Clinical trial NCT00817635: A Study to Evaluate the Efficacy and Safety of LCI699 Compared to Placebo in Participants With Resistant Hypertension
Official title: A Phase II, Randomized, Double-blind, Placebo and Active Controlled, Parallel Group, Multi-center, Dose Ranging Study to Evaluate the Efficacy and Safety of LCI699 Compared to Placebo After 8 Weeks Treatment in Patients With Resistant Hypertension
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hypertension
Keywords: Blood Pressure
Hypertension
Resistant Hypertension
Lead sponsor: Novartis
Sponsor class: INDUSTRY
Collaborators: name: Great Lakes Drug Development, Inc.
name: Integrium
First posted: 2009-01-06
Enrollment: 155
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 assessed the blood pressure effect, safety and tolerability of LCI699 compared to placebo and eplerenone in participants with resistant hypertension.


Eligibility criteria: Inclusion criteria:

* Diagnosis of hypertension with mean sitting systolic blood pressure (MSSBP) ≥140 millimeters of mercury (mmHg) and \<180 mmHg
* Stable on a three-drug regimen (including a diuretic) for at least 4 weeks for the treatment of resistant hypertension
* Male and female participants 18 to 75 years of age

Exclusion criteria:

* Recent history of myocardial infarction (MI), heart failure, unstable angina, coronary artery bypass graft, percutaneous coronary intervention, hypertensive encephalopathy, cerebrovascular accident, or transient ischemic attack
* Clinically significant electrocardiography (ECG) findings related to cardiac conduction defects
* Type 1 diabetes or uncontrolled type 2 diabetes (haemoglobin A1c \[HbA1c\] \>9%)
* Malignancies within the last 5 years (excluding basal cell skin cancer)

Other protocol-defined inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Change From Baseline in MSSBP at Week 8 Last Observation Carried Forward (LOCF)
timeFrame: Baseline, Week 8
Secondary outcomes:
measure: Change From Baseline in MSDBP at Week 8 LOCF
timeFrame: Baseline, Week 8
measure: Percentage of Participants With a MSSBP Response and MSSBP Control at Week 8, as Measured by Office Blood Pressure (OBP)
timeFrame: Week 8
measure: Percentage of Participants With a MSDBP Response and MSDBP Control at Week 8, as Measured by OBP
timeFrame: Week 8
measure: Dose/Exposure BP Response Relationship of LCI699, as Measured by Change From Baseline in MSSBP at Week 8
timeFrame: Baseline, Week 8
measure: Dose/Exposure BP Response Relationship of LCI699, as Measured by Change From Baseline in MSDBP at Week 8
timeFrame: Baseline, Week 8
measure: Change From Baseline in Mean 24 Hours, Mean Daytime and Mean Nighttime Systolic Blood Pressure (SBP) at Week 8 LOCF, as Measured by Ambulatory Blood Pressure Measurement (ABPM)
timeFrame: Baseline, Week 8
measure: Change From Baseline in Mean 24 Hours, Mean Daytime and Mean Nighttime Diastolic Blood Pressure (DBP) at Week 8 LOCF, as Measured by ABPM
timeFrame: Baseline, Week 8
measure: Change From Baseline in Mean 24 Hours, Mean Daytime and Mean Nighttime SBP in LCI699 1mg QD Versus LCI699 0.5mg BID Arm at Week 4, as Measured by ABPM
timeFrame: Baseline, Week 4
measure: Change From Baseline in Mean 24 Hours, Mean Daytime and Mean Nighttime DBP in LCI699 1mg QD Versus LCI699 0.5mg BID Arm at Week 4, as Measured by ABPM
timeFrame: Baseline, Week 4
measure: Number of Participants With Adverse Event (AEs), Serious Adverse Events (SAEs), Hyperkalemia, and Hyponatremia
timeFrame: AEs, Hyperkalemia, and Hyponatremia: From start of the study drug treatment up to 10 weeks; SAE: From signing of the informed consent up to 10 weeks
measure: Number of Participants With Cortisol Levels Below 500 Nmol/L at 1 Hour After Adrenocorticotropic Hormone (ACTH) Injection at Week 8
timeFrame: 1-hour post-dose at Week 8
measure: Percent Change From Baseline in Renin-Angiotensin-Aldosterone-System (RAAS) Biomarker: Plasma Aldosterone (PA) in LCI699 Compared to Eplerenone 50 mg at Week 8 LOCF
timeFrame: Baseline, Week 8
measure: Percent Change From Baseline in RAAS Biomarker: Plasma Renin Activity (PRA) in LCI699 Compared to Eplerenone 50mg at Week 8 LOCF
timeFrame: Baseline, Week 8
measure: Percent Change From Baseline in RAAS Biomarker: Active Renin (ARC) in LCI699 Compared to Eplerenone 50mg at Week 8 LOCF
timeFrame: Baseline, Week 8
measure: Percent Change From Baseline in RAAS Biomarker: Ratio of PA to PRA in LCI699 Compared to Eplerenone 50mg at Week 8 LOCF
timeFrame: Baseline, Week 8
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Horizon Research Group, Inc
state: Alabama
city: Sierra Vista
country: United States
facility: Cochise Clinical Research
state: Arizona
city: Buena Park
country: United States
facility: Clinical Solutions Advantage
state: California
city: Irvine
country: United States
facility: Michael Waldman, MD
state: California
city: Long Beach
country: United States
facility: Long Beach Center for Clinical Research
state: California
city: Roseville
country: United States
facility: Clinical Trials Research
state: California
city: Tustin
country: United States
facility: Orange County Research Center
state: California
city: Littleton
country: United States
facility: Metro Clinical Research
state: Colorado
city: Bradenton
country: United States
facility: Meridien Research
state: Florida
city: Coral Gables
country: United States
facility: Clinical Research of So. Florida
state: Florida
city: Jacksonville Beach
country: United States
facility: Jacksonville Heart Center
state: Florida
city: Kissimmee
country: United States
facility: FPA Clinical Research
state: Florida
city: Melbourne
country: United States
facility: Accelovance
state: Florida
city: Plantation
country: United States
facility: Cardio-Pulminary Associates
state: Florida
city: Saint Petersburg
country: United States
facility: Meridien Research
state: Florida
city: Boise
country: United States
facility: Northwest Clinical Trials
state: Idaho
city: Addison
country: United States
facility: Provident Clinical Research
state: Illinois
city: Chicago
country: United States
facility: Cedar-Crosse Research Centereet
state: Illinois
city: Bloomington
country: United States
facility: Provident Clinical Research
state: Indiana
city: South Bend
country: United States
facility: Accelovance
state: Indiana
city: Baltimore
country: United States
facility: Peter A. Holt
state: Maryland
city: Oxon Hill
country: United States
facility: MD Medical Research
state: Maryland
city: Chelsea
country: United States
facility: Chelsea Internal Medicine
state: Michigan
city: New York
country: United States
facility: New York Cardiovascular Associates
state: New York
city: Charlotte
country: United States
facility: Charlotte Clinical Research
state: North Carolina
city: Lenoir
country: United States
facility: Northstate Clinical Research
state: North Carolina
city: Cincinnati
country: United States
facility: Community Research
state: Ohio
city: Tipton
country: United States
facility: Tipton Medical & Diagnostic Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical Research South
state: South Carolina
city: Greer
country: United States
facility: Mountain View Clinical Research Associates
state: South Carolina
city: Nashville
country: United States
facility: Clinical Research Associates, Inc
state: Tennessee
city: Carrollton
country: United States
facility: Punzi Medical Center
state: Texas
city: Dallas
country: United States
facility: KRK Medical Research
state: Texas
city: Longview
country: United States
facility: DCOL Center for Clinical Research
state: Texas
city: Burien
country: United States
facility: Daniel Gottlieb, MD
state: Washington
city: Renton
country: United States
facility: Rainier Clinical Research Center
state: Washington
city: Madison
country: United States
facility: Gemini Scientific
state: Wisconsin
city: Reykjavik
country: Iceland
facility: Encode Clinic
state: SA
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.