Azilsartan is a novel angiotensin receptor blocker being developed for hypertension treatment. This 16-week, multicenter, randomized, double-blind study compared the efficacy and safety of azilsartan (20–40 mg once daily by forced titration) and its ability to provide 24-h blood pressure (BP) control, with that of candesartan cilexetil (candesartan; 8–12 mg once daily by forced titration) in 622 Japanese patients with grade I–II essential hypertension. Efficacy was evaluated by clinic-measured sitting BP, and by ambulatory BP monitoring (ABPM) at week 14. Participants (mean age: 57 years, 61% males) had a mean baseline sitting BP of 159.8/100.4 mm Hg. The mean change from baseline in sitting diastolic BP at week 16 (primary endpoint) was −12.4 mm Hg in the azilsartan group and −9.8 mm Hg in the candesartan group, demonstrating a statistically significant greater reduction with azilsartan vs. candesartan (difference: −2.6 mm Hg, 95% confidence interval (CI): −4.08 to −1.22 mm Hg, P=0.0003). The week 16 (secondary endpoint) mean change from baseline in sitting systolic BP was −21.8 mm Hg and −17.5 mm Hg, respectively, a significant decrease with azilsartan vs. candesartan (difference: −4.4 mm Hg, 95% CI: −6.53 to −2.20 mm Hg, P<0.0001). On ABPM, the week 14 mean changes from baseline in diastolic and systolic BP were also significantly greater with azilsartan over a 24-h period, and during the daytime, night-time and early morning. Safety and tolerability were similar among the two groups. These data demonstrate that once-daily azilsartan provides a more potent 24-h sustained antihypertensive effect than that of candesartan but with equivalent safety.

AimTo assess the efficacy and safety of fasiglifam 25 and 50 mg in Japanese patients with type 2 diabetes inadequately controlled by diet and exercise.MethodsThis phase III, double-blind, placebo-controlled, multicentre study included 192 patients randomized to once-daily treatment with fasiglifam 25 mg (n = 63) or 50 mg (n = 62) or placebo (n = 67) for 24 weeks. The primary efficacy endpoint was the change from baseline in glycated haemoglobin (HbA1c) at week 24.ResultsAt week 24, both fasiglifam groups had significantly reduced HbA1c levels compared with the placebo group (p < 0.0001). The least squares mean change from baseline in HbA1c was 0.16% with placebo, −0.57% with fasiglifam 25 mg and −0.83% with fasiglifam 50 mg. The percentage of patients who achieved an HbA1c target of <6.9% at week 24 was also significantly higher (p < 0.05) for fasiglifam 25 mg (30.2%) and 50 mg (54.8%) compared with placebo (13.8%). Fasiglifam significantly reduced fasting plasma glucose levels at all assessment points, starting from week 2. The incidence and types of treatment-emergent adverse events in each fasiglifam group were similar to those in the placebo group, and hypoglycaemia was reported in 1 patient receiving fasiglifam 50 mg. There were no clinically meaningful changes in body weight in any treatment group.ConclusionsFasiglifam significantly improved glycaemic control and was well tolerated, with a low risk of hypoglycaemia in Japanese patients with type 2 diabetes inadequately controlled by diet and exercise; however, in a recent review of data from overall fasiglifam global clinical trials, concerns about liver safety arose and the clinical development of fasiglifam was terminated after this trial was completed.

Objective: To investigate the efficacy and safety of the oral gonadotropin-releasing hormone receptor antagonist, relugolix, in patients experiencing uterine fibroid-associated pain. Design: Phase 3, multicenter, randomized, double-blind, placebo-controlled study. Setting: Medical centers. Patient(s): Premenopausal Japanese women (N ¼ 65) experiencing moderate-to-severe uterine fibroid-associated pain with a maximum Numerical Rating Scale (NRS) score of R4 were randomized and completed the study. Intervention(s): Once-daily 40 mg relugolix (n ¼ 33) or placebo (n ¼ 32) for 12 weeks. Main Outcome Measure(s): Primary end point: proportion of patients with a maximum NRS score of %1 during the 28-day period before the final dose of study drug. Secondary end points: proportion of patients with no pain (NRS ¼ 0) and percentage of days without pain during the 28-day period before the final dose of study drug; adverse events. Result(s): More patients receiving relugolix versus placebo achieved a maximum NRS score of %1 during the 28-day period before the final dose of study drug (57.6% vs. 3.1%). Similarly, more patients receiving relugolix versus placebo achieved a maximum NRS score of 0 (48.5% vs. 3.1%) and experienced more days without pain (96.4% vs. 71.4%). More patients receiving relugolix versus placebo experienced treatment-emergent adverse events (TEAEs; 87.9% vs. 56.3%); however, the rate of treatment discontinuation was low and not different between groups. Most TEAEs were mild to moderate in intensity. TEAEs (R10%) included hot flush, metrorrhagia, hyperhidrosis, and menorrhagia, consistent with relugolix's mechanism of action, and viral upper respiratory tract infection. Conclusion(s):Relugolix improved uterine fibroid-associated pain and was well tolerated. Clinical Trial Registration Numbers: NCT02655224.

(Abstracted from Obstet Gynecol 2019;133:423–433) Uterine leiomyomas occur in approximately 20% to 40% of women. A major symptom in women with fibroids is persistent heavy menstrual bleeding, resulting in anemia with fatigue and reduced quality of life.