821 A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED PHASE IIA TRIAL OF A CA2+ CHANNEL α2Δ LIGAND, PD-0299685, FOR THE TREATMENT OF INTERSTITIAL CYSTITIS/BLADDER PAIN SYNDROME

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You have accessJournal of UrologyInfections/Inflammation of the Genitourinary Tract: Interstitial Cystitis1 Apr 2012821 A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED PHASE IIA TRIAL OF A CA2+ CHANNEL α2Δ LIGAND, PD-0299685, FOR THE TREATMENT OF INTERSTITIAL CYSTITIS/BLADDER PAIN SYNDROME J. Curtis Nickel, Anna Crossland, Edward Davis, Francois Haab, Ian Mills, Eric Rovner, David Scholfield, and Tim Crook J. Curtis NickelJ. Curtis Nickel Kingston, Canada More articles by this author , Anna CrosslandAnna Crossland Sandwich, United Kingdom More articles by this author , Edward DavisEdward Davis Glendora, CA More articles by this author , Francois HaabFrancois Haab Paris, France More articles by this author , Ian MillsIan Mills Sandwich, United Kingdom More articles by this author , Eric RovnerEric Rovner Glendora, CA More articles by this author , David ScholfieldDavid Scholfield Sandwich, United Kingdom More articles by this author , and Tim CrookTim Crook Sandwich, United Kingdom More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.911AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The α2Δ subunit of ligand-gated calcium ion channels mediates afferent pain fibers and is implicated in chronic pain. There are a small number of uncontrolled reports suggesting that an α2Δ ligand (eg gabapentin and pregabalin) may have efficacy in refractory genito-urinary pain and interstitial cystitis/bladder pain syndrome (IC/BPS). The objective of this study was to investigate the efficacy, tolerability and safety of PD-0299685, a potent Ca2+ channel α2Δ ligand, for pain and symptoms associated with IC/BPS. METHODS Following a 2 week single blind placebo run-in, patients with IC/BPS were randomized to placebo, 15 mg or 30 mg PD-0299685 BID for 12 weeks, with stratification by cystoscopic features of IC and baseline worst pain severity score. Patients assigned to 30 mg were initially treated with 15 mg bid for 2 weeks, prior to up-titrating to 30 mg BID. Primary endpoints were change in mean daily worst pain severity score on an 11-point numerical rating scale and change in Interstitial Cystitis Symptom Index from baseline to week 12. Secondary endpoints included global response assessment, micturition and urgency episode frequency per 24 hours, and mean voided volume per micturition. Vital signs, weight, physical exams, concomitant medications, PVR volume, adverse events, laboratory assessments were recorded through the study. RESULTS 54 patients received 15 mg, 55 patients received 30 mg PD-0299685 BID and 52 patients received placebo. At week 12, PD-0299685 30 mg BID PD-0299685 produced a reduction of worst daily pain severity score from baseline compared with placebo (treatment difference [90% CI]: -0.82 [–1.72, 0.08]). At week 12, the difference in ICSI score reduction from baseline for PD-0299685 30 mg BID compared with placebo was –1.58 (90% CI –3.24, 0.09). The 15 mg group differences over placebo for the primary endpoints were minimal. A higher proportion of patients taking PD-0299685 30 mg BID reported improved global response assessment. More patients discontinued due to treatment-related adverse events with PD-0299685 15 mg BID and 30 mg BID than with placebo. CONCLUSIONS PD-0299685 did not demonstrate proof-of-concept for the treatment of pain and other urinary endpoints associated with IC/BPS by showing unfavorable benefit-tolerability profile in this patient population at both doses tested. Clinical and biomarker phenotyping is required to improve our therapeutic results for IC/BPS patients with neuropathic pain. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e335 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information J. Curtis Nickel Kingston, Canada More articles by this author Anna Crossland Sandwich, United Kingdom More articles by this author Edward Davis Glendora, CA More articles by this author Francois Haab Paris, France More articles by this author Ian Mills Sandwich, United Kingdom More articles by this author Eric Rovner Glendora, CA More articles by this author David Scholfield Sandwich, United Kingdom More articles by this author Tim Crook Sandwich, United Kingdom More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...