- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00817635
A Study to Evaluate the Efficacy and Safety of LCI699 Compared to Placebo in Participants With Resistant Hypertension
May 6, 2021 updated by: Novartis
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
This study assessed the blood pressure effect, safety and tolerability of LCI699 compared to placebo and eplerenone in participants with resistant hypertension.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
155
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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SA
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Reykjavik, SA, Iceland
- Encode Clinic
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Alabama
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Mobile, Alabama, United States, 36608
- Horizon Research Group, Inc
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Arizona
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Sierra Vista, Arizona, United States, 85635
- Cochise Clinical Research
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California
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Buena Park, California, United States, 90620
- Clinical Solutions Advantage
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Irvine, California, United States, 92618
- Michael Waldman, MD
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Long Beach, California, United States, 90806
- Long Beach Center For Clinical Research
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Roseville, California, United States, 95661
- Clinical Trials Research
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Tustin, California, United States, 92780
- Orange County Research Center
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Colorado
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Littleton, Colorado, United States, 80120
- Metro Clinical Research
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Florida
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Bradenton, Florida, United States, 34203
- Meridien Research
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Coral Gables, Florida, United States, 33134
- Clinical Research of So. Florida
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Jacksonville Beach, Florida, United States, 32250
- Jacksonville Heart Center
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Kissimmee, Florida, United States, 34741
- FPA Clinical Research
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Melbourne, Florida, United States, 32935
- Accelovance
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Plantation, Florida, United States, 33317
- Cardio-Pulminary Associates
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Saint Petersburg, Florida, United States, 33709
- Meridien Research
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Idaho
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Boise, Idaho, United States, 83704
- Northwest Clinical Trials
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Illinois
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Addison, Illinois, United States, 60101
- Provident Clinical Research
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Chicago, Illinois, United States, 60607
- Cedar-Crosse Research Centereet
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Indiana
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Bloomington, Indiana, United States, 47403
- Provident Clinical Research
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South Bend, Indiana, United States, 46601
- Accelovance
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Maryland
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Baltimore, Maryland, United States, 21239
- Peter A. Holt
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Oxon Hill, Maryland, United States, 20745
- MD Medical Research
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Michigan
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Chelsea, Michigan, United States, 48118
- Chelsea Internal Medicine
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New York
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New York, New York, United States, 10001
- New York Cardiovascular Associates
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North Carolina
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Charlotte, North Carolina, United States, 28211
- Charlotte Clinical Research
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Lenoir, North Carolina, United States, 28645
- Northstate Clinical Research
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Ohio
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Cincinnati, Ohio, United States, 45245
- Community Research
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Pennsylvania
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Tipton, Pennsylvania, United States, 16684
- Tipton Medical & Diagnostic Center
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South Carolina
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Charleston, South Carolina, United States, 29407
- Medical Research South
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Greer, South Carolina, United States, 29651
- Mountain View Clinical Research Associates
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Tennessee
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Nashville, Tennessee, United States, 37203
- Clinical Research Associates, Inc
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Texas
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Carrollton, Texas, United States, 75006
- Punzi Medical Center
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Dallas, Texas, United States, 75230
- KRK Medical Research
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Longview, Texas, United States, 75605
- DCOL Center for Clinical Research
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Washington
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Burien, Washington, United States, 98166
- Daniel Gottlieb, MD
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Renton, Washington, United States, 98057
- Rainier Clinical Research Center
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Wisconsin
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Madison, Wisconsin, United States, 83719
- Gemini Scientific
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 75 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: LCI699 0.25 mg BID
Following a 2-week placebo run-in period, participants received LCI699 0.25 mg, capsules, orally, twice daily (BID), with or without food for up to 8 weeks.
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LCI699 oral capsules
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Experimental: LCI699 1 mg QD
Following a 2-week placebo run-in period, participants received LCI699 1 mg, capsules, orally, once daily (QD), with or without food for up to 8 weeks.
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LCI699 oral capsules
|
Experimental: LCI699 0.5 mg followed by LCI699 1 mg BID
Following a 2-week placebo run-in period, participants received LCI699 0.5 mg, capsules, orally, BID, with or without food for up to 4 weeks, followed by LCI699 1 mg, capsules, orally, BID with or without food for up to 4 weeks.
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LCI699 oral capsules
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Active Comparator: Eplerenone 50 mg BID
Following a 2-week placebo run-in period, participants received eplerenone 50 mg, capsules, orally, BID, with or without food for up to 8 weeks.
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Eplerenone oral capsules
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Placebo Comparator: Placebo
For a 2-week placebo run-in period, followed by 8 weeks of the treatment period, participants received LCI699-matching placebo or eplerenone-matching placebo, capsules, orally, QD or BID, with or without food.
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LCI699-matching placebo oral capsules
Eplerenone-matching placebo oral capsules
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change From Baseline in MSSBP at Week 8 Last Observation Carried Forward (LOCF)
Time Frame: Baseline, Week 8
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Arterial blood pressure (BP) determinations were made after the participant was in the sitting position for 5 minutes according to the American Heart Association guidelines using a calibrated standard aneroid or mercury sphygmomanometer or a calibrated standard sphygmomanometer.
The change in the MSSBP was calculated comparing the Week 8 readings to the readings taken at Baseline.
The change from Baseline in MSSBP was analyzed using an analysis of covariance model (ANCOVA) with treatment and country as factors and Baseline MSSBP as a covariate.
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Baseline, Week 8
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change From Baseline in MSDBP at Week 8 LOCF
Time Frame: Baseline, Week 8
|
Arterial BP determinations were made after the participant was in the sitting position for 5 minutes according to the American Heart Association guidelines using a calibrated standard aneroid or mercury sphygmomanometer or a calibrated standard sphygmomanometer.
The change in the MSDBP was calculated comparing the Week 8 readings to the readings taken at Baseline.
The change from Baseline in MSDBP was analyzed using an ANCOVA with treatment and country as factors and Baseline MSDBP as a covariate.
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Baseline, Week 8
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Percentage of Participants With a MSSBP Response and MSSBP Control at Week 8, as Measured by Office Blood Pressure (OBP)
Time Frame: Week 8
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MSSBP response was defined as the percentage of participants with a MSSBP <140 mmHg or a >=20 mmHg reduction from baseline reduction from baseline.
MSSBP control was defined as the percentage of participants with a MSSBP <140 mmHg for non-diabetic participants and <130mHg for diabetic participants.
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Week 8
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Percentage of Participants With a MSDBP Response and MSDBP Control at Week 8, as Measured by OBP
Time Frame: Week 8
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MSDBP response was defined as the percentage of participants with a MSDBP <90 mmHg or a >=10 mmHg reduction from baseline.
MSDBP control was defined as the percentage of participants with a MSDBP <90 mmHg for non-diabetic participants and <80mHg for diabetic participants.
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Week 8
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Dose/Exposure BP Response Relationship of LCI699, as Measured by Change From Baseline in MSSBP at Week 8
Time Frame: Baseline, Week 8
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Arterial BP determinations were made after the participant was in the sitting position for 5 minutes according to the American Heart Association guidelines using a calibrated standard aneroid or mercury sphygmomanometer or a calibrated standard sphygmomanometer.
The change in the MSSBP was calculated comparing the Week 8 readings to the readings taken at Baseline.
The change from Baseline in MSSBP was analyzed using an ANCOVA with treatment and country as factors and Baseline MSSBP as a covariate.
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Baseline, Week 8
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Dose/Exposure BP Response Relationship of LCI699, as Measured by Change From Baseline in MSDBP at Week 8
Time Frame: Baseline, Week 8
|
Arterial BP determinations were made after the participant was in the sitting position for 5 minutes according to the American Heart Association guidelines using a calibrated standard aneroid or mercury sphygmomanometer or a calibrated standard sphygmomanometer.
The change in the MSDBP was calculated comparing the Week 8 readings to the readings taken at Baseline.
The change from Baseline in MSDBP was analyzed using an ANCOVA with treatment and country as factors and Baseline MSDBP as a covariate.
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Baseline, Week 8
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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)
Time Frame: Baseline, Week 8
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An ABPM measured a participant's blood pressure over a 24-hour period including daytime and nighttime readings, using an automated validated monitoring device from Baseline to Week 8.
The 24-hour SBP was calculated by taking the mean of all ambulatory systolic blood pressure readings for the 24-hour period.
The change from Baseline in SBP was analyzed using ANCOVA with treatment and country as factors and Baseline MSSBP as a covariate.
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Baseline, Week 8
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Change From Baseline in Mean 24 Hours, Mean Daytime and Mean Nighttime Diastolic Blood Pressure (DBP) at Week 8 LOCF, as Measured by ABPM
Time Frame: Baseline, Week 8
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An ABPM measured a participant's blood pressure over a 24-hour period including daytime and nighttime readings, using an automated validated monitoring device from Baseline to Week 8.
The 24-hour DBP was calculated by taking the mean of all ambulatory diastolic blood pressure readings for the 24-hour period.
The change from Baseline in DBP was analyzed using an ANCOVA with treatment and country as factors and Baseline MSDBP as a covariate.
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Baseline, Week 8
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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
Time Frame: Baseline, Week 4
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An ABPM measured a participant's blood pressure over a 24-hour period including daytime and nighttime readings using an automated validated monitoring device from Baseline to Week 4. The 24-hour SBP was calculated by taking the mean of all ambulatory systolic blood pressure readings for the 24-hour period.
The change from Baseline in SBP was analyzed using an ANCOVA with treatment and country as factors and Baseline MSDBP as a covariate.
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Baseline, Week 4
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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
Time Frame: Baseline, Week 4
|
An ABPM measured a participant's blood pressure over a 24-hour period including daytime and nighttime readings using an automated validated monitoring device from Baseline to Week 4. The 24-hour DBP was calculated by taking the mean of all ambulatory diastolic blood pressure readings for the 24-hour period.
The change from Baseline in DBP was analyzed using an ANCOVA with treatment and country as factors and Baseline MSDBP as a covariate.
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Baseline, Week 4
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Number of Participants With Adverse Event (AEs), Serious Adverse Events (SAEs), Hyperkalemia, and Hyponatremia
Time Frame: 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
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An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives.
SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Hyperkalemia was defined as potassium level >5.5 millimoles per liter (mmol/L).
It is the medical term that describes a potassium level that's higher than normal.
Hyponatremia was defined as sodium level <135 mmol/L.
It is the medical term that describes a sodium level that's lesser than normal.
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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
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Number of Participants With Cortisol Levels Below 500 Nmol/L at 1 Hour After Adrenocorticotropic Hormone (ACTH) Injection at Week 8
Time Frame: 1-hour post-dose at Week 8
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Serum cortisol concentrations at 1 hour after injection were measured to assess the maximum stimulated cortisol level achieved.
Potential adrenal suppression was indicated if the serum cortisol concentration was <500 nanomoles per liter (nmol/L) at 1 hour after the injection.
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1-hour post-dose at Week 8
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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
Time Frame: Baseline, Week 8
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Percent change from Baseline was analyzed by ANCOVA model using PA values measured at Baseline and Week 8 LOCF, with treatment and country as factors and Baseline value as the covariate.
Negative percent change from Baseline shows improvement.
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Baseline, Week 8
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Percent Change From Baseline in RAAS Biomarker: Plasma Renin Activity (PRA) in LCI699 Compared to Eplerenone 50mg at Week 8 LOCF
Time Frame: Baseline, Week 8
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Percent change from Baseline was analyzed by ANCOVA model using plasma renin values measured at Baseline and Week 8 LOCF, with treatment and country as factors and Baseline value as the covariate.
Negative percent change from Baseline shows improvement.
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Baseline, Week 8
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Percent Change From Baseline in RAAS Biomarker: Active Renin (ARC) in LCI699 Compared to Eplerenone 50mg at Week 8 LOCF
Time Frame: Baseline, Week 8
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Percent change from Baseline was analyzed by ANCOVA model using active renin values measured at Baseline and Week 8 LOCF, with treatment and country as factors and Baseline value as the covariate.
Negative percent change from Baseline shows improvement.
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Baseline, Week 8
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Percent Change From Baseline in RAAS Biomarker: Ratio of PA to PRA in LCI699 Compared to Eplerenone 50mg at Week 8 LOCF
Time Frame: Baseline, Week 8
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Percent change from Baseline was analyzed by ANCOVA model using percent ratio of PA to PRA values measured at Baseline and Week 8 LOCF, with treatment and country as factors and Baseline value as the covariate.
Negative percent change from Baseline shows improvement.
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Baseline, Week 8
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
December 22, 2008
Primary Completion (Actual)
October 13, 2009
Study Completion (Actual)
October 13, 2009
Study Registration Dates
First Submitted
January 5, 2009
First Submitted That Met QC Criteria
January 5, 2009
First Posted (Estimate)
January 6, 2009
Study Record Updates
Last Update Posted (Actual)
June 2, 2021
Last Update Submitted That Met QC Criteria
May 6, 2021
Last Verified
May 1, 2021
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- CLCI699A2216
- 2008-007338-23 (EudraCT Number)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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