Efficacy and Safety of LCZ696 200 mg + Amlodipine 5 mg in Comparison With Amlodipine 5 mg in Hypertensive Patients Not Responding to Amlodipine

A Randomized, 8-week, Double-blind, Parallel-group, Active-controlled, Multicenter Study to Evaluate the Efficacy and Safety of the Combination of LCZ696 200 mg + Amlodipine 5 mg in Comparison With Amlodipine 5 mg in Patients With Essential Hypertension Not Adequately Responsive to Amlodipine 5 mg Monotherapy Treatment

This study will assess whether LCZ696 when used in combination with amlodipine will provide greater BP lowering benefit compared to amlodipine alone in Asian hypertensive patients not adequately responsive to amlodipine therapy.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 266
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Chongqing, China, 400042
    • Novartis Investigative Site
  • Shanghai, China, 200025
    • Novartis Investigative Site
  • Tianjin, China, 300142
    • Novartis Investigative Site
  • Hebei
    • Shijiazhuang, Hebei, China, 050000
      • Novartis Investigative Site
• Japan
  • Tokyo
    • Edogawa-ku, Tokyo, Japan, 133-0061
      • 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
    • Shibuya-ku, Tokyo, Japan, 150-0002
      • Novartis Investigative Site
    • Shinagawa-ku, Tokyo, Japan, 142-0063
      • Novartis Investigative Site
    • Toshima-ku, Tokyo, Japan, 171-0021
      • Novartis Investigative Site
• Korea, Republic of
  • Busan, Korea, Republic of, 602-739
    • Novartis Investigative Site
  • Daegu, Korea, Republic of, 705-703
    • Novartis Investigative Site
  • Daegu, Korea, Republic of, 705-718
    • Novartis Investigative Site
  • Seoul, Korea, Republic of, 150-713
    • Novartis Investigative Site
  • Gangwon-Do
    • Wonju, Gangwon-Do, Korea, Republic of, 220-701
      • Novartis Investigative Site
  • Kyunggi
    • Koyang, Kyunggi, Korea, Republic of, 410-719
      • Novartis Investigative Site
• Malaysia
  • Kuala Lumpur, Malaysia, 56000
    • Novartis Investigative Site
  • Sarawak
    • Kuching, Sarawak, Malaysia, 94300
      • Novartis Investigative Site
• Philippines
  • Quezon City, Philippines, 1102
    • Novartis Investigative Site
  • Quezon City, Philippines, 1100
    • Novartis Investigative Site
  • Valenzuela City, Philippines, 1441
    • Novartis Investigative Site
  • Manila
    • Quezon City, Manila, Philippines, 1100
      • Novartis Investigative Site
  • Metro Manila
    • Manila, Metro Manila, Philippines, 1000
      • Novartis Investigative Site
• Taiwan
  • Taichung, Taiwan, 40447
    • Novartis Investigative Site
  • Taipei, Taiwan, 10002
    • Novartis Investigative Site
  • Taipei, Taiwan, 114
    • Novartis Investigative Site
  • Taiwan, ROC
    • Taipei, Taiwan, ROC, Taiwan, 112
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Patients must give written informed consent and have a diagnosis of hypertension:

Untreated patients must have an msSBP ≥ 150 mmHg and < 180 mmHg at both Visit 1 and Visit 101. Pre-treated patients must have an msSBP ≥ 145 mmHg and < 180 mmHg after wash out at Visit 101. All patients must have an office msSBP ≥ 145 mmHg and < 180 mmHg at the completion of the 4-week run-in epoch (at the randomization visit (Visit 201).

Patients must successfully complete ABPM and pass technical requirements at Visit 201.

Exclusion Criteria:

Malignant or severe hypertension (grade 3 of WHO classification; msDBP ≥110 mmHg and/or msSBP ≥ 180 mmHg).

History of angioedema, drug-related or otherwise. History or evidence of a secondary form of hypertension. Transient ischemic cerebral attack (TIA) during the 12 months prior to Visit 1 or any history of stroke.

History of myocardial infarction, coronary bypass surgery or PCI during the 12 months prior to Visit 1

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: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LCZ696 and amlodipine; Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (had an office msSBP ≥145 mmHg and <180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 200mg of LCZ696 in combination with 5 mg of amlodipine for 8 weeks.	Drug: LCZ696; LCZ696 will use tablets available at a strength of 200mg. Patients will be instructed to take the prescribed medication once a day.; Drug: Amlodipine; Amlodipine will use tablets available at a strength of 5 mg. Patients will be instructed to take the prescribed medication once a day.
Active Comparator: Amlodipine; Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (had an office msSBP ≥145 mmHg and <180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 5 mg of amlodipine and placebo to LCZ696 for 8 weeks.	Drug: Amlodipine; Amlodipine will use tablets available at a strength of 5 mg. Patients will be instructed to take the prescribed medication once a day.; Drug: Placebo; Matching placebo to LCZ696

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Mean 24-hour Ambulatory Blood Pressure Monitoring (ABPM) Systolic Blood Pressure (maSBP)	The change in mean 24 hour ambulatory systolic blood pressure (maSBP) from baseline to end of the study (week 8) in the 2 groups was measured. A greater reduction from baseline in the LCZ696 group indicates a positive treatment effect.	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Mean 24-hour ABPM Diastolic Blood Pressure (maDBP)	The change in mean 24 hour maDBP from baseline to end of the study was measured. A reduction from baseline indicates a positive treatment effect.	8 weeks
Change in Mean Sitting Systolic Blood Pressure (msSBP)	The change in the patient's msSBP from baseline to end of the study was measured. A reduction from baseline indicates a positive treatment effect.	8 weeks
Change in Mean Sitting Diastolic Blood Pressure (msDBP)	The change in the patient's msDBP from baseline to end of the study was measured. A reduction from baseline indicates a positive treatment effect.	8 weeks
Change in Sitting Pulse Pressure (PP)	The change in the patient's mean sitting PP from baseline to end of the study was measured. Pulse pressure measures the difference in mean sitting systolic blood pressure and mean sitting diastolic blood pressure.	8 weeks
Number of Participants Achieving Systolic and Diastolic Blood Pressure Control (< 140/90 mmHg)	The number of participants achieving a systolic and diastolic blood pressure < 140/90 mmHg was measured. This outcome measure shows how well a given blood pressure treatment can achieve a given blood pressure target or goal. Participants who achieved the target blood pressure were determined based on the mean SBP and DBP measurements taken at the end of the study. If the participants' BP measurement was below the above target, they were considered to have successful blood pressure control.	8 weeks
Number of Participants Achieving Successful Response in msSBP (< 140 mmHg or a Reduction ≥ 20 mmHg From Baseline)	The number of participants who achieved successful treatment response in the msSBP of < 140mmHg or a reduction ≥ 20 mmHg from baseline after completing study treatment was measured. Participants who achieved either of the above targets were deemed as a having a successful response.	8 weeks
Number of Participants Achieving Successful Response in msDBP (< 90 mmHg or a Reduction ≥ 10 mmHg From Baseline)	The number of participants who achieved successful treatment response in msDBP of < 90mmHg or a reduction ≥ 10mmHg from baseline after completing study treatment was measured. Participants who achieved either of the above targets were deemed as having a successful response.	8 weeks of treatment
Number of Participants With Adverse Event	Participants were monitored for adverse events, serious adverse events and death.	8 weeks

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (Actual): May 1, 2013
• Study Completion (Actual): May 1, 2013

Study Registration Dates

• First Submitted: August 8, 2012
• First Submitted That Met QC Criteria: August 10, 2012
• First Posted (Estimate): August 13, 2012

Study Record Updates

• Last Update Posted (Estimate): October 23, 2015
• Last Update Submitted That Met QC Criteria: October 1, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: Essential hypertension; High blood pressure
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Essential Hypertension; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Angiotensin Receptor Antagonists; Amlodipine; Sacubitril and valsartan sodium hydrate drug combination
• Other Study ID Numbers: CLCZ696A2319