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

• ClinicalTrials.gov Identifier: NCT01646671
• Recruitment Status: Completed
• First Posted: July 20, 2012
• Results First Posted: September 7, 2015
• Last Update Posted: October 23, 2015
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Severe Hypertension	Drug: LCZ696	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 35 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (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
• Study Start Date: July 2012
• Actual Primary Completion Date: February 2013
• Actual Study Completion Date: February 2013

Arms and Interventions

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
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

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Change From Baseline in msSBP and msDBP at Week 8 [ Time Frame: Baseline, 8 weeks ]
   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.
2. Percentage of Participants With Successful Blood Pressure (BP) Control in msSBP/msDBP at End of Study [ Time Frame: 8 weeks ]
   Successful BP control in patients with severe hypertension at the end of study treatment was defined as follows: msSBP/msDBP< 140/90 mmHg.
3. Percentage of Participants Achieving Successful msSBP Control at End of Study [ Time Frame: 8 weeks ]
   Successful msSBP control in patients with severe hypertension at the end of study treatment was defined as msSBP <140 mmHg.
4. Percentage of Participants Achieving Successful msDBP Control at End of Study [ Time Frame: 8 weeks ]
   Successful msDBP control in patients with severe hypertension at the end of study treatment was defined as msDBP < 90 mmHg.
5. Percentage of Participants With SBP Response at End of Study [ Time Frame: Baseline, 8 weeks ]
   SBP response was defined as <140 mmHg or a reduction ≥ 20 mmHg from baseline.
6. Percentage of Participants With DBP Response at End of Study [ Time Frame: Baseline, 8 weeks ]
   DBP response was defined as <90 mmHg or a reduction ≥ 10 mmHg from baseline.

Eligibility Criteria

• Ages Eligible for Study: 20 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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, 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

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

More Information

Publications of Results:

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.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01646671
• Other Study ID Numbers: CLCZ696A1305
• First Posted: July 20, 2012
• Results First Posted: September 7, 2015
• Last Update Posted: October 23, 2015
• Last Verified: October 2015

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

Hypertension, Severe, LCZ696

Additional relevant MeSH terms:

Hypertension; Vascular Diseases; Cardiovascular Diseases; Sacubitril and valsartan sodium hydrate drug combination; Angiotensin Receptor Antagonists; Molecular Mechanisms of Pharmacological Action