Search

Introduction: Orlistat is an inhibitor of pancreatic lipase and is used as an anti-obesity drug in many countries. However, there are no data available regarding the effects of orlistat on visceral fat accumulation in Japanese subjects. Therefore, this comparative, placebo-controlled, double-blind, randomized study aimed to evaluate the efficacy and safety of orlistat in Japanese participants with excessive visceral fat accumulation and without dyslipidemia, diabetes mellitus, and hypertension ("metabolic diseases").Methods: The study population included Japanese participants with excessive visceral fat accumulation (waist circumference ≥ 85 cm in males and ≥ 90 cm in females, which corresponds to a visceral fat area of 100 cm2) and without metabolic diseases. Following a 12-week observation term, participants were randomized to the orlistat 60 mg group (n = 100) or placebo group (n = 100). Both drugs were administered orally three times daily for 24 weeks. Participants were also counseled to improve their diet and to maintain exercise throughout the study. Visceral fat area, subcutaneous fat area, waist circumference, body weight, body mass index, adverse reactions, laboratory tests, and blood pressure were regularly assessed.Results: Visceral fat area, waist circumference, and body weight were significantly reduced in the orlistat group (mean ± standard error, - 13.50 ± 1.52%, - 2.51 ± 0.25%, and - 2.79 ± 0.30%, respectively) compared to the placebo group (- 5.45 ± 1.50%, - 1.55 ± 0.26%, and - 1.22 ± 0.28%, respectively) at the last assessment. The main adverse reactions were defecation-related symptoms including oily spotting and flatus with discharge, resulting from the pharmacological effects of orlistat. Most adverse reactions were mild, and none were serious or severe.Conclusion: Orlistat administration reduced visceral fat area, waist circumference, and body weight in Japanese participants with excessive visceral fat and without metabolic diseases. In addition, safety was confirmed with a tolerable profile. Orlistat may be useful to reduce excessive visceral fat accumulation when used in combination with diet and exercise.Trial Registration: Japan Pharmaceutical Information Center identifier, JapicCTI-184005.Funding: Taisho Pharmaceutical Co., Ltd. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy and safety of dienogest (DNG), a progestational 19-norsteroid, in patients with symptomatic adenomyosis.Design: Phase III, randomized, double-blind, multicenter, placebo-controlled study.Setting: Clinical study sites in Japan.Patient(s): Sixty-seven patients with adenomyosis.Intervention(s): Patients were randomly assigned to receive DNG (2 mg/d, orally) or placebo for 16 weeks. In cases of complicated anemia, patients were treated for anemia before randomization.Main Outcome Measure(s): The primary end point was the change from baseline to after treatment pain score, using zero- to three-point verbal rating scales that defined pain severity according to limited ability to work and need for analgesics. The visual analogue scale was used as another pain parameter.Result(s): Decreases from baseline in the pain score and the visual analogue scale at the end of treatment were significantly more in the DNG group than in the placebo group (P<.001). During the treatment period, almost all of the patients treated with DNG experienced irregular uterine bleeding and one patient had mild anemia. No severe cases of anemia were observed.Conclusion(s): These results suggest that DNG is effective and well tolerated in the treatment for painful symptoms associated with adenomyosis not complicated by severe uterine enlargement or severe anemia.Clinical Trial Registration Number: JapicCTI-142642(en). [ABSTRACT FROM AUTHOR]

Pranlukast (PLK) is a cysteinyl leukotriene receptor 1 antagonist approved for the treatment of bronchial asthma and allergic rhinitis in Japan. We previously reported that PLK dry syrup (DS) improved the total nasal symptom score, as well as sneezing, nasal discharge, and nasal obstruction scores over placebo. We investigated the efficacy of PLK DS with a noninvasive method in 10- to 15-year-old children with Japanese cedar (JC) pollinosis challenged with pollen allergen using an artificial exposure chamber (OHIO Chamber). Levels of eosinophil cationic protein (ECP) in nasal secretions, nasal obstruction score, and the relationship with nasal obstruction scores were analyzed. The estimated difference of means in ECP levels (PLK DS - placebo) was -22.9 micrograms (95% CI, -45.2 to -0.5), suggesting PLK DS reduced ECP significantly when compared with placebo (p = 0.0454). The difference in the least square means for nasal obstruction between the PLK DS and placebo was -0.25 (95% CI, -0.36 to -0.14) with a value of p < 0.0001. In addition, a statistically significant, although weak, positive correlation between the nasal obstruction score and nasal ECP levels was observed with placebo treatment (correlation coefficient = 0.2394; p = 0.0428). Moreover, the inhibition rate of nasal ECP with PLK DS relative to placebo was statistically significant, although weak, positively correlated with the inhibition rate of nasal obstruction (correlation coefficient = 0.3373; p = 0.0219). PLK DS significantly decreases nasal ECP levels and nasal obstruction score compared with placebo in children with JC pollinosis challenged with pollen allergen. Suppression of mucosal eosinophilic inflammation is one of the pathways by which PLK DS improves pollinosis-induced nasal obstruction. [ABSTRACT FROM AUTHOR]

Pranlukast (PLK) is a leukotriene receptor antagonist (LTRA) that has been approved for treatment of asthma in patients of all ages and allergic rhinitis (AR) in adults but not for AR in children in Japan. This randomized, double-blind, placebo-controlled, crossover study used an artificial exposure chamber (OHIO Chamber) to investigate the efficacy and safety of PLK in children from 10 to 15 years old with seasonal AR (SAR) due to Japanese cedar (JC) pollen. Eighty-four subjects were enrolled and randomized to the treatment arm and 74 were included in the per protocol set. Subjects received either PLK dry syrup (DS) or placebo for 1 week. They were challenged with JC pollen in the OHIO Chamber for 3 hours. Total nasal symptom scores (TNSSs) were recorded every 30 minutes during the exposure. PLK DS treatment suppressed the TNSS changes from baseline significantly when compared with placebo. The difference in the least square means in TNSS between the PLK DS-treated group and placebo group was -0.37 (95% CI, -0.54, -0.20) with a value of p < 0.0001, showing that PLK DS significantly suppressed the nasal symptoms. Regarding specific nasal symptoms, PLK DS significantly suppressed sneezing, nasal discharge, and nasal obstruction. The effect of PLK DS on nasal obstruction was most prominent, with significant improvement relative to placebo beginning 60 minutes after the start of exposure. No serious adverse events were reported during the study. In this study, PLK DS is effective and safe for treatment in children with SAR. [ABSTRACT FROM AUTHOR]

We aimed to verify the effect of new low-sodium high-potassium seasonings and processed foods containing poly-γ-glutamic acid on blood pressure in free-living settings. To this end, we conducted a randomized, double-blind controlled trial on 187 Japanese men, aged 35-67 years, who did not use antihypertensives. Participants were randomly allocated to an intervention ( n = 93) or a control group ( n = 94). They were given a boxed lunch and miso soup (average Na and K content for the intervention group: 1175 and 1476 mg; for the control group: 2243 and 703 mg, respectively). Blood pressure was measured three times every morning for 1 week immediately before and during the final week of the trial. On the day before and the final day of the intervention period, 24 h urine samples were collected. After intervention, the intervention group showed a significantly stronger decrease in the urinary sodium-to-potassium ratio than the control group ( p < 0.001). The mean difference in systolic blood pressure change after adjustment for baseline values between the two groups was -2.1 (95% CI: -3.6, -0.6) mmHg. Compliance between the groups was similar, suggesting successful blinding. In conclusion, the use of new seasonings and processed foods aimed at lowering blood pressure in free-living settings may be feasible and effective.

Objective: To evaluate the efficacy and safety of dienogest (DNG), a progestational 19-norsteroid, in patients with primary and secondary dysmenorrhea.Design: Phase III, randomized, double-blind, multicenter, placebo-controlled study.Setting: Clinical study sites in Japan.Patient(s): Ninety-four women with dysmenorrhea.Intervention(s): Random assignment to receive DNG (1 mg/day, orally) or placebo for 12 weeks; patients treated for anemia before randomization in cases of complicated anemia.Main Outcome Measure(s): Change in the dysmenorrhea score from baseline to week 12 of treatment with visual analog scale used for pain assessment.Result(s): The DNG group was superior to the placebo group in terms of the change from baseline in the dysmenorrhea score at week 12 of treatment in patients with dysmenorrhea. In both primary and secondary dysmenorrhea, the DNG group was superior to the placebo group for each diagnostic category. The mean serum estradiol concentrations were similar between the DNG and the placebo groups. Although the incidence of irregular uterine bleeding was higher in the DNG group, there were no severe or serious events. Most events of genital bleeding were spotting or breakthrough bleeding, suggesting DNG was well tolerated.Conclusion(s): In both primary and secondary dysmenorrhea, DNG at 1 mg/day relieved pain and was well tolerated.Clinical Trial Registration Number: JapicCTI-173547(en). [ABSTRACT FROM AUTHOR]

Background and Objectives: Daprodustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis and regulates genes related to iron metabolism. The efficacy (noninferiority) and safety of daprodustat compared with standard therapy (darbepoetin alfa) was evaluated., Design, Setting, Participants, & Measurements: This was a randomized, phase 3, double-blind, active-control study in Japanese patients receiving hemodialysis with anemia of CKD. Participants' treatment was switched from current erythropoiesis-stimulating agents (ESAs) to daprodustat 4 mg once daily or darbepoetin alfa 10-60 μ g once weekly (on the basis of the prestudy ESA dose). Dose was adjusted every 4 weeks for daprodustat or every 2 weeks for darbepoetin alfa, according to a protocol-specified algorithm. The primary end point was mean hemoglobin during weeks 40-52 in the intent-to-treat population., Results: Of 332 participants screened, 271 participants were randomized (safety evaluation: 271 participants; efficacy evaluation: 267 intent-to-treat population). The mean hemoglobin during weeks 40-52 were maintained within the target range in both groups (10.9 g/dl [95% confidence interval (95% CI), 10.8 to 11.0] for daprodustat, and 10.8 g/dl [95% CI, 10.7 to 11.0] for darbepoetin alfa). Daprodustat was noninferior to darbepoetin alfa, as the lower bound of the confidence interval for the treatment difference (0.1 g/dl; 95% CI, -0.1 to 0.2 g/dl) was greater than the noninferiority criterion of -1.0 g/dl. For most participants, hemoglobin was maintained within the target range (10.0-12.0 g/dl) during weeks 40-52 (88% daprodustat; 90% darbepoetin alfa). Geometric mean hepcidin levels decreased more at week 52 with daprodustat (-37%; 95% CI, -49 to -23) than with darbepoetin alfa (-20%; 95% CI, -36 to -1), and an increase in total iron-binding capacity was observed in the daprodustat group. Frequency of adverse events were generally similar between daprodustat and darbepoetin alfa., Conclusions: Oral daprodustat was noninferior to darbepoetin alfa as measured by mean hemoglobin over weeks 40-52 in Japanese patients receiving hemodialysis switched from ESAs., Clinical Trial Registry Name and Registration Number: 201754, Clinicaltrials.gov, NCT02969655., (Copyright © 2020 by the American Society of Nephrology.)

Background and Objectives: Imarikiren is a novel, potent, and selective direct renin inhibitor that has shown high oral availability during clinical development for the treatment of diabetic nephropathy. We evaluated the efficacy and safety of imarikiren in patients with type 2 diabetes mellitus and microalbuminuria., Design, Setting, Participants, & Measurements: This was a randomized, multicenter, placebo-controlled, double-blind, phase 2, dose-finding trial. A total of 415 patients were randomized to imarikiren 5, 20, 40, or 80 mg; placebo; or candesartan cilexetil 8 mg treatment for 12 weeks. The primary end point was change in log-transformed urine albumin-to-creatinine ratio from baseline to the end of treatment analyzed using analysis of covariance and a fixed sequence testing procedure. Secondary efficacy end points included urine albumin-to-creatinine ratio at each assessment point and remission and progression rates. Exploratory efficacy end points included eGFR and sitting BP before dosing., Results: Changes in the urine albumin-to-creatinine ratio from baseline to the end of treatment were 16% (placebo), -16% (imarikiren 5 mg), -27% (imarikiren 20 mg), -38% (imarikiren 40 mg), -39% (imarikiren 80 mg), and -31% (candesartan cilexetil 8 mg). Urine albumin-to-creatinine ratio reductions from baseline were statistically significant in all imarikiren groups versus placebo ( P <0.001 each) as well as for candesartan cilexetil 8 mg versus placebo ( P <0.001). Remission rates (urine albumin-to-creatinine ratio <30 mg/g creatinine and decreased ≥30% from baseline) were higher in all imarikiren groups versus the placebo group. Incidence of adverse events was higher in the imarikiren 80-mg group (52%) versus placebo (42%) and candesartan cilexetil (43%) groups. Incidence of adverse events for the other imarikiren groups ranged from 33% to 42%. Adverse events were mild or moderate in severity. All imarikiren doses were well tolerated., Conclusions: Imarikiren resulted in a dose-dependent improvement in albuminuria compared with placebo, and it was well tolerated in patients with type 2 diabetes mellitus and microalbuminuria., (Copyright © 2019 by the American Society of Nephrology.)

Background: Fluticasone propionate 50 μg/salmeterol xinafoate 25 μg (FP/SAL) is widely used in adults and children with asthma, but there is sparse information on its use in very young children., Methods: This was a randomized, double-blind, multicentre, controlled trial conducted in children aged 8 months to 4 years. During a 2-week run-in period, they all received FP twice daily. At randomization, they commenced FP/SAL or FP twice daily for 8 weeks. All were then given FP/SAL only, in a 16-week open-label study continuation. Medications were inhaled through an AeroChamber Plus with attached face mask. The primary end-point was mean change in total asthma symptom scores from baseline to the last 7 days of the double-blind period. Analyses were undertaken in all children randomized to treatment and who received at least one dose of study medication., Results: Three hundred children were randomized 1:1 to receive FP/SAL or FP. Mean change from baseline in total asthma symptom scores was -3.97 for FP/SAL and -3.01 with FP. The between-group difference was not statistically significant (P = 0.21; 95% confidence interval: -2.47, 0.54). No new safety signals were seen with FP/SAL., Conclusion: This is the first randomized, double-blind study of this size to evaluate FP/SAL in very young children with asthma. FP/SAL did not show superior efficacy to FP; no clear add-on effect of SAL was demonstrated. No clinically significant differences in safety were noted with FP/SAL usage., (© 2018 The Authors. Pediatric Allergy and Immunology Published by John Wiley & Sons Ltd.)