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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01615198
First received: June 6, 2012
Last updated: October 28, 2013
Last verified: October 2013
  Purpose

The purpose of this study is to access the efficacy and safety of LCZ696 compared to olmesartan in elderly Asian patients for the treatment of hypertension.


Condition Intervention Phase
Essential Hypertension
Drug: Olmersartan
Drug: Placebo
Drug: LCZ696
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A 14 Week, Randomized, Double-blind, Multi-center, Parallel Group, Active Controlled Study to Evaluate the Efficacy and Safety of LCZ696 in Comparison to Olmesartan in Elderly Patients With Essential Hypertension

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Change from baseline in mean sitting systolic blood pressure (msSBP) [ Time Frame: Baseline, 10 weeks ] [ Designated as safety issue: No ]
    Sitting BP measurements will be performed at trough (immediately prior to dosing at the clinic). At study entry BP should be measured in both arms. The arm with the higher SBP reading should be used for the 4 measurements at screening visit and the same arm should be used at all subsequent visits.


Secondary Outcome Measures:
  • Change from baseline in mean 24 hour ambulatory systolic blood pressure (maSBP) [ Time Frame: Baseline, 10 weeks ] [ Designated as safety issue: No ]
    ABPM over a 24-hour period will be conducted at two time-points during the study in a subset of patients. Readings will be taken every 20 minutes over the 24 hour period in the non-dominant arm.

  • Change from baseline in mean sitting systolic blood pressure (msSBP) and mean sitting diastolic blood pressure (msDBP) [ Time Frame: Baseline to 4 weeks, 14 weeks ] [ Designated as safety issue: No ]
    Sitting BP measurements will be performed at trough (immediately prior to dosing at the clinic). At study entry BP should be measured in both arms. The arm with the higher SBP reading should be used for the 4 measurements at screening visit and the same arm should be used at all subsequent visits.

  • Change in baseline in mean 24 hour ambulatory diastolic blood pressure (maDBP) [ Time Frame: Baseline, 10 weeks ] [ Designated as safety issue: No ]
    ABPM over a 24-hour period will be conducted at two time-points during the study in a subset of patients. Readings will be taken every 20 minutes over the 24 hour period in the non-dominant arm.

  • Change from baseline in mean sitting diastolic blood pressure (msDBP) [ Time Frame: Baseline, 10 weeks ] [ Designated as safety issue: No ]
    Sitting BP measurements will be performed at trough (immediately prior to dosing at the clinic). At study entry BP should be measured in both arms. The arm with the higher SBP reading should be used for the 4 measurements at screening visit and the same arm should be used at all subsequent visits.

  • Office pulse pressure measurement [ Time Frame: 4 weeks, 10 weeks, 14 weeks ] [ Designated as safety issue: No ]
    Pulse rate will be taken with automated BP device after the 4th blood pressure measurement at each visit

  • Change from baseline in daytime and nighttime maSBP/maDBP [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
    ABPM over a 24-hour period will be conducted at two time-points during the study in a subset of patients. Readings will be taken every 20 minutes over the 24 hour period in the non-dominant arm.

  • Change from baseline in maSBP and maDBP for daytime/nightime [ Time Frame: Baseline, 10 weeks ] [ Designated as safety issue: No ]
    ABPM over a 24-hour period will be conducted at two time-points during the study in a subset of patients. Readings will be taken every 20 minutes over the 24 hour period in the non-dominant arm.

  • The precentage of patients achieving overall blood pressure control in mean sitting systolic blood pressure (msSBP) and mean sitting diastolic blood pressure (msDBP) [ Time Frame: 4 weeks, 10 weeks, 14 weeks ] [ Designated as safety issue: No ]
    A successful response in overall BP control rate defined as msSBP < 140 mmHg and msDBP <90 mmHg

  • Percentage of patients achieving successful response in diastolic blood pressure (msDBP) [ Time Frame: 4 weeks,10 weeks, 14 weeks ] [ Designated as safety issue: No ]
    A successful response in overall BP control rate defined as msSBP (<140 mmHg or a reduction ≥ 20 mmHg from baseline) and msDBP (< 90 mmHg or a reduction ≥ 10 mmHg from baseline).

  • Number of patients with adverse events, serius adverse events and death [ Time Frame: 14 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 588
Study Start Date: August 2012
Study Completion Date: July 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LCZ696
Patients will be treated with one LCZ696 100 mg tablet and one placebo of LCZ696 qd for 4 weeks along with placebo of Olmesartan 10 mg capsule qd. Patients will then be up-titrated to LCZ 200 mg tablet and one placebo of LCZ696 qd for 8 weeks along with placebo of Olmesartan 20 mg capsule qd. Those patients not at goal BP will be uptitrated to 2 LCZ696 200 mg tablets (LCZ696 400 mg) qd for 4 weeks along with placebo of Olmesartan 40 mg capsule qd.
Drug: Placebo
Matching placebo of LCZ696 tablet, matching placebo of Olmersartan capsule
Drug: LCZ696
100 mg, 200 mg tablets
Active Comparator: Olmersartan
Patients will be treated with olmesartan 10 mg qd for 4 weeks along with 2 placebo of LCZ696 tablets qd. Patients will then be uptitrated to olmesartaan 20 mg qd for 8 weeks along with 2 placebo of LCZ696 tablets qd. Those patients not at the goal BP will be uptitrated to olmesartan 40 mg qd for the remaining 4 weeks and 2 placebo LCZ696 tablets qd.
Drug: Olmersartan
10 mg, 20 mg, 40 mg capsules
Drug: Placebo
Matching placebo of LCZ696 tablet, matching placebo of Olmersartan capsule

  Eligibility

Ages Eligible for Study:   65 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must give written informed consent before any assessment is performed
  • Patients with essential hypertension, untreated or currently taking antihypertensive therapy must have a mean sitting systolic blood pressure ≥ 150 mmHg and < 180 mmHg
  • Patients must be able to communicate and comply with all study requirements and demonstrate good medication compliance

Exclusion criteria:

  • Patients with severe hypertension. Patients with history of angioedema, drug-related or otherwise
  • Patients with 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 any percutaneous coronary intervention (PCI) during the 12 months prior to Visit 1.
  • Current angina pectoris requiring medication (other than patients on a stable dose of oral or topical nitrates).
  • Patients with Type 1 or Type 2 diabetes mellitus who are not well controlled and are not on a stable dose of antidiabetic medication
  • Patients with previous or current diagnosis of heart failure (NYHA Class II-IV).
  • Patients with a clinically significant valvular heart disease at the time of screening
  • Women of child-bearing potential, who do not use adequate birth control methods Other protocol-defined inclusion/exclusion criteria may apply
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01615198

  Show 78 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01615198     History of Changes
Other Study ID Numbers: CLCZ696A2316
Study First Received: June 6, 2012
Last Updated: October 28, 2013
Health Authority: China: Food and Drug Administration
Korea: Food and Drug Administration
Japan: Pharmaceuticals and Medical Devices Agency, Ministry of Health, Labor and Welfare
Taiwan: Department of Health
Thailand: Ministry of Public Health
Hong Kong: Department of Health
Philippines: Department of Health

Keywords provided by Novartis:
Hypertension, blood pressure, LCZ696, dual inhibitor, neprilysin, NEP inhibition, vasopeptidase, ARNi, angiotensin receptor

Additional relevant MeSH terms:
Hypertension
Cardiovascular Diseases
Vascular Diseases
Olmesartan
Olmesartan medoxomil
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Antihypertensive Agents
Cardiovascular Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014