This study assessed the antihypertensive efficacy of a triple combination, fixed-dose therapy of losartan 50 mg (L50)/hydrochlorothiazide 12.5 mg (H12.5)/amlodipine 5 mg (A5) versus co-administration of L50 plus A5 (L50+A5) in Japanese subjects with uncontrolled essential hypertension. Initially, all subjects received single-blind treatment with L50+A5 for 8 weeks. Subjects whose blood pressure (BP) remained stable within pre-specified limits during the last 4 weeks of L50+A5 administration were randomized (n =3 27) to double-blind treatment with L50/H12.5/A5 or L50+A5 for 8 weeks. Primary and secondary efficacy endpoints were mean change from baseline to Week 8 in trough diastolic BP (DBP) and trough systolic BP (SBP), respectively. Safety was assessed throughout the study. The treatment difference for L50/H12.5/A5 versus L50+A5 in mean change from baseline in DBP at Week 8 was -1.1 mm Hg (95% confidence interval (CI) -2.7, 0.6; P = 0.205). However, the treatment difference in mean change from baseline in SBP at Week 8 was -3.2 mm Hg (95% CI: -5.7, -0.8; P=0.011). A chance imbalance in the change in DBP before randomization between groups was identified in a post-hoc analysis as a major reason for the smaller-than-expected difference in DBP between groups. The overall safety profile was generally similar between groups. In conclusion, treatment with L50/H12.5/A5 for 8 weeks did not demonstrate a significant difference in DBP reduction, but demonstrated a nominally significant difference in SBP reduction, compared with L50+A5. L50/H12.5/A5 was well tolerated. (ClinicalTrials.gov identifier NCT01302691.).
BackgroundRecent evidence points to an increased incidence of new-onset diabetes and a negative impact on glucose parameters with statin use. This study examined the safety of ezetimibe vs placebo for change from baseline to week 24 in HbA1c (primary endpoint), glycoalbumin, and fasting plasma glucose (secondary endpoints) in Japanese subjects with type 2 diabetes and hypercholesterolemia.MethodsThis was a randomized, double-blind, placebo-controlled, parallel-group, multi-site trial. Adults with type 2 diabetes and hypercholesterolemia whose LDL-C measured <140 mg/dl (subjects receiving lipid-lowering drugs) or <160 mg/dl (subjects not receiving lipid-lowering drugs) at the start of the screening phase, were randomized after a 5-week wash-out period to ezetimibe 10 mg or placebo (1:1) for 24 weeks. Changes in HbA1c, glycoalbumin and fasting plasma glucose from baseline to week 24 were evaluated. The non-inferiority margin was set at 0.5% for HbA1c.ResultsOverall, 152 subjects were randomized (75 to ezetimibe and 77 to placebo). From baseline to 24 weeks, HbA1c significantly increased in both the ezetimibe and placebo groups (between-treatment difference 0.08 [95% CI: −0.07 to 0.23]). Ezetimibe was statistically non-inferior to placebo. At 24 weeks, the mean change from baseline in glycoalbumin levels (between-treatment differences 0.00 [95% CI: −0.47, 0.47]) and fasting plasma glucose (between-treatment differences −4.8 [95% CI: −12.1, 2.1]) were similar in both treatment groups.ConclusionsThese results suggest that ezetimibe 10 mg does not result in dysregulation of glucose metabolism in Japanese patients with type 2 diabetes and hypercholesterolemia over 24 weeks of treatment.Trial registrationClinicalTrials.gov identifier NCT01611883.Electronic supplementary materialThe online version of this article (doi:10.1186/s12944-015-0036-z) contains supplementary material, which is available to authorized users.
Japanese patients with uncontrolled essential hypertension received single-blind losartan 50 mg/hydrochlorothiazide 12.5 mg (L50/H12.5) for 8 weeks. Patients whose blood pressure (BP) remained uncontrolled were randomized double-blind to fixed-dose losartan 50 mg/hydrochlorothiazide 12.5 mg/amlodipine 5 mg (L50/H12.5/A5) or L50/H12.5 for 8 weeks followed by open-label L50/H12.5/A5 for 44 weeks. Adverse events were assessed. After 8 weeks, diastolic and systolic BP were reduced significantly more with L50/H12.5/A5 versus L50/H12.5 (both p < 0.001). Mean changes in diastolic and systolic BP were sustained for 44 weeks. L50/H12.5/A5 was well-tolerated and improved BP significantly versus L50/H12.5 in Japanese patients with uncontrolled essential hypertension.
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