Essential HypertensionPhase 2NCT00758524

A Study to Evaluate Efficacy and Safety of LCI699 in Participants With Essential Hypertension

A Phase 2 study testing LCI699 and Eplerenone in people with Essential Hypertension, run by Novartis Pharmaceuticals at 1 site in United States.

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 was a proof-of-efficacy, dose finding study of LCI699 in participants with mild-to-moderate uncomplicated essential hypertension in order to assess the blood pressure (BP) lowering effect, safety and tolerability of LCI699 as compared to placebo and eplerenone. Read more about this study

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Essential Hypertension
What is being tested?: LCI699 and Eplerenone
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 628 participants
Where: 1 siteUnited States
Study dates: 11 Sep 2008to 2 Jul 2009
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 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Males and non-fertile females.
18-75 years inclusive.
Participants with mild-to-moderate uncomplicated essential hypertension.

Who cannot join

All women of child bearing potential.
Female participants on hormone replacement therapy.
Severe hypertension.
History or evidence of a secondary form of hypertension.
Known moderate or malignant retinopathy.
History of angina pectoris, myocardial infarction, coronary bypass surgery,ischemic heart disease, surgical or percutaneous arterial intervention of any kind (coronary, carotid or peripheral vessels), stroke, transient ischemic attack (TIA), carotid artery stenosis, aortic aneurysm or peripheral arterial disease.

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Type 1 or type 2 diabetes mellitus.
Clinically significant valvular heart disease.
Congestive heart failure (New York Heart Association [NYHA] class II-IV).
Cardiac electrical abnormalities indicating significant risk of safety for participant taking part in the study.
History of malignancy of any organ system, treated or untreated, within the past 5 years.
Liver disease such as cirrhosis or chronic active hepatitis.
Any surgical or medical conditions that may significantly alter the absorption, distribution, metabolism or excretion of any drug substance
Any surgical or medical conditions, not identified in the protocol that in the opinion of the investigator or the monitor, place the participant at higher risk from his/her participation in the study, or is likely to prevent the participant from complying with the requirements of the study or completing the trial period.
Participant unwilling or not able to discontinue safely the use of current antihypertensive medications during the study period
Any contraindication or history of hypersensitivity to any of the study drugs or to drugs with similar chemical structures.
Chronic oral or parenteral corticosteroid treatment.
Treatment with potassium supplement or potassium sparing diuretics.
Treatment with potent cytochrome P450 3A4 (CYP3A4) inhibitors during the study period.
Use of other investigational drugs at Visit 1, or within 30 days or 5 half-lives of Visit 1, whichever is longer, unless local health authority guidelines mandate a longer period.
Serum potassium > 5.2 milliequivalents per liter (mEq/L) or < 3.5 mEq/L at Visit 1.
Serum sodium < 132 mEq/L at Visit 1.
Aspartate aminotransferase (ALT) or alanine aminotransferase (AST) > 2 times the upper limit of the normal range (ULN) at Visit 1.
Bilirubin (total) > 1.5 x ULN at Visit 1.
Modification of diet in renal disease estimated glomerular filtration rate (MDRD eGFR) < 60 milliliters per minute (ml/min)/1.73 m^2 at Visit 1.
Other clinically significant laboratory abnormalities, confirmed by repeat measurements, at Visit 1.
History of active substance abuse (including alcohol).
Participants with night-shift employment.

Trial locations and contacts

1 site in 1 country.

United States1 site

Novartis Pharmaceuticals
East Hanover, New Jersey

Other trials in United States

About this study

Official title: A Multi-center, Randomized, Double-blind, Placebo and Active Controlled, Parallel Group, Dose Finding Study to Evaluate the Efficacy and Safety of LCI699 Compared to Placebo After 8 Weeks Treatment in Patients With Essential Hypertension

Conditions: Essential Hypertension
Being tested: LCI699, Eplerenone, LCI699-matching Placebo, Eplerenone-matching Placebo
Keywords: Essential hypertension, Phase 2 study, Antihypertensive agent
Medical subject headings: Essential Hypertension

What participants receive

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

LCI699Drug
LCI699 oral capsules
EplerenoneDrug
Eplerenone oral capsules
LCI699-matching PlaceboDrug
LCI699-matching placebo oral capsules
Eplerenone-matching PlaceboDrug
Eplerenone-matching placebo oral capsules

Study groups in NCT00758524
Study group	Role	What they receive
Core Period: LCI699 0.25 mg QD	Experimental	Participants received LCI699 0.25 mg capsules, orally, once daily (QD), with or without food for up to 8 weeks. Receives: Drug: LCI699
Core Period: LCI699 0.5 mg QD	Experimental	Participants received LCI699 0.5 mg capsules, orally, QD, with or without food for up to 8 weeks. Receives: Drug: LCI699
Core Period: LCI699 1.0 mg QD	Experimental	Participants received LCI699 1 mg capsules, orally, QD, with or without food for up to 8 weeks. Receives: Drug: LCI699
Core Period: LCI699 0.5 mg BID	Experimental	Participants received LCI699 0.5 mg capsules, orally, twice daily (BID), with or without food for up to 8 weeks. Receives: Drug: LCI699
Core Period: Eplerenone 50 mg BID	Active comparator	Participants received eplerenone 50 mg capsules, orally, BID, with or without food for up to 8 weeks. Receives: Drug: Eplerenone
Core Period: Placebo	Placebo comparator	Participants received LCI699-matching placebo or eplerenone-matching placebo, capsules, orally, QD or BID, with or without food for up to 8 weeks. Receives: Drug: LCI699-matching Placebo; Drug: Eplerenone-matching Placebo
Withdrawal Period: LCI699 0.25 mg QD	Experimental	Participants received LCI699 0.25 mg capsules, orally, QD, with or without food for up to 1 week (Week 8 to Week 9). Receives: Drug: LCI699
Withdrawal Period: LCI699 0.25 mg QD Placebo	Placebo comparator	Participants received LCI699 matching placebo capsules, orally, QD, with or without food for up to 1 week (Week 8 to Week 9). Receives: Drug: LCI699-matching Placebo
Withdrawal Period: LCI699 0.5 mg QD	Experimental	Participants received LCI699 0.5 mg capsules, orally, QD, with or without food for up to 1 week (Week 8 to Week 9). Receives: Drug: LCI699
Withdrawal Period: LCI699 0.5 mg QD Placebo	Placebo comparator	Participants received LCI699 matching placebo capsules, orally, QD, with or without food for up to 1 week (Week 8 to Week 9). Receives: Drug: LCI699-matching Placebo
Withdrawal Period: LCI699 1.0 mg QD	Experimental	Participants received LCI699 1 mg capsules, orally, QD, with or without food for up to 1 week (Week 8 to Week 9). Receives: Drug: LCI699
Withdrawal Period: LCI699 1.0 mg QD Placebo	Placebo comparator	Participants received LCI699 matching placebo capsules, orally, QD, with or without food for up to 1 week (Week 8 to Week 9). Receives: Drug: LCI699-matching Placebo
Withdrawal Period: LCI699 0.5 mg BID	Experimental	Participants received LCI699 0.5 mg capsules, orally, BID, with or without food for up to 1 week (Week 8 to Week 9). Receives: Drug: LCI699
Withdrawal Period: LCI699 0.5 mg BID Placebo	Placebo comparator	Participants received LCI699 matching placebo capsules, orally, BID, with or without food for up to 1 week (Week 8 to Week 9). Receives: Drug: LCI699-matching Placebo
Withdrawal Period: Eplerenone 50 mg BID	Active comparator	Participants received eplerenone 50 mg capsules, orally, BID, with or without food for up to 1 week (Week 8 to Week 9). Receives: Drug: Eplerenone
Withdrawal Period: Eplerenone 50 mg BID Placebo	Placebo comparator	Participants received eplerenone matching placebo capsules, orally, BID, with or without food for up to 1 week (Week 8 to Week 9). Receives: Drug: Eplerenone-matching Placebo
Withdrawal Period: Placebo	Placebo comparator	Participants received LCI699-matching placebo or eplerenone-matching placebo, capsules, orally, QD or BID, with or without food for up to 1 week (Week 8 to Week 9). Receives: Drug: LCI699-matching Placebo; Drug: Eplerenone-matching Placebo

What is being measured

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

Core Period: Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP) at Week 8 Last Observation Carried Forward (LOCF), as Measured by Office Blood Pressure (OBP)
Automated arterial BP determinations were made after the participant was in the sitting position for 5 minutes according to the Guidelines for management of hypertension: report of the 4th working party of the British Hypertension Society, 2004-BHS IV, using an automated BP device (such as the Omron BP monitor). The change in the MSDBP was calculated comparing the Week 8 readings to the readings taken at Baseline. The change from baseline in MSDBP was analyzed using an analysis of covariance model (ANCOVA) with treatment and region as factors and baseline MSDBP level as a covariate.
Measured: Baseline, Week 8

Secondary outcomes (14)

Core Period: Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP) at Week 8 LOCF, as Measured by OBP
Automated arterial BP determinations were made after the participant was in the sitting position for 5 minutes according to the Guidelines for management of hypertension: report of the 4th working party of the British Hypertension Society, 2004-BHS IV, using an automated BP device (such as the Omron BP monitor). The change in the MSSBP was calculated comparing the Week 8 readings to the readings taken at Baseline. The change from baseline in MSSBP was analyzed using an ANCOVA with treatment and region as factors and baseline MSSBP levels as a covariate.
Measured: Baseline, Week 8
Core Period: Number of Participants With Adverse Event (AEs), Serious Adverse Events (SAEs), and Deaths
An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Measured: AEs: From start of the study drug treatment up to 8 weeks; SAE: From signing of the informed consent up to 8 weeks
Core Period: Dose Response Relationship of LCI699 as Measured by Change From Baseline in MSDBP at Week 8
Automated arterial BP determinations were made after the participant was in the sitting position for 5 minutes according to the Guidelines for management of hypertension: report of the 4th working party of the British Hypertension Society, 2004-BHS IV, using an automated BP device (such as the Omron BP monitor). The change in the MSDBP was calculated comparing the Week 8 readings to the readings taken at Baseline. The change from baseline in MSDBP was analyzed using an analysis of covariance model (ANCOVA) with treatment and region as factors and baseline MSDBP level as a covariate.
Measured: Baseline, Week 8
Core Period: Dose Response Relationship of LCI699 as Measured by Change From Baseline in MSSBP at Week 8
Automated arterial BP determinations were made after the participant was in the sitting position for 5 minutes according to the Guidelines for management of hypertension: report of the 4th working party of the British Hypertension Society, 2004-BHS IV, using an automated BP device (such as the Omron BP monitor). The change in the MSSBP was calculated comparing the Week 8 readings to the readings taken at Baseline. The change from baseline in MSSBP was analyzed using an ANCOVA with treatment and region as factors and baseline MSSBP levels as a covariate.
Measured: Baseline, Week 8
Core Period: Change From Baseline in Mean 24 Hour Ambulatory SBP at Week 8 as Measured by Ambulatory Blood Pressure Monitoring (ABPM)
An ABPM measured a participant's BP over a 24-hour period readings using an automated validated monitoring device from Baseline to Week 8. The 24-hour SBP was calculated by taking the mean of all ambulatory SBP readings for the 24-hour period.
Measured: Baseline, Week 8
Core Period: Change From Baseline in Mean 24 Hour Ambulatory DBP at Week 8, as Measured by ABPM
An ABPM measured a participant's BP over a 24-hour period readings using an automated validated monitoring device from Baseline to Week 8. The 24-hour DBP was calculated by taking the mean of all ambulatory DBP readings for the 24-hour period.
Measured: Baseline, Week 8
Core Period: Trough to Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory DBP at Week 8
Trough to peak ratios were derived from an ANCOVA model containing treatment, region, hour, treatment by hour interaction as factors with Baseline as a covariate.
Measured: Baseline, every hour up to 24 hours post-dose at Week 8
Core Period: Trough to Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory SBP at Week 8
Trough to peak ratios were derived from an ANCOVA model containing treatment, region, hour, treatment by hour interaction as factors with Baseline as a covariate.
Measured: Baseline, every hour up to 24 hours post-dose at Week 8
Core Period: Change From Baseline in Plasma Aldosterone Levels at Week 8
Change from baseline was analyzed using plasma aldosterone values measured at Baseline and Week 8.
Measured: Baseline, Week 8
Core Period: Percentage of Participants With a MSDBP Response and MSDBP Control at Week 8 LOCF
MSDBP response was defined as the percentage of participants with a MSDBP <90 mmHg or a >=10 mmHg reduction from Baseline. MSDBP control was defined as the percentage of participants with a MSDBP <90 mmHg.
Measured: Baseline, Week 8
Core Period: Percentage of Participants With a MSSBP Response and MSSBP Control at Week 8 LOCF
MSSBP response was defined as the percentage of participants with a MSSBP <140 mmHg or a >=20 mmHg reduction from baseline reduction from baseline. MSSBP control was defined as the percentage of participants with a MSSBP <140 mmHg.
Measured: Baseline, Week 8
Core Period: Change From Baseline in Plasma Cortisol Levels by Adrenocorticotropic Hormone (ACTH) Stimulation Test
The ACTH stimulation cortisol test was a standard procedure to measure the ability of adrenal cortex to respond to exogenous ACTH and directly assess the adrenal reserve. Serum cortisol concentrations at 1 hour after injection were measured to assess the maximum stimulated cortisol level achieved. Potential adrenal suppression was indicated if the serum cortisol concentration was <500 nanomoles per liter (nmol/L) at 1 hour after the injection.
Measured: Baseline, 1 hour post-dose at Week 8
Withdrawal Period: Change From Week 8 to Week 9 in MSDBP at Week 9, as Measured by OBP
Automated arterial BP determinations were made after the participant was in the sitting position for 5 minutes according to the Guidelines for management of hypertension: report of the 4th working party of the British Hypertension Society, 2004-BHS IV, using an automated BP device (such as the Omron BP monitor). The change in the MSDBP was calculated comparing the Week 9 readings to the readings taken at Week 8 (Baseline). The change from Week 8 to week 9 in MSDBP was analyzed using an ANCOVA with treatment and region as factors and Week 8 MSDBP level as a covariate.
Measured: From Week 8 to Week 9
Withdrawal Period: Change From Week 8 to Week 9 in MSSBP at Week 9 as Measured by OBP
Automated arterial BP determinations were made after the participant was in the sitting position for 5 minutes according to the Guidelines for management of hypertension: report of the 4th working party of the British Hypertension Society, 2004-BHS IV, using an automated BP device (such as the Omron BP monitor). The change in the MSSBP was calculated comparing the Week 9 readings to the readings taken at Week 8 (Baseline). The change from Week 8 to week 9 in MSSBP was analyzed using an ANCOVA with treatment and region as factors and Week 8 MSSBP level as a covariate.
Measured: From Week 8 to Week 9

Timeline

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

11 Sep 20082 Jul 2009

First posted25 Sep 2008 (estimated)
Study start11 Sep 2008
Primary completion2 Jul 2009
Study completion2 Jul 2009

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 (2)Papers the sponsor has linked to this study.
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 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 628 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00758524
Sponsor's protocol ID: CLCI699A2201
Status last verified: Jun 2021
First submitted: 23 Sep 2008
Last updated: 6 Jul 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

Schumacher CD, Steele RE, Brunner HR. Aldosterone synthase inhibition for the treatment of hypertension and the derived mechanistic requirements for a new therapeutic strategy. J Hypertens. 2013 Oct;31(10):2085-93. doi: 10.1097/HJH.0b013e328363570c.
PubMed 24107737
Calhoun DA, White WB, Krum H, Guo W, Bermann G, Trapani A, Lefkowitz MP, Menard J. Effects of a novel aldosterone synthase inhibitor for treatment of primary hypertension: results of a randomized, double-blind, placebo- and active-controlled phase 2 trial. Circulation. 2011 Nov 1;124(18):1945-55. doi: 10.1161/CIRCULATIONAHA.111.029892. Epub 2011 Oct 10.
PubMed 21986283

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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Pregnancy-Associated Hypertension, Gestational Hypertension

All Essential Hypertension trials

Study at a glance

From the registry record, last updated by the sponsor on 6 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Multi-center, Randomized, Double-blind, Placebo and Active Controlled, Parallel Group, Dose Finding Study to Evaluate the Efficacy and Safety of LCI699 Compared to Placebo After 8 Weeks Treatment in Patients With Essential Hypertension
ClinicalTrials.gov ID: NCT00758524
Acronym / sponsor ID: CLCI699A2201
Conditions: Essential Hypertension
Keywords: Essential hypertension, Phase 2 study, Antihypertensive agent
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 628 participants (actual)
Lead sponsor: Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: 11 Sep 2008 (actual)
Primary completion: 2 Jul 2009 (actual)
Study completion: 2 Jul 2009 (actual)
First posted: 25 Sep 2008 (estimated)
Results: Posted 6 Jul 2021

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: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 17

Arm	Type	Receives
Core Period: LCI699 0.25 mg QD	Experimental	Drug: LCI699Participants received LCI699 0.25 mg capsules, orally, once daily (QD), with or without food for up to 8 weeks.
Core Period: LCI699 0.5 mg QD	Experimental	Drug: LCI699Participants received LCI699 0.5 mg capsules, orally, QD, with or without food for up to 8 weeks.
Core Period: LCI699 1.0 mg QD	Experimental	Drug: LCI699Participants received LCI699 1 mg capsules, orally, QD, with or without food for up to 8 weeks.
Core Period: LCI699 0.5 mg BID	Experimental	Drug: LCI699Participants received LCI699 0.5 mg capsules, orally, twice daily (BID), with or without food for up to 8 weeks.
Core Period: Eplerenone 50 mg BID	Active comparator	Drug: EplerenoneParticipants received eplerenone 50 mg capsules, orally, BID, with or without food for up to 8 weeks.
Core Period: Placebo	Placebo comparator	Drug: LCI699-matching Placebo, Drug: Eplerenone-matching PlaceboParticipants received LCI699-matching placebo or eplerenone-matching placebo, capsules, orally, QD or BID, with or without food for up to 8 weeks.
Withdrawal Period: LCI699 0.25 mg QD	Experimental	Drug: LCI699Participants received LCI699 0.25 mg capsules, orally, QD, with or without food for up to 1 week (Week 8 to Week 9).
Withdrawal Period: LCI699 0.25 mg QD Placebo	Placebo comparator	Drug: LCI699-matching PlaceboParticipants received LCI699 matching placebo capsules, orally, QD, with or without food for up to 1 week (Week 8 to Week 9).
Withdrawal Period: LCI699 0.5 mg QD	Experimental	Drug: LCI699Participants received LCI699 0.5 mg capsules, orally, QD, with or without food for up to 1 week (Week 8 to Week 9).
Withdrawal Period: LCI699 0.5 mg QD Placebo	Placebo comparator	Drug: LCI699-matching PlaceboParticipants received LCI699 matching placebo capsules, orally, QD, with or without food for up to 1 week (Week 8 to Week 9).
Withdrawal Period: LCI699 1.0 mg QD	Experimental	Drug: LCI699Participants received LCI699 1 mg capsules, orally, QD, with or without food for up to 1 week (Week 8 to Week 9).
Withdrawal Period: LCI699 1.0 mg QD Placebo	Placebo comparator	Drug: LCI699-matching PlaceboParticipants received LCI699 matching placebo capsules, orally, QD, with or without food for up to 1 week (Week 8 to Week 9).
Withdrawal Period: LCI699 0.5 mg BID	Experimental	Drug: LCI699Participants received LCI699 0.5 mg capsules, orally, BID, with or without food for up to 1 week (Week 8 to Week 9).
Withdrawal Period: LCI699 0.5 mg BID Placebo	Placebo comparator	Drug: LCI699-matching PlaceboParticipants received LCI699 matching placebo capsules, orally, BID, with or without food for up to 1 week (Week 8 to Week 9).
Withdrawal Period: Eplerenone 50 mg BID	Active comparator	Drug: EplerenoneParticipants received eplerenone 50 mg capsules, orally, BID, with or without food for up to 1 week (Week 8 to Week 9).
Withdrawal Period: Eplerenone 50 mg BID Placebo	Placebo comparator	Drug: Eplerenone-matching PlaceboParticipants received eplerenone matching placebo capsules, orally, BID, with or without food for up to 1 week (Week 8 to Week 9).
Withdrawal Period: Placebo	Placebo comparator	Drug: LCI699-matching Placebo, Drug: Eplerenone-matching PlaceboParticipants received LCI699-matching placebo or eplerenone-matching placebo, capsules, orally, QD or BID, with or without food for up to 1 week (Week 8 to Week 9).

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

Males and non-fertile females.
18-75 years inclusive.
Participants with mild-to-moderate uncomplicated essential hypertension.

Key exclusion criteria (28 listed)

All women of child bearing potential.
Female participants on hormone replacement therapy.
Severe hypertension.
History or evidence of a secondary form of hypertension.
Known moderate or malignant retinopathy.

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
LCI699LCI699 oral capsules	Drug	Core Period: LCI699 0.25 mg QD, Core Period: LCI699 0.5 mg BID, Core Period: LCI699 0.5 mg QD, Core Period: LCI699 1.0 mg QD, Withdrawal Period: LCI699 0.25 mg QD, Withdrawal Period: LCI699 0.5 mg BID, Withdrawal Period: LCI699 0.5 mg QD, Withdrawal Period: LCI699 1.0 mg QD
EplerenoneEplerenone oral capsules	Drug	Core Period: Eplerenone 50 mg BID, Withdrawal Period: Eplerenone 50 mg BID
LCI699-matching PlaceboLCI699-matching placebo oral capsules	Drug	Core Period: Placebo, Withdrawal Period: LCI699 0.25 mg QD Placebo, Withdrawal Period: LCI699 0.5 mg BID Placebo, Withdrawal Period: LCI699 0.5 mg QD Placebo, Withdrawal Period: LCI699 1.0 mg QD Placebo, Withdrawal Period: Placebo
Eplerenone-matching PlaceboEplerenone-matching placebo oral capsules	Drug	Core Period: Placebo, Withdrawal Period: Eplerenone 50 mg BID Placebo, Withdrawal Period: Placebo

Primary outcome

Core Period: Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP) at Week 8 Last Observation Carried Forward (LOCF), as Measured by Office Blood Pressure (OBP)
Time frame: Baseline, Week 8
Automated arterial BP determinations were made after the participant was in the sitting position for 5 minutes according to the Guidelines for management of hypertension: report of the 4th working party of the British Hypertension Society, 2004-BHS IV, using an automated BP device (such as the Omron BP monitor). The change in the MSDBP was calculated comparing the Week 8 readings to the readings taken at Baseline. The change from baseline in MSDBP was analyzed using an analysis of covariance model (ANCOVA) with treatment and region as factors and baseline MSDBP level as a covariate.

14 secondary outcomes

Core Period: Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP) at Week 8 LOCF, as Measured by OBP
Time frame: Baseline, Week 8
Core Period: Number of Participants With Adverse Event (AEs), Serious Adverse Events (SAEs), and Deaths
Time frame: AEs: From start of the study drug treatment up to 8 weeks; SAE: From signing of the informed consent up to 8 weeks
Core Period: Dose Response Relationship of LCI699 as Measured by Change From Baseline in MSDBP at Week 8
Time frame: Baseline, Week 8
Core Period: Dose Response Relationship of LCI699 as Measured by Change From Baseline in MSSBP at Week 8
Time frame: Baseline, Week 8
Core Period: Change From Baseline in Mean 24 Hour Ambulatory SBP at Week 8 as Measured by Ambulatory Blood Pressure Monitoring (ABPM)
Time frame: Baseline, Week 8
Core Period: Change From Baseline in Mean 24 Hour Ambulatory DBP at Week 8, as Measured by ABPM
Time frame: Baseline, Week 8
Core Period: Trough to Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory DBP at Week 8
Time frame: Baseline, every hour up to 24 hours post-dose at Week 8
Core Period: Trough to Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory SBP at Week 8
Time frame: Baseline, every hour up to 24 hours post-dose at Week 8
Core Period: Change From Baseline in Plasma Aldosterone Levels at Week 8
Time frame: Baseline, Week 8
Core Period: Percentage of Participants With a MSDBP Response and MSDBP Control at Week 8 LOCF
Time frame: Baseline, Week 8
Core Period: Percentage of Participants With a MSSBP Response and MSSBP Control at Week 8 LOCF
Time frame: Baseline, Week 8
Core Period: Change From Baseline in Plasma Cortisol Levels by Adrenocorticotropic Hormone (ACTH) Stimulation Test
Time frame: Baseline, 1 hour post-dose at Week 8
Withdrawal Period: Change From Week 8 to Week 9 in MSDBP at Week 9, as Measured by OBP
Time frame: From Week 8 to Week 9
Withdrawal Period: Change From Week 8 to Week 9 in MSSBP at Week 9 as Measured by OBP
Time frame: From Week 8 to Week 9

Results and safety

Results posted to the registry on 6 Jul 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Core Period: LCI699 0.25 mg QD	92	84
Core Period: LCI699 0.5 mg QD	88	81
Core Period: LCI699 1.0 mg QD	86	77
Core Period: LCI699 0.5 mg BID	97	90
Core Period: Eplerenone 50 mg BID	84	75
Core Period: Placebo	77	67
Withdrawal Period: LCI699 0.25 mg QD	0	0
Withdrawal Period: LCI699 0.25 mg QD Placebo	0	0
Withdrawal Period: LCI699 0.5 mg QD	0	0
Withdrawal Period: LCI699 0.5 mg QD Placebo	0	0
Withdrawal Period: LCI699 1.0 mg QD	0	0
Withdrawal Period: LCI699 1.0 mg QD Placebo	0	0
Withdrawal Period: LCI699 0.5 mg BID	0	0
Withdrawal Period: LCI699 0.5 mg BID Placebo	0	0
Withdrawal Period: Eplerenone 50 mg BID	0	0
Withdrawal Period: Eplerenone 50 mg BID Placebo	0	0
Withdrawal Period: Placebo	0	0

Primary outcome: Core Period: Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP) at Week 8 Last Observation Carried Forward (LOCF), as Measured by Office Blood Pressure (OBP)

Time frame: Baseline, Week 8. Mean (Standard Error). Unit: mm Hg

Measure	Core Period: LCI699 0.25 mg QD n = 92	Core Period: LCI699 0.5 mg QD n = 85	Core Period: LCI699 1.0 mg QD n = 86	Core Period: LCI699 0.5 mg BID n = 96	Core Period: Eplerenone 50 mg BID n = 84	Core Period: Placebo n = 76
Value	-4.47 (0.60)	-5.50 (0.57)	-7.11 (0.88)	-4.25 (0.95)	-7.49 (0.97)	-3.22 (0.87)

Population analysed: FAS population included all randomized participants or participants that met the inclusion criteria as described in study documentation protocol excluding misrandomized participants or participants with protocol violations. Overall number of participants analyzed signifies the number of participants who were evaluable for this outcome measure.

14 secondary outcomes are reported in the full results.

Adverse events

Time frame: AEs: From start of the study drug treatment up to 9 weeks; SAE: From signing of the informed consent up to 9 weeks. Other adverse events reported at 1% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Core Period: LCI699 0.25 mg QD	1 of 92 (1.1%)	22 of 92 (23.9%)	0 of 92
Core Period: LCI699 0.5 mg QD	0 of 87 (0%)	22 of 87 (25.3%)	0 of 87
Core Period: LCI699 1.0 mg QD	0 of 87 (0%)	24 of 87 (27.6%)	0 of 87
Core Period: LCI699 0.5 mg BID	0 of 97 (0%)	27 of 97 (27.8%)	0 of 97
Core Period: Eplerenone 50 mg BID	0 of 84 (0%)	26 of 84 (31%)	0 of 84
Core Period: Placebo	1 of 76 (1.3%)	23 of 76 (30.3%)	0 of 76
Withdrawal Period: LCI699 0.25 mg QD	0 of 46 (0%)	2 of 46 (4.3%)	0 of 46
Withdrawal Period: LCI699 0.25 mg QD Placebo	0 of 38 (0%)	1 of 38 (2.6%)	0 of 38
Withdrawal Period: LCI699 0.5 mg QD	0 of 44 (0%)	1 of 44 (2.3%)	0 of 44
Withdrawal Period: LCI699 0.5 mg QD Placebo	0 of 37 (0%)	0 of 37 (0%)	0 of 37
Withdrawal Period: LCI699 1.0 mg QD	0 of 41 (0%)	3 of 41 (7.3%)	0 of 41
Withdrawal Period: LCI699 1.0 mg QD Placebo	0 of 37 (0%)	5 of 37 (13.5%)	0 of 37
Withdrawal Period: LCI699 0.5 mg BID	0 of 45 (0%)	4 of 45 (8.9%)	0 of 45
Withdrawal Period: LCI699 0.5 mg BID Placebo	0 of 45 (0%)	3 of 45 (6.7%)	0 of 45
Withdrawal Period: Eplerenone 50 mg BID	0 of 39 (0%)	2 of 39 (5.1%)	0 of 39
Withdrawal Period: Eplerenone 50 mg BID Placebo	0 of 36 (0%)	0 of 36 (0%)	0 of 36
Withdrawal Period: Placebo	0 of 66 (0%)	3 of 66 (4.5%)	0 of 66

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 6 Jul 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 24107737Schumacher CD, Steele RE, Brunner HR. Aldosterone synthase inhibition for the treatment of hypertension and the derived mechanistic requirements for a new therapeutic strategy. J Hypertens. 2013 Oct;31(10):2085-93. doi: 10.1097/HJH.0b013e328363570c.
Derived from this study: PubMed 21986283Calhoun DA, White WB, Krum H, Guo W, Bermann G, Trapani A, Lefkowitz MP, Menard J. Effects of a novel aldosterone synthase inhibitor for treatment of primary hypertension: results of a randomized, double-blind, placebo- and active-controlled phase 2 trial. Circulation. 2011 Nov 1;124(18):1945-55. doi: 10.1161/CIRCULATIONAHA.111.029892. Epub 2011 Oct 10.

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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

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

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing LCI699 and Eplerenone in people with Essential Hypertension, run by Novartis Pharmaceuticals at 1 site in United States.

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 28 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 6 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. 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. Some participants in this study may receive a placebo. 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 6 Jul 2021). 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?

Core Period: Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP) at Week 8 Last Observation Carried Forward (LOCF), as Measured by Office Blood Pressure (OBP) (time frame: Baseline, 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 NCT00758524, which also lists 2 linked publications.

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 6 Jul 2021.