111. Efficacy and Safety of MIN-101: A New Drug for the Treatment of Negative Symptoms in Schizophrenia. A 12-Week Randomized, Double-Blind, Placebo-Controlled Trial
Notice bibliographique
Résumé
Background: To compare the efficacy, safety, and tolerability of MIN-101, a compound with high affinities for sigma 2 and 5-HT2A receptors, to placebo in treating negative symptoms, in stabilized patients with schizophrenia. Methods: This multi-national Phase 2b trial enrolled 244 patients diagnosed with schizophrenia who were symptomatically stable for ≥3 months prior to entering the trial and had scores ≥20 on the three factors negative subscale of the Positive and Negative Syndrome Scale (PANSS). Patients were randomized to monotherapy with MIN 101 32 mg/day, MIN-101 64 mg/day or placebo in a 1:1:1 ratio. The primary endpoint was the PANSS negative symptom score based on the five factors (pentagonal) model. Secondary outcomes were the three factors PANSS negative symptom subscale score, the PANSS total score, the PANSS positive symptom score, the Clinical Global Impression (CGI), the Brief Negative Symptoms Scale (BNSS), the Brief Assessment of Cognition in Schizophrenia (BACS), the Calgary Depression Scale for Schizophrenia (CDSS), and the Personal and Social Performance (PSP) scale. Safety parameters included treatment-emergent adverse events (TEAE), clinical laboratory, vital signs, electrocardiograms, Sheehan-suicidality tracking scale (S-STS), and the Abnormal Involuntary Movement Scale (AIMS). The Mixed-Effect Model Repeated Measure (MMRM) was used for analyzing the efficacy data. Results: The three treatment groups were balanced on all demographic and illness-related baseline characteristics. Statistically significant reduction in the primary endpoint score was demonstrated for MIN-101 32 mg and 64 mg compared to placebo (P ≤ .022, ES 0.45 and ≤ .003, ES 0.58, respectively). This was supported by similar effects on most of the secondary measurements including: the PANSS three factors negative symptoms subscale, PANSS total score, CGI, BACS, CDSS, and PSP. There were no statistically significant differences in PANSS positive subscale scores between MIN 101 and placebo. No weight gain or clinically significant changes in vital sings, prolactin levels, routine laboratory values, metabolic indices and extrapyramidal symptom scores (EPS) were observed. One patient on 64 mg MIN-101 was discontinued from the trial based on a-priori established QT interval prolongation criteria and a second one following an episode of syncope. Conclusion: MIN-101 at dosages of 32 and 64 mg/day demonstrated statistically significant efficacy of medium ES in reducing negative symptoms and good tolerability in stable schizophrenia patients. Since positive symptoms and EPS did not change, the improvement in negative symptoms was not secondary to improvement in positive symptoms or EPS, suggesting that MIN-101 might be the first specific treatment to have a direct effect on negative symptoms.
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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 | 0,001 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| 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 ».