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

Essential Hypertension Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01663233
• Other study ID #: CLCZ696A2319
• Status: Completed
• Phase: Phase 3
• First received: August 8, 2012
• Last updated: October 1, 2015
• Start date: August 2012
• Est. completion date: May 2013

Study information

• Verified date: October 2015
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Pharmaceuticals and Medical Devices AgencyChina: Food and Drug AdministrationKorea: Food and Drug AdministrationMalaysia: Ministry of HealthPhilippines: Bureau of Food and DrugsTaiwan: Center for Drug Evaluation
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 266
• Est. completion date: May 2013
• Est. primary completion date: May 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Essential Hypertension
• Hypertension

Intervention

Drug:
• LCZ696
LCZ696 will use tablets available at a strength of 200mg. Patients will be instructed to take the prescribed medication once a day.
• Amlodipine
Amlodipine will use tablets available at a strength of 5 mg. Patients will be instructed to take the prescribed medication once a day.
• Placebo
Matching placebo to LCZ696

Locations

Country	Name	City	State
China	Novartis Investigative Site	Chongqing
China	Novartis Investigative Site	Shanghai
China	Novartis Investigative Site	Shijiazhuang	Hebei
China	Novartis Investigative Site	Tianjin
Japan	Novartis Investigative Site	Edogawa-ku	Tokyo
Japan	Novartis Investigative Site	Katsushika-ku	Tokyo
Japan	Novartis Investigative Site	Kiyose-city	Tokyo
Japan	Novartis Investigative Site	Kunitachi	Tokyo
Japan	Novartis Investigative Site	Shibuya-ku	Tokyo
Japan	Novartis Investigative Site	Shinagawa-ku	Tokyo
Japan	Novartis Investigative Site	Toshima-ku	Tokyo
Korea, Republic of	Novartis Investigative Site	Busan
Korea, Republic of	Novartis Investigative Site	Daegu
Korea, Republic of	Novartis Investigative Site	Daegu
Korea, Republic of	Novartis Investigative Site	Koyang	Kyunggi
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Wonju	Gangwon-Do
Malaysia	Novartis Investigative Site	Kuala Lumpur
Malaysia	Novartis Investigative Site	Kuching	Sarawak
Philippines	Novartis Investigative Site	Manila	Metro Manila
Philippines	Novartis Investigative Site	Quezon City
Philippines	Novartis Investigative Site	Quezon City
Philippines	Novartis Investigative Site	Quezon City	Manila
Philippines	Novartis Investigative Site	Valenzuela City
Taiwan	Novartis Investigative Site	Taichung
Taiwan	Novartis Investigative Site	Taipei
Taiwan	Novartis Investigative Site	Taipei
Taiwan	Novartis Investigative Site	Taipei	Taiwan, ROC

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

China,  Japan,  Korea, Republic of,  Malaysia,  Philippines,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Number of Participants With Adverse Event	Participants were monitored for adverse events, serious adverse events and death.	8 weeks	Yes