RESUMEN
OBJECTIVE: To compare outcomes between two doses of lubiprostone in patients with chronic constipation (CC), to assess whether dose reduction affects efficacy. METHODS: This open-label exploratory study involved 146 patients with CC treated initially with lubiprostone 24 mcg twice daily for a planned duration of 4 weeks. Patients who experienced adverse events (AEs) had their dose reduced to 12 mcg twice daily (for 4 weeks). RESULTS: Lubiprostone dose was unchanged in 104 patients and reduced due to AEs in 42 patients. Significant differences in the mean number of bowel movements per week favored the dose-reduced group at Week 1 and end of follow-up. No between-group differences were observed over time for mean number of days per week with bowel movements or mean Bristol Stool Form Scale scores. Symptoms of abdominal bloating, strained defecation, and sensation of incomplete evacuation improved in both groups. Before dose reduction, nausea was reported by 64.3% and diarrhea by 45.2% of patients in the dose-reduced group; after dose reduction, no patients reported nausea and one patient reported diarrhea. CONCLUSION: Dose reduction of lubiprostone reduced the incidence of AEs, with no compromise to efficacy, and may be a suitable approach for patients who develop AEs during treatment.
Asunto(s)
Alprostadil , Reducción Gradual de Medicamentos , Alprostadil/efectos adversos , Estreñimiento/diagnóstico , Estreñimiento/tratamiento farmacológico , Diarrea/tratamiento farmacológico , Método Doble Ciego , Humanos , Japón , Lubiprostona/efectos adversos , Náusea/inducido químicamente , Resultado del TratamientoRESUMEN
Elevated serum uric acid is a cardiovascular risk factor in patients with hypertension, even when blood pressure (BP) is well controlled. Xanthine oxidoreductase inhibitors (XORi) reduce serum uric acid levels and have several other potential effects. This multicenter, randomized, open-label study compared the effects of two XORi, topiroxostat and febuxostat, on arterial stiffness, uric acid levels, and BP in hypertensive patients with hyperuricemia. Patients received topiroxostat 40-160 mg/day or febuxostat 10-60 mg/day, titrated to maintain serum uric acid <6 mg/dl, for 24 weeks. The primary endpoint was change in the cardio-ankle vascular index (CAVI) from baseline to 24 weeks. There were no significant changes in CAVI from baseline to 24 weeks (from 9.13 to 9.16 [feboxustat] and 8.98 to 9.01 [topiroxostat]). Compared with baseline, there were significant reductions in serum uric acid (-2.9 and -2.5 mg/dl; both p < 0.001) and morning home systolic BP (-3.6 and -5.1 mm Hg; both p < 0.01) after 24 weeks' treatment with febuxostat and topiroxostat. BP decreased to the greatest extent in the subgroup of patients with uncontrolled blood pressure at baseline. Topiroxostat, but not febuxostat, significantly decreased plasma xanthine oxidoreductase activity versus baseline. The urinary albumin-creatinine ratio (UACR) decreased significantly from baseline to 24 weeks with topiroxostat (-20.8%; p = 0.021), but not febuxostat (-8.8%; p = 0.362). In conclusion, neither topiroxostat nor febuxostat had any significant effects on arterial stiffness over 24 weeks' treatment.
Asunto(s)
Hipertensión , Hiperuricemia , Febuxostat/uso terapéutico , Supresores de la Gota/uso terapéutico , Humanos , Hipertensión/tratamiento farmacológico , Hiperuricemia/complicaciones , Hiperuricemia/tratamiento farmacológico , Nitrilos , Piridinas , Resultado del Tratamiento , Ácido ÚricoRESUMEN
OBJECTIVE: To investigate the continuation rate with a reduced lubiprostone dose (12 mcg twice daily, BD) after the onset of adverse events (AEs) in patients with chronic constipation (CC). METHODS: In this exploratory, open-label, multicenter study, patients with CC received lubiprostone 24 mcg BD and the dose was reduced to 12 mcg BD in subjects experiencing AEs. The primary objective was the continuation rate after dose reduction due to nausea/vomiting. Secondary objectives included the continuation rate after dose reduction due to diarrhea/any AE and efficacy, including changes in number of weekly bowel movements and Bristol Stool Form Scale. RESULTS: Of the 146 patients included in the study, 42 (28.8%) received lubiprostone 12 mcg BD (dose-reduced group) due to any AE. Thirty-six (85.7%) subjects in the dose-reduced group continued treatment and completed the study. 22/27 (81.5%) and 17/19 (89.5%) patients in whom the dose was reduced due to nausea/vomiting or diarrhea, respectively, continued treatment. There was no clinically relevant difference in efficacy after dose reduction. CONCLUSION: These results suggest that treatment withdrawal due to AEs associated with lubiprostone 24 mcg BD could be minimized in patients with CC after dose reduction to 12 mcg BD, thus resulting in improved long-term outcomes. CLINICAL TRIAL REGISTRATION: Japan Registry of Clinical Trials (https://jrct.niph.go.jp/latest-detail/jRCTs031180069).