Rabeprazole extended-release 50 mg compared with esomeprazole 40 mg and rabeprazole delayed release 20 mg: authors’ reply
Notice bibliographique
Résumé
Sirs, We appreciate the comments by Yuan & Hunt.1 Maintenance of gastric pH has been traditionally measured by the percentage of time over 24-h gastric pH is >4.0. This parameter has been widely used in PPI drug development and was well accepted by regulatory agencies. As pointed out in their letter, this parameter has been shown to be positively correlated with clinical outcomes such as healing of erosive oesophagitis (EO).2-4 This was also the parameter used in their recently published article.5 The primary objective of our study6 was to evaluate pharmacodynamic (PD) properties of different prototype formulations; evaluation of pharmacokinetic (PK) parameters was secondary. PK parameters such as Tlast and Clast were estimated as presented, and these parameters were as informative as t1/2 in understanding the relative differences in PD and PK profiles of various prototypes. Furthermore, Clast parameter demonstrated a better correlation with the PD and in vitro dissolution profiles than t1/2. Of note, the t1/2 value from a later study of a 50 mg rabeprazole extended-release formulation was approximately twice (∼4 h) that of rabeprazole delayed-release 20 mg in healthy subjects. Since the study evaluated six prototype formulations and two comparators, a comparison adjusting for multiplicity would not have been practical. Furthermore, data from PK and PD studies are not intended to make any claim of clinical outcomes, but to provide insights on the PK and PD behaviours of prototypes in guiding further clinical development. This was the reason why we only presented P-values for the primary PD endpoint. The choice of different combinations of enteric-coated and pulsatile release tablets that were evaluated in our study were guided by data from other earlier exploratory PK studies, as well as in vitro dissolution profiles. As discussed in our article, the final decision in choosing Group 5 was based on the combination of PK and PD data, as well as other characteristics, such as dissolution profiles and manufacturing feasibility. A direct comparison of the mean percentage of time pH was >4.0 over 24-h period from our study with that in other studies requires caution, due to factors such as the study population. A direct comparison of the mean percentage of time pH was >4.0 during the night-time period from our study with that from their study4 would not be feasible since ‘night-time period’ was defined differently. While mean or median gastric pH is a useful parameter, we believe that averaging the pH value over the 24-h duration is not as valuable as the pH holding time in assessing relative differences in PD profiles of various prototypes. Furthermore, the pH holding time during the night-time period appeared to be the most useful parameter in differentiating between prototypes. The clinical efficacy data from two randomised controlled studies of rabeprazole extended-release 50 mg in moderate to severe EO (baseline Los Angeles Grade C or D) had been published online since November 2010.7 While these data did not demonstrate statistically significant superiority of rabeprazole extended-release 50 mg to esomeprazole 40 mg in healing of moderate and severe EO patients, the data suggest a potential benefit in the most severe patients. The data also support the notion that further prolonged acid suppression may translate into additional benefits in the most severe EO patients. Declaration of personal interests: Drs H. Chen, G. Rossiter, B. Rege, and Y. Lu are employees of Eisai Inc. Declaration of funding interests: The study was funded by Eisai Inc.
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 | 0,006 | 0,059 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,002 | 0,001 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,001 | 0,002 |
| Communication savante | 0,002 | 0,003 |
| Science ouverte | 0,002 | 0,001 |
| Intégrité de la recherche | 0,015 | 0,016 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,008 | 0,004 |
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 ».