Efficacy and Safety of LCZ696 in Comparison to Olmesartan in Japanese Patients With Essential Hypertension

A Multi-center, Randomized, Double-blind, Active-controlled, 8-week Study to Evaluate the Efficacy and Safety of LCZ696 in Comparison to Olmesartan in Japanese Patients With Essential Hypertension

This study assessed the efficacy of LCZ696 in Japanese patients with essential hypertension

Study Overview

• Status: Completed
• Conditions: Essential Hypertension
• Intervention / Treatment: Drug: LCZ696; Drug: Placebo; Drug: Olmesartan

• Study Type: Interventional
• Enrollment (Actual): 1161
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan, 814-0032
    • Novartis Investigative Site
  • Osaka, Japan, 536-0008
    • Novartis Investigative Site
  • Osaka, Japan, 550-0013
    • Novartis Investigative Site
  • Osaka, Japan, 560-0005
    • Novartis Investigative Site
  • Saitama, Japan, 337-0012
    • Novartis Investigative Site
  • Chiba
    • Kamogawa-City, Chiba, Japan, 296-8602
      • Novartis Investigative Site
  • Fukuoka
    • Chikushi-gun, Fukuoka, Japan, 811-1244
      • Novartis Investigative Site
    • Fukuoka-city, Fukuoka, Japan, 812-8582
      • Novartis Investigative Site
    • Fukuoka-city, Fukuoka, Japan, 810-0014
      • Novartis Investigative Site
    • Fukuoka-city, Fukuoka, Japan, 810-0066
      • Novartis Investigative Site
    • Kitakyushu-city, Fukuoka, Japan, 800-0225
      • Novartis Investigative Site
    • Kitakyushu-city, Fukuoka, Japan, 807-0856
      • Novartis Investigative Site
  • Hokkaido
    • Asahikawa, Hokkaido, Japan, 078-8214
      • Novartis Investigative Site
    • Sapporo, Hokkaido, Japan, 003-0026
      • Novartis Investigative Site
    • Sapporo, Hokkaido, Japan, 003-0825
      • Novartis Investigative Site
    • Sapporo-city, Hokkaido, Japan, 006-0811
      • Novartis Investigative Site
    • Sapporo-city, Hokkaido, Japan, 062-0053
      • Novartis Investigative Site
    • Sapporo-city, Hokkaido, Japan, 063-0842
      • Novartis Investigative Site
  • Hyogo
    • Amagasaki, Hyogo, Japan, 660-0814
      • Novartis Investigative Site
  • Ibaraki
    • Hitachi-city, Ibaraki, Japan, 317-0077
      • Novartis Investigative Site
  • Kanagawa
    • Kawasaki-city, Kanagawa, Japan, 210-0852
      • Novartis Investigative Site
    • Yokohama-city, Kanagawa, Japan, 231-0023
      • Novartis Investigative Site
    • Yokohama-city, Kanagawa, Japan, 236-0004
      • Novartis Investigative Site
  • Kyoto
    • Kyotanabe-city, Kyoto, Japan, 610-0361
      • Novartis Investigative Site
    • Kyoto-city, Kyoto, Japan, 615-0035
      • Novartis Investigative Site
    • Kyoto-city, Kyoto, Japan, 615-8125
      • Novartis Investigative Site
  • Nara
    • Kashihara-city, Nara, Japan, 634-8522
      • Novartis Investigative Site
  • Osaka
    • Ibadraki, Osaka, Japan, 567-0876
      • Novartis Investigative Site
    • Osaka-city, Osaka, Japan, 547-0013
      • Novartis Investigative Site
    • Toyonaka-city, Osaka, Japan, 560-0082
      • Novartis Investigative Site
  • Saitama
    • Ageo-city, Saitama, Japan, 362-8588
      • Novartis Investigative Site
    • Fujimino, Saitama, Japan, 356-0053
      • Novartis Investigative Site
    • Hiki-Gun, Saitama, Japan, 355-0328
      • Novartis Investigative Site
    • Koshigaya city, Saitama, Japan, 343-0826
      • Novartis Investigative Site
    • Niiza-city, Saitama, Japan, 352-0014
      • Novartis Investigative Site
    • Sakado, Saitama, Japan, 350-0202
      • Novartis Investigative Site
    • Tokorozawa-city, Saitama, Japan, 359-1161
      • Novartis Investigative Site
  • Tochigi
    • Shimotsuke-city, Tochigi, Japan, 329-0498
      • Novartis Investigative Site
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-0031
      • Novartis Investigative Site
    • Bunkyo-ku, Tokyo, Japan, 113-8655
      • Novartis Investigative Site
    • Chiyoda-ku, Tokyo, Japan, 100-0005
      • Novartis Investigative Site
    • Edogawa-ku, Tokyo, Japan, 133-0061
      • Novartis Investigative Site
    • Edogawa-ku, Tokyo, Japan, 134-0084
      • Novartis Investigative Site
    • Hachioji, Tokyo, Japan, 192-0046
      • Novartis Investigative Site
    • Hachioji-city, Tokyo, Japan, 192-0918
      • Novartis Investigative Site
    • Katsushika-ku, Tokyo, Japan, 124-0024
      • Novartis Investigative Site
    • Kiyose-city, Tokyo, Japan, 204-0021
      • Novartis Investigative Site
    • Kunitachi, Tokyo, Japan, 186-0001
      • Novartis Investigative Site
    • Meguro-ku, Tokyo, Japan, 152-0031
      • Novartis Investigative Site
    • Minato-ku, Tokyo, Japan, 105-7390
      • Novartis Investigative Site
    • Minato-ku, Tokyo, Japan, 108-0075
      • Novartis Investigative Site
    • Nerima-ku, Tokyo, Japan, 177-0051
      • Novartis Investigative Site
    • Ota-ku, Tokyo, Japan, 143-0023
      • Novartis Investigative Site
    • Shibuya-ku, Tokyo, Japan, 150-0002
      • Novartis Investigative Site
    • Shinagawa-ku, Tokyo, Japan, 141-0032
      • Novartis Investigative Site
    • Shinagawa-ku, Tokyo, Japan, 142-0053
      • Novartis Investigative Site
    • Shinagawa-ku, Tokyo, Japan, 142-0063
      • Novartis Investigative Site
    • Shinjuku-ku, Tokyo, Japan, 160-8582
      • Novartis Investigative Site
    • Tachikawa, Tokyo, Japan, 190-0013
      • Novartis Investigative Site
    • Taito, Tokyo, Japan, 111-0052
      • Novartis Investigative Site
    • Toshima-ku, Tokyo, Japan, 171-0021
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with mild-to-moderate hypertension, untreated or currently taking antihypertensive therapy.
• Treated patients (using antihypertensive treatments within 4 weeks prior to Visit 1) must have an msSBP ≥ 150 mmHg and < 180 mmHg at the randomization visit (Visit 201) and msSBP ≥140 mmHg < 180 mmHg at the visit immediately proceeding Visit 201 (Visit 102 or 103).
• Untreated patients (newly diagnosed with essential hypertension or having a history of hypertension but have not been taking any antihypertensive drugs for at least 4 weeks prior to Visit 1) must have an msSBP ≥ 150 mmHg and < 180 mmHg at both Visit 1 and Visit 201.
• Patients must have an absolute difference of ≤15 mmHg in msSBP between Visit 201 and the immediately preceding visit;

Exclusion Criteria:

• Severe hypertension (msDBP ≥110 mmHg and/or msSBP ≥ 180 mmHg).
• History of angioedema, drug-related or otherwise, as reported by the patient.
• History or evidence of a secondary form of hypertension, including but not limited to any of the following: renal parenchymal hypertension, renovascular hypertension (unilateral or bilateral renal artery stenosis), coarctation of the aorta, primary hyperaldosteronism, Cushing's disease, pheochromocytoma, polycystic kidney disease, and drug-induced hypertension.
• Patients who previously entered a LCZ696 study and had been randomized or enrolled into the active drug treatment epoch.

Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LCZ696 200 mg; LCZ696 200 mg tablet and placebo to both LCZ696 (1 tablet) and Olmesartan (1 capsule) tablet once daily for 8 weeks	Drug: LCZ696; 200 mg (one tablet) or 400 mg (2 tablets of 200mg) once daily; Drug: Placebo; Placebo to LCZ696 or Olmesartan
Experimental: LCZ696 400 mg; LCZ696 200 mg tablet and a placebo to both LCZ696 (1 tablet) and Olmesartan (1 capsule) once daily for one week; then up-titrated to LCZ696 400 mg and placebo to Olmesartan (1 capsule) once daily for the remaining 7 weeks	Drug: LCZ696; 200 mg (one tablet) or 400 mg (2 tablets of 200mg) once daily; Drug: Placebo; Placebo to LCZ696 or Olmesartan
Active Comparator: Olmesartan 20 mg; Olmesartan 20 mg capsule and placebo to LCZ696 (2 tablets) once daily for 8 weeks	Drug: Placebo; Placebo to LCZ696 or Olmesartan; Drug: Olmesartan; Olmesartan 20 mg capsule one daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP)	Sitting BP measurements were performed at screening through the end of study at every visit. Four separate sitting BP were obtained with a full two-minute interval between measurements. The 4 measurements were summed and averaged, and then the baseline BP value was subtracted from the average value to get the change from baseline.	Baseline, 8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Mean 24-hour Ambulatory SBP (maSBP) at Week 8	Ambulatory blood pressure monitoring (ABPM) over a 24-hour period was conducted at two time-points during the study in a subset of participants.	Baseline, 8 weeks
Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP)	Sitting BP measurement was performed at screening through the end of study at every visit. Four separate sitting BP were obtained with a full two-minute interval between measurement. The 4 measurements were summed and averaged, and then the baseline BP value was subtracted from the average value to get the change from baseline.	Baseline, 8 weeks
Percentage of Participants Achieving a Successful Response in Overall Blood Pressure Control at Week 8	A successful response in overall BP control rate was defined as msSBP < 140 mmHg and msDBP <90 mmHg.	8 weeks
Percentage of Participants Achieving a Successful msSBP Response	Successful msSBP response was defined as < 140 mmHg or ≥ 20 mmHg reduction from baseline.	8 weeks
Percentage of Participants Achieving a Successful msDBP Response	Successfull msDBP response was defined as <90 mmHg or ≥10 mmHg reduction from baseline.	8 weeks
Change From Baseline in Mean 24-hour Ambulatory DBP (maDBP) at Week 8	ABPM over a 24-hour period was conducted at two time-points during the study in a subset of participants.	Baseline, 8 weeks
Change From Baseline in maSBP and maDBP for Daytime/Nighttime	ABPM over a 24-hour period was conducted at two time-points during the study in a subset of participants.	Baseline, 8 weeks
Change From Baseline in Office Pulse Pressure	Office pulse pressure was calculated as msSBP minus msDBP. Sitting blood pressure (BP) measurement was performed at screening through the end of study at every visit. Four separate sitting BP were obtained with a full two-minute interval between measurement. The 4 measurements were summed and then averaged to calculate the mean BP value. The baseline PP value was subtracted from the week 8 PP value to determine the change from baseline in PP.	Baseline, 8 weeks
Change From Baseline in Mean 24-hour Ambulatory Pulse Pressure	Ambulatory pulse pressure was calculated as hourly ambulatory SBP minus hourly ambulatory DBP in a subset of participants.	Baseline, 8 weeks
Number of Patients With Adverse Events, Serious Adverse Events and Death	Participants were monitored for adverse events, serious adverse events and deaths throughout the study.	8 weeks

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (Actual): April 1, 2013
• Study Completion (Actual): April 1, 2013

Study Registration Dates

• First Submitted: May 13, 2012
• First Submitted That Met QC Criteria: May 13, 2012
• First Posted (Estimate): May 15, 2012

Study Record Updates

• Last Update Posted (Estimate): October 16, 2015
• Last Update Submitted That Met QC Criteria: September 25, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Keywords: Essential hypertension; LCZ696
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Essential Hypertension; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Olmesartan; Sacubitril and valsartan sodium hydrate drug combination
• Other Study ID Numbers: CLCZ696A1306