Efficacy and Safety of LCZ696 Compared to Olmesartan in Essential Hypertensive Patients Not Responsive to Olmesartan

A Randomized 8-week Double-blind, Parallel-group, Active-controlled, Multicenter Study to Evaluate Efficacy and Safety of LCZ696 200 mg in Comparison With Olmesartan 20 mg in Essential Hypertensive Patients Not Responsive to Olmesartan

This study will assess the efficacy and safety of LCZ696 in comparison to olmesartan in essential hypertensive patients not adequately responsive to olmesartan

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 376
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos aires, Argentina, C1120AAC
    • Novartis Investigative Site
  • Corrientes, Argentina, W3400
    • Novartis Investigative Site
  • Buenos Aires
    • Caba, Buenos Aires, Argentina, C1429BWN
      • Novartis Investigative Site
    • Ciudad Autonoma de Bs As, Buenos Aires, Argentina, C1119ACN
      • Novartis Investigative Site
    • Ciudad Autonoma de Bs As, Buenos Aires, Argentina, C1430AAQ
      • Novartis Investigative Site
  • Capital Federal
    • Caba, Capital Federal, Argentina, C1425FVH
      • Novartis Investigative Site
  • Misiones
    • Posadas, Misiones, Argentina, N3300AHX
      • Novartis Investigative Site
• Guatemala
  • Guatemala City, Guatemala, 01010
    • Novartis Investigative Site
  • Guatemala City, Guatemala, 01001
    • Novartis Investigative Site
• Philippines
  • Quezon City, Philippines, 1102
    • Novartis Investigative Site
  • Quezon City, Philippines, 1100
    • Novartis Investigative Site
  • Manila
    • Quezon City, Manila, Philippines, 1100
      • Novartis Investigative Site
  • Metro Manila
    • Manila, Metro Manila, Philippines, 1000
      • Novartis Investigative Site
• Puerto Rico
  • Manati, Puerto Rico, 00674
    • Novartis Investigative Site
  • Ponce, Puerto Rico, 00717
    • Novartis Investigative Site
  • Ponce, Puerto Rico, 00716
    • Novartis Investigative Site
• Russian Federation
  • Moscow, Russian Federation, 117198
    • Novartis Investigative Site
  • Moscow, Russian Federation, 129301
    • Novartis Investigative Site
  • Moscow, Russian Federation, 101990
    • Novartis Investigative Site
  • Moscow, Russian Federation, 111539
    • Novartis Investigative Site
  • Saint Petersburg, Russian Federation, 199106
    • Novartis Investigative Site
  • Saratov, Russian Federation, 410012
    • Novartis Investigative Site
  • St.- Petersburg, Russian Federation, 197110
    • Novartis Investigative Site
• Spain
  • Madrid, Spain, 28046
    • Novartis Investigative Site
  • Andalucia
    • Sevilla, Andalucia, Spain, 41009
      • Novartis Investigative Site
  • Cataluña
    • Centelles, Cataluña, Spain, 08540
      • Novartis Investigative Site
    • Hostalets de Balenya, Cataluña, Spain, 08550
      • Novartis Investigative Site
  • Comunidad Valenciana
    • Alzira, Comunidad Valenciana, Spain, 46600
      • Novartis Investigative Site
  • Galicia
    • Santiago de Compostela, Galicia, Spain, 15706
      • Novartis Investigative Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-2041
      • Novartis Investigative Site
  • California
    • Fair Oaks, California, United States, 95628
      • Novartis Investigative Site
    • Hawaiian Gardens, California, United States, 90716
      • Novartis Investigative Site
    • Long Beach, California, United States, 90806
      • Novartis Investigative Site
    • Los Angeles, California, United States, 90057
      • Novartis Investigative Site
    • Orangevale, California, United States, 95662
      • Novartis Investigative Site
    • Westlake Village, California, United States, 91361
      • Novartis Investigative Site
  • Colorado
    • Denver, Colorado, United States, 80206
      • Novartis Investigative Site
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Novartis Investigative Site
    • Conyers, Georgia, United States, 30094
      • Novartis Investigative Site
  • Illinois
    • Chicago, Illinois, United States, 60607
      • Novartis Investigative Site
    • Chicago, Illinois, United States, 60610
      • Novartis Investigative Site
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Novartis Investigative Site
  • Minnesota
    • Edina, Minnesota, United States, 55435
      • Novartis Investigative Site
  • Mississippi
    • Belzoni, Mississippi, United States, 39038
      • Novartis Investigative Site
    • Jackson, Mississippi, United States, 39209
      • Novartis Investigative Site
  • New York
    • New York, New York, United States, 10708
      • Novartis Investigative Site
  • Ohio
    • Cincinnati, Ohio, United States, 45246
      • Novartis Investigative Site
  • Oregon
    • Oregon City, Oregon, United States, 97045
      • Novartis Investigative Site
    • Portland, Oregon, United States, 97225
      • Novartis Investigative Site
  • South Carolina
    • Varnville, South Carolina, United States, 29944
      • Novartis Investigative Site
  • Virginia
    • Richmond, Virginia, United States, 23294
      • 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 with mild to moderate hypertension, untreated or currently taking antihypertensive therapy
• treated patients (using antihypertensive drugs within 4 weeks prior to first visit) must have an office msSBP ≥ 145 mmHg and < 180 mmHg after washout epoch and after 4 weeks run-in epoch
• untreated patients (either newly diagnosed or those patients with a history of hypertension but have not been taking any antihypertensive drugs for at least 4 weeks prior to first visit) must have an offcie msSBP ≥ 150 mmHg and < 180 mmHg at screening and 1 week after screening and must have an office msSBP ≥ 145 mmHg and < 180 mmHg after 4 weeks run-in epoch
• patients must successfully complete ABPM and pass technical requirements to be qualified for randomization

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, 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 (PKD), drug-induced hypertension
• Patients who previously entered a LCZ696 study and had been randomized or enrolled to receive active drug treatment

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LCZ696 200 mg; Patients will be treated with one LCZ696 200 mg tablet and one placebo of olmesartan 20 mg capsule once daily for 8 weeks.	Drug: Placebo of LCZ696; Drug: LCZ696
Active Comparator: Olmesartan 20 mg; Patients will be treated with one placebo of LCZ696 200 mg tablet and one olmesartan 20 mg capsule once daily for 8 weeks.	Drug: Placebo of Olmesartan; Drug: Olmesartan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in 24-hour Mean Ambulatory Systolic Blood Pressure (maSBP)	Twenty-four hour mean ambulatory blood pressure measurements (ABPM) will be performed at baseline and at end of study (week 8). The first 24-hour ABPM will be performed beginning at 24 hours prior to baseline visit and the second will be performed 24 hours prior to week 8 visit.	baseline, 8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Mean 24-hour Ambulatory Diastolic Blood Pressure (maDBP)	Twenty-four hour mean ambulatory blood pressure measurements (ABPM) will be performed at baseline and at end of study (week 8). The 24-hour ABPM measurements are performed beginning 24 hours prior to baseline and week 8 visits.	baseline, 8 weeks
Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP)	Sitting blood pressure (BP) measurement will be taken at every visit from screening through end of study. For each participant at each visit, four separate sitting BP measurements will be obtained (with a full two minute interval between measurements) and averaged to obtain the mean	baseline, 8 weeks
Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP)	Sitting blood pressure (BP) measurement will be taken at every visit from screening through end of study. For each participant at each visit, four separate sitting BP measurements will be obtained (with a full two minute interval between measurements) and averaged to obtain the mean	baseline, 8 weeks
Change From Baseline in Office Pulse Pressure	Mean sitting pulse pressure (msPP) will be calculated at screening through end of study at every visit. Mean sitting pulse pressure is calculated as msSBP-msDBP.	baseline, 8 weeks
Number of Patients Achieving Successful Overall Blood Pressure Control	Successful overall blood pressure control is defined as both msSBP/msDBP <140/90 mmHg	8 weeks
Number of Patients Achieving Successful Mean Sitting Systolic Blood Pressure (msSBP) Control	Successful mean sitting systolic blood pressure control is defined as msSBP <140 mmHg	8 weeks
Number of Patients Achieving Successful Mean Sitting Diastolic Blood Pressure (msDBP) Control	Successful mean sitting diastolic blood pressure control is defined as msDBP <90 mmHg	8 weeks
Number of Patients Achieving Successful Mean Sitting Systolic Blood Pressure (msSBP) Response	Successful mean sitting systolic blood pressure response is defined as msSBP <140 mmHg or a reduction ≥ 20 mmHg from baseline.	baseline, 8 weeks
Number of Patients Achieving Successful Mean Sitting Diastolic Blood Pressure (msDBP) Response	Successful mean sitting diastolic blood pressure response is defined as msDBP <90 mmHg or a reduction ≥10 mmHg from baseline.	baseline, 8 weeks
Number of Patients With Total Adverse Events, Serious Adverse Events and Death	Number of patients with total adverse events, serious adverse events and death were reported.	8 weeks

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: September 1, 2013
• Primary Completion (Actual): August 1, 2014
• Study Completion (Actual): August 1, 2014

Study Registration Dates

• First Submitted: June 9, 2013
• First Submitted That Met QC Criteria: June 9, 2013
• First Posted (Estimate): June 12, 2013

Study Record Updates

• Last Update Posted (Estimate): December 7, 2015
• Last Update Submitted That Met QC Criteria: November 3, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: LCZ696,; olmesartan; hypertension,
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Olmesartan; Olmesartan Medoxomil; Sacubitril and valsartan sodium hydrate drug combination
• Other Study ID Numbers: CLCZ696A2318; 2013-001783-36 (EudraCT Number)