Takeda Announces the New Drug Application Approval of Zacras® Combination Tablets LD and Zacras® Combination Tablets HD in Japan for the Treatment of Hypertension

March 24, 2014

Osaka, Japan, March 24, 2014— Takeda Pharmaceutical Company Limited (“Takeda”) announced today that the Japanese Ministry of Health, Labour and Welfare has approved the New Drug Application (NDA) of Zacras® tablets, a fixed-dose combination ("FDC") of azilsartan* (generic name) and amlodipine besylate hydrochloride (generic name, "amlodipine"), for treatment of hypertension.

Zacras is a tablet taken orally once daily and has two dosage strengths, “Zacras® Combination Tablets LD” and “Zacras® Combination Tablets HD” which contain 20mg azilsartan / 2.5mg amlodipine, and 20mg azilsartan / 5mg amlodipine respectively.

Discovered by Takeda, azilsartan is a potent and lasting angiotensin II receptor blocker ("ARB") that lowers blood pressure by inhibiting the action of angiotensin II, a vasopressor hormone. Amlodipine is a calcium channel blocker ("CCB") having a hypotensive action by blocking inward calcium ion channels mainly in vascular smooth-muscle cells, resulting in peripheral arteriolar vasodilation. The ARB-CCB combination is one of the recommended treatments regimens as a combination therapy for the hypertension in the Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH2009), issued by the Japanese Society of Hypertension, from the standpoint of safety and efficacy.

The application approval was based on results of phase 3 clinical trials conducted in Japan. A multi-center, randomized, double-blind controlled phase 3 clinical trial with 603 patients with grade I (mild) and II  (moderate) hypertension, in which the efficacy and safety of an FDC of azilsartan and amlodipine were compared with monotherapy of either azilsartan or amlodipine. The anti-hypertensive effect in diastolic blood pressure in the sitting position as the primary endpoint, of the FDC of azilsartan and amlodipine was statistically significant compared to monotherapy with either monotherapy of the two drugs. The FDC therapy was also demonstrated a safety and tolerability profile comparable to each of the monotherapies.

Given the demand for appropriate blood pressure control that fits the clinical conditions of individual patients, the FDC of azilsartan and amlodipine is a new beneficial hypertension treatment option that is expected to further help control blood pressure for patients. Takeda will continue contributing to the treatment of the disease by delivering a wider range of treatment options, including the FDC, to patients and healthcare professionals.

* Approved in Japan in January 2012 and launched under the brand name "Azilva®" in May 2012.

References
Japanese Brand Name
Zacras® Combination Tablets LD and Zacras® Combination Tablets HD
Generic Name
Azilsartan / Amlodipine besylate hydrochloride

Dosage and Administration

For adults, a tablet, 20mg azilsartan / 2.5mg amlodipine, or 20mg azilsartan / 5mg amlodipine, is orally administered once a day. It is not able to be used for the first line treatment of hypertension.
Indication
Hypertension

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