Hypertension
Conditions
Keywords
Blood Pressure, Hypertension, Resistant Hypertension
Brief summary
This study assessed the blood pressure effect, safety and tolerability of LCI699 compared to placebo and eplerenone in participants with resistant hypertension.
Interventions
DRUGLCI699
LCI699 oral capsules
DRUGEplerenone
Eplerenone oral capsules
LCI699-matching placebo oral capsules
Eplerenone-matching placebo oral capsules
Sponsors
Great Lakes Drug Development, Inc.
Integrium
Novartis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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 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 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. |
| 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 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. |
| 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. |
| 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. |
Countries
Iceland, United States
Participant flow
Recruitment details
Participants took part in this study at 35 investigative sites in the United States and in Iceland from 22 December 2008 to 13 October 2009.
Pre-assignment details
Participants with a diagnosis of resistant hypertension were enrolled in a run-in period (Week -2 to 0). After that, the participants who fulfilled the inclusion criteria and did not meet any of the exclusion criteria at Week -2 and Week 0 were randomized to receive LCI699 or eplerenone in comparison with placebo for 8 weeks.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 32 |
| 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. | 26 |
| 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. | 31 |
| 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. | 33 |
| 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. | 33 |
| Total | 155 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Abnormal Laboratory Value(s) | 1 | 1 | 0 | 0 | 1 |
| Overall Study | Administrative Problems | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Adverse Event | 1 | 0 | 0 | 1 | 1 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 1 | 0 |
| Overall Study | Protocol Violation | 5 | 1 | 3 | 2 | 3 |
| Overall Study | Withdrawal by Subject | 2 | 1 | 0 | 1 | 2 |
Baseline characteristics
| Characteristic | LCI699 0.25 mg BID | LCI699 1 mg QD | LCI699 0.5 mg Followed by LCI699 1 mg BID | Eplerenone 50 mg BID | Placebo | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 53.6 years STANDARD_DEVIATION 10.36 | 55.4 years STANDARD_DEVIATION 9.58 | 57.2 years STANDARD_DEVIATION 10.77 | 56.2 years STANDARD_DEVIATION 7.7 | 59.8 years STANDARD_DEVIATION 9.33 | 56.5 years STANDARD_DEVIATION 9.69 |
| Baseline Mean Sitting Diastolic Blood Pressure (MSDBP) | 91.8 mmHg STANDARD_DEVIATION 11.68 | 89.2 mmHg STANDARD_DEVIATION 9.56 | 88.9 mmHg STANDARD_DEVIATION 11.89 | 89.1 mmHg STANDARD_DEVIATION 9.84 | 90.1 mmHg STANDARD_DEVIATION 11.65 | 89.8 mmHg STANDARD_DEVIATION 10.92 |
| Baseline Mean Sitting Systolic Blood Pressure (MSSBP) | 152.4 millimeters of mercury (mmHg) STANDARD_DEVIATION 11.21 | 152.5 millimeters of mercury (mmHg) STANDARD_DEVIATION 9.79 | 152.2 millimeters of mercury (mmHg) STANDARD_DEVIATION 7.58 | 153.8 millimeters of mercury (mmHg) STANDARD_DEVIATION 8.92 | 153.4 millimeters of mercury (mmHg) STANDARD_DEVIATION 9.61 | 152.9 millimeters of mercury (mmHg) STANDARD_DEVIATION 9.39 |
| Sex: Female, Male Female | 12 Participants | 8 Participants | 13 Participants | 14 Participants | 11 Participants | 58 Participants |
| Sex: Female, Male Male | 20 Participants | 18 Participants | 18 Participants | 19 Participants | 22 Participants | 97 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 32 | 0 / 26 | 0 / 31 | 0 / 33 | 0 / 33 |
| other Total, other adverse events | 15 / 32 | 15 / 26 | 8 / 31 | 13 / 33 | 16 / 33 |
| serious Total, serious adverse events | 0 / 32 | 0 / 26 | 0 / 31 | 1 / 33 | 0 / 33 |
Outcome results
Primary
Change From Baseline in MSSBP at Week 8 Last Observation Carried Forward (LOCF)
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.
Time frame: Baseline, Week 8
Population: FAS population included all participants who were randomized and received at least 1 dose of study drug. Overall number of participants analyzed signifies the number of participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LCI699 0.25 mg BID | Change From Baseline in MSSBP at Week 8 Last Observation Carried Forward (LOCF) | -11.4 mmHg | Standard Error 2.96 |
| LCI699 1 mg QD | Change From Baseline in MSSBP at Week 8 Last Observation Carried Forward (LOCF) | -13.1 mmHg | Standard Error 3.24 |
| LCI699 0.5 mg Followed by LCI699 1 mg BID | Change From Baseline in MSSBP at Week 8 Last Observation Carried Forward (LOCF) | -12.5 mmHg | Standard Error 2.96 |
| Eplerenone 50 mg BID | Change From Baseline in MSSBP at Week 8 Last Observation Carried Forward (LOCF) | -18.7 mmHg | Standard Error 2.92 |
| Placebo | Change From Baseline in MSSBP at Week 8 Last Observation Carried Forward (LOCF) | -8.8 mmHg | Standard Error 2.87 |
Secondary
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
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.
Time frame: Baseline, Week 4
Population: FAS population included all participants who were randomized and received at least 1 dose of study drug. Overall number of participants analyzed signifies the number of participants who were evaluable for this measure. Here, Number Analyzed 'n' represents number of participants who were evaluable for that specific category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LCI699 0.25 mg BID | 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 | 24-hour Mean DBP | -4.3 mmHg | Standard Error 1.98 |
| LCI699 0.25 mg BID | 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 | Daytime Mean DBP | -3.9 mmHg | Standard Error 2.04 |
| LCI699 0.25 mg BID | 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 | Nighttime Mean DBP | -4.5 mmHg | Standard Error 2.21 |
| LCI699 1 mg QD | 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 | 24-hour Mean DBP | -2.5 mmHg | Standard Error 1.67 |
| LCI699 1 mg QD | 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 | Daytime Mean DBP | -2.6 mmHg | Standard Error 1.73 |
| LCI699 1 mg QD | 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 | Nighttime Mean DBP | -2.8 mmHg | Standard Error 1.87 |
Secondary
Change From Baseline in Mean 24 Hours, Mean Daytime and Mean Nighttime Diastolic Blood Pressure (DBP) at Week 8 LOCF, as Measured by ABPM
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.
Time frame: Baseline, Week 8
Population: FAS population included all participants who were randomized and received at least 1 dose of study drug. Overall number of participants analyzed signifies the number of participants who were evaluable for this measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LCI699 0.25 mg BID | Change From Baseline in Mean 24 Hours, Mean Daytime and Mean Nighttime Diastolic Blood Pressure (DBP) at Week 8 LOCF, as Measured by ABPM | Nighttime Mean DBP | 1.9 mmHg | Standard Error 2.17 |
| LCI699 0.25 mg BID | Change From Baseline in Mean 24 Hours, Mean Daytime and Mean Nighttime Diastolic Blood Pressure (DBP) at Week 8 LOCF, as Measured by ABPM | Daytime Mean DBP | 0.6 mmHg | Standard Error 2.31 |
| LCI699 0.25 mg BID | Change From Baseline in Mean 24 Hours, Mean Daytime and Mean Nighttime Diastolic Blood Pressure (DBP) at Week 8 LOCF, as Measured by ABPM | 24-hour Mean DBP | 1.0 mmHg | Standard Error 2.15 |
| LCI699 1 mg QD | Change From Baseline in Mean 24 Hours, Mean Daytime and Mean Nighttime Diastolic Blood Pressure (DBP) at Week 8 LOCF, as Measured by ABPM | Daytime Mean DBP | -3.6 mmHg | Standard Error 2.06 |
| LCI699 1 mg QD | Change From Baseline in Mean 24 Hours, Mean Daytime and Mean Nighttime Diastolic Blood Pressure (DBP) at Week 8 LOCF, as Measured by ABPM | 24-hour Mean DBP | -3.4 mmHg | Standard Error 1.94 |
| LCI699 1 mg QD | Change From Baseline in Mean 24 Hours, Mean Daytime and Mean Nighttime Diastolic Blood Pressure (DBP) at Week 8 LOCF, as Measured by ABPM | Nighttime Mean DBP | -2.5 mmHg | Standard Error 1.98 |
| LCI699 0.5 mg Followed by LCI699 1 mg BID | Change From Baseline in Mean 24 Hours, Mean Daytime and Mean Nighttime Diastolic Blood Pressure (DBP) at Week 8 LOCF, as Measured by ABPM | Nighttime Mean DBP | -4.6 mmHg | Standard Error 1.69 |
| LCI699 0.5 mg Followed by LCI699 1 mg BID | Change From Baseline in Mean 24 Hours, Mean Daytime and Mean Nighttime Diastolic Blood Pressure (DBP) at Week 8 LOCF, as Measured by ABPM | 24-hour Mean DBP | -3.7 mmHg | Standard Error 1.67 |
| LCI699 0.5 mg Followed by LCI699 1 mg BID | Change From Baseline in Mean 24 Hours, Mean Daytime and Mean Nighttime Diastolic Blood Pressure (DBP) at Week 8 LOCF, as Measured by ABPM | Daytime Mean DBP | -3.4 mmHg | Standard Error 1.78 |
| Eplerenone 50 mg BID | Change From Baseline in Mean 24 Hours, Mean Daytime and Mean Nighttime Diastolic Blood Pressure (DBP) at Week 8 LOCF, as Measured by ABPM | Nighttime Mean DBP | -9.6 mmHg | Standard Error 1.75 |
| Eplerenone 50 mg BID | Change From Baseline in Mean 24 Hours, Mean Daytime and Mean Nighttime Diastolic Blood Pressure (DBP) at Week 8 LOCF, as Measured by ABPM | 24-hour Mean DBP | -9.6 mmHg | Standard Error 1.74 |
| Eplerenone 50 mg BID | Change From Baseline in Mean 24 Hours, Mean Daytime and Mean Nighttime Diastolic Blood Pressure (DBP) at Week 8 LOCF, as Measured by ABPM | Daytime Mean DBP | -9.5 mmHg | Standard Error 1.86 |
| Placebo | Change From Baseline in Mean 24 Hours, Mean Daytime and Mean Nighttime Diastolic Blood Pressure (DBP) at Week 8 LOCF, as Measured by ABPM | Daytime Mean DBP | -0.8 mmHg | Standard Error 1.87 |
| Placebo | Change From Baseline in Mean 24 Hours, Mean Daytime and Mean Nighttime Diastolic Blood Pressure (DBP) at Week 8 LOCF, as Measured by ABPM | 24-hour Mean DBP | -0.2 mmHg | Standard Error 1.74 |
| Placebo | Change From Baseline in Mean 24 Hours, Mean Daytime and Mean Nighttime Diastolic Blood Pressure (DBP) at Week 8 LOCF, as Measured by ABPM | Nighttime Mean DBP | 1.2 mmHg | Standard Error 1.76 |
Secondary
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
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.
Time frame: Baseline, Week 4
Population: FAS population included all participants who were randomized and received at least 1 dose of study drug. Overall number of participants analyzed signifies the number of participants who were evaluable for this measure. Here, Number Analyzed 'n' represents number of participants who were evaluable for that specific category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LCI699 0.25 mg BID | 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 | 24-hour Mean SBP | -7.8 mmHg | Standard Error 2.72 |
| LCI699 0.25 mg BID | 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 | Daytime Mean SBP | -8.1 mmHg | Standard Error 2.69 |
| LCI699 0.25 mg BID | 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 | Nighttime Mean SBP | -6.8 mmHg | Standard Error 3.17 |
| LCI699 1 mg QD | 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 | 24-hour Mean SBP | -4.7 mmHg | Standard Error 2.29 |
| LCI699 1 mg QD | 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 | Daytime Mean SBP | -5.3 mmHg | Standard Error 2.27 |
| LCI699 1 mg QD | 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 | Nighttime Mean SBP | -4.5 mmHg | Standard Error 2.7 |
Secondary
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)
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.
Time frame: Baseline, Week 8
Population: FAS population included all participants who were randomized and received at least 1 dose of study drug. Overall number of participants analyzed signifies the number of participants who were evaluable for this measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LCI699 0.25 mg BID | 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) | 24-hour Mean SBP | -4.4 mmHg | Standard Error 3.22 |
| LCI699 0.25 mg BID | 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) | Nighttime Mean SBP | -3.2 mmHg | Standard Error 3.49 |
| LCI699 0.25 mg BID | 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) | Daytime Mean SBP | -4.9 mmHg | Standard Error 3.29 |
| LCI699 1 mg QD | 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) | Daytime Mean SBP | -6.0 mmHg | Standard Error 2.92 |
| LCI699 1 mg QD | 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) | 24-hour Mean SBP | -5.7 mmHg | Standard Error 2.87 |
| LCI699 1 mg QD | 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) | Nighttime Mean SBP | -4.8 mmHg | Standard Error 3.13 |
| LCI699 0.5 mg Followed by LCI699 1 mg BID | 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) | Daytime Mean SBP | -6.3 mmHg | Standard Error 2.52 |
| LCI699 0.5 mg Followed by LCI699 1 mg BID | 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) | 24-hour Mean SBP | -6.3 mmHg | Standard Error 2.47 |
| LCI699 0.5 mg Followed by LCI699 1 mg BID | 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) | Nighttime Mean SBP | -7.0 mmHg | Standard Error 2.67 |
| Eplerenone 50 mg BID | 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) | 24-hour Mean SBP | -15.7 mmHg | Standard Error 2.59 |
| Eplerenone 50 mg BID | 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) | Nighttime Mean SBP | -15.4 mmHg | Standard Error 2.81 |
| Eplerenone 50 mg BID | 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) | Daytime Mean SBP | -15.7 mmHg | Standard Error 2.65 |
| Placebo | 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) | Daytime Mean SBP | -1.6 mmHg | Standard Error 2.65 |
| Placebo | 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) | 24-hour Mean SBP | -1.0 mmHg | Standard Error 2.59 |
| Placebo | 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) | Nighttime Mean SBP | 0.4 mmHg | Standard Error 2.81 |
Secondary
Change From Baseline in MSDBP at Week 8 LOCF
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.
Time frame: Baseline, Week 8
Population: FAS population included all participants who were randomized and received at least 1 dose of study drug. Overall number of participants analyzed signifies the number of participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LCI699 0.25 mg BID | Change From Baseline in MSDBP at Week 8 LOCF | -4.5 mmHg | Standard Error 1.72 |
| LCI699 1 mg QD | Change From Baseline in MSDBP at Week 8 LOCF | -6.0 mmHg | Standard Error 1.88 |
| LCI699 0.5 mg Followed by LCI699 1 mg BID | Change From Baseline in MSDBP at Week 8 LOCF | -6.1 mmHg | Standard Error 1.72 |
| Eplerenone 50 mg BID | Change From Baseline in MSDBP at Week 8 LOCF | -7.7 mmHg | Standard Error 1.69 |
| Placebo | Change From Baseline in MSDBP at Week 8 LOCF | -4.8 mmHg | Standard Error 1.66 |
Secondary
Dose/Exposure BP Response Relationship of LCI699, as Measured by Change From Baseline in MSDBP at 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.
Time frame: Baseline, Week 8
Population: FAS population included all participants who were randomized and received at least 1 dose of study drug. Overall number of participants analyzed signifies the number of participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LCI699 0.25 mg BID | Dose/Exposure BP Response Relationship of LCI699, as Measured by Change From Baseline in MSDBP at Week 8 | -4.5 mmHg | Standard Error 1.72 |
| LCI699 1 mg QD | Dose/Exposure BP Response Relationship of LCI699, as Measured by Change From Baseline in MSDBP at Week 8 | -6.0 mmHg | Standard Error 1.88 |
| LCI699 0.5 mg Followed by LCI699 1 mg BID | Dose/Exposure BP Response Relationship of LCI699, as Measured by Change From Baseline in MSDBP at Week 8 | -6.1 mmHg | Standard Error 1.72 |
Secondary
Dose/Exposure BP Response Relationship of LCI699, as Measured by Change From Baseline in MSSBP at 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.
Time frame: Baseline, Week 8
Population: FAS population included all participants who were randomized and received at least 1 dose of study drug. Overall number of participants analyzed signifies the number of participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LCI699 0.25 mg BID | Dose/Exposure BP Response Relationship of LCI699, as Measured by Change From Baseline in MSSBP at Week 8 | -11.4 mmHg | Standard Error 2.96 |
| LCI699 1 mg QD | Dose/Exposure BP Response Relationship of LCI699, as Measured by Change From Baseline in MSSBP at Week 8 | -13.1 mmHg | Standard Error 3.24 |
| LCI699 0.5 mg Followed by LCI699 1 mg BID | Dose/Exposure BP Response Relationship of LCI699, as Measured by Change From Baseline in MSSBP at Week 8 | -12.5 mmHg | Standard Error 2.96 |
Secondary
Number of Participants With Adverse Event (AEs), Serious Adverse Events (SAEs), Hyperkalemia, and Hyponatremia
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.
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
Population: Safety set population included all participants who were randomized and received at least 1 dose of study drug. Here, Number Analyzed represents the number of participants who were evaluable for that specific category.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| LCI699 0.25 mg BID | Number of Participants With Adverse Event (AEs), Serious Adverse Events (SAEs), Hyperkalemia, and Hyponatremia | AE(s) | 15 Participants |
| LCI699 0.25 mg BID | Number of Participants With Adverse Event (AEs), Serious Adverse Events (SAEs), Hyperkalemia, and Hyponatremia | SAE(s) | 0 Participants |
| LCI699 0.25 mg BID | Number of Participants With Adverse Event (AEs), Serious Adverse Events (SAEs), Hyperkalemia, and Hyponatremia | Hyperkalemia [potassium level >5.5 mmol/L] | 2 Participants |
| LCI699 0.25 mg BID | Number of Participants With Adverse Event (AEs), Serious Adverse Events (SAEs), Hyperkalemia, and Hyponatremia | Hyperkalemia [potassium level ≥6.0 mmol/L] | 2 Participants |
| LCI699 0.25 mg BID | Number of Participants With Adverse Event (AEs), Serious Adverse Events (SAEs), Hyperkalemia, and Hyponatremia | Hyponatremia [sodium level <130 and ≥125 mmol/L] | 0 Participants |
| LCI699 0.25 mg BID | Number of Participants With Adverse Event (AEs), Serious Adverse Events (SAEs), Hyperkalemia, and Hyponatremia | Hyponatremia [sodium level <135 mmol/L and ≥130mmol/L] | 3 Participants |
| LCI699 1 mg QD | Number of Participants With Adverse Event (AEs), Serious Adverse Events (SAEs), Hyperkalemia, and Hyponatremia | Hyponatremia [sodium level <130 and ≥125 mmol/L] | 0 Participants |
| LCI699 1 mg QD | Number of Participants With Adverse Event (AEs), Serious Adverse Events (SAEs), Hyperkalemia, and Hyponatremia | Hyponatremia [sodium level <135 mmol/L and ≥130mmol/L] | 2 Participants |
| LCI699 1 mg QD | Number of Participants With Adverse Event (AEs), Serious Adverse Events (SAEs), Hyperkalemia, and Hyponatremia | AE(s) | 15 Participants |
| LCI699 1 mg QD | Number of Participants With Adverse Event (AEs), Serious Adverse Events (SAEs), Hyperkalemia, and Hyponatremia | Hyperkalemia [potassium level >5.5 mmol/L] | 0 Participants |
| LCI699 1 mg QD | Number of Participants With Adverse Event (AEs), Serious Adverse Events (SAEs), Hyperkalemia, and Hyponatremia | Hyperkalemia [potassium level ≥6.0 mmol/L] | 0 Participants |
| LCI699 1 mg QD | Number of Participants With Adverse Event (AEs), Serious Adverse Events (SAEs), Hyperkalemia, and Hyponatremia | SAE(s) | 0 Participants |
| LCI699 0.5 mg Followed by LCI699 1 mg BID | Number of Participants With Adverse Event (AEs), Serious Adverse Events (SAEs), Hyperkalemia, and Hyponatremia | Hyperkalemia [potassium level ≥6.0 mmol/L] | 0 Participants |
| LCI699 0.5 mg Followed by LCI699 1 mg BID | Number of Participants With Adverse Event (AEs), Serious Adverse Events (SAEs), Hyperkalemia, and Hyponatremia | Hyponatremia [sodium level <130 and ≥125 mmol/L] | 0 Participants |
| LCI699 0.5 mg Followed by LCI699 1 mg BID | Number of Participants With Adverse Event (AEs), Serious Adverse Events (SAEs), Hyperkalemia, and Hyponatremia | AE(s) | 8 Participants |
| LCI699 0.5 mg Followed by LCI699 1 mg BID | Number of Participants With Adverse Event (AEs), Serious Adverse Events (SAEs), Hyperkalemia, and Hyponatremia | Hyperkalemia [potassium level >5.5 mmol/L] | 0 Participants |
| LCI699 0.5 mg Followed by LCI699 1 mg BID | Number of Participants With Adverse Event (AEs), Serious Adverse Events (SAEs), Hyperkalemia, and Hyponatremia | SAE(s) | 0 Participants |
| LCI699 0.5 mg Followed by LCI699 1 mg BID | Number of Participants With Adverse Event (AEs), Serious Adverse Events (SAEs), Hyperkalemia, and Hyponatremia | Hyponatremia [sodium level <135 mmol/L and ≥130mmol/L] | 7 Participants |
| Eplerenone 50 mg BID | Number of Participants With Adverse Event (AEs), Serious Adverse Events (SAEs), Hyperkalemia, and Hyponatremia | Hyperkalemia [potassium level ≥6.0 mmol/L] | 0 Participants |
| Eplerenone 50 mg BID | Number of Participants With Adverse Event (AEs), Serious Adverse Events (SAEs), Hyperkalemia, and Hyponatremia | SAE(s) | 1 Participants |
| Eplerenone 50 mg BID | Number of Participants With Adverse Event (AEs), Serious Adverse Events (SAEs), Hyperkalemia, and Hyponatremia | Hyperkalemia [potassium level >5.5 mmol/L] | 0 Participants |
| Eplerenone 50 mg BID | Number of Participants With Adverse Event (AEs), Serious Adverse Events (SAEs), Hyperkalemia, and Hyponatremia | Hyponatremia [sodium level <135 mmol/L and ≥130mmol/L] | 3 Participants |
| Eplerenone 50 mg BID | Number of Participants With Adverse Event (AEs), Serious Adverse Events (SAEs), Hyperkalemia, and Hyponatremia | Hyponatremia [sodium level <130 and ≥125 mmol/L] | 1 Participants |
| Eplerenone 50 mg BID | Number of Participants With Adverse Event (AEs), Serious Adverse Events (SAEs), Hyperkalemia, and Hyponatremia | AE(s) | 13 Participants |
| Placebo | Number of Participants With Adverse Event (AEs), Serious Adverse Events (SAEs), Hyperkalemia, and Hyponatremia | Hyponatremia [sodium level <130 and ≥125 mmol/L] | 0 Participants |
| Placebo | Number of Participants With Adverse Event (AEs), Serious Adverse Events (SAEs), Hyperkalemia, and Hyponatremia | Hyperkalemia [potassium level >5.5 mmol/L] | 1 Participants |
| Placebo | Number of Participants With Adverse Event (AEs), Serious Adverse Events (SAEs), Hyperkalemia, and Hyponatremia | SAE(s) | 0 Participants |
| Placebo | Number of Participants With Adverse Event (AEs), Serious Adverse Events (SAEs), Hyperkalemia, and Hyponatremia | Hyponatremia [sodium level <135 mmol/L and ≥130mmol/L] | 2 Participants |
| Placebo | Number of Participants With Adverse Event (AEs), Serious Adverse Events (SAEs), Hyperkalemia, and Hyponatremia | Hyperkalemia [potassium level ≥6.0 mmol/L] | 0 Participants |
| Placebo | Number of Participants With Adverse Event (AEs), Serious Adverse Events (SAEs), Hyperkalemia, and Hyponatremia | AE(s) | 16 Participants |
Secondary
Number of Participants With Cortisol Levels Below 500 Nmol/L at 1 Hour After Adrenocorticotropic Hormone (ACTH) Injection 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.
Time frame: 1-hour post-dose at Week 8
Population: ACTH stimulation test subset population included all participants prior to treatment with LCI699 and at the end of the treatment interval (Week 8).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| LCI699 0.25 mg BID | Number of Participants With Cortisol Levels Below 500 Nmol/L at 1 Hour After Adrenocorticotropic Hormone (ACTH) Injection at Week 8 | 0 Participants |
| LCI699 1 mg QD | Number of Participants With Cortisol Levels Below 500 Nmol/L at 1 Hour After Adrenocorticotropic Hormone (ACTH) Injection at Week 8 | 1 Participants |
| LCI699 0.5 mg Followed by LCI699 1 mg BID | Number of Participants With Cortisol Levels Below 500 Nmol/L at 1 Hour After Adrenocorticotropic Hormone (ACTH) Injection at Week 8 | 4 Participants |
| Eplerenone 50 mg BID | Number of Participants With Cortisol Levels Below 500 Nmol/L at 1 Hour After Adrenocorticotropic Hormone (ACTH) Injection at Week 8 | 0 Participants |
| Placebo | Number of Participants With Cortisol Levels Below 500 Nmol/L at 1 Hour After Adrenocorticotropic Hormone (ACTH) Injection at Week 8 | 0 Participants |
Secondary
Percentage of Participants With a MSDBP Response and MSDBP Control at Week 8, as Measured by OBP
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.
Time frame: Week 8
Population: FAS population included all participants who were randomized and received at least 1 dose of study drug. Overall number of participants analyzed signifies the number of participants who were evaluable for this measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LCI699 0.25 mg BID | Percentage of Participants With a MSDBP Response and MSDBP Control at Week 8, as Measured by OBP | MSDBP Response | 67.7 percentage of participants |
| LCI699 0.25 mg BID | Percentage of Participants With a MSDBP Response and MSDBP Control at Week 8, as Measured by OBP | MSDBP Control | 54.8 percentage of participants |
| LCI699 1 mg QD | Percentage of Participants With a MSDBP Response and MSDBP Control at Week 8, as Measured by OBP | MSDBP Response | 73.1 percentage of participants |
| LCI699 1 mg QD | Percentage of Participants With a MSDBP Response and MSDBP Control at Week 8, as Measured by OBP | MSDBP Control | 65.4 percentage of participants |
| LCI699 0.5 mg Followed by LCI699 1 mg BID | Percentage of Participants With a MSDBP Response and MSDBP Control at Week 8, as Measured by OBP | MSDBP Response | 71.0 percentage of participants |
| LCI699 0.5 mg Followed by LCI699 1 mg BID | Percentage of Participants With a MSDBP Response and MSDBP Control at Week 8, as Measured by OBP | MSDBP Control | 58.1 percentage of participants |
| Eplerenone 50 mg BID | Percentage of Participants With a MSDBP Response and MSDBP Control at Week 8, as Measured by OBP | MSDBP Control | 56.3 percentage of participants |
| Eplerenone 50 mg BID | Percentage of Participants With a MSDBP Response and MSDBP Control at Week 8, as Measured by OBP | MSDBP Response | 71.9 percentage of participants |
| Placebo | Percentage of Participants With a MSDBP Response and MSDBP Control at Week 8, as Measured by OBP | MSDBP Response | 57.6 percentage of participants |
| Placebo | Percentage of Participants With a MSDBP Response and MSDBP Control at Week 8, as Measured by OBP | MSDBP Control | 54.5 percentage of participants |
Secondary
Percentage of Participants With a MSSBP Response and MSSBP Control at Week 8, as Measured by Office Blood Pressure (OBP)
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.
Time frame: Week 8
Population: FAS population included all participants who were randomized and received at least 1 dose of study drug. Overall number of participants analyzed signifies the number of participants who were evaluable for this measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LCI699 0.25 mg BID | Percentage of Participants With a MSSBP Response and MSSBP Control at Week 8, as Measured by Office Blood Pressure (OBP) | MSSBP Control | 51.6 percentage of participants |
| LCI699 0.25 mg BID | Percentage of Participants With a MSSBP Response and MSSBP Control at Week 8, as Measured by Office Blood Pressure (OBP) | MSSBP Response | 54.8 percentage of participants |
| LCI699 1 mg QD | Percentage of Participants With a MSSBP Response and MSSBP Control at Week 8, as Measured by Office Blood Pressure (OBP) | MSSBP Response | 57.7 percentage of participants |
| LCI699 1 mg QD | Percentage of Participants With a MSSBP Response and MSSBP Control at Week 8, as Measured by Office Blood Pressure (OBP) | MSSBP Control | 50.0 percentage of participants |
| LCI699 0.5 mg Followed by LCI699 1 mg BID | Percentage of Participants With a MSSBP Response and MSSBP Control at Week 8, as Measured by Office Blood Pressure (OBP) | MSSBP Response | 41.9 percentage of participants |
| LCI699 0.5 mg Followed by LCI699 1 mg BID | Percentage of Participants With a MSSBP Response and MSSBP Control at Week 8, as Measured by Office Blood Pressure (OBP) | MSSBP Control | 32.3 percentage of participants |
| Eplerenone 50 mg BID | Percentage of Participants With a MSSBP Response and MSSBP Control at Week 8, as Measured by Office Blood Pressure (OBP) | MSSBP Control | 53.1 percentage of participants |
| Eplerenone 50 mg BID | Percentage of Participants With a MSSBP Response and MSSBP Control at Week 8, as Measured by Office Blood Pressure (OBP) | MSSBP Response | 65.6 percentage of participants |
| Placebo | Percentage of Participants With a MSSBP Response and MSSBP Control at Week 8, as Measured by Office Blood Pressure (OBP) | MSSBP Response | 42.4 percentage of participants |
| Placebo | Percentage of Participants With a MSSBP Response and MSSBP Control at Week 8, as Measured by Office Blood Pressure (OBP) | MSSBP Control | 36.4 percentage of participants |
Secondary
Percent Change From Baseline in RAAS Biomarker: Active Renin (ARC) in LCI699 Compared to Eplerenone 50mg at Week 8 LOCF
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.
Time frame: Baseline, Week 8
Population: FAS population included all participants who were randomized and received at least 1 dose of study drug. Overall number of participants analyzed signifies the number of participants who were evaluable for this measure.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LCI699 0.25 mg BID | Percent Change From Baseline in RAAS Biomarker: Active Renin (ARC) in LCI699 Compared to Eplerenone 50mg at Week 8 LOCF | 73.1 percent change in ARC | Standard Error 0.24 |
| LCI699 1 mg QD | Percent Change From Baseline in RAAS Biomarker: Active Renin (ARC) in LCI699 Compared to Eplerenone 50mg at Week 8 LOCF | 72.8 percent change in ARC | Standard Error 0.27 |
| LCI699 0.5 mg Followed by LCI699 1 mg BID | Percent Change From Baseline in RAAS Biomarker: Active Renin (ARC) in LCI699 Compared to Eplerenone 50mg at Week 8 LOCF | 156.4 percent change in ARC | Standard Error 0.23 |
| Eplerenone 50 mg BID | Percent Change From Baseline in RAAS Biomarker: Active Renin (ARC) in LCI699 Compared to Eplerenone 50mg at Week 8 LOCF | 430.6 percent change in ARC | Standard Error 0.22 |
Secondary
Percent Change From Baseline in RAAS Biomarker: Plasma Renin Activity (PRA) in LCI699 Compared to Eplerenone 50mg at Week 8 LOCF
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.
Time frame: Baseline, Week 8
Population: FAS population included all participants who were randomized and received at least 1 dose of study drug. Overall number of participants analyzed signifies the number of participants who were evaluable for this measure.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LCI699 0.25 mg BID | Percent Change From Baseline in RAAS Biomarker: Plasma Renin Activity (PRA) in LCI699 Compared to Eplerenone 50mg at Week 8 LOCF | 41.6 percent change in PRA | Standard Error 0.24 |
| LCI699 1 mg QD | Percent Change From Baseline in RAAS Biomarker: Plasma Renin Activity (PRA) in LCI699 Compared to Eplerenone 50mg at Week 8 LOCF | 74.3 percent change in PRA | Standard Error 0.28 |
| LCI699 0.5 mg Followed by LCI699 1 mg BID | Percent Change From Baseline in RAAS Biomarker: Plasma Renin Activity (PRA) in LCI699 Compared to Eplerenone 50mg at Week 8 LOCF | 107.7 percent change in PRA | Standard Error 0.24 |
| Eplerenone 50 mg BID | Percent Change From Baseline in RAAS Biomarker: Plasma Renin Activity (PRA) in LCI699 Compared to Eplerenone 50mg at Week 8 LOCF | 414.1 percent change in PRA | Standard Error 0.22 |
Secondary
Percent Change From Baseline in RAAS Biomarker: Ratio of PA to PRA in LCI699 Compared to Eplerenone 50mg at Week 8 LOCF
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.
Time frame: Baseline, Week 8
Population: FAS population included all participants who were randomized and received at least 1 dose of study drug. Overall number of participants analyzed signifies the number of participants who were evaluable for this measure.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LCI699 0.25 mg BID | Percent Change From Baseline in RAAS Biomarker: Ratio of PA to PRA in LCI699 Compared to Eplerenone 50mg at Week 8 LOCF | -46.7 percent change in ratio of PA to PRA | Standard Error 0.26 |
| LCI699 1 mg QD | Percent Change From Baseline in RAAS Biomarker: Ratio of PA to PRA in LCI699 Compared to Eplerenone 50mg at Week 8 LOCF | -50.0 percent change in ratio of PA to PRA | Standard Error 0.29 |
| LCI699 0.5 mg Followed by LCI699 1 mg BID | Percent Change From Baseline in RAAS Biomarker: Ratio of PA to PRA in LCI699 Compared to Eplerenone 50mg at Week 8 LOCF | -78.3 percent change in ratio of PA to PRA | Standard Error 0.25 |
| Eplerenone 50 mg BID | Percent Change From Baseline in RAAS Biomarker: Ratio of PA to PRA in LCI699 Compared to Eplerenone 50mg at Week 8 LOCF | -57.1 percent change in ratio of PA to PRA | Standard Error 0.23 |
Secondary
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
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.
Time frame: Baseline, Week 8
Population: FAS population included all participants who were randomized and received at least 1 dose of study drug. Overall number of participants analyzed signifies the number of participants who were evaluable for this measure.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LCI699 0.25 mg BID | 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 | -22.3 percent change in aldosterone | Standard Error 0.16 |
| LCI699 1 mg QD | 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 | -30.4 percent change in aldosterone | Standard Error 0.17 |
| LCI699 0.5 mg Followed by LCI699 1 mg BID | 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 | -53.1 percent change in aldosterone | Standard Error 0.15 |
| Eplerenone 50 mg BID | 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 | 115.0 percent change in aldosterone | Standard Error 0.15 |