Study of the Efficacy and Safety of LCZ696 Alone and in Combination With Amlodipine in Patients With Hypertension

Hypertension Clinical Trial

Official title:

An 8-week Randomized, Double-blind, Placebo-controlled Factorial Study to Evaluate the Efficacy and Safety of LCZ696 Alone and in Combination With Amlodipine in Patients With Essential Hypertension

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01865188
• Other study ID #: CLCZ696A2320
• Secondary ID: 2013-001643-30
• Status: Withdrawn
• Phase: Phase 3
• First received: May 24, 2013
• Last updated: August 4, 2014
• Start date: April 2014
• Est. completion date: April 2015

Study information

• Verified date: August 2014
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Argentina: Ministry of HealthBrazil: Ministry of HealthColombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y AlimentosDominican Republic: Secretaría del Estado de Salud Pública y Asistencia Social (SESPAS)Ecuador: Public Health MinistryGuatemala: Ministry of Public Health and Social AssistanceMexico: Ministry of HealthPanama: Ministry of HealthPeru: Ministry of HealthPhilippines: Bureau of Food and DrugsRussia: Pharmacological Committee, Ministry of HealthSouth Africa: Department of HealthSolvak Republic: Ethics CommitteeSpain: Ministry of HealthThailand: Food and Drug AdministrationVietnam: Ministry of HealthUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

To evaluate the blood pressure lowering effect and safety of LCZ696 when given alone and in combination with amlodipine in patients with essential hypertension.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: April 2015
• Est. primary completion date: April 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Male or female outpatients

2. Patients with mild-to-moderate hypertension, untreated or currently taking antihypertensive therapy

3. Treated patients (using antihypertensive treatments within 4 weeks prior to Visit 1) must have an msSBP =150 mmHg and <180 mmHg at the randomization visit and msSBP =140 mmHg <180 mmHg at the preceding visit.

4. Untreated patients (newly diagnosed with essential hypertension or having a history of hypertension but have not been taking any antihypertensive drugs for at least 4 weeks prior to Visit 1) must have an msSBP =150 mmHg and <180 mmHg at both the randomization visit and the preceding visit.

5. Patients must have an absolute difference of =15 mmHg in msSBP between the randomization visit and the preceding visit.

6. Ability to communicate and comply with all study requirements and demonstrate good medication compliance (= 80% compliance rate) during the treatment run-in period.

Exclusion Criteria:

1. Severe hypertension (msDBP =110 mmHg and/or msSBP = 180 mmHg)

2. History of angioedema, drug-related or otherwise

3. 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, and drug-induced hypertension

4. Transient ischemic cerebral attack (TIA) during the 12 months prior to Visit 1 or any history of stroke

5. History of myocardial infarction, coronary bypass surgery or any percutaneous coronary intervention (PCI) during the 12 months prior to Visit 1

6. Pregnant or lactating women

7. Women of child-bearing potential not using highly effective methods of contraception Other protocol defined inclusion/exclusion criteria may apply

Study Design

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

Related Conditions & MeSH terms

• Hypertension

Intervention

Drug:
• LCZ696
Experimental monotherapy doses
• Amlodipine
Active comparator monotherapy doses
• LCZ696 and amlodipine combination
Experimental combination doses
• Placebo
Placebo comparator dose

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in mean sitting systolic blood pressure (msSBP) of LCZ696 monotherapy compared to placebo	Sitting blood pressure will be measured at trough (immediately prior to dosing at clinic) and recorded at all study visits. At the first study visit, blood pressure will be measured in both arms and the arm with highest sitting SBP will be found and used for all subsequent readings throughout the study. The 4 repeat sitting measurements will be made at 2 minute intervals and the mean of these four sitting systolic blood pressure measurements will be used as the mean sitting systolic blood pressure for that visit.	baseline, 8 weeks	No
Primary	Change from baseline in mean sitting systolic blood pressure (msSBP) of the combination of LCZ696 and amlodipine compared to LCZ696 and amlodipine alone.	Sitting blood pressure will be measured at trough (immediately prior to dosing at clinic) and recorded at all study visits. The 4 repeat sitting measurements will be made at 2 minute intervals and the mean of these four sitting systolic blood pressure measurements will be used as the mean sitting systolic blood pressure for that visit.	baseline, 8 weeks	No
Secondary	Change from baseline in mean sitting Diastolic Blood Pressure (msDBP) of LCZ696 monotherapy compared to placebo	Sitting blood pressure will be measured at trough (immediately prior to dosing at clinic) and recorded at all study visits. The 4 repeat sitting measurements will be made at 2 minute intervals and the mean of these four sitting diastolic blood pressure measurements will be used as the mean sitting diastolic blood pressure for that visit.	baseline, 8 weeks	No
Secondary	Change from baseline in mean sitting Diastolic Blood Pressure of the combination of LCZ696 and amlodipine compared to LCZ696 and amlodipine alone	Sitting blood pressure will be measured at trough (immediately prior to dosing at clinic) and recorded at all study visits. The 4 repeat sitting measurements will be made at 2 minute intervals and the mean of these four sitting diastolic blood pressure measurements will be used as the mean sitting diastolic blood pressure for that visit.	baseline, 8 weeks	No
Secondary	Change from baseline in pulse pressure	Pulse pressure will be calculated as the difference between msSBP and msDBP for both office BP and ABPM.	baseline, 8 weeks	No
Secondary	Change from baseline in mean 24-hour ambulatory Systolic Blood Pressure of LCZ696 monotherapy compared to placebo	The ABPM cuff will be placed on the non-dominant arm between approximately 7:00 am and 11:00 am and the device will measure blood pressure 3 times per hour for 24 hours.	baseline, 8 weeks	No
Secondary	Change from baseline in mean 24-hour ambulatory Diastolic Blood Pressure of LCZ696 monotherapy compared to placebo	The ABPM cuff will be placed on the non-dominant arm between approximately 7:00 am and 11:00 am and the device will measure blood pressure 3 times per hour for 24 hours.	baseline, 8 weeks	No
Secondary	Change from baseline in mean daytime ( > 6am and = 10 pm) ambulatory Systolic Blood Pressure of LCZ696 monotherapy compared to placebo	The ABPM cuff will be placed on the non-dominant arm between approximately 7:00 am and 11:00 am and the device will measure blood pressure 3 times per hour for 24 hours.	baseline, 8 weeks	No
Secondary	Change from baseline in mean daytime ( > 6am and = 10 pm) ambulatory Diastolic Blood Pressure of LCZ696 monotherapy compared to placebo	The ABPM cuff will be placed on the non-dominant arm between approximately 7:00 am and 11:00 am and the device will measure blood pressure 3 times per hour for 24 hours.	baseline, 8 weeks	No
Secondary	Change from baseline in mean nighttime (> 10 pm and = 6 am) ambulatory Systolic Blood Pressure of LCZ696 monotherapy compared to placebo	The ABPM cuff will be placed on the non-dominant arm between approximately 7:00 am and 11:00 am and the device will measure blood pressure 3 times per hour for 24 hours.	baseline, 8 weeks	No
Secondary	Change from baseline in mean nighttime (> 10 pm and = 6 am) ambulatory Diastolic Blood Pressure of LCZ696 monotherapy compared to placebo	The ABPM cuff will be placed on the non-dominant arm between approximately 7:00 am and 11:00 am and the device will measure blood pressure 3 times per hour for 24 hours.	baseline, 8 weeks	No
Secondary	Change from baseline in trough to peak ratio of mean 24-hour ambulatory Systolic Blood Pressure of LCZ696 monotherapy compared to placebo	The trough to peak ratio of mean 24-hour ambulatory Systolic Blood Pressure will be calculated using the systolic blood pressure effects at trough (post-dosing hour 24) compared to the maximum systolic blood pressure effect found in the hours after dosing.	baseline, 8 weeks	No
Secondary	Change from baseline in trough to peak ratio of mean 24-hour ambulatory Diastolic Blood Pressure of LCZ696 monotherapy compared to placebo	The trough to peak ratio of mean 24-hour ambulatory Diastolic Blood Pressure will be calculated using the diastolic blood pressure effects at trough (post-dosing hour 24) compared to the maximum diastolic blood pressure effect found in the hours after dosing.	baseline, 8 weeks	No
Secondary	Change from baseline in mean 24-hour ambulatory Systolic Blood Pressure of the combination of LCZ696 and amlodipine compared to LCZ696 and amlodipine alone	The ABPM cuff will be placed on the non-dominant arm between approximately 7:00 am and 11:00 am and the device will measure blood pressure 3 times per hour for 24 hours.	baseline, 8 weeks	No
Secondary	Change from baseline in mean 24-hour ambulatory Diastolic Blood Pressure of the combination of LCZ696 and amlodipine compared to LCZ696 and amlodipine alone	The ABPM cuff will be placed on the non-dominant arm between approximately 7:00 am and 11:00 am and the device will measure blood pressure 3 times per hour for 24 hours.	baseline, 8 weeks	No
Secondary	Change from baseline in mean daytime ( > 6am and = 10 pm) ambulatory Systolic Blood Pressure of the combination of LCZ696 and amlodipine compared to LCZ696 and amlodipine alone	The ABPM cuff will be placed on the non-dominant arm between approximately 7:00 am and 11:00 am and the device will measure blood pressure 3 times per hour for 24 hours.	baseline, 8 weeks	No
Secondary	Change from baseline in mean daytime ( > 6am and = 10 pm) ambulatory Diastolic Blood Pressure of the combination of LCZ696 and amlodipine compared to LCZ696 and amlodipine alone	The ABPM cuff will be placed on the non-dominant arm between approximately 7:00 am and 11:00 am and the device will measure blood pressure 3 times per hour for 24 hours.	baseline, 8 weeks	No
Secondary	Change from baseline in mean nighttime (> 10 pm and = 6 am) ambulatory Systolic Blood Pressure of the combination of LCZ696 and amlodipine compared to LCZ696 and amlodipine alone	The ABPM cuff will be placed on the non-dominant arm between approximately 7:00 am and 11:00 am and the device will measure blood pressure 3 times per hour for 24 hours.	baseline, 8 weeks	No
Secondary	Change from baseline in mean nighttime (> 10 pm and = 6 am) ambulatory Diastolic Blood Pressure of the combination of LCZ696 and amlodipine compared to LCZ696 and amlodipine alone	The ABPM cuff will be placed on the non-dominant arm between approximately 7:00 am and 11:00 am and the device will measure blood pressure 3 times per hour for 24 hours.	baseline, 8 weeks	No
Secondary	Percentage of patients achieving msSBP <140 mmHg and msDBP <90 mmHg	The percentage of patients achieving blood pressure control (msSBP <140 mmHg and msDBP <90 mmHg) after 8 weeks of treatment will be calculated.	8 weeks	No
Secondary	Percentage of patients achieving msSBP <140 mmHg or a reduction =20 mmHg from baseline	The percentage of patients achieving a successful response in msSBP (msSBP <140 mmHg or a reduction =20 mmHg from baseline) after 8 weeks of treatment will be calculated.	Baseline, 8 weeks	No
Secondary	Percentage of patients achieving msDBP <90 mmHg or a reduction =10 mmHg from baseline	The percentage of patients achieving a successful response in msSBP (msDBP <90 mmHg or a reduction =10 mmHg from baseline) after 8 weeks of treatment will be calculated.	Baseline, 8 weeks	No
Secondary	Number of patients reporting adverse events	As an assessment of safety of monotherapy and combination therapy of LCZ696, total adverse events, serious adverse events and deaths after 8 weeks of treatment will be reported .	8 weeks	Yes