Clinical trial NCT00758524: A Study to Evaluate Efficacy and Safety of LCI699 in Participants With Essential Hypertension
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Essential Hypertension
Keywords: Essential hypertension
Phase 2 study
Antihypertensive agent
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2008-09-25
Enrollment: 628
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
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)
timeFrame: Baseline, Week 8
Secondary outcomes:
measure: Core Period: Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP) at Week 8 LOCF, as Measured by OBP
timeFrame: Baseline, Week 8
measure: Core Period: Number of Participants With Adverse Event (AEs), Serious Adverse Events (SAEs), and Deaths
timeFrame: AEs: From start of the study drug treatment up to 8 weeks; SAE: From signing of the informed consent up to 8 weeks
measure: Core Period: Dose Response Relationship of LCI699 as Measured by Change From Baseline in MSDBP at Week 8
timeFrame: Baseline, Week 8
measure: Core Period: Dose Response Relationship of LCI699 as Measured by Change From Baseline in MSSBP at Week 8
timeFrame: Baseline, Week 8
measure: Core Period: Change From Baseline in Mean 24 Hour Ambulatory SBP at Week 8 as Measured by Ambulatory Blood Pressure Monitoring (ABPM)
timeFrame: Baseline, Week 8
measure: Core Period: Change From Baseline in Mean 24 Hour Ambulatory DBP at Week 8, as Measured by ABPM
timeFrame: Baseline, Week 8
measure: Core Period: Trough to Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory DBP at Week 8
timeFrame: Baseline, every hour up to 24 hours post-dose at Week 8
measure: Core Period: Trough to Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory SBP at Week 8
timeFrame: Baseline, every hour up to 24 hours post-dose at Week 8
measure: Core Period: Change From Baseline in Plasma Aldosterone Levels at Week 8
timeFrame: Baseline, Week 8
measure: Core Period: Percentage of Participants With a MSDBP Response and MSDBP Control at Week 8 LOCF
timeFrame: Baseline, Week 8
measure: Core Period: Percentage of Participants With a MSSBP Response and MSSBP Control at Week 8 LOCF
timeFrame: Baseline, Week 8
measure: Core Period: Change From Baseline in Plasma Cortisol Levels by Adrenocorticotropic Hormone (ACTH) Stimulation Test
timeFrame: Baseline, 1 hour post-dose at Week 8
measure: Withdrawal Period: Change From Week 8 to Week 9 in MSDBP at Week 9, as Measured by OBP
timeFrame: From Week 8 to Week 9
measure: Withdrawal Period: Change From Week 8 to Week 9 in MSSBP at Week 9 as Measured by OBP
timeFrame: From Week 8 to Week 9
Other outcomes:
Locations:
city: East Hanover
country: United States
facility: Novartis Pharmaceuticals
state: New Jersey
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.