RationaleQuetiapine fumarate is an atypical antipsychotic indicated for various mental disorders, but it has not been studied in Japanese patients with bipolar depression.ObjectivesTo evaluate the efficacy and safety of quetiapine XR (extended release) in Japanese patients with bipolar depression.MethodsIn this multi-center, randomized, double-blind, placebo-controlled, fixed-dose study of 431 Japanese adults with bipolar I or II disorder, efficacy was determined by analyzing the mean change from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) total score. Secondary end points included MADRS response and remission rates, Hamilton Depression Scale 17-Item (HAM-D17), and Clinical Global Impressions-Bipolar (CGI-BP) scale scores. Safety was determined by monitoring adverse events and clinical assessments.ResultsThis study revealed a statistically significantly greater decrease in MADRS total score after 8 weeks of quetiapine XR 300 mg/day monotherapy compared with placebo (− 12.6 vs. − 10.1; p = 0.034). There were also improvements in MADRS response (44.1 vs. 35.6%) and remission (38.0 vs. 26.6%) rates as well as in HAM-D17 and CGI-BP scale scores compared with placebo. In the subgroup analysis of patients with bipolar I or II disorder, the adjusted mean changes in MADRS total score compared to placebo were − 2.3 and − 2.1, respectively. Adverse events occurred in 149 patients (83.2%) receiving quetiapine XR 300 mg/day and in 81 patients (45.8%) receiving placebo. The most common adverse events were somnolence and thirst, which is consistent with the previously reported safety profile.ConclusionsOnce-daily monotherapy with quetiapine XR is an effective and well-tolerated treatment for bipolar depression in Japanese patients.
Background
A previous phase II dose‐ranging study of linaclotide in a Japanese chronic constipation (CC) population showed that 0.5 mg was the most effective dose. This study aimed to verify the hypothesis that 0.5 mg of linaclotide is effective and safe in Japanese CC patients.
Methods
This was a Japanese phase III randomized, double‐blind, placebo‐controlled (part 1), and long‐term, open‐label extension (part 2) study of linaclotide. CC patients (n = 186) diagnosed using the Rome III criteria were randomly assigned to linaclotide 0.5 mg (n = 95) or placebo (n = 91) for a 4‐week double‐blind treatment period in part 1, followed by an additional 52 weeks of open‐label treatment with linaclotide in part 2. The primary efficacy endpoint was the change from baseline in weekly spontaneous bowel movement (SBM) frequency at the first week. Secondary endpoints included responder rate for complete SBM (CSBM), changes in stool consistency, and severity of straining.
Key Results
Part 1: Change in weekly mean SBM frequency in the first week of treatment with linaclotide (4.02) was significantly greater than that with placebo (1.48, P < 0.001). Linaclotide produced a higher CSBM responder rate (52.7%) compared to placebo (26.1%, P < 0.001). Part 2: Patients continued to show improved SBM frequency with linaclotide. Through parts 1 and 2, the most common drug‐related adverse event was mild and occasionally moderate diarrhea.
Conclusions and Inferences
The results of this study indicate that a linaclotide dose of 0.5 mg/day is effective and safe in Japanese CC patients.
Our results suggest that 0.0625, 0.125, 0.25, and 0.5 mg/d are effective doses of linaclotide for treating CC in Japanese patients. ClinicalTrials.gov: NCT02425722, supported by Astellas Pharma, Inc.
Objectives
To evaluate the long‐term safety (primary objective) and efficacy (secondary objective) of antimuscarinic add‐on therapy in patients receiving mirabegron.
Methods
During a 2‐week screening period, patients (aged ≥20 years, mirabegron treatment for ≥6 weeks, residual overactive bladder symptoms) received mirabegron 50 mg once daily. These patients were subsequently randomized to 52 weeks’ treatment with mirabegron 50 mg/day plus an antimuscarinic (solifenacin 5 mg, propiverine 20 mg, imidafenacin 0.2 mg, or tolterodine 4 mg) with the potential to double the antimuscarinic dose (except for tolterodine) at week 8. Safety assessments included treatment‐emergent adverse events, vital signs, 12‐lead electrocardiograms, post‐void residual volume, and laboratory evaluations. Efficacy was assessed using changes from baseline in overactive bladder symptom score total score; overactive bladder questionnaire short form score; micturitions, urgency episodes, urinary incontinence episodes, and urgency urinary incontinence episodes/24 h; mean volume voided per micturition; and number of night‐time micturitions.
Results
Overall, 80.2% of patients (88.1% women, mean age 65 years) experienced at least one treatment‐emergent adverse event, with similar rates for all treatments. The adverse events most commonly reported were dry mouth, nasopharyngitis, and constipation. No marked change was observed in systolic or diastolic blood pressure for any treatment, although pulse rate increased slightly in the mirabegron and propiverine, and mirabegron and tolterodine groups. For all treatments, significant improvements were observed in all efficacy parameters, including overactive bladder symptom score total and questionnaire short form scores.
Conclusions
Antimuscarinic add‐on therapy is well tolerated and effective after initial treatment with mirabegron in patients with overactive bladder symptoms.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.