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

Novartis

Status and phase: Completed; Phase 2

Conditions: Essential Hypertension

Treatments: Drug: Eplerenone; Drug: LCI699-matching Placebo; Drug: LCI699; Drug: Eplerenone-matching Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT00758524

CLCI699A2201

Details and patient eligibility

About

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.

Enrollment: 628 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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628 participants in 17 patient groups, including a placebo group

Core Period: LCI699 0.25 mg QD

Experimental group

Description:

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

Treatment:

Drug: LCI699

Core Period: LCI699 0.5 mg QD

Experimental group

Description:

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

Treatment:

Drug: LCI699

Core Period: LCI699 1.0 mg QD

Experimental group

Description:

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

Treatment:

Drug: LCI699

Core Period: LCI699 0.5 mg BID

Experimental group

Description:

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

Treatment:

Drug: LCI699

Core Period: Eplerenone 50 mg BID

Active Comparator group

Description:

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

Treatment:

Drug: Eplerenone

Core Period: Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: LCI699-matching Placebo

Drug: Eplerenone-matching Placebo

Withdrawal Period: LCI699 0.25 mg QD

Experimental group

Description:

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

Treatment:

Drug: LCI699

Withdrawal Period: LCI699 0.25 mg QD Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: LCI699-matching Placebo

Withdrawal Period: LCI699 0.5 mg QD

Experimental group

Description:

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

Treatment:

Drug: LCI699

Withdrawal Period: LCI699 0.5 mg QD Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: LCI699-matching Placebo

Withdrawal Period: LCI699 1.0 mg QD

Experimental group

Description:

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

Treatment:

Drug: LCI699

Withdrawal Period: LCI699 1.0 mg QD Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: LCI699-matching Placebo

Withdrawal Period: LCI699 0.5 mg BID

Experimental group

Description:

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

Treatment:

Drug: LCI699

Withdrawal Period: LCI699 0.5 mg BID Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: LCI699-matching Placebo

Withdrawal Period: Eplerenone 50 mg BID

Active Comparator group

Description:

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

Treatment:

Drug: Eplerenone

Withdrawal Period: Eplerenone 50 mg BID Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Eplerenone-matching Placebo

Withdrawal Period: Placebo

Placebo Comparator group

Description:

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).

Treatment:

Drug: LCI699-matching Placebo

Drug: Eplerenone-matching Placebo