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| ID | Type | Description | Link |
|---|---|---|---|
| 2008-007338-23 | EudraCT Number |
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| Name | Class |
|---|---|
| Great Lakes Drug Development, Inc. | INDUSTRY |
| Integrium | INDUSTRY |
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This study assessed the blood pressure effect, safety and tolerability of LCI699 compared to placebo and eplerenone in participants with resistant hypertension.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| LCI699 0.25 mg BID | Experimental | 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 | Experimental | 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 | Experimental | 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. |
|
| Eplerenone 50 mg BID | Active Comparator | 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. |
|
| Placebo | Placebo Comparator | 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LCI699 | Drug | LCI699 oral capsules |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline, Week 8 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion criteria:
Exclusion criteria:
Other protocol-defined inclusion/exclusion criteria may apply.
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Horizon Research Group, Inc | Mobile | Alabama | 36608 | United States | ||
| Cochise Clinical Research |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24107737 | Derived | 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. |
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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 took part in this study at 35 investigative sites in the United States and in Iceland from 22 December 2008 to 13 October 2009.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | LCI699 1 mg QD |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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|
| Eplerenone | Drug | Eplerenone oral capsules |
|
| LCI699-matching Placebo | Drug | LCI699-matching placebo oral capsules |
|
| Eplerenone-matching Placebo | Drug | Eplerenone-matching placebo oral capsules |
|
| Baseline, Week 8 |
| 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. | Week 8 |
| 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. | Week 8 |
| 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. | Baseline, Week 8 |
| 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. | Baseline, Week 8 |
| 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. | Baseline, Week 8 |
| 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. | Baseline, Week 8 |
| 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. | Baseline, Week 4 |
| 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. | Baseline, Week 4 |
| 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. | 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 |
| 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. | 1-hour post-dose at Week 8 |
| 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. | Baseline, Week 8 |
| 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. | Baseline, Week 8 |
| 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. | Baseline, Week 8 |
| 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. | Baseline, Week 8 |
| Sierra Vista |
| Arizona |
| 85635 |
| United States |
| Clinical Solutions Advantage | Buena Park | California | 90620 | United States |
| Michael Waldman, MD | Irvine | California | 92618 | United States |
| Long Beach Center for Clinical Research | Long Beach | California | 90806 | United States |
| Clinical Trials Research | Roseville | California | 95661 | United States |
| Orange County Research Center | Tustin | California | 92780 | United States |
| Metro Clinical Research | Littleton | Colorado | 80120 | United States |
| Meridien Research | Bradenton | Florida | 34203 | United States |
| Clinical Research of So. Florida | Coral Gables | Florida | 33134 | United States |
| Jacksonville Heart Center | Jacksonville Beach | Florida | 32250 | United States |
| FPA Clinical Research | Kissimmee | Florida | 34741 | United States |
| Accelovance | Melbourne | Florida | 32935 | United States |
| Cardio-Pulminary Associates | Plantation | Florida | 33317 | United States |
| Meridien Research | St. Petersburg | Florida | 33709 | United States |
| Northwest Clinical Trials | Boise | Idaho | 83704 | United States |
| Provident Clinical Research | Addison | Illinois | 60101 | United States |
| Cedar-Crosse Research Centereet | Chicago | Illinois | 60607 | United States |
| Provident Clinical Research | Bloomington | Indiana | 47403 | United States |
| Accelovance | South Bend | Indiana | 46601 | United States |
| Peter A. Holt | Baltimore | Maryland | 21239 | United States |
| MD Medical Research | Oxon Hill | Maryland | 20745 | United States |
| Chelsea Internal Medicine | Chelsea | Michigan | 48118 | United States |
| New York Cardiovascular Associates | New York | New York | 10001 | United States |
| Charlotte Clinical Research | Charlotte | North Carolina | 28211 | United States |
| Northstate Clinical Research | Lenoir | North Carolina | 28645 | United States |
| Community Research | Cincinnati | Ohio | 45245 | United States |
| Tipton Medical & Diagnostic Center | Tipton | Pennsylvania | 16684 | United States |
| Medical Research South | Charleston | South Carolina | 29407 | United States |
| Mountain View Clinical Research Associates | Greer | South Carolina | 29651 | United States |
| Clinical Research Associates, Inc | Nashville | Tennessee | 37203 | United States |
| Punzi Medical Center | Carrollton | Texas | 75006 | United States |
| KRK Medical Research | Dallas | Texas | 75230 | United States |
| DCOL Center for Clinical Research | Longview | Texas | 75605 | United States |
| Daniel Gottlieb, MD | Burien | Washington | 98166 | United States |
| Rainier Clinical Research Center | Renton | Washington | 98057 | United States |
| Gemini Scientific | Madison | Wisconsin | 83719 | United States |
| Encode Clinic | Reykjavik | SA | Iceland |
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.
| FG002 | 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. |
| FG003 | 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. |
| FG004 | 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. |
| COMPLETED |
|
| NOT COMPLETED |
|
|
Full Analysis set (FAS) population included all participants who were randomized and received at least 1 dose of study drug.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | 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. |
| BG002 | 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. |
| BG003 | 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. |
| BG004 | 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. |
| BG005 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Baseline Mean Sitting Systolic Blood Pressure (MSSBP) | Mean | Standard Deviation | millimeters of mercury (mmHg) |
| |||||||||||||||
| Baseline Mean Sitting Diastolic Blood Pressure (MSDBP) | Mean | Standard Deviation | mmHg |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 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. | Posted | Mean | Standard Error | mmHg | Baseline, Week 8 |
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| 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. | 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. | Posted | Mean | Standard Error | mmHg | Baseline, Week 8 |
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| 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. | 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. | Posted | Number | percentage of participants | Week 8 |
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| 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. | 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. | Posted | Number | percentage of participants | Week 8 |
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| 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. | 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. | Posted | Mean | Standard Error | mmHg | Baseline, Week 8 |
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| 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. | 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. | Posted | Mean | Standard Error | mmHg | Baseline, Week 8 |
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| 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. | 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. | Posted | Mean | Standard Error | mmHg | Baseline, Week 8 |
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| 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. | 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. | Posted | Mean | Standard Error | mmHg | Baseline, Week 8 |
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| 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. | 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. | Posted | Mean | Standard Error | mmHg | Baseline, Week 4 |
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| 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. | 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. | Posted | Mean | Standard Error | mmHg | Baseline, Week 4 |
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| 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. | 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. | Posted | Count of Participants | Participants | 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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| 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. | ACTH stimulation test subset population included all participants prior to treatment with LCI699 and at the end of the treatment interval (Week 8). | Posted | Count of Participants | Participants | 1-hour post-dose at Week 8 |
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| 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. | 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. | Posted | Geometric Least Squares Mean | Standard Error | percent change in aldosterone | Baseline, Week 8 |
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| 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. | 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. | Posted | Geometric Least Squares Mean | Standard Error | percent change in PRA | Baseline, Week 8 |
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| 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. | 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. | Posted | Geometric Least Squares Mean | Standard Error | percent change in ARC | Baseline, Week 8 |
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| 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. | 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. | Posted | Geometric Least Squares Mean | Standard Error | percent change in ratio of PA to PRA | Baseline, Week 8 |
|
AEs: From start of the study drug treatment up to 10 weeks; SAE: From signing of the informed consent up to 10 weeks
Safety set population included all participants who were randomized and received at least 1 dose of study drug.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. | 0 | 32 | 0 | 32 | 15 | 32 |
| EG001 | LCI699 1.0 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. | 0 | 26 | 0 | 26 | 15 | 26 |
| EG002 | 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. | 0 | 31 | 0 | 31 | 8 | 31 |
| EG003 | 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. | 0 | 33 | 1 | 33 | 13 | 33 |
| EG004 | 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. | 0 | 33 | 0 | 33 | 16 | 33 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cerebrovascular accident | Nervous system disorders | MedDRA (unspecified) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Palpitations | Cardiac disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Inner ear inflammation | Ear and labyrinth disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Goitre | Endocrine disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Conjunctival haemorrhage | Eye disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Food poisoning | Gastrointestinal disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Frequent bowel movements | Gastrointestinal disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Haematochezia | Gastrointestinal disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Oedema | General disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Pain | General disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Multiple allergies | Immune system disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA (unspecified) | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA (unspecified) | Systematic Assessment |
| |
| Tooth infection | Infections and infestations | MedDRA (unspecified) | Systematic Assessment |
| |
| Arthropod bite | Injury, poisoning and procedural complications | MedDRA (unspecified) | Systematic Assessment |
| |
| Chest injury | Injury, poisoning and procedural complications | MedDRA (unspecified) | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA (unspecified) | Systematic Assessment |
| |
| Joint sprain | Injury, poisoning and procedural complications | MedDRA (unspecified) | Systematic Assessment |
| |
| Muscle strain | Injury, poisoning and procedural complications | MedDRA (unspecified) | Systematic Assessment |
| |
| Scratch | Injury, poisoning and procedural complications | MedDRA (unspecified) | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA (unspecified) | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA (unspecified) | Systematic Assessment |
| |
| Blood chloride increased | Investigations | MedDRA (unspecified) | Systematic Assessment |
| |
| Blood cortisol decreased | Investigations | MedDRA (unspecified) | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA (unspecified) | Systematic Assessment |
| |
| Blood glucose increased | Investigations | MedDRA (unspecified) | Systematic Assessment |
| |
| Blood potassium increased | Investigations | MedDRA (unspecified) | Systematic Assessment |
| |
| Blood sodium decreased | Investigations | MedDRA (unspecified) | Systematic Assessment |
| |
| Blood sodium increased | Investigations | MedDRA (unspecified) | Systematic Assessment |
| |
| Blood urea increased | Investigations | MedDRA (unspecified) | Systematic Assessment |
| |
| Blood uric acid increased | Investigations | MedDRA (unspecified) | Systematic Assessment |
| |
| Eosinophil count increased | Investigations | MedDRA (unspecified) | Systematic Assessment |
| |
| Glucose urine present | Investigations | MedDRA (unspecified) | Systematic Assessment |
| |
| Heart rate irregular | Investigations | MedDRA (unspecified) | Systematic Assessment |
| |
| Anorexia | Metabolism and nutrition disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Type 2 diabetes mellitus | Metabolism and nutrition disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Costochondritis | Musculoskeletal and connective tissue disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Joint swelling | Musculoskeletal and connective tissue disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Hypoaesthesia | Nervous system disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Somnolence | Nervous system disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Speech disorder | Nervous system disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Tremor | Nervous system disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Anxiety disorder | Psychiatric disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Disorientation | Psychiatric disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Mood altered | Psychiatric disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Dysuria | Renal and urinary disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Polyuria | Renal and urinary disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Pyuria | Renal and urinary disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Urine odour abnormal | Renal and urinary disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Rhinitis allergic | Respiratory, thoracic and mediastinal disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Upper respiratory tract congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Petechiae | Skin and subcutaneous tissue disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Flushing | Vascular disorders | MedDRA (unspecified) | Systematic Assessment |
| |
| Venous thrombosis | Vascular disorders | MedDRA (unspecified) | Systematic Assessment |
|
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | 862-778-8300 | Novartis.email@novartis.com |
| ID | Term |
|---|---|
| D006973 | Hypertension |
| ID | Term |
|---|---|
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C553306 | Osilodrostat |
| D000077545 | Eplerenone |
| ID | Term |
|---|---|
| D007783 | Lactones |
| D009930 | Organic Chemicals |
| D011283 | Pregnenes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
Not provided
Not provided
| Male |
|
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.
| OG003 | 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. |
| OG004 | 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. |
|
|
| OG003 | 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. |
| OG004 | 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. |
|
|
| OG003 | 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. |
| OG004 | 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. |
|
|
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. |
|
|
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. |
|
|
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. |
| OG003 | 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. |
| OG004 | 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. |
|
|
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. |
| OG003 | 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. |
| OG004 | 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. |
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
| OG002 | 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. |
| OG003 | 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. |
| OG004 | 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. |
|
|
| OG003 | 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. |
| OG004 | 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. |
|
|
| OG003 | 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. |
|
|
| OG003 | 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. |
|
|
| OG003 | 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. |
|
|
| OG003 | 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. |
|
|
|
|
|
|
|