Efficacy and Safety of LCZ696 in Comparison to Olmesartan in Asian Patients With Essential Hypertension

This study is currently recruiting participants.
Verified December 2013 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01785472
First received: February 5, 2013
Last updated: December 13, 2013
Last verified: December 2013
  Purpose

This study will assess the efficacy and safety of multiple doses of LCZ696 compared to olmesartan in Asian patients with essential hypertension


Condition Intervention Phase
Essential Hypertension
Drug: LCZ696
Drug: Olmesartan
Drug: Placebo of LCZ696
Drug: Placebo of Olmesartan
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Multi-center, Randomized, Double-blind, Active-controlled, 8-week Study to Evaluate the Efficacy and Safety of LCZ696 in Comparison to Olmesartan in Patients With Essential Hypertension

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Change from baseline in mean sitting systolic blood pressure (msSBP) between LCZ696 200 mg versus olmesartan 20 mg [ Time Frame: baseline, 8 weeks ] [ Designated as safety issue: No ]
    Sitting BP measurements will be performed at screening through end of study at every visit. Four separate sitting BP measurements will be obtained with a full two minute interval between measurements.


Secondary Outcome Measures:
  • Change from baseline in mean sitting systolic blood pressure between LCZ696 400 mg versus olmesartan 20 mg [ Time Frame: baseline, 8 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in mean sitting diastolic blood pressure [ Time Frame: baseline, 8 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in office pulse pressure [ Time Frame: baseline, 8 weeks ] [ Designated as safety issue: No ]
    Four separate sitting BP measurements should be obtained with a full two minute interval between measurements.

  • Change from baseline in mean 24-hour ambulatory blood pressure [ Time Frame: baseline, 8 weeks ] [ Designated as safety issue: No ]
    In this analysis, mean 24 hour ambulatory systolic blood pressure maSBP, mean 24 hour ambulatory diastolic blood pressure maDBP, daytime and nightime maSBP and maDBP will be reported. Ambulatory blood pressure monitoring over a 24 hour period will be conducted at two time points during the study in a subset of patients.

  • Sub-group analysis for change from baseline in mean ambulatory systolic and diastolic blood pressure for nocturnal blood pressure dipper and non-dipper [ Time Frame: baseline, 8 weeks ] [ Designated as safety issue: No ]
    Non-dipper is a patient with a mean nighttime ambulatory blood pressure (10 pm - 6 am) that does not drop ≥ 10% below their mean daytime ambulatory blood pressure (6 am - 10 pm)

  • Percentage of patients achieving successful blood pressure control [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Successful blood pressure control is defined as msSBP <140 mmHg and msDBP <90 mmHg.

  • Number of patients with adverse events, serious adverse events, and death as assessment of safety and tolerability [ Time Frame: baseline, 8 weeks ] [ Designated as safety issue: Yes ]
  • Change from baseline in ambulatory pulse pressure [ Time Frame: baseline, 8 weeks ] [ Designated as safety issue: No ]
  • Percentage of responders [ Time Frame: baseline, 8 weeks ] [ Designated as safety issue: No ]
    Responders are patients with msSBP response (<140 mmHg or ≥20 mmHg reduction from baseline) and msDBP response (<90 mmHg or ≥10 mmHg reduction from baseline)


Estimated Enrollment: 1425
Study Start Date: April 2013
Estimated Study Completion Date: August 2014
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LCZ696 200 mg
Patients will be treated with one LCZ696 200 mg tablet and one placebo of LCZ696 once daily(qd) for eight weeks along with placebo of Olmesartan 20 mg capsule once daily.
Drug: LCZ696
LCZ696 200 mg tablet
Drug: Placebo of LCZ696
Placebo tablet of LCZ696 200 mg once daily
Drug: Placebo of Olmesartan
Placebo capsule of olmesartan 20 mg once daily
Experimental: LCZ696 400 mg
Patients will start with one LCZ696 200 mg tablet and one placebo of LCZ696 once daily (qd) for one week, thereafter all patients in the treatment group will be up-titrated to two LCZ696 200 mg tablets (400 mg of LCZ696) qd for the remaining seven weeks. Placebo of Olmesartan 20 mg capsule once daily also will be taken.
Drug: LCZ696
LCZ696 200 mg tablet
Drug: Placebo of LCZ696
Placebo tablet of LCZ696 200 mg once daily
Drug: Placebo of Olmesartan
Placebo capsule of olmesartan 20 mg once daily
Active Comparator: Olmesartan 20 mg
Patients will be treated with Olmesartan 20 mg for eight weeks once daily along with placebo of LCZ696 tablets once daily.
Drug: Olmesartan
Olmesartan 20 mg capsule
Drug: Placebo of LCZ696
Placebo tablet of LCZ696 200 mg once daily

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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 (Visit 201) and msSBP≥140 mmHg <180 mmHg at the visit immediately preceding Visit 201 (Visit 102 or 103).
  • 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 Visit 1 and Visit 201.
  • Patients must have an absolute difference of ≤15 mmHg in msSBP between Visit 201 and the immediately preceding visit.

Exclusion Criteria:

  • Patients with severe hypertension (msDBP ≥110 mmHg and or msSBP ≥180 mmHg).
  • History of angioedema, drug-related or otherwise, as reported by the patient.
  • 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.
  • Patients who previously entered a LCZ696 study and had been randomized or enrolled into the active drug treatment epoch.

Other protocol-defined inclusion/exclusion criteria may apply.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01785472

Contacts
Contact: Novartis Pharmaceuticals +41613241111
Contact: Novartis Pharmaceuticals

  Show 59 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01785472     History of Changes
Other Study ID Numbers: CLCZ696A2315, CLCZ696A2315
Study First Received: February 5, 2013
Last Updated: December 13, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Novartis:
Essential hypertension
LCZ696

Additional relevant MeSH terms:
Hypertension
Vascular Diseases
Cardiovascular Diseases
Olmesartan
Olmesartan medoxomil
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 17, 2014