Essential HypertensionPhase 3NCT01663233

Efficacy and Safety of LCZ696 200 mg + Amlodipine 5 mg in Comparison With Amlodipine 5 mg in Hypertensive Patients Not Responding to Amlodipine

A Phase 3 study testing LCZ696 and Amlodipine in people with Essential Hypertension, run by Novartis Pharmaceuticals at 28 sites in 6 countries.

Completed

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

Official record

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Trial summary

This study will assess whether LCZ696 when used in combination with amlodipine will provide greater BP lowering benefit compared to amlodipine alone in Asian hypertensive patients not adequately responsive to amlodipine therapy. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Essential Hypertension
What is being tested?: LCZ696 and Amlodipine
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 266 participants
Where: 28 sitesin 6 countries
Study dates: Aug 2012to May 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 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Patients must give written informed consent and have a diagnosis of hypertension:
Untreated patients must have an msSBP ≥ 150 mmHg and < 180 mmHg at both Visit 1 and Visit 101. Pre-treated patients must have an msSBP ≥ 145 mmHg and < 180 mmHg after wash out at Visit 101. All patients must have an office msSBP ≥ 145 mmHg and < 180 mmHg at the completion of the 4-week run-in epoch (at the randomization visit (Visit 201).
Patients must successfully complete ABPM and pass technical requirements at Visit 201.

Who cannot join

Malignant or severe hypertension (grade 3 of WHO classification; msDBP ≥110 mmHg and/or msSBP ≥ 180 mmHg).
History of angioedema, drug-related or otherwise. History or evidence of a secondary form of hypertension. Transient ischemic cerebral attack (TIA) during the 12 months prior to Visit 1 or any history of stroke.
History of myocardial infarction, coronary bypass surgery or PCI during the 12 months prior to Visit 1
Other protocol-defined inclusion/exclusion criteria may apply

Trial locations and contacts

28 sites in 6 countries.

Country

City, postcode or hospital

28 sites in 6 countries

Japan7 sites

Novartis Investigative Site
Edogawa-ku, Tokyo, 133-0061
Novartis Investigative Site
Katsushika-ku, Tokyo, 124-0024
Novartis Investigative Site
Kiyose, Tokyo, 204-0021
Novartis Investigative Site
Kunitachi, Tokyo, 186-0001
Novartis Investigative Site
Shibuya-ku, Tokyo, 150-0002
Novartis Investigative Site
Shinagawa-ku, Tokyo, 142-0063
Novartis Investigative Site
Toshima-ku, Tokyo, 171-0021

Other trials in Japan

South Korea6 sites

Novartis Investigative Site
Busan, Busan, 602-739
Novartis Investigative Site
Daegu, 705-703
Novartis Investigative Site
Daegu, 705-718
Novartis Investigative Site
Koyang, Kyunggi, 410-719
Novartis Investigative Site
Seoul, Seoul, 150-713
Novartis Investigative Site
Wŏnju, Gangwon-do, 220-701

Other trials in South Korea

Philippines5 sites

Novartis Investigative Site
Manila, National Capital Region, 1000
Novartis Investigative Site
Quezon City, Manila, 1100
Novartis Investigative Site
Quezon City, 1100
Novartis Investigative Site
Quezon City, 1102
Novartis Investigative Site
Valenzuela, 1441

Other trials in Philippines

China4 sites

Novartis Investigative Site
Chongqing, 400042
Novartis Investigative Site
Shanghai, 200025
Novartis Investigative Site
Shijiazhuang, Hebei, 050000
Novartis Investigative Site
Tianjin, 300142

Other trials in China

Taiwan4 sites

Novartis Investigative Site
Taichung, Taiwan, 40447
Novartis Investigative Site
Taipei, Taiwan, 10002
Novartis Investigative Site
Taipei, Taiwan, 114
Novartis Investigative Site
Taipei, Taiwan, ROC, 112

Other trials in Taiwan

Malaysia2 sites

Novartis Investigative Site
Kuala Lumpur, 56000
Novartis Investigative Site
Kuching, Sarawak, 94300

Other trials in Malaysia

About this study

Official title: A Randomized, 8-week, Double-blind, Parallel-group, Active-controlled, Multicenter Study to Evaluate the Efficacy and Safety of the Combination of LCZ696 200 mg + Amlodipine 5 mg in Comparison With Amlodipine 5 mg in Patients With Essential Hypertension Not Adequately Responsive to Amlodipine 5 mg Monotherapy Treatment

Conditions: Essential Hypertension
Being tested: LCZ696, Amlodipine, Placebo
Keywords: Essential hypertension, High blood pressure
Medical subject headings: Essential Hypertension, Hypertension

What participants receive

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

LCZ696Drug
LCZ696 will use tablets available at a strength of 200mg. Patients will be instructed to take the prescribed medication once a day.
AmlodipineDrug
Amlodipine will use tablets available at a strength of 5 mg. Patients will be instructed to take the prescribed medication once a day.
PlaceboDrug
Matching placebo to LCZ696

Study groups in NCT01663233
Study group	Role	What they receive
LCZ696 and amlodipine	Experimental	Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (had an office msSBP ≥145 mmHg and <180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 200mg of LCZ696 in combination with 5 mg of amlodipine for 8 weeks. Receives: Drug: LCZ696; Drug: Amlodipine
Amlodipine	Active comparator	Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (had an office msSBP ≥145 mmHg and <180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 5 mg of amlodipine and placebo to LCZ696 for 8 weeks. Receives: Drug: Amlodipine; Drug: Placebo

What is being measured

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

Change in Mean 24-hour Ambulatory Blood Pressure Monitoring (ABPM) Systolic Blood Pressure (maSBP)
The change in mean 24 hour ambulatory systolic blood pressure (maSBP) from baseline to end of the study (week 8) in the 2 groups was measured. A greater reduction from baseline in the LCZ696 group indicates a positive treatment effect.
Measured: 8 weeks

Secondary outcomes (8)

Change in Mean 24-hour ABPM Diastolic Blood Pressure (maDBP)
The change in mean 24 hour maDBP from baseline to end of the study was measured. A reduction from baseline indicates a positive treatment effect.
Measured: 8 weeks
Change in Mean Sitting Systolic Blood Pressure (msSBP)
The change in the patient's msSBP from baseline to end of the study was measured. A reduction from baseline indicates a positive treatment effect.
Measured: 8 weeks
Change in Mean Sitting Diastolic Blood Pressure (msDBP)
The change in the patient's msDBP from baseline to end of the study was measured. A reduction from baseline indicates a positive treatment effect.
Measured: 8 weeks
Change in Sitting Pulse Pressure (PP)
The change in the patient's mean sitting PP from baseline to end of the study was measured. Pulse pressure measures the difference in mean sitting systolic blood pressure and mean sitting diastolic blood pressure.
Measured: 8 weeks
Number of Participants Achieving Systolic and Diastolic Blood Pressure Control (< 140/90 mmHg)
The number of participants achieving a systolic and diastolic blood pressure < 140/90 mmHg was measured. This outcome measure shows how well a given blood pressure treatment can achieve a given blood pressure target or goal. Participants who achieved the target blood pressure were determined based on the mean SBP and DBP measurements taken at the end of the study. If the participants' BP measurement was below the above target, they were considered to have successful blood pressure control.
Measured: 8 weeks
Number of Participants Achieving Successful Response in msSBP (< 140 mmHg or a Reduction ≥ 20 mmHg From Baseline)
The number of participants who achieved successful treatment response in the msSBP of < 140mmHg or a reduction ≥ 20 mmHg from baseline after completing study treatment was measured. Participants who achieved either of the above targets were deemed as a having a successful response.
Measured: 8 weeks
Number of Participants Achieving Successful Response in msDBP (< 90 mmHg or a Reduction ≥ 10 mmHg From Baseline)
The number of participants who achieved successful treatment response in msDBP of < 90mmHg or a reduction ≥ 10mmHg from baseline after completing study treatment was measured. Participants who achieved either of the above targets were deemed as having a successful response.
Measured: 8 weeks of treatment
Number of Participants With Adverse Event
Participants were monitored for adverse events, serious adverse events and death.
Measured: 8 weeks

Timeline

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

Aug 2012May 2013

First posted13 Aug 2012 (estimated)
Study startAug 2012
Primary completionMay 2013
Study completionMay 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.
Other trials for Essential 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: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 266 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01663233
Sponsor's protocol ID: CLCZ696A2319
Status last verified: Oct 2015
First submitted: 8 Aug 2012
Last updated: 23 Oct 2015
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

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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Smartphone-Guided Paced Breathing and Aerobic Exercise for Essential Hypertension
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All Essential 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 Randomized, 8-week, Double-blind, Parallel-group, Active-controlled, Multicenter Study to Evaluate the Efficacy and Safety of the Combination of LCZ696 200 mg + Amlodipine 5 mg in Comparison With Amlodipine 5 mg in Patients With Essential Hypertension Not Adequately Responsive to Amlodipine 5 mg Monotherapy Treatment
ClinicalTrials.gov ID: NCT01663233
Acronym / sponsor ID: CLCZ696A2319
Conditions: Essential Hypertension
Keywords: Essential hypertension, High blood pressure
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 266 participants (actual)
Lead sponsor: Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: Aug 2012
Primary completion: May 2013 (actual)
Study completion: May 2013 (actual)
First posted: 13 Aug 2012 (estimated)
Results: Posted 18 Aug 2015

Clinical summary

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

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 2

Arm	Type	Receives
LCZ696 and amlodipine	Experimental	Drug: LCZ696, Drug: AmlodipineParticipants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (had an office msSBP ≥145 mmHg and <180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 200mg of LCZ696 in combination with 5 mg of amlodipine for 8 weeks.
Amlodipine	Active comparator	Drug: Amlodipine, Drug: PlaceboParticipants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (had an office msSBP ≥145 mmHg and <180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 5 mg of amlodipine and placebo to LCZ696 for 8 weeks.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

Untreated patients must have an msSBP ≥ 150 mmHg and < 180 mmHg at both Visit 1 and Visit 101. Pre-treated patients must have an msSBP ≥ 145 mmHg and < 180 mmHg after wash out at Visit 101. All patients must have an office msSBP ≥ 145 mmHg and < 180 mmHg at the completion of the 4-week run-in epoch (at the randomization visit (Visit 201).
Patients must successfully complete ABPM and pass technical requirements at Visit 201.

Key exclusion criteria (4 listed)

Malignant or severe hypertension (grade 3 of WHO classification; msDBP ≥110 mmHg and/or msSBP ≥ 180 mmHg).
History of angioedema, drug-related or otherwise. History or evidence of a secondary form of hypertension. Transient ischemic cerebral attack (TIA) during the 12 months prior to Visit 1 or any history of stroke.
History of myocardial infarction, coronary bypass surgery or PCI during the 12 months prior to Visit 1
Other protocol-defined inclusion/exclusion criteria may apply

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 will use tablets available at a strength of 200mg. Patients will be instructed to take the prescribed medication once a day.	Drug	LCZ696 and amlodipine
AmlodipineAmlodipine will use tablets available at a strength of 5 mg. Patients will be instructed to take the prescribed medication once a day.	Drug	Amlodipine, LCZ696 and amlodipine
PlaceboMatching placebo to LCZ696	Drug	Amlodipine

Primary outcome

Change in Mean 24-hour Ambulatory Blood Pressure Monitoring (ABPM) Systolic Blood Pressure (maSBP)
Time frame: 8 weeks
The change in mean 24 hour ambulatory systolic blood pressure (maSBP) from baseline to end of the study (week 8) in the 2 groups was measured. A greater reduction from baseline in the LCZ696 group indicates a positive treatment effect.

8 secondary outcomes

Change in Mean 24-hour ABPM Diastolic Blood Pressure (maDBP)
Time frame: 8 weeks
Change in Mean Sitting Systolic Blood Pressure (msSBP)
Time frame: 8 weeks
Change in Mean Sitting Diastolic Blood Pressure (msDBP)
Time frame: 8 weeks
Change in Sitting Pulse Pressure (PP)
Time frame: 8 weeks
Number of Participants Achieving Systolic and Diastolic Blood Pressure Control (< 140/90 mmHg)
Time frame: 8 weeks
Number of Participants Achieving Successful Response in msSBP (< 140 mmHg or a Reduction ≥ 20 mmHg From Baseline)
Time frame: 8 weeks
Number of Participants Achieving Successful Response in msDBP (< 90 mmHg or a Reduction ≥ 10 mmHg From Baseline)
Time frame: 8 weeks of treatment
Number of Participants With Adverse Event
Time frame: 8 weeks

Results and safety

Results posted to the registry on 18 Aug 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 and Amlodipine	130	126
Amlodipine	136	129

Primary outcome: Change in Mean 24-hour Ambulatory Blood Pressure Monitoring (ABPM) Systolic Blood Pressure (maSBP)

Time frame: 8 weeks. Least squares mean (Standard Error). Unit: mmHg

Measure	LCZ696 and Amlodipine n = 123	Amlodipine n = 128
Value	-13.93 (0.56)	-0.82 (0.56)

Population analysed: FAS: This set included all randomized participants who received at least one dose of study medication. Among the 266 Full Analysis Set (FAS) participants, 251 participants (123 participants in the LCZ696 + amlodipine group and 128 participants in the amlodipine group) had eligible ABPM at both baseline and endpoint.

8 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 2% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
LCZ696 and Amlodipine	0 of 130 (0%)	13 of 130 (10%)	Not reported
Amlodipine	0 of 136 (0%)	19 of 136 (14%)	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.

Related trials for Essential Hypertension

Recruiting
The Effect of Self-Acupressure on Blood Pressure, Stress, and Well-Being Levels in Individuals With Hypertension
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Active, not recruiting
Smartphone-Guided Paced Breathing and Aerobic Exercise for Essential Hypertension
Essential (Primary) Hypertension
Recruiting
Isometric Resistance Exercise on Accelerated Atherosclerosis in Hypertension
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Not yet recruitingObservational study
A Study to Evaluate the Effectiveness and Safety of S-amlodipine-based Monotherapy and Combination Therapy
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Recruiting
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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

28 sites in 6 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing LCZ696 and Amlodipine in people with Essential Hypertension, run by Novartis Pharmaceuticals at 28 sites in 6 countries.

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 3 inclusion and 4 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 28 sites in Japan, South Korea, Philippines, China, Taiwan and 1 more country. 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 18 Aug 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?

Change in Mean 24-hour Ambulatory Blood Pressure Monitoring (ABPM) Systolic Blood Pressure (maSBP) (time frame: 8 weeks). 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 NCT01663233.

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.