Safety and Tolerability and Efficacy of LCZ696 in Japanese Severe Hypertensive Patients

A Multi-center, Open Label Study for Evaluation of the Safety, Tolerability and Efficacy of 8-week Treatment With LCZ696 in Japanese Patients With Severe Hypertension

This study assessed the safety, tolerability, and efficacy of LCZ696 in severe hypertensive Japanese patients

Study Overview

• Status: Completed
• Conditions: Severe Hypertension
• Intervention / Treatment: Drug: LCZ696; Drug: LCZ696; Drug: LCZ696

Detailed Description

Summaries for treatment-emergent adverse events, serious adverse events and death were provided by the following actual treatment regimen (actual treatment patients received) in addition to all patients: LCZ696 200mg, 400mg, 400mg+other hypertensive medications.

Summaries for others than above were provided by the following treatment regimen (determined by the maximal treatment patients received) in addition to all patients: LCZ696 200mg, 400mg, 400mg+other hypertensive medications.

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Kanagawa
    • Yokohama-city, Kanagawa, Japan, 231-0023
      • Novartis Investigative Site
  • Kyoto
    • Kyoto-city, Kyoto, Japan, 606-8507
      • Novartis Investigative Site
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-0031
      • Novartis Investigative Site
    • Hachioji-city, Tokyo, Japan, 192-0918
      • Novartis Investigative Site
    • Minato-ku, Tokyo, Japan, 105-7390
      • Novartis Investigative Site
    • Minato-ku, Tokyo, Japan, 108-0075
      • Novartis Investigative Site
    • Ota-ku, Tokyo, Japan, 143-0023
      • Novartis Investigative Site
    • Shibuya-ku, Tokyo, Japan, 150-0002
      • Novartis Investigative Site
    • Shinagawa-ku, Tokyo, Japan, 141-0032
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Satisfy office msSBP ≥180 mmHg or office msDBP ≥110 mmHg at baseline

Exclusion Criteria:

• Patients show msSBP ≥220 mmHg and/or msDBP ≥120 mmHg
• History of angioedema, drug-related or otherwise, as reported by the patient
• Patients unwilling or not able to discontinue safely the use of current antihypertensive medications during the study, as required by the protocol.
• Patients have significant cardiovascular co-morbidities
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LCZ696 200 mg; All participants were started on LCZ696 200 mg once daily on day 1. Participants who achieved mean sitting diastolic blood pressure (msDBP) of < 100 mmHg and mean sitting systolic blood pressure (msSBP) of < 160 mmHg at week 2 or a msDBP < 90 mmHg and msSBP < 140 mmHg at or after week 4 and for the duration of the study continued at 200 mg LCZ696 once daily.	Drug: LCZ696; LCZ696 200 mg tablet once daily; Drug: LCZ696; 2 tablets of LCZ696 200 mg once daily titrated up from 1 tablet of 200 mg once daily; Drug: LCZ696; 2 tablets of LCZ696 200 mg once daily titrated up from 1 tablet of 200 mg once daily plus other HTN medications
Experimental: LCZ696 400 mg; All participants were started on LCZ696 200 mg once daily on day 1. For participants who did not achieve mean sitting diastolic blood pressure (msDBP) of < 100 mmHg and mean sitting systolic blood pressure (msSBP) of < 160 mmHg at week 2 or a msDBP < 90 mmHg and msSBP < 140 mmHg at or after week 4, and did not have any signs of safety concerns, the LCZ696 dose was increased to 400 mg once daily.	Drug: LCZ696; LCZ696 200 mg tablet once daily; Drug: LCZ696; 2 tablets of LCZ696 200 mg once daily titrated up from 1 tablet of 200 mg once daily; Drug: LCZ696; 2 tablets of LCZ696 200 mg once daily titrated up from 1 tablet of 200 mg once daily plus other HTN medications
Experimental: LCZ696 400 mg plus other hypertension (HTN) medications; All participants were started on LCZ696 200 mg once daily on day 1. For participants who received LCZ696 400 mg and did not achieve msDBP < 90 mmHg and msSBP < 140 mmHg at or after week 4 and had no signs of safety concerns, another class of antihypertensive drugs (other than Angiotensin II receptor blockers or Angiotensin Converting Enzyme Inhibitor (ACEi) could be added, or the dose of concomitant antihypertensive drugs could be increased as per the package insert. Participants who received LCZ696 400 mg once daily did not change their dose for the remainder of the study.	Drug: LCZ696; LCZ696 200 mg tablet once daily; Drug: LCZ696; 2 tablets of LCZ696 200 mg once daily titrated up from 1 tablet of 200 mg once daily; Drug: LCZ696; 2 tablets of LCZ696 200 mg once daily titrated up from 1 tablet of 200 mg once daily plus other HTN medications

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Adverse Events (AEs), Serious Adverse Events and Deaths	Adverse events, serious adverse events deaths were monitored from screening to week 8.	Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in msSBP and msDBP at Week 8	Sitting BP measurements were performed at screening through the end of study at every visit. Four separate sitting BP measurements were obtained with a full two-minute interval between measurements. The 4 measurements were summed and averaged, and then the baseline BP value was subtracted from the average value to get the change from baseline value.	Baseline, 8 weeks
Percentage of Participants With Successful Blood Pressure (BP) Control in msSBP/msDBP at End of Study	Successful BP control in patients with severe hypertension at the end of study treatment was defined as follows: msSBP/msDBP< 140/90 mmHg.	8 weeks
Percentage of Participants Achieving Successful msSBP Control at End of Study	Successful msSBP control in patients with severe hypertension at the end of study treatment was defined as msSBP <140 mmHg.	8 weeks
Percentage of Participants Achieving Successful msDBP Control at End of Study	Successful msDBP control in patients with severe hypertension at the end of study treatment was defined as msDBP < 90 mmHg.	8 weeks
Percentage of Participants With SBP Response at End of Study	SBP response was defined as <140 mmHg or a reduction ≥ 20 mmHg from baseline.	Baseline, 8 weeks
Percentage of Participants With DBP Response at End of Study	DBP response was defined as <90 mmHg or a reduction ≥ 10 mmHg from baseline.	Baseline, 8 weeks

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Kario K, Tamaki Y, Okino N, Gotou H, Zhu M, Zhang J. LCZ696, a First-in-Class Angiotensin Receptor-Neprilysin Inhibitor: The First Clinical Experience in Patients With Severe Hypertension. J Clin Hypertens (Greenwich). 2016 Apr;18(4):308-14. doi: 10.1111/jch.12667. Epub 2015 Sep 24.

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (Actual): February 1, 2013
• Study Completion (Actual): February 1, 2013

Study Registration Dates

• First Submitted: July 18, 2012
• First Submitted That Met QC Criteria: July 18, 2012
• First Posted (Estimate): July 20, 2012

Study Record Updates

• Last Update Posted (Estimate): October 23, 2015
• Last Update Submitted That Met QC Criteria: October 2, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: Hypertension, Severe, LCZ696
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Molecular Mechanisms of Pharmacological Action; Angiotensin Receptor Antagonists; Sacubitril and valsartan sodium hydrate drug combination
• Other Study ID Numbers: CLCZ696A1305

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No