NEW YORK (Reuters Health) – In patients with stage 1 and 2 hypertension, the experimental angiotensin receptor blocker (ARB) azilsartan medoxomil lowers blood pressure better than maximal doses of either valsartan or olmesartan, a study shows.

“Azilsartan medoxomil could provide higher rates of hypertension control within the ARB class,” the study team concludes in the March issue of Hypertension, available online now.

Azilsartan medoxomil is being developed by Takeda Pharmaceutical Company, which funded the study. The company submitted a new drug application for the drug to the US Food and Drug Administration (FDA) in April 2010.

In a telephone interview with Reuters Health, Dr. William B. White, of University of Connecticut Health Center in Farmington, who’s been involved in azilsartan medoxomil studies, said a decision by FDA is expected “in the next few weeks,” adding, “I don’t think it will have to go to advisory committee because it’s a standard antihypertensive and a very good one.”

Dr. White is first author on the study reported in Hypertension. This study is “both first phase 3, double-blind active comparator trial of azilsartan medoxomil in patients with hypertension and the first phase 3 antihypertensive drug development program that used 24-hour ambulatory systolic BP monitoring for its primary efficacy end point,” he and colleagues say.

The randomized study involved 1,291 men and women, with a mean age of 56 years, and baseline 24-hour systolic BP of 145 mm Hg. Following a 3- to 4-week washout of previous antihypertensive medication and a coincident 2-week placebo run-in period, patients were randomly assigned to placebo, 20 or 40 mg azilsartan medoxomil, 160 mg valsartan or 20 mg olmesartan once daily for 2 weeks. They were then force-titrated to 40 or 80 mg azilsartan, 320 mg valsartan, 40 mg olmesartan, or continuation of placebo for an additional 4 weeks.

The researchers report that the change from baseline in 24-hour mean systolic BP, the primary efficacy end point, favored maximum-dose azilsartan medoxomil over maximum-dose valsartan or olmesartan.

Systolic BP was lowered on average by 14.3 mm Hg with azilsartan medoxomil 80 mg daily, compared with 10.0 mm Hg and 11.7 mm Hg, respectively, with valsartan 320 mg daily and olmesartan 40 mg daily.

With azilsartan medoxomil at its highest dose, BP control and response rates are “greater than other drugs in the same class by absolute rates of 8% to 10%,” the researchers note

They also report that the lower dose of azilsartan medoxomil (40 mg daily) was noninferior to 40 mg of olmesartan daily by 24-hour mean systolic BP monitoring. Both doses of azilsartan medoxomil lowered systolic BP measured in the clinic to a greater extent than the comparator ARBs.

Safety and tolerability were similar among the placebo and the four active treatment arms, the investigators report in their paper. “With azilsartan,” Dr. White commented, “you are not substituting better efficacy with more side effects; that just simply didn’t happen.”

Dr. White said it’s not entirely clear why azilsartan medoxomil seems to work better than other ARBs. “It most likely has a different kind of biology and probably binds more intensely to the angiotensin receptors in blood vessels,” he told Reuters Health. “There is no other rationale because the 80 milligram dose of azilsartan medoxomil (the highest dose) was tested against the other drug’s highest approved doses.”

Dr. White and three co-investigators have been paid consultants for Takeda Global Research and Development, the sponsor of this clinical trial. Three other investigators are employees of the company.

Hypertension, March 2011.