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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01663233
First received: August 8, 2012
Last updated: August 29, 2013
Last verified: August 2013
  Purpose

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.


Condition Intervention Phase
Essential Hypertension
Drug: LCZ696
Drug: Amlodipine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Change in mean 24-hour ABPM systolic blood pressure (maSBP) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Measure the change in mean 24 hour ambulatory systolic blood pressure (maSBP) from baseline to end of the study (week 8) in the 2 groups. A greater reduction from baseline in the LCZ696 group will indicate whether there is a positive treatment effect.


Secondary Outcome Measures:
  • Change in mean 24-hour ABPM diastolic blood pressure (maDBP) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Measure the change in mean 24 hour ambulatory diastolic blood pressure (maDBP) from baseline to end of the study. A reduction from baseline will indicate whether there is a positive treatment effect.

  • Change in mean sitting systolic blood pressure (msSBP) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Measure the change in the patient's mean sitting systolic blood pressure (msSBP) from baseline to end of the study. A reduction from baseline will indicate whether there is a positive treatment effect.

  • Change in mean sitting diastolic blood pressure (msDBP) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Measure the change in the patient's mean sitting diastolic blood pressure (msDBP) from baseline to end of the study. A reduction from baseline will indicate whether there is a positive treatment effect.

  • Change in sitting pulse pressure [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Measure the change in the patient's mean sitting pulse pressure from baseline to end of the study. Pulse pressure measures the difference in mean sitting systolic blood pressure and mean sitting diastolic blood pressure.

  • Percentage of patients achieving systolic and diastolic blood pressure control (< 140/90 mmHg) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    The Percentage of patients achieving a systolic and diastolic blood pressure < 140/90 mmHg is a measure of how well a given blood pressure treatment can achieve a given blood pressure target or goal. Patient that achieve the target blood pressure will be determined based on the mean sitting diastolic and systolic blood measurements taken at the end of the study. If the patient BP measurement is below the above target they will be considered as a success.

  • Percentage of patients achieving successful response in msSBP (< 140 mmHg or a reduction ≥ 20 mmHg from baseline) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    The percentage of patients that achieve successful treatment response in the mean sitting systolic blood pressure (msSBP) of < 140mmHg or a reduction ≥ 20 mmHg from baseline after completing study treatment. Patients that achieve either of the above targets will be deemed as a having a successful response.

  • Percentage of patients achieving successful response in msDBP (< 90 mmHg or a reduction ≥ 10 mmHg from baseline) [ Time Frame: 8 weeks of treatment ] [ Designated as safety issue: No ]
    The percentage of patients that achieve successful treatment response in the mean sitting diastolic blood pressure (msDBP) of < 90mmHg or a reduction ≥ 10mmHg from baseline after completing study treatment. Patients that achieve either of the above targets will be deemed as having a successful response.

  • Number of patients with adverse event [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
    Summarized statistics on adverse events will be reported under categories such as total adverse events, serious adverse events and death.


Enrollment: 266
Study Start Date: August 2012
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LCZ696 and amlodipine
118 patients will first be treated to receive 5 mg of amlodipine for 4 weeks to deter if that they are not adequately responding to amlodipine (must have a systolic BP >/= 145mmHg and meet all inclusion and exclusion criteria) will be randomized to receive 200mg of LCZ696 in combination with 5 mg of amlodipine for 8 weeks.
Drug: LCZ696
LCZ696 will used 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
118 patients will first be treated to receive 5 mg of amlodipine for 4 weeks to determine if that they are not adequately responding to amlodipine (must have a systolic BP >/= 145mmHg and meet all inclusion and exclusion criteria) will be randomized to receive 5 mg 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Patients must 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

  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: NCT01663233

Locations
China, Hebei
Novartis Investigative Site
Shijiazhuang, Hebei, China, 050000
China
Novartis Investigative Site
Chongqing, China, 400042
Novartis Investigative Site
Shanghai, China, 200025
Novartis Investigative Site
Tianjin, China, 300142
Japan
Novartis Investigative Site
Edogawa-ku, Tokyo, Japan, 133-0061
Novartis Investigative Site
Katsushika-ku, Tokyo, Japan, 124-0024
Novartis Investigative Site
Kiyose, 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
Korea, Republic of
Novartis Investigative Site
Wonju, Gangwon-Do, Korea, Republic of, 220-701
Novartis Investigative Site
Koyang, Kyunggi, Korea, Republic of, 410-719
Novartis Investigative Site
Busan, Korea, Republic of, 602-739
Novartis Investigative Site
Daegu, Korea, Republic of, 705-718
Novartis Investigative Site
Daegu, Korea, Republic of, 705-717
Novartis Investigative Site
Seoul, Korea, Republic of, 150-713
Malaysia
Novartis Investigative Site
Kuching, Sarawak, Malaysia, 94300
Novartis Investigative Site
Kuala Lumpur, Malaysia, 56000
Philippines
Novartis Investigative Site
Manila, Philippines, 1000
Novartis Investigative Site
Quezon City, Philippines, 1102
Novartis Investigative Site
Quezon City, Philippines, 1100
Novartis Investigative Site
Valenzuela City, Philippines, 1441
Taiwan
Novartis Investigative Site
Taipei, Taiwan, ROC, Taiwan, 112
Novartis Investigative Site
Taichung, Taiwan, 40447
Novartis Investigative Site
Taipei, Taiwan, 10002
Novartis Investigative Site
Taipei, Taiwan, 114
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: NCT01663233     History of Changes
Other Study ID Numbers: CLCZ696A2319
Study First Received: August 8, 2012
Last Updated: August 29, 2013
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency
China: Food and Drug Administration
Korea: Food and Drug Administration
Malaysia: Ministry of Health
Philippines: Bureau of Food and Drugs
Taiwan: Center for Drug Evaluation

Keywords provided by Novartis:
Essential hypertension
High blood pressure

Additional relevant MeSH terms:
Hypertension
Cardiovascular Diseases
Vascular Diseases
Amlodipine
Antihypertensive Agents
Calcium Channel Blockers
Cardiovascular Agents
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Vasodilator Agents

ClinicalTrials.gov processed this record on November 24, 2014