Severe HypertensionPhase 3NCT01646671

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

A Phase 3 study testing LCZ696 in people with Severe Hypertension, run by Novartis Pharmaceuticals at 9 sites in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

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

Who is it for?: Ages 20 years and older
Conditions the study is for: Severe Hypertension
What is being tested?: LCZ696
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 35 participants
Where: 9 sitesJapan
Study dates: Jul 2012to Feb 2013
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 20 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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.

Trial locations and contacts

9 sites in 1 country.

City, postcode or hospital

9 sites in 1 country

Japan9 sites

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

Other trials in Japan

About this study

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

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

Read the 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.

Conditions: Severe Hypertension
Being tested: LCZ696
Keywords: Hypertension, Severe, LCZ696
Medical subject headings: Hypertension

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

LCZ696Drug
LCZ696 200 mg tablet once daily
LCZ696Drug
2 tablets of LCZ696 200 mg once daily titrated up from 1 tablet of 200 mg once daily
LCZ696Drug
2 tablets of LCZ696 200 mg once daily titrated up from 1 tablet of 200 mg once daily plus other HTN medications

Study groups in NCT01646671
Study group	Role	What they receive
LCZ696 200 mg	Experimental	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. Receives: Drug: LCZ696
LCZ696 400 mg	Experimental	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. Receives: Drug: LCZ696
LCZ696 400 mg plus other hypertension (HTN) medications	Experimental	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. Receives: Drug: LCZ696

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Week 8

Secondary outcomes (6)

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline, 8 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jul 2012Feb 2013

First posted20 Jul 2012 (estimated)
Study startJul 2012
Primary completionFeb 2013
Study completionFeb 2013

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Severe HypertensionStudies of the same condition, open and under way.
More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 35 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01646671
Sponsor's protocol ID: CLCZ696A1305
Status last verified: Oct 2015
First submitted: 18 Jul 2012
Last updated: 23 Oct 2015
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

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.
PubMed 26402918

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Severe Hypertension trials

Study at a glance

From the registry record, last updated by the sponsor on 23 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT01646671
Acronym / sponsor ID: CLCZ696A1305
Conditions: Severe Hypertension
Keywords: Hypertension, Severe, LCZ696
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 35 participants (actual)
Lead sponsor: Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: Jul 2012
Primary completion: Feb 2013 (actual)
Study completion: Feb 2013 (actual)
First posted: 20 Jul 2012 (estimated)
Results: Posted 7 Sep 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Detailed description

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
LCZ696 200 mg	Experimental	Drug: LCZ696All 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.
LCZ696 400 mg	Experimental	Drug: LCZ696All 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.
LCZ696 400 mg plus other hypertension (HTN) medications	Experimental	Drug: LCZ696All 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.

Who may qualify

Ages: 20 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (1 listed)

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

Key exclusion criteria (6 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
LCZ696LCZ696 200 mg tablet once daily	Drug	LCZ696 200 mg
LCZ6962 tablets of LCZ696 200 mg once daily titrated up from 1 tablet of 200 mg once daily	Drug	LCZ696 400 mg
LCZ6962 tablets of LCZ696 200 mg once daily titrated up from 1 tablet of 200 mg once daily plus other HTN medications	Drug	LCZ696 400 mg plus other hypertension (HTN) medications

Primary outcome

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.

6 secondary outcomes

Change From Baseline in msSBP and msDBP at Week 8
Time frame: Baseline, 8 weeks
Percentage of Participants With Successful Blood Pressure (BP) Control in msSBP/msDBP at End of Study
Time frame: 8 weeks
Percentage of Participants Achieving Successful msSBP Control at End of Study
Time frame: 8 weeks
Percentage of Participants Achieving Successful msDBP Control at End of Study
Time frame: 8 weeks
Percentage of Participants With SBP Response at End of Study
Time frame: Baseline, 8 weeks
Percentage of Participants With DBP Response at End of Study
Time frame: Baseline, 8 weeks

Results and safety

Results posted to the registry on 7 Sep 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
LCZ696 200 mg	3	3
LCZ696 400 mg	11	11
LCZ696 400 mg Plus Other Hypertension (HTN) Medications	21	21

Primary outcome: Percentage of Participants With Adverse Events (AEs), Serious Adverse Events and Deaths

Time frame: Week 8. Number. Unit: Percentage of participants

Measure	LCZ696 200 mg n = 35	LCZ696 400 mg n = 32	LCZ696 400 mg Plus Other Hypertension (HTN) Medications n = 21	Total Participants n = 35
Adverse Events (serious and non-serious)	20.0	12.5	33.3	48.6
Serious Adverse Events	2.9	0	0	2.9
Deaths	0	0	0	0

Population analysed: AE analysis was determined by actual treatment, i.e. the LCZ696 dose and use of newly introduced anti-HTN medication/dose escalation of base anti-HTN medication on the day in which the corresponding summary was targeting. Participants could be counted in more than one category. Other safety analysis was determined by the maximum treatment.

6 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
LCZ 200 mg	1 of 35 (2.9%)	4 of 35 (11.4%)	Not reported
LCZ 400 mg	0 of 32 (0%)	2 of 32 (6.3%)	Not reported
LCZ 400 mg + Other HTN Medications	0 of 21 (0%)	5 of 21 (23.8%)	Not reported
Total Participants	1 of 35 (2.9%)	10 of 35 (28.6%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 23 Oct 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 26402918Kario 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Novartis Pharmaceuticals study director

Novartis Pharmaceuticals

9 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing LCZ696 in people with Severe Hypertension, run by Novartis Pharmaceuticals at 9 sites in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Sep 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With Adverse Events (AEs), Serious Adverse Events and Deaths (time frame: Week 8). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01646671, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Oct 2015.