SYNOPSIS
Name of sponsor/company

Daiichi Sankyo Co., Ltd.

Name of finished product

REZALTASⓇ COMBINATION TABLETS LD・COMBINATIONTABLETS HD

Name of active ingredientCS-866AZ (Olmesartan medoxomil/Azelnidipine)

Title of study

A randomized-controlled, double-blinded phase III study ofCS-866AZ

Study centre(s)Thirty-eight sites in Japan

Publication (reference)

Hypertension Research 32: 1148-1154, 2009

Studied period

July 2006 to August 2007

Phase of development

Phase III

Objectives

The antihypertensive effect and safety of co-administration ofolmesartan medoxomil (OLM) and azelnidipine (AZL) werecompared to those of administration of OLM or AZL alone inpatients with mild to moderate essential hypertension to verify thesuperiority of combination therapy to monotherapies.

Methodology

A multicenter, randomized, double-blind, 4-group, parallel,
comparative study

Number of patients

Number of patients planned: 760(planned and analysed)

Number of patients analyzed:
Full analysis set; 862
Safety analysis set; 866

Diagnosis and main criteria

Main inclusion criteria:

for inclusion

・ Age ≥20 years
・ Baseline BP during the run-in period was stable and fulfilled
the criterion: "systolic BP ≥ 140 mmHg and < 180 mmHg, anddiastolic BP ≥ 90 mmHg and < 110 mmHg."
・ The 24-hour BP determined by ambulatory blood pressure
monitoring (ABPM) during the run-in period met the criterion:"systolic BP ≥ 135 mmHg and diastolic BP ≥ 80 mm Hg."
Main exclusion criteria:
・ Secondary or malignant hypertension
・ Myocardial infarction or cerebrovascular disorder・ Night-shift workers

Test product, dose and mode

Co-administration of OLM 20 mg tablet and AZL 16 mg tabletof administration

Co-administration of OLM 10 mg tablet and AZL 8 mg tablet

Study drugs were administered orally once a day after breakfast.
Duration of treatment

Run-in period, 4 weeks; Treatment period, 12 weeks

Reference therapy

OLM 20 mg and AZL 16 mg

Criteria for evaluation

Efficacy (primary endpoint): The difference between sitting BP(systolic BP and diastolic BP) during the run-in period and that at
the end of treatment (ΔBP)
Safety: Adverse events (occurrence or exacerbation of subjective
symptoms/objective findings and abnormal changes in clinicallaboratory values)

Statistical method

Efficacy (primary endpoint): In the treatment comparison for ΔBP,
P-values were calculated by an analysis of covariance with the BP
value at baseline and gender and weight as covariates. The adjusted
mean value for each treatment group and the 95% confidence
interval were also calculated.
Safety: The number and percentage of patients who developed AEs
with a possible causal relationship to the study drug and all AEs
were determined.

Summary-conclusions

The difference in sitting BP during the run-in period and that at theend of treatment was -23.6/-14.2 mmHg (systolic/diastolic BP) in
the OLM 20 mg/AZL 16 mg group, and -20.3/-13.0 mmHg in theOLM 10 mg /AZL 8 mg group, which was a significantly greater
reduction in BP compared with either monotherapy groups(-15.7/-9.9 mmHg in OLM 20 mg [p<0.001] or -15.0/-9.4 mmHg
in AZL 16 mg [p<0.001]).
The incidence of adverse events in the OLM/AZL combinationgroups was similar with the monotherapy groups.
These results showed that combination therapy with OLM/AZL
was well tolerated and exerted a stronger antihypertensive effectcompared to monotherapy with OLM or AZL in patients withessential hypertension.

Date of report

October 14, 2010