A Study to Evaluate the Efficacy and Safety of LCI699 Compared to Placebo in Participants With Resistant Hypertension
- Conditions
- Hypertension
- Interventions
- Registration Number
- NCT00817635
- Lead Sponsor
- Novartis
- Brief Summary
This study assessed the blood pressure effect, safety and tolerability of LCI699 compared to placebo and eplerenone in participants with resistant hypertension.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 155
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description LCI699 0.25 mg BID LCI699 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. LCI699 1 mg QD LCI699 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. LCI699 0.5 mg followed by LCI699 1 mg BID LCI699 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. Placebo LCI699-matching 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. Placebo Eplerenone-matching 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. Eplerenone 50 mg BID Eplerenone 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.
- Primary Outcome Measures
Name Time Method Change From Baseline in MSSBP at Week 8 Last Observation Carried Forward (LOCF) Baseline, Week 8 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.
- Secondary Outcome Measures
Name Time Method Dose/Exposure BP Response Relationship of LCI699, as Measured by Change From Baseline in MSSBP at Week 8 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 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.
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) Baseline, Week 8 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.
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 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 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.
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 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.
Change From Baseline in MSDBP at Week 8 LOCF 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.
Percentage of Participants With a MSDBP Response and MSDBP Control at Week 8, as Measured by OBP Week 8 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.
Percentage of Participants With a MSSBP Response and MSSBP Control at Week 8, as Measured by Office Blood Pressure (OBP) Week 8 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.
Dose/Exposure BP Response Relationship of LCI699, as Measured by Change From Baseline in MSDBP at Week 8 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.
Change From Baseline in Mean 24 Hours, Mean Daytime and Mean Nighttime Diastolic Blood Pressure (DBP) at Week 8 LOCF, as Measured by ABPM Baseline, Week 8 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.
Number of Participants With Adverse Event (AEs), Serious Adverse Events (SAEs), Hyperkalemia, and Hyponatremia 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 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.
Number of Participants With Cortisol Levels Below 500 Nmol/L at 1 Hour After Adrenocorticotropic Hormone (ACTH) Injection at Week 8 1-hour post-dose at Week 8 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.
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 Baseline, Week 8 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.
Percent Change From Baseline in RAAS Biomarker: Plasma Renin Activity (PRA) in LCI699 Compared to Eplerenone 50mg at Week 8 LOCF Baseline, Week 8 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.
Percent Change From Baseline in RAAS Biomarker: Active Renin (ARC) in LCI699 Compared to Eplerenone 50mg at Week 8 LOCF Baseline, Week 8 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.
Percent Change From Baseline in RAAS Biomarker: Ratio of PA to PRA in LCI699 Compared to Eplerenone 50mg at Week 8 LOCF Baseline, Week 8 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.
Trial Locations
- Locations (35)
Horizon Research Group, Inc
🇺🇸Mobile, Alabama, United States
Northwest Clinical Trials
🇺🇸Boise, Idaho, United States
KRK Medical Research
🇺🇸Dallas, Texas, United States
Community Research
🇺🇸Cincinnati, Ohio, United States
Encode Clinic
🇮🇸Reykjavik, SA, Iceland
Clinical Trials Research
🇺🇸Roseville, California, United States
Jacksonville Heart Center
🇺🇸Jacksonville Beach, Florida, United States
MD Medical Research
🇺🇸Oxon Hill, Maryland, United States
Clinical Solutions Advantage
🇺🇸Buena Park, California, United States
New York Cardiovascular Associates
🇺🇸New York, New York, United States
Michael Waldman, MD
🇺🇸Irvine, California, United States
FPA Clinical Research
🇺🇸Kissimmee, Florida, United States
Cedar-Crosse Research Centereet
🇺🇸Chicago, Illinois, United States
Long Beach Center for Clinical Research
🇺🇸Long Beach, California, United States
Cochise Clinical Research
🇺🇸Sierra Vista, Arizona, United States
Cardio-Pulminary Associates
🇺🇸Plantation, Florida, United States
Meridien Research
🇺🇸Saint Petersburg, Florida, United States
Provident Clinical Research
🇺🇸Bloomington, Indiana, United States
Clinical Research of So. Florida
🇺🇸Coral Gables, Florida, United States
Accelovance
🇺🇸South Bend, Indiana, United States
Peter A. Holt
🇺🇸Baltimore, Maryland, United States
Metro Clinical Research
🇺🇸Littleton, Colorado, United States
Tipton Medical & Diagnostic Center
🇺🇸Tipton, Pennsylvania, United States
Punzi Medical Center
🇺🇸Carrollton, Texas, United States
Daniel Gottlieb, MD
🇺🇸Burien, Washington, United States
Northstate Clinical Research
🇺🇸Lenoir, North Carolina, United States
Chelsea Internal Medicine
🇺🇸Chelsea, Michigan, United States
Charlotte Clinical Research
🇺🇸Charlotte, North Carolina, United States
Gemini Scientific
🇺🇸Madison, Wisconsin, United States
DCOL Center for Clinical Research
🇺🇸Longview, Texas, United States
Rainier Clinical Research Center
🇺🇸Renton, Washington, United States
Orange County Research Center
🇺🇸Tustin, California, United States
Mountain View Clinical Research Associates
🇺🇸Greer, South Carolina, United States
Medical Research South
🇺🇸Charleston, South Carolina, United States
Clinical Research Associates, Inc
🇺🇸Nashville, Tennessee, United States