A randomized, double blind, placebo-controlled, multicenter phase II trial of Allisartan Isoproxil in essential hypertensive population at low-medium risk

PLoS One. 2015 Feb 18;10(2):e0117560. doi: 10.1371/journal.pone.0117560. eCollection 2015.

Abstract

Background: Angiotensin II receptor blockers (ARBs) is a well-tolerated class of antihypertensive agents, exhibiting effective antihypertensive and cardiovascular protective function. The objective of the study was to examine the efficacy and safety of Allisartan Isoproxil, a newly developed, selective, nonpeptide blocker of the angiotensin II type 1 receptor (AT1R), in essential hypertensive patients at low-medium risk.

Methods and findings: A Phase II prospective, randomized, double-blind, placebo-controlled, multicenter trial comparing Allisartan Isoproxil 240mg versus placebo was conducted in essential hypertensive patients at low-medium risk at 8 sites in China. After a 2-week placebo baseline period, 275 patients received once-daily treatment with Allisartan Isoproxil 240mg or placebo randomly for 8 weeks. Systolic/diastolic blood pressure (SBP/DBP) was measured at week 2, 4 and 8. By the end of treatment, mean reductions from baseline of SBP and DBP in Allisartan Isoproxil and placebo groups were 14.5/10.4 and 8.3/7.7 mmHg, respectively (P<0.01). The rate of effective blood pressure control in Allisartan Isoproxil group was significantly higher than in placebo group at week 4 (61.3% vs 50.0%, P<0.05) and week 8 (67.2% vs 48.6%, P<0.01). In terms of safety and tolerability, there were no report of death and serious adverse event (SAE) in all subjects. There was no difference of frequency between two groups in adverse event (AE) and adverse drug reaction (ADR) (P>0.05). No one withdraw because of an ADR in two groups. 124 patients received additional 56 weeks treatment with Allisartan Isoproxil and 84 of them completed the study. The rate of effective BP control kept up to 80% since week 24. No significant clinical change was observed and ADRs were generally mild or moderate during the long-term study.

Conclusions/significance: Allisartan Isoproxil 240mg was effective and safe for essential hypertension patients at low-medium risk.

Trial registration: http://www.chictr.org/cn/ ChiCTR-TRC-10000886.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II Type 1 Receptor Blockers / adverse effects*
  • Angiotensin II Type 1 Receptor Blockers / pharmacology*
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use
  • Antihypertensive Agents / adverse effects*
  • Antihypertensive Agents / pharmacology*
  • Antihypertensive Agents / therapeutic use
  • Biphenyl Compounds / adverse effects*
  • Biphenyl Compounds / pharmacology*
  • Biphenyl Compounds / therapeutic use
  • Double-Blind Method
  • Endpoint Determination
  • Essential Hypertension
  • Female
  • Humans
  • Hypertension / drug therapy*
  • Imidazoles / adverse effects*
  • Imidazoles / pharmacology*
  • Imidazoles / therapeutic use
  • Male
  • Middle Aged
  • Placebos
  • Risk
  • Safety

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Antihypertensive Agents
  • Biphenyl Compounds
  • Imidazoles
  • Placebos
  • allisartan isoproxil

Grants and funding

This Trial is funded by Shenzhen Salubris Pharmaceuticals Co.,Ltd. All clinical investigators received support budgets from Shenzhen Salubris Pharmaceuticals Co., Ltd for the conduct of the clinical trial. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Hangzhou Tigermed Co. Ltd is independently in charge of data collection and statistical analysis.