An 8-week study to evaluate the efficacy (blood pressure lowering effect) and safety of LCZ696 given alone and in combination with amlodipine

• Register: EUCTR
• Last refreshed on: 5 August 2014
• Main ID: EUCTR2013-001643-30-ES
• Date of registration: 12/07/2013
• Prospective Registration: Yes
• Primary sponsor: Novartis Farmacéutica S. A
• Public title: An 8-week study to evaluate the efficacy (blood pressure lowering effect) and safety of LCZ696 given alone and in combination with amlodipine
• Scientific 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
• Date of first enrolment: 29/08/2013
• Target sample size: 1386
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-001643-30
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no Number of treatment arms in the trial: 9

Countries of recruitment

Argentina, Brazil, Colombia, Dominican Republic, Ecuador, Guatemala, Mexico, Panama, Peru, Philippines, Russian Federation, Slovakia, South Africa, Spain, Thailand, Vietnam

Contacts

• Name: departamento Médico
• Affiliation: Novartis Farmacéutica S.A

• Name: departamento Médico
• Affiliation: Novartis Farmacéutica S.A

Key inclusion & exclusion criteria

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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 1100
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 286

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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Essential hypertension
MedDRA version: 16.0 Level: PT Classification code 10015488 Term: Essential hypertension System Organ Class: 10047065 - Vascular disorders

Intervention(s)

Product Code: LCZ696
Pharmaceutical Form: Tablet
INN or Proposed INN: NA
CAS Number: 936623-90-4
Current Sponsor code: LCZ696
Other descriptive name: LCZ696
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Trade Name: Amlodipine Hexal
Product Name: amlodipine besylate
Pharmaceutical Form: Tablet
INN or Proposed INN: NA
Other descriptive name: AMLODIPINE BESILATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): 1.Change from baseline in mean sitting systolic blood pressure (msSBP) of LCZ696 monotherapy compared to placebo.
2.Change from baseline in mean sitting systolic blood pressure (msSBP) of the combination of LCZ696 and amlodipine compared to LCZ696 and amlodipine alone.

Timepoint(s) of evaluation of this end point: 1.at baseline, 8 weeks
2.at baseline, 8 weeks

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

Secondary Objective: 1.evaluate efficacy of LCZ696 cmp to placebo, measured by change in mean sitting BP (msDBP) from BS after 8 weeks treatment in patients with essential HT.
2.evaluate efficacy of combination of LCZ696 and amlodipine cmp to monotherapy, measured by change msDBP from BS after 8 weeks treatment in pts with essential HT.
3.evaluate office and ambulatory pulse pressure for all trtment groups after 8 wks trtment.
4.evaluate efficacy of LCZ696 cmp to placebo, measured by change in mean 24-hour ambulatory (maSBP), mean 24-hour ambulatory (maDBP), daytime and nighttime maSBP/maDBP, trough/peak ratios of maSBP and maDBP from baseline after 8 wks trtment in a subset of patients with essential HT.
5.evaluate efficacy of combination of LCZ696 and amlodipine compared to monotherapy, measured by change in mean 24-hour ambulatory maSBP), mean 24-hour ambulatory (maDBP), daytime and nighttime maSBP/maDBP from baseline after 8 weeks treatment in a subset of patients with essential HT.

Secondary Outcome(s)

Secondary end point(s): 1. To evaluate the efficacy of LCZ696 200mg and 400mg compared to placebo, as measured by change in mean sitting diastolic BP (msDBP) from baseline after 8 weeks of treatment in patients with essential hypertension.
2. To evaluate the efficacy of combination of LCZ696 and amlodipine (200/5mg, 200/10mg, 400/5mg and 400/10 mg) compared to monotherapy, as measured by change in msDBP from baseline after 8 weeks of treatment in patients with essential hypertension.
3. To evaluate office and ambulatory pulse pressure for all treatment groups after 8 weeks of treatment.
4. To evaluate the efficacy of LCZ696 200mg and 400mg compared to placebo, as measured by change in mean 24-hour ambulatory SBP (maSBP), mean 24-hour ambulatory DBP (maDBP), daytime and nighttime maSBP/maDBP, trough/peak ratios of maSBP and maDBP from baseline after 8 weeks of treatment in a subset of patients with essential hypertension.
5. To evaluate the efficacy of combination of LCZ696 and amlodipine (200/5mg, 200/10mg, 400/5mg and 400/10 mg) compared to monotherapy, as measured by change in mean 24-hour ambulatory SBP (maSBP), mean 24-hour ambulatory DBP (maDBP), daytime and nighttime maSBP/maDBP from baseline after 8 weeks of treatment in a subset of patients with essential hypertension.
6. To assess the proportion of patients achieving blood pressure control (msSBP<140 mmHg and msDBP <90 mmHg) for all treatment groups after 8 weeks of treatment.
7. To assess the proportion of patients achieving a successful response in msSBP (< 140 mmHg or a reduction ? 20 mmHg from baseline) for all treatment groups after 8 weeks of treatment.
8. To assess the proportion of patients achieving a successful response (msDBP < 90 mmHg or a reduction ? 10 mmHg from baseline) for all treatment groups after 8 weeks of treatment.
9. To evaluate the safety of LCZ696 and its combination with amlodipine (200/5mg, 200/10mg, 400/5mg and 400/10 mg) in patients with essential hypertension.

Timepoint(s) of evaluation of this end point: 1. from baseline after 8 weeks of treatment.
2. from baseline after 8 weeks of treatment.
3. after 8 weeks of treatment.
4. from baseline after 8 weeks of treatment.
5. from baseline after 8 weeks of treatment.
6. after 8 weeks of treatment.
7. after 8 weeks of treatment.
8. after 8 weeks of treatment.
9. after 8 weeks of treatment.

Secondary ID(s)

2013-001643-30-SK

CLCZ696A2320

Source(s) of Monetary Support

Novartis Pharma Services AG, Switzerland