Efficacy of Fenoverine and Trimebutine in the Management of Irritable Bowel Syndrome: Multicenter Randomized Double-blind Non-inferiority Clinical Study / 대한소화기학회지

BACKGROUND/AIMS: Antispasmodic agents have been used in the management of irritable bowel syndrome. However, systematic reviews have come to different conclusions about the efficacy in irritable bowel syndrome. Fenoverine acts as a synchronizer of smooth muscle in modulating the intracellular influx of calcium. We compared fenoverine with trimebutine for the treatment of patients with IBS. METHODS: A multicenter, randomized, double-blind, non-inferiority clinical study was conducted to compared fenoverine with trimebutine. Subjects were randomized to receive either fenoverine (100 mg three times a day) or trimebutine (150 mg three times a day) for 8 weeks. A total of 197 patients were analyzed by the intention-to-treat approach. The primary endpoint was the proportion of patients who had 30% reduction in abdominal pain or discomfort measured by bowel symptom scale (BSS) score at week 8 compared to the baseline. The secondary endpoints were changes of abdominal bloating, diarrhea, constipation, overall and total scores of BSS, and overall satisfaction. RESULTS: At week 8, fenoverine was shown to be non-inferior to trimebutine (treatment difference, 1.76%; 90% CI, -10.30-13.82; p=0.81); 69.23% (54 of 78 patients) of patients taking fenoverine and 67.47% (56 of 83 patients) of patients taking trimebutine showed 30% reduction in abdominal pain or discomfort compared to the baseline. There results of the secondary endpoints were also comparable between the fenoverine group and the trimebutine group. CONCLUSIONS: Fenoverine is non-inferior to trimebutine for treating IBS in terms of both efficacy and tolerability.

Estudio de bioequivalencia entre dos productos: trimebutina de liberación prolongada de laboratorios Leti SAV vs debridat AP® de laboratorios Pfizer, luego de administar una dosis única de 300 mg en voluntarios sanos / Bioequivalence study of two products trimebutine extended release vs debridat SAV Leti laboratories AP Pzizer after administering a single dose of 300 mg in healthy volunteers

El objetivo del estudio fue evaluar la bioequivalencia entre dos formulaciones de liberación prolongada de trimebutina 300 mg, luego de una administración única en voluntarios sanos, a través de la determinación de su metabolito activo la desmetil-trimebutina. Se trata de un estudio abierto, randomizado, balanceado, con control activo, de dosis simple, cruzado, con dos períodos separados por un período de descanso y secuencial, realizado en 12 voluntarios sanos de ambos sexos. Los voluntarios recibieron de acuerdo al esquema asignado por la aleatorización y en dos períodos, una dosis única por vía oral después de un ayuno de 10 horas, de un comprimido de una formulación conteniendo 300 mg de Trimebutina AP de Laboratorios LETI S.A.V., o del producto de referencia DEBRIDAT AP®, de Laboratorios Pfizer. Después de la última muestra de sangre del primer período hubo un tiempo de lavado de siete días, luego del cual los voluntarios que recibieron el producto test en el primer período recibieron el producto de referencia y viceversa. Las tomas de muestras se realizaron antes de la dosis (tiempo cero), 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 10 h, 12 h, 14 h, 18 h, 24 h y 36 h. El análisis estadístico se realizó utilizando un paquete estadístico del programa Equiv test, empleándose el análisis de la varianza (ANOVA) de los parámetros cinéticos AUC 0-inf, AUC 0-36 h y Cmax y la aplicación de los intervalos de confianza para el 90%. En el análisis comparativo se tomaron los intervalos de confianza con el rango de referencia de 0.8-1.25%. Para la Trimebutina test los valores fueron: Cmax 1343.49 +/- 585.58, AUC 0-36 de 8197.19 +/- 3995.23 y AUC 0-inf de 8198.36 +/- 3995.3. Para la formulación de referencia los valores fueron de: Cmax 1023.99 +/- 587.57, AUC 0-36 7221.15 +/- 3211.97 y AUC 0-inf de 7225.97 +/- 3211.62 sin diferencias significativas entre los grupos...

The objective of this study is to assess the bioequivalence of two sustained release formulations of trimebutine 300 mg, after a single administration in healthy volunteers, through determination of the active metabolite desmethyl-trimebutine. This is an open, randomized, balanced, active controlled, single dose, crossover study with two periods separated by a rest period and sequentially, conducted in 12 healthy volunteers of both sexes. Volunteers were assigned according to the randomization scheme and two periods, a single oral dose after fasting for 10 hours, a tablet formulation containing 300 mg of trimebutine AP LETI SAV Laboratories, or product Reference DEBRIDAT AP®, Pfizer Laboratories. After the last blood sample of the first period there will be a wash time of seven days, after which the volunteers received the test product in the first period will received the reference product and viceversa. The sampling is performed: before dosing (time zero), 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 10 h, 12 h, 14 h, 18 h, 24 h and 36 h. Statistical analysis was performed using a statistical package Equiv test program, using analysis of variance (ANOVA) of the kinetic parameters AUC 0-inf, AUC 0-36h and Cmax and application of confidence intervals for 90%. In the comparative analysis we used the confidence intervals with the reference range of 0.8-1.25%. For the Trimebutine test values were Cmax 1343.49 +/- 585.58, AUC 0-36 of 8197.19 +/- 3995.23 and AUC 0-inf 8198.36 +/- 3995.3. For the formulation of reference values were: Cmax 1023.99 +/- 587.57, AUC 0-36 7221.15 +/- 3211.97 y AUC 0-inf of 7225.97 +/- 3211.62 no significant differences between groups. This study found that the Cmax and AUC, its log-transformed means and confidence intervals 90% away from each other not less than 80% or over 125%, so that both products are considered bioequivalent and therefore interchangeable