The effects of KT3‐671, a new angiotensin II (AT 1) receptor blocker in mild to moderate hypertension

Abstract

AimsTo compare the antihypertensive effect, and tolerability and safety of once daily doses of KT3-671 with that of placebo in patients with mild to moderate uncomplicated essential hypertension. Methods A randomised, multicentre, double blind, parallel-group comparison of KT3-671 with placebo. Hypertensive patients [Ambulatory Blood Pressure Monitoring (ABPM), mean daytime DBP > 90 mmHg, Office sitting mean DBP 95-114 after a 7-28 day washout period] entered a 2-week, single blind, run-in phase. Patients eligible for the double-blind phase were randomised to receive KT3-671 40 mg, 80 mg, 160 mg or placebo once daily over 4 weeks. The primary end-point was trough mean sitting office DBP. The study had 90% power to detect a 5 mmHg change between treatments and placebo at the 5% level of significance. The secondary end-points were 24 hour, daytime and night time mean ABPM. Results Office DBP was significantly lower with KT3-671 40 mg but not the other 2 dosage groups ( -3.2; 95% CL -6.1 : -0.3 P < 0.03). Office SBP was significantly reduced with all dosage groups (40 mg -5.9, 95% CL -11 : -0.9; 80 mg -4.9, 95% CL -9.9 : 0.1 and 160 mg -5.7, 95% CL -10.8 : -0.7 P < 0.05). All doses of KT3-671 reduced systolic and diastolic ABPM. The number of patients with treatment related adverse events were comparable to placebo (38.8% KT3-671 vs 32.8% placebo). There was some evidence of a dose-response relationship with fall in nocturnal ABPM. Conclusions Oral KT3-671 was well tolerated. KT3-671 reduced office systolic BP at all doses and diastolic BP at some of the doses. Due to greater precision and power, the falls in mean ambulatory systolic and diastolic pressure were all significantly lower than placebo.

Concentration-Dependent Mode of Interaction of Angiotensin II Receptor Blockers with Uric Acid Transporter

“…Valsartan was purchased from Livzon Group Changzhou Kony Pharmaceutical (Changzhou, China). EXP3174, pratosartan (Patterson et al, 2003), candesartan, and olmesartan were synthesized and kindly supplied by Kotobuki Pharmaceutical (Nagano, Japan). Benzbromarone and PZA were purchased from Sigma-Aldrich (St. Louis, MO) and Wako Pure Chemical Industries (Osaka, Japan), respectively.…”

Clinical Efficacy of a New Angiotensin II Type 1 Receptor Blocker, Pratosartan, in Hypertensive Patients

“…In rat models of spontaneous hypertension and renal hypertension, once daily administration of PRT resulted in a maintenance of blood pressure (BP) reduction (4). And in a study using ambulatory BP measurements to measure the antihypertensive effects of PRT in Caucasians, the drug was shown to achieve good blood pressure control (5).…”