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

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Primary Purpose

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

LCZ696

Amlodipine

Placebo

About this trial

This is an interventional treatment trial for Essential Hypertension focused on measuring Essential hypertension, High blood pressure

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

LCZ696 and amlodipine

Amlodipine

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

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.

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.

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.

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.

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.

Number of Participants With Adverse Event

Participants were monitored for adverse events, serious adverse events and death.

Full Information

NCT ID

NCT01663233

First Posted

August 8, 2012

Last Updated

October 1, 2015

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT01663233

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2015

Overall Recruitment Status

Completed

Study Start Date

August 2012 (undefined)

Primary Completion Date

May 2013 (Actual)

Study Completion Date

May 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Essential Hypertension

Keywords

Essential hypertension, High blood pressure

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

266 (Actual)

8. Arms, Groups, and Interventions

Arm Title

LCZ696 and amlodipine

Arm Type

Experimental

Arm Description

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.

Arm Title

Amlodipine

Arm Type

Active Comparator

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

LCZ696

Intervention Description

LCZ696 will use tablets available at a strength of 200mg. Patients will be instructed to take the prescribed medication once a day.

Intervention Type

Drug

Intervention Name(s)

Amlodipine

Intervention Description

Amlodipine will use tablets available at a strength of 5 mg. Patients will be instructed to take the prescribed medication once a day.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Matching placebo to LCZ696

Primary Outcome Measure Information:

Title

Change in Mean 24-hour Ambulatory Blood Pressure Monitoring (ABPM) Systolic Blood Pressure (maSBP)

Description

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.

Time Frame

8 weeks

Secondary Outcome Measure Information:

Title

Change in Mean 24-hour ABPM Diastolic Blood Pressure (maDBP)

Description

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.

Time Frame

8 weeks

Title

Change in Mean Sitting Systolic Blood Pressure (msSBP)

Description

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.

Time Frame

8 weeks

Title

Change in Mean Sitting Diastolic Blood Pressure (msDBP)

Description

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.

Time Frame

8 weeks

Title

Change in Sitting Pulse Pressure (PP)

Description

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.

Time Frame

8 weeks

Title

Number of Participants Achieving Systolic and Diastolic Blood Pressure Control (< 140/90 mmHg)

Description

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.

Time Frame

8 weeks

Title

Number of Participants Achieving Successful Response in msSBP (< 140 mmHg or a Reduction ≥ 20 mmHg From Baseline)

Description

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.

Time Frame

8 weeks

Title

Number of Participants Achieving Successful Response in msDBP (< 90 mmHg or a Reduction ≥ 10 mmHg From Baseline)

Description

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.

Time Frame

8 weeks of treatment

Title

Number of Participants With Adverse Event

Description

Participants were monitored for adverse events, serious adverse events and death.

Time Frame

8 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Novartis Pharmaceuticals

Organizational Affiliation

Novartis Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

Novartis Investigative Site

City

Shijiazhuang

State/Province

Hebei

ZIP/Postal Code

050000

Country

China

Facility Name

Novartis Investigative Site

City

Chongqing

ZIP/Postal Code

400042

Country

China

Facility Name

Novartis Investigative Site

City

Shanghai

ZIP/Postal Code

200025

Country

China

Facility Name

Novartis Investigative Site

City

Tianjin

ZIP/Postal Code

300142

Country

China

Facility Name

Novartis Investigative Site

City

Edogawa-ku

State/Province

Tokyo

ZIP/Postal Code

133-0061

Country

Japan

Facility Name

Novartis Investigative Site

City

Katsushika-ku

State/Province

Tokyo

ZIP/Postal Code

124-0024

Country

Japan

Facility Name

Novartis Investigative Site

City

Kiyose-city

State/Province

Tokyo

ZIP/Postal Code

204-0021

Country

Japan

Facility Name

Novartis Investigative Site

City

Kunitachi

State/Province

Tokyo

ZIP/Postal Code

186-0001

Country

Japan

Facility Name

Novartis Investigative Site

City

Shibuya-ku

State/Province

Tokyo

ZIP/Postal Code

150-0002

Country

Japan

Facility Name

Novartis Investigative Site

City

Shinagawa-ku

State/Province

Tokyo

ZIP/Postal Code

142-0063

Country

Japan

Facility Name

Novartis Investigative Site

City

Toshima-ku

State/Province

Tokyo

ZIP/Postal Code

171-0021

Country

Japan

Facility Name

Novartis Investigative Site

City

Wonju

State/Province

Gangwon-Do

ZIP/Postal Code

220-701

Country

Korea, Republic of

Facility Name

Novartis Investigative Site

City

Koyang

State/Province

Kyunggi

ZIP/Postal Code

410-719

Country

Korea, Republic of

Facility Name

Novartis Investigative Site

City

Busan

ZIP/Postal Code

602-739

Country

Korea, Republic of

Facility Name

Novartis Investigative Site

City

Daegu

ZIP/Postal Code

705-703

Country

Korea, Republic of

Facility Name

Novartis Investigative Site

City

Daegu

ZIP/Postal Code

705-718

Country

Korea, Republic of

Facility Name

Novartis Investigative Site

City

Seoul

ZIP/Postal Code

150-713

Country

Korea, Republic of

Facility Name

Novartis Investigative Site

City

Kuching

State/Province

Sarawak

ZIP/Postal Code

94300

Country

Malaysia

Facility Name

Novartis Investigative Site

City

Kuala Lumpur

ZIP/Postal Code

56000

Country

Malaysia

Facility Name

Novartis Investigative Site

City

Quezon City

State/Province

Manila

ZIP/Postal Code

1100

Country

Philippines

Facility Name

Novartis Investigative Site

City

Manila

State/Province

Metro Manila

ZIP/Postal Code

1000

Country

Philippines

Facility Name

Novartis Investigative Site

City

Quezon City

ZIP/Postal Code

1100

Country

Philippines

Facility Name

Novartis Investigative Site

City

Quezon City

ZIP/Postal Code

1102

Country

Philippines

Facility Name

Novartis Investigative Site

City

Valenzuela City

ZIP/Postal Code

1441

Country

Philippines

Facility Name

Novartis Investigative Site

City

Taipei

State/Province

Taiwan, ROC

ZIP/Postal Code

112

Country

Taiwan

Facility Name

Novartis Investigative Site

City

Taichung

ZIP/Postal Code

40447

Country

Taiwan

Facility Name

Novartis Investigative Site

City

Taipei

ZIP/Postal Code

10002

Country

Taiwan

Facility Name

Novartis Investigative Site

City

Taipei

ZIP/Postal Code

114

Country

Taiwan

Essential Hypertension

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial