HypertensionPhase 2NCT01631864

Evaluation of the Metabolic Effects of LCZ696 and Amlodipine in Obese Hypertensive Subjects

A Phase 2 study testing LCZ696 and amlodipine in people with Hypertension and Concurrent Obesity, run by Novartis Pharmaceuticals at 3 sites in 2 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 investigated the effects of LCZ696 on insulin sensitivity, lipolysis, and oxidative metabolism in obese hypertensive subjects. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Hypertension, Concurrent Obesity
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: 98 participants
Where: 3 sitesin 2 countries
Study dates: Oct 2012to Jul 2013
Phase: Phase 2
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

Written informed consent must be obtained before any study assessment is performed.
Males and females of non-childbearing potential ≥ 18 years of age.
Subjects with mild to moderate essential hypertension,
Untreated subjects must have a mean seated SBP (msSBP) ≥ 130 mmHg and < 180 mmHg at screening.
Pre-treated subjects must have a msSBP ≤ 160 mmHg at screening and < 180 mmHg at the end of the washout period.
Waist circumference ≥ 102 cm (men) and ≥ 88 cm (women);

Who cannot join

Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer; or longer if required by local regulations.
History of angioedema, drug-related or otherwise
History of hypersensitivity to LCZ696, amlodipine, or drugs of similar chemical classes.
Severe hypertension (grade 3 of WHO classification; msDBP ≥100 mmHg and/or msSBP ≥ 180 mmHg) at screening or at the end of the washout period.
Type 1 or Type 2 diabetes mellitus.
Dyslipidemia requiring pharmacological therapy with a fibrate or nicotinic acid.
Concomitant use of anti-hypertensives, anti-diabetics, or drugs with effects on glucose or lipid metabolism for the duration of the study.
Other protocol defined inclusion/exclusion criteria may apply

Trial locations and contacts

3 sites in 2 countries.

Country

City, postcode or hospital

3 sites in 2 countries

Germany2 sites

Novartis Investigative Site
Hanover, 30625
Novartis Investigative Site
Neuss, 41460

Other trials in Germany

Netherlands1 site

Novartis Investigative Site
Maastricht, 5800

Other trials in Netherlands

About this study

Official title: A Randomized, Double-blind, Parallel Group Study to Evaluate Metabolic Effects of LCZ696 and Amlodipine in Obese Hypertensive Subjects

This study investigated the effects of LCZ696 on insulin sensitivity, lipolysis, and oxidative metabolism in obese hypertensive subjects.

Conditions: Hypertension, Concurrent Obesity
Being tested: LCZ696, amlodipine, Placebo
Keywords: Hypertension, obesity, insulin sensitivity, lipolysis, LCZ696
Medical subject headings: Hypertension, Obesity, Insulin Resistance

What participants receive

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

LCZ696Drug
LCZ696 was provided as 400 mg tablets.
amlodipineDrug
amlodipine was provided as 5 mg tablets.
PlaceboDrug
Matching placebo to LCZ696 and amlodipine.

Study groups in NCT01631864
Study group	Role	What they receive
LCZ696	Experimental	LCZ696 400 mg plus placebo to amlodipine once daily for 8 weeks Receives: Drug: LCZ696; Drug: Placebo
amlodipine	Active comparator	amlodipine 10 mg plus placebo to LCZ696 once daily 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 From Baseline in Insulin Sensitivity Index
The insulin sensitivity index was assessed by hyperinsulinemic euglycemic clamp (HEGC). A positive change from baseline indicates improvement.
Measured: baseline, 8 weeks

Secondary outcomes (3)

Local Adipose Tissue Lipolysis, Glycerol Concentrations
Lipolysis was assessed through subcutaneous adipose tissue microdialysis. The actual measure type is adjusted geometric mean.
Measured: 57 days
Oxidative Metabolism
Oxidative metabolism was assessed by indirect calorimetry.
Measured: 57 days
Number of Participants With Adverse Events, Serious Adverse Events and Deaths
Adverse event monitoring was conducted throughout the study.
Measured: 8 weeks

Timeline

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

Oct 2012Jul 2013

First posted29 Jun 2012 (estimated)
Study startOct 2012
Primary completionJul 2013
Study completionJul 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 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 2
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 98 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01631864
Sponsor's protocol ID: CLCZ696B2207
Other IDs: 2012-002606-40
Status last verified: Jun 2015
First submitted: 27 Jun 2012
Last updated: 10 Aug 2015
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Engeli S, Stinkens R, Heise T, May M, Goossens GH, Blaak EE, Havekes B, Jax T, Albrecht D, Pal P, Tegtbur U, Haufe S, Langenickel TH, Jordan J. Effect of Sacubitril/Valsartan on Exercise-Induced Lipid Metabolism in Patients With Obesity and Hypertension. Hypertension. 2018 Jan;71(1):70-77. doi: 10.1161/HYPERTENSIONAHA.117.10224. Epub 2017 Nov 27.
PubMed 29180454

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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Study at a glance

From the registry record, last updated by the sponsor on 10 Aug 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Double-blind, Parallel Group Study to Evaluate Metabolic Effects of LCZ696 and Amlodipine in Obese Hypertensive Subjects
ClinicalTrials.gov ID: NCT01631864
Acronym / sponsor ID: CLCZ696B2207
Conditions: Hypertension, Concurrent Obesity
Keywords: Hypertension, obesity, insulin sensitivity, lipolysis, LCZ696
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 98 participants (actual)
Lead sponsor: Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: Oct 2012
Primary completion: Jul 2013 (actual)
Study completion: Jul 2013 (actual)
First posted: 29 Jun 2012 (estimated)
Results: Posted 10 Aug 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 investigated the effects of LCZ696 on insulin sensitivity, lipolysis, and oxidative metabolism in obese hypertensive subjects.

Study design

Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
LCZ696	Experimental	Drug: LCZ696, Drug: PlaceboLCZ696 400 mg plus placebo to amlodipine once daily for 8 weeks
amlodipine	Active comparator	Drug: amlodipine, Drug: Placeboamlodipine 10 mg plus placebo to LCZ696 once daily 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 (6 listed)

Written informed consent must be obtained before any study assessment is performed.
Males and females of non-childbearing potential ≥ 18 years of age.
Subjects with mild to moderate essential hypertension,
Waist circumference ≥ 102 cm (men) and ≥ 88 cm (women);

Key exclusion criteria (8 listed)

Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer; or longer if required by local regulations.
History of angioedema, drug-related or otherwise
History of hypersensitivity to LCZ696, amlodipine, or drugs of similar chemical classes.
Severe hypertension (grade 3 of WHO classification; msDBP ≥100 mmHg and/or msSBP ≥ 180 mmHg) at screening or at the end of the washout period.
Type 1 or Type 2 diabetes mellitus.

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 was provided as 400 mg tablets.	Drug	LCZ696
amlodipineamlodipine was provided as 5 mg tablets.	Drug	amlodipine
PlaceboMatching placebo to LCZ696 and amlodipine.	Drug	LCZ696, amlodipine

Primary outcome

Change From Baseline in Insulin Sensitivity Index
Time frame: baseline, 8 weeks
The insulin sensitivity index was assessed by hyperinsulinemic euglycemic clamp (HEGC). A positive change from baseline indicates improvement.

3 secondary outcomes

Local Adipose Tissue Lipolysis, Glycerol Concentrations
Time frame: 57 days
Oxidative Metabolism
Time frame: 57 days
Number of Participants With Adverse Events, Serious Adverse Events and Deaths
Time frame: 8 weeks

Results and safety

Results posted to the registry on 10 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	50	48
Amlodipine	48	44

Primary outcome: Change From Baseline in Insulin Sensitivity Index

Time frame: baseline, 8 weeks. Mean (95% Confidence Interval). Unit: ug/kg*min/(mmol/L*pmol/L)

Measure	LCZ696 n = 48	Amlodipine n = 41
Value	0.192 (0.025 to 0.359)	0.065 (-0.0116 to 0.246)

Population analysed: Pharmacodynamic Analysis Set (PDS): Only participants from the PDS, who had both baseline and day 56 values, were included in the analysis. The PDS included all randomized participants who received at least one dose of study drug and had no protocol deviations with relevant impact on PD data.

3 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
LCZ696	1 of 50 (2%)	23 of 50 (46%)	Not reported
Amlodipine	1 of 48 (2.1%)	26 of 48 (54.2%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 10 Aug 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 29180454Engeli S, Stinkens R, Heise T, May M, Goossens GH, Blaak EE, Havekes B, Jax T, Albrecht D, Pal P, Tegtbur U, Haufe S, Langenickel TH, Jordan J. Effect of Sacubitril/Valsartan on Exercise-Induced Lipid Metabolism in Patients With Obesity and Hypertension. Hypertension. 2018 Jan;71(1):70-77. doi: 10.1161/HYPERTENSIONAHA.117.10224. Epub 2017 Nov 27.

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Chronic Kidney Disease, Hypertension (HTN)
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

3 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing LCZ696 and amlodipine in people with Hypertension and Concurrent Obesity, run by Novartis Pharmaceuticals at 3 sites in 2 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 6 inclusion and 8 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 10 Aug 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Germany, Netherlands. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 10 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 From Baseline in Insulin Sensitivity Index (time frame: baseline, 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 NCT01631864, 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 10 Aug 2015.