821 A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED PHASE IIA TRIAL OF A CA <sup>2+</sup> CHANNEL α2Δ LIGAND, PD-0299685, FOR THE TREATMENT OF INTERSTITIAL CYSTITIS/BLADDER PAIN SYNDROME
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Résumé
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 ...
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,002 | 0,001 |
| Méta-épidémiologie (sens large) | 0,002 | 0,002 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,001 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,003 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,021 | 0,002 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».