee review of unblinded data, which occurred after day 28.<h4>Results</h4>Beyond the planned enrollment of 44 subjects, four additional subjects were enrolled into to the intravenous BG00010 200 μg/kg cohort after one original subject experienced mild generalized pruritus. Therefore, a total of 48 subjects were enrolled between August 2009 and December 2011; all were included in the safety analyses. BG00010 was generally well tolerated: in primary analyses, the most common treatment-emergent adverse events were changes in temperature perception, pruritus, rash, or headache; no trends were observed in clinical laboratory parameters, vital signs, intra-epidermal nerve fiber density, or quantitative sensory testing. BG00010 was not associated with any clear, dose-dependent trends in Likert pain scores. BG00010 was rapidly distributed, with a prolonged terminal elimination phase.<h4>Conclusions</h4>These data support the development of BG00010 for the treatment of neuropathic pain.<h4>Trial registration</h4>ClinicalTrials.gov NCT00961766.https://doi.org/10.1371/journal.pone.0125034 |
| spellingShingle | Paul E Rolan Gilmore O'Neill Eve Versage Jitesh Rana Yongqiang Tang Gerald Galluppi Ernesto Aycardi First-In-Human, Double-Blind, Placebo-Controlled, Randomized, Dose-Escalation Study of BG00010, a Glial Cell Line-Derived Neurotrophic Factor Family Member, in Subjects with Unilateral Sciatica. PLoS ONE |
| title | First-In-Human, Double-Blind, Placebo-Controlled, Randomized, Dose-Escalation Study of BG00010, a Glial Cell Line-Derived Neurotrophic Factor Family Member, in Subjects with Unilateral Sciatica. |
| title_full | First-In-Human, Double-Blind, Placebo-Controlled, Randomized, Dose-Escalation Study of BG00010, a Glial Cell Line-Derived Neurotrophic Factor Family Member, in Subjects with Unilateral Sciatica. |
| title_fullStr | First-In-Human, Double-Blind, Placebo-Controlled, Randomized, Dose-Escalation Study of BG00010, a Glial Cell Line-Derived Neurotrophic Factor Family Member, in Subjects with Unilateral Sciatica. |
| title_full_unstemmed | First-In-Human, Double-Blind, Placebo-Controlled, Randomized, Dose-Escalation Study of BG00010, a Glial Cell Line-Derived Neurotrophic Factor Family Member, in Subjects with Unilateral Sciatica. |
| title_short | First-In-Human, Double-Blind, Placebo-Controlled, Randomized, Dose-Escalation Study of BG00010, a Glial Cell Line-Derived Neurotrophic Factor Family Member, in Subjects with Unilateral Sciatica. |
| title_sort | first in human double blind placebo controlled randomized dose escalation study of bg00010 a glial cell line derived neurotrophic factor family member in subjects with unilateral sciatica |
| url | https://doi.org/10.1371/journal.pone.0125034 |
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