Investigation of the impact of urine handling procedures on interpretation of urinalysis findings and product safety in subjects treated with ezogabine
Notice bibliographique
Résumé
BACKGROUND: Ezogabine (also known by the international nonproprietary name of retigabine) is an antiepileptic drug codeveloped and comarketed by Valeant Pharmaceuticals North America and GlaxoSmithKline, which reduces neuronal excitability by enhancing the activity of potassium channels and has the potential to have effects on the urinary system through a pharmacologic action on bladder smooth muscle. In a single post-herpetic neuralgia trial, but not in an extensive epilepsy development program, proteinuria was unexpectedly reported in patients receiving ezogabine. Consequently, investigations were conducted to determine whether the reported proteinuria represented a true or false-positive finding. METHODS: Patients receiving ezogabine 900-1200 mg/day in an open-label extension (Study 303) of a Phase III epilepsy trial voluntarily provided urine samples. Fresh samples were analyzed immediately at the study site, and stabilized aliquots were analyzed 1-3 days after collection at two central laboratories. In an open-label study in healthy volunteers receiving ezogabine 600-900 mg/day (Study RTG114137), urine samples were analyzed fresh (<2 hours after collection) and, using two different stabilizers and storage at room temperature, after 24 and 72 hours. Fluid intake was restricted prior to one sample point. Albumin:creatinine ratios were assessed in both studies. RESULTS: In Study 303, there was notable variation in clarity, color, and proteinuria between fresh and stored urine samples, and between samples analyzed at different laboratories. In RTG114137, reporting rates of proteinuria were elevated following storage using one stabilizer, and the frequency of color change from fresh to stored samples differed between the stabilizers and between 24 and 72 hours with one stabilizer. Following fluid restriction, proteinuria rates were elevated with both stabilizers. Poor tolerability of ezogabine 750-900 mg/day resulted in limited titration beyond 750 mg/day and early termination of RTG114137. CONCLUSION: Hydration status, interval between urine collection and analysis, and the type of stabilizer used are all factors that may lead to false-positive proteinuria findings in patients receiving ezogabine and should be borne in mind if abnormalities are reported.
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 distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
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 tête enseignante, 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 ».