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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01646671
First received: July 18, 2012
Last updated: October 2, 2015
Last verified: October 2015
  Purpose
This study assessed the safety, tolerability, and efficacy of LCZ696 in severe hypertensive Japanese patients

Condition Intervention Phase
Severe Hypertension
Drug: LCZ696
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Percentage of Participants With Adverse Events (AEs), Serious Adverse Events and Deaths [ Time Frame: Week 8 ] [ Designated as safety issue: Yes ]
    Adverse events, serious adverse events deaths were monitored from screening to week 8.


Secondary Outcome Measures:
  • Change From Baseline in msSBP and msDBP at Week 8 [ Time Frame: Baseline, 8 weeks ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Successful Blood Pressure (BP) Control in msSBP/msDBP at End of Study [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Successful BP control in patients with severe hypertension at the end of study treatment was defined as follows: msSBP/msDBP< 140/90 mmHg.

  • Percentage of Participants Achieving Successful msSBP Control at End of Study [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Successful msSBP control in patients with severe hypertension at the end of study treatment was defined as msSBP <140 mmHg.

  • Percentage of Participants Achieving Successful msDBP Control at End of Study [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Successful msDBP control in patients with severe hypertension at the end of study treatment was defined as msDBP < 90 mmHg.

  • Percentage of Participants With SBP Response at End of Study [ Time Frame: Baseline, 8 weeks ] [ Designated as safety issue: No ]
    SBP response was defined as <140 mmHg or a reduction ≥ 20 mmHg from baseline.

  • Percentage of Participants With DBP Response at End of Study [ Time Frame: Baseline, 8 weeks ] [ Designated as safety issue: No ]
    DBP response was defined as <90 mmHg or a reduction ≥ 10 mmHg from baseline.


Enrollment: 35
Study Start Date: July 2012
Study Completion Date: February 2013
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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
2 tablets of LCZ696 200 mg once daily titrated up from 1 tablet of 200 mg once daily
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
2 tablets of LCZ696 200 mg once daily titrated up from 1 tablet of 200 mg once daily plus other HTN medications

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.

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01646671

Locations
Japan
Novartis Investigative Site
Yokohama-city, Kanagawa, Japan, 231-0023
Novartis Investigative Site
Kyoto-city, Kyoto, Japan, 606-8507
Novartis Investigative Site
Bunkyo-ku, Tokyo, Japan, 113-0031
Novartis Investigative Site
Hachioji-city, Tokyo, Japan, 192-0918
Novartis Investigative Site
Minato-ku, Tokyo, Japan, 108-0075
Novartis Investigative Site
Minato-ku, Tokyo, Japan, 105-7390
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
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Publications:
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01646671     History of Changes
Other Study ID Numbers: CLCZ696A1305 
Study First Received: July 18, 2012
Results First Received: July 8, 2015
Last Updated: October 2, 2015
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by Novartis:
Hypertension, Severe, LCZ696

Additional relevant MeSH terms:
Hypertension
Cardiovascular Diseases
Vascular Diseases

ClinicalTrials.gov processed this record on February 04, 2016