A Study to Evaluate Efficacy and Safety of LCI699 in Participants With Essential Hypertension
Condition: Essential Hypertension
MeSH terms: Hypertension; Essential Hypertension
Intervention: LCI699; Eplerenone; LCI699-matching Placebo; Eplerenone-matching Placebo
Intervention description: LCI699 oral capsules; Eplerenone oral capsules; LCI699-matching placebo oral capsules; Eplerenone-matching placebo oral capsules
Intervention MeSH terms: Eplerenone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 628.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Essential hypertension; Phase 2 study; Antihypertensive agent

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.
    

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.