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

NCT ID: NCT00758524

Last Updated: 2021-07-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 628 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-09-11
• Study Completion Date: 2009-07-02

Brief 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.

Conditions

Essential Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Core Period: LCI699 0.25 mg QD

Participants received LCI699 0.25 mg capsules, orally, once daily (QD), with or without food for up to 8 weeks.

Group Type: EXPERIMENTAL

LCI699

Intervention Type: DRUG

LCI699 oral capsules

Core Period: LCI699 0.5 mg QD

Participants received LCI699 0.5 mg capsules, orally, QD, with or without food for up to 8 weeks.

Group Type: EXPERIMENTAL

LCI699

Intervention Type: DRUG

LCI699 oral capsules

Core Period: LCI699 1.0 mg QD

Participants received LCI699 1 mg capsules, orally, QD, with or without food for up to 8 weeks.

Group Type: EXPERIMENTAL

LCI699

Intervention Type: DRUG

LCI699 oral capsules

Core Period: LCI699 0.5 mg BID

Participants received LCI699 0.5 mg capsules, orally, twice daily (BID), with or without food for up to 8 weeks.

Group Type: EXPERIMENTAL

LCI699

Intervention Type: DRUG

LCI699 oral capsules

Core Period: Eplerenone 50 mg BID

Participants received eplerenone 50 mg capsules, orally, BID, with or without food for up to 8 weeks.

Group Type: ACTIVE_COMPARATOR

Eplerenone

Intervention Type: DRUG

Eplerenone oral capsules

Core Period: Placebo

Participants received LCI699-matching placebo or eplerenone-matching placebo, capsules, orally, QD or BID, with or without food for up to 8 weeks.

Group Type: PLACEBO_COMPARATOR

LCI699-matching Placebo

Intervention Type: DRUG

LCI699-matching placebo oral capsules

Eplerenone-matching Placebo

Intervention Type: DRUG

Eplerenone-matching placebo oral capsules

Withdrawal Period: LCI699 0.25 mg QD

Participants received LCI699 0.25 mg capsules, orally, QD, with or without food for up to 1 week (Week 8 to Week 9).

Group Type: EXPERIMENTAL

LCI699

Intervention Type: DRUG

LCI699 oral capsules

Withdrawal Period: LCI699 0.25 mg QD Placebo

Participants received LCI699 matching placebo capsules, orally, QD, with or without food for up to 1 week (Week 8 to Week 9).

Group Type: PLACEBO_COMPARATOR

LCI699-matching Placebo

Intervention Type: DRUG

LCI699-matching placebo oral capsules

Withdrawal Period: LCI699 0.5 mg QD

Participants received LCI699 0.5 mg capsules, orally, QD, with or without food for up to 1 week (Week 8 to Week 9).

Group Type: EXPERIMENTAL

LCI699

Intervention Type: DRUG

LCI699 oral capsules

Withdrawal Period: LCI699 0.5 mg QD Placebo

Participants received LCI699 matching placebo capsules, orally, QD, with or without food for up to 1 week (Week 8 to Week 9).

Group Type: PLACEBO_COMPARATOR

LCI699-matching Placebo

Intervention Type: DRUG

LCI699-matching placebo oral capsules

Withdrawal Period: LCI699 1.0 mg QD

Participants received LCI699 1 mg capsules, orally, QD, with or without food for up to 1 week (Week 8 to Week 9).

Group Type: EXPERIMENTAL

LCI699

Intervention Type: DRUG

LCI699 oral capsules

Withdrawal Period: LCI699 1.0 mg QD Placebo

Participants received LCI699 matching placebo capsules, orally, QD, with or without food for up to 1 week (Week 8 to Week 9).

Group Type: PLACEBO_COMPARATOR

LCI699-matching Placebo

Intervention Type: DRUG

LCI699-matching placebo oral capsules

Withdrawal Period: LCI699 0.5 mg BID

Participants received LCI699 0.5 mg capsules, orally, BID, with or without food for up to 1 week (Week 8 to Week 9).

Group Type: EXPERIMENTAL

LCI699

Intervention Type: DRUG

LCI699 oral capsules

Withdrawal Period: LCI699 0.5 mg BID Placebo

Participants received LCI699 matching placebo capsules, orally, BID, with or without food for up to 1 week (Week 8 to Week 9).

Group Type: PLACEBO_COMPARATOR

LCI699-matching Placebo

Intervention Type: DRUG

LCI699-matching placebo oral capsules

Withdrawal Period: Eplerenone 50 mg BID

Participants received eplerenone 50 mg capsules, orally, BID, with or without food for up to 1 week (Week 8 to Week 9).

Group Type: ACTIVE_COMPARATOR

Eplerenone

Intervention Type: DRUG

Eplerenone oral capsules

Withdrawal Period: Eplerenone 50 mg BID Placebo

Participants received eplerenone matching placebo capsules, orally, BID, with or without food for up to 1 week (Week 8 to Week 9).

Group Type: PLACEBO_COMPARATOR

Eplerenone-matching Placebo

Intervention Type: DRUG

Eplerenone-matching placebo oral capsules

Withdrawal Period: Placebo

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).

Group Type: PLACEBO_COMPARATOR

LCI699-matching Placebo

Intervention Type: DRUG

LCI699-matching placebo oral capsules

Eplerenone-matching Placebo

Intervention Type: DRUG

Eplerenone-matching placebo oral capsules

Interventions

LCI699

LCI699 oral capsules

Intervention Type: DRUG

Eplerenone

Eplerenone oral capsules

Intervention Type: DRUG

LCI699-matching Placebo

LCI699-matching placebo oral capsules

Intervention Type: DRUG

Eplerenone-matching Placebo

Eplerenone-matching placebo oral capsules

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

• 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.
• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Novartis Pharmaceuticals

East Hanover, New Jersey, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 24107737 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 21986283 (View on PubMed)

Other Identifiers

CLCI699A2201

Identifier Type: -

Identifier Source: org_study_id