A Study to Evaluate the Effect of LCZ696 on Aortic Stiffness in Subjects With Hypertension

Novartis

Status and phase: Completed; Phase 2

Conditions: Hypertension

Treatments: Other: placebo to sacubitril/valsartan (LCZ696); Drug: olmesartan; Drug: Amlodipine (Optional); Other: placebo to olmesartan; Drug: sacubitril/valsartan (LCZ696)

Study type: Interventional

Funder types: Industry

Identifiers

NCT01870739

CLCZ696A2224

2012-005720-15 (EudraCT Number)

Details and patient eligibility

About

This was the first evaluation of the effects of LCZ696 on local and regional measures of aortic stiffness in subjects with mild to moderate hypertension and widened pulse pressure. The results of this exploratory study will help to understand the mechanism of action of LCZ696 and used to inform the design of future clinical studies with LCZ696 in subjects with cardiovascular diseases.

Enrollment: 115 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Subjects with essential hypertension, untreated or currently taking antihypertensive therapy

Key exclusion Criteria:

• women of child bearing potential (WOCBP) if not on highly effective contraception
• Malignant or severe hypertension (grade 3 of WHO classification)
• History or evidence of a secondary form of hypertension
• Transient ischemic cerebral attack (TIA) during the 12 months prior to screening or any history of stroke.
• Previous or current diagnosis of heart failure (New York Heart Association Class II-IV).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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115 participants in 2 patient groups

sacubitril/valsartan (LCZ696)

Experimental group

Description:

Single drug treatment period: Patients received LCZ696 200mg once daily (q.d.) + placebo to 20 mg olmesartan q.d for 2 weeks. After 2 weeks, patients were dosed at the maintenance dose level (400 mg qd LCZ696 + placebo to 40 mg qd olmesartan) for 10 weeks. Add-on Period: After 12 weeks on single-drug treatment, patients continued in the study on the blinded maintenance dose and if required, open label amlodipine (2.5 mg, 5 mg, or 10 mg qd) was added to the treatment regimen and titrated according to the investigator's discretion to achieve target blood pressure.

Treatment:

Drug: Amlodipine (Optional)

Other: placebo to olmesartan

Drug: sacubitril/valsartan (LCZ696)

olmesartan

Active Comparator group

Description:

Single drug treatment period: Patients received 20 mg olmesartan q.d + placebo to LCZ696 200mg once daily (q.d.) for 2 weeks. After 2 weeks, patients were dosed at the maintenance dose level (40 mg olmesartan q.d + placebo to 400 mg qd LCZ696) for 10 weeks. Add-on Period: After 12 weeks on single-drug treatment, patients continued in the study on the blinded maintenance dose and if required, open label amlodipine (2.5 mg, 5 mg, or 10 mg qd) was added to the treatment regimen and titrated according to the investigator's discretion to achieve target blood pressure.

Treatment:

Drug: olmesartan

Other: placebo to sacubitril/valsartan (LCZ696)

Drug: Amlodipine (Optional)