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

NCT01865188 | Withdrawn Phase 3 DMC

• 2 other identifiers: CLCZ696A23202013-001643-30
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Hypertension

Keywords

LCZ696,; amlodipine,; hypertension,; ABPM

Outcome Measures

Primary Outcomes (2)

• 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

• 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

Secondary Outcomes (21)

• Change from baseline in mean sitting Diastolic Blood Pressure (msDBP) of LCZ696 monotherapy compared to placebo

  baseline, 8 weeks

• Change from baseline in mean sitting Diastolic Blood Pressure of the combination of LCZ696 and amlodipine compared to LCZ696 and amlodipine alone

  baseline, 8 weeks

• Change from baseline in pulse pressure

  baseline, 8 weeks

• Change from baseline in mean 24-hour ambulatory Systolic Blood Pressure of LCZ696 monotherapy compared to placebo

  baseline, 8 weeks

• Change from baseline in mean 24-hour ambulatory Diastolic Blood Pressure of LCZ696 monotherapy compared to placebo

  baseline, 8 weeks

Study Arms (9)

LCZ696 200 mg

EXPERIMENTAL

Patients randomized to this treatment arm will receive LCZ696 200 mg once daily for 8 weeks.

Drug: LCZ696

LCZ696 400 mg

EXPERIMENTAL

Patients randomized to this treatment arm will receive LCZ696 400 mg once daily for 8 weeks.

Drug: LCZ696

Amlodipine 5 mg

ACTIVE COMPARATOR

Patients randomized to this treatment arm will receive amlodipine 5 mg once daily for 8 weeks.

Drug: Amlodipine

Amlodipine 10 mg

ACTIVE COMPARATOR

Patients randomized to this treatment arm will receive amlodipine 10 mg once daily for 8 weeks.

Drug: Amlodipine

LCZ696 200 mg and amlodipine 5 mg

EXPERIMENTAL

Patients randomized to this treatment arm will receive LCZ696 200 mg and amlodipine 5 mg once daily for 8 weeks.

Drug: LCZ696 and amlodipine combination

LCZ696 200 mg and amlodipine 10 mg

EXPERIMENTAL

Patients randomized to this treatment arm will receive LCZ696 200 mg and amlodipine 5 mg once daily for 1 week followed by LCZ696 200 mg and amlodipine 10 mg once daily for 7 weeks.

Drug: LCZ696 and amlodipine combination

LCZ696 400 mg and amlodipine 5 mg

EXPERIMENTAL

Patients randomized to this treatment arm will receive LCZ696 200 mg and amlodipine 5 mg once daily for 1 week followed by LCZ696 400 mg and amlodipine 5 mg once daily for 7 weeks.

Drug: LCZ696 and amlodipine combination

LCZ696 400 mg and amlodipine 10 mg

EXPERIMENTAL

Patients randomized to this treatment arm will receive LCZ696 200 mg and amlodipine 5 mg once daily for 1 week followed by LCZ696 400 mg and amlodipine 10 mg once daily for 7 weeks.

Drug: LCZ696 and amlodipine combination

Placebo

PLACEBO COMPARATOR

Patients randomized to this treatment arm will receive placebo once daily for 8 weeks.

Drug: Placebo

Interventions

LCZ696 DRUG

Experimental monotherapy doses

LCZ696 200 mg; LCZ696 400 mg

Amlodipine DRUG

Active comparator monotherapy doses

Amlodipine 10 mg; Amlodipine 5 mg

LCZ696 and amlodipine combination DRUG

Experimental combination doses

LCZ696 200 mg and amlodipine 10 mg; LCZ696 200 mg and amlodipine 5 mg; LCZ696 400 mg and amlodipine 10 mg; LCZ696 400 mg and amlodipine 5 mg

Placebo DRUG

Placebo comparator dose

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female outpatients
• Patients with mild-to-moderate hypertension, untreated or currently taking antihypertensive therapy
• 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.
• 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.
• Patients must have an absolute difference of ≤15 mmHg in msSBP between the randomization visit and the preceding visit.
• Ability to communicate and comply with all study requirements and demonstrate good medication compliance (≥ 80% compliance rate) during the treatment run-in period.

You may not qualify if:

• Severe hypertension (msDBP ≥110 mmHg and/or msSBP ≥ 180 mmHg)
• History of angioedema, drug-related or otherwise
• 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
• 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 any percutaneous coronary intervention (PCI) during the 12 months prior to Visit 1
• Pregnant or lactating women

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

MeSH Terms

Conditions

Hypertension

Interventions

sacubitril and valsartan sodium hydrate drug combination; Amlodipine

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2013
• First Posted: May 30, 2013
• Study Start: April 1, 2014
• Primary Completion: April 1, 2015
• Study Completion: April 1, 2015
• Last Updated: August 5, 2014

Record last verified: 2014-08