A Study to Evaluate the Efficacy and Safety of LCI699 Compared to Placebo in Participants With Resistant Hypertension
Sponsor
Novartis (Industry)
Overall Status
Completed
CT.gov ID
NCT00817635
Collaborator
Great Lakes Drug Development, Inc. (Industry), Integrium (Industry)
155
38
5
9.7
4.1
0.4
Study Details
Study Description
Brief Summary
This study assessed the blood pressure effect, safety and tolerability of LCI699 compared to placebo and eplerenone in participants with resistant hypertension.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
155 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Phase II, Randomized, Double-blind, Placebo and Active Controlled, Parallel Group, Multi-center, Dose Ranging Study to Evaluate the Efficacy and Safety of LCI699 Compared to Placebo After 8 Weeks Treatment in Patients With Resistant Hypertension
Actual Study Start Date
:
Dec 22, 2008
Actual Primary Completion Date
:
Oct 13, 2009
Actual Study Completion Date
:
Oct 13, 2009
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: LCI699 0.25 mg BID Following a 2-week placebo run-in period, participants received LCI699 0.25 mg, capsules, orally, twice daily (BID), with or without food for up to 8 weeks. |
Drug: LCI699
LCI699 oral capsules
|
| Experimental: LCI699 1 mg QD Following a 2-week placebo run-in period, participants received LCI699 1 mg, capsules, orally, once daily (QD), with or without food for up to 8 weeks. |
Drug: LCI699
LCI699 oral capsules
|
| Experimental: LCI699 0.5 mg followed by LCI699 1 mg BID Following a 2-week placebo run-in period, participants received LCI699 0.5 mg, capsules, orally, BID, with or without food for up to 4 weeks, followed by LCI699 1 mg, capsules, orally, BID with or without food for up to 4 weeks. |
Drug: LCI699
LCI699 oral capsules
|
| Active Comparator: Eplerenone 50 mg BID Following a 2-week placebo run-in period, participants received eplerenone 50 mg, capsules, orally, BID, with or without food for up to 8 weeks. |
Drug: Eplerenone
Eplerenone oral capsules
|
| Placebo Comparator: Placebo For a 2-week placebo run-in period, followed by 8 weeks of the treatment period, participants received LCI699-matching placebo or eplerenone-matching placebo, capsules, orally, QD or BID, with or without food. |
Drug: LCI699-matching Placebo
LCI699-matching placebo oral capsules
Drug: Eplerenone-matching Placebo
Eplerenone-matching placebo oral capsules
|
Outcome Measures
Primary Outcome Measures
- Change From Baseline in MSSBP at Week 8 Last Observation Carried Forward (LOCF) [Baseline, Week 8]
Arterial blood pressure (BP) determinations were made after the participant was in the sitting position for 5 minutes according to the American Heart Association guidelines using a calibrated standard aneroid or mercury sphygmomanometer or a calibrated standard sphygmomanometer. The change in the MSSBP was calculated comparing the Week 8 readings to the readings taken at Baseline. The change from Baseline in MSSBP was analyzed using an analysis of covariance model (ANCOVA) with treatment and country as factors and Baseline MSSBP as a covariate.
Secondary Outcome Measures
- Change From Baseline in MSDBP at Week 8 LOCF [Baseline, Week 8]
Arterial BP determinations were made after the participant was in the sitting position for 5 minutes according to the American Heart Association guidelines using a calibrated standard aneroid or mercury sphygmomanometer or a calibrated standard sphygmomanometer. The change in the MSDBP was calculated comparing the Week 8 readings to the readings taken at Baseline. The change from Baseline in MSDBP was analyzed using an ANCOVA with treatment and country as factors and Baseline MSDBP as a covariate.
- Percentage of Participants With a 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 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.
- 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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 75 Years
Sexes Eligible for Study:
All
Accepts 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/exclusion criteria may apply.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Horizon Research Group, Inc | Mobile | Alabama | United States | 36608 |
| 2 | Cochise Clinical Research | Sierra Vista | Arizona | United States | 85635 |
| 3 | Clinical Solutions Advantage | Buena Park | California | United States | 90620 |
| 4 | Michael Waldman, MD | Irvine | California | United States | 92618 |
| 5 | Long Beach Center for Clinical Research | Long Beach | California | United States | 90806 |
| 6 | Clinical Trials Research | Roseville | California | United States | 95661 |
| 7 | Orange County Research Center | Tustin | California | United States | 92780 |
| 8 | Metro Clinical Research | Littleton | Colorado | United States | 80120 |
| 9 | Meridien Research | Bradenton | Florida | United States | 34203 |
| 10 | Clinical Research of So. Florida | Coral Gables | Florida | United States | 33134 |
| 11 | Jacksonville Heart Center | Jacksonville Beach | Florida | United States | 32250 |
| 12 | FPA Clinical Research | Kissimmee | Florida | United States | 34741 |
| 13 | Accelovance | Melbourne | Florida | United States | 32935 |
| 14 | Cardio-Pulminary Associates | Plantation | Florida | United States | 33317 |
| 15 | Meridien Research | Saint Petersburg | Florida | United States | 33709 |
| 16 | Northwest Clinical Trials | Boise | Idaho | United States | 83704 |
| 17 | Provident Clinical Research | Addison | Illinois | United States | 60101 |
| 18 | Cedar-Crosse Research Centereet | Chicago | Illinois | United States | 60607 |
| 19 | Provident Clinical Research | Bloomington | Indiana | United States | 47403 |
| 20 | Accelovance | South Bend | Indiana | United States | 46601 |
| 21 | Peter A. Holt | Baltimore | Maryland | United States | 21239 |
| 22 | MD Medical Research | Oxon Hill | Maryland | United States | 20745 |
| 23 | Chelsea Internal Medicine | Chelsea | Michigan | United States | 48118 |
| 24 | New York Cardiovascular Associates | New York | New York | United States | 10001 |
| 25 | Charlotte Clinical Research | Charlotte | North Carolina | United States | 28211 |
| 26 | Northstate Clinical Research | Lenoir | North Carolina | United States | 28645 |
| 27 | Community Research | Cincinnati | Ohio | United States | 45245 |
| 28 | Tipton Medical & Diagnostic Center | Tipton | Pennsylvania | United States | 16684 |
| 29 | Medical Research South | Charleston | South Carolina | United States | 29407 |
| 30 | Mountain View Clinical Research Associates | Greer | South Carolina | United States | 29651 |
| 31 | Clinical Research Associates, Inc | Nashville | Tennessee | United States | 37203 |
| 32 | Punzi Medical Center | Carrollton | Texas | United States | 75006 |
| 33 | KRK Medical Research | Dallas | Texas | United States | 75230 |
| 34 | DCOL Center for Clinical Research | Longview | Texas | United States | 75605 |
| 35 | Daniel Gottlieb, MD | Burien | Washington | United States | 98166 |
| 36 | Rainier Clinical Research Center | Renton | Washington | United States | 98057 |
| 37 | Gemini Scientific | Madison | Wisconsin | United States | 83719 |
| 38 | Encode Clinic | Reykjavik | SA | Iceland |
Sponsors and Collaborators
- Novartis
- Great Lakes Drug Development, Inc.
- Integrium
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Novartis
ClinicalTrials.gov Identifier:
NCT00817635
Other Study ID Numbers:
- CLCI699A2216
- 2008-007338-23
First Posted:
Jan 6, 2009
Last Update Posted:
Jun 2, 2021
Last Verified:
May 1, 2021
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Novartis
Additional relevant MeSH terms:
Study Results
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 Detail | 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. |
| Arm/Group Title | LCI699 0.25 mg BID | LCI699 1 mg QD | LCI699 0.5 mg Followed by LCI699 1 mg BID | Eplerenone 50 mg BID | Placebo |
|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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 eplerenone 50 mg, capsules, orally, BID, with or without food for up to 8 weeks. | 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. |
| Period Title: Overall Study | |||||
| STARTED | 32 | 26 | 31 | 33 | 33 |
| COMPLETED | 23 | 22 | 28 | 28 | 25 |
| NOT COMPLETED | 9 | 4 | 3 | 5 | 8 |
Baseline Characteristics
| Arm/Group Title | 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 |
|---|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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 eplerenone 50 mg, capsules, orally, BID, with or without food for up to 8 weeks. | 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. | Total of all reporting groups |
| Overall Participants | 32 | 26 | 31 | 33 | 33 | 155 |
| Age (years) [Mean (Standard Deviation) ] | ||||||
| Mean (Standard Deviation) [years] |
53.6
(10.36)
|
55.4
(9.58)
|
57.2
(10.77)
|
56.2
(7.70)
|
59.8
(9.33)
|
56.5
(9.69)
|
| Sex: Female, Male (Count of Participants) | ||||||
| Female |
12
37.5%
|
8
30.8%
|
13
41.9%
|
14
42.4%
|
11
33.3%
|
58
37.4%
|
| Male |
20
62.5%
|
18
69.2%
|
18
58.1%
|
19
57.6%
|
22
66.7%
|
97
62.6%
|
| Baseline Mean Sitting Systolic Blood Pressure (MSSBP) (millimeters of mercury (mmHg)) [Mean (Standard Deviation) ] | ||||||
| Mean (Standard Deviation) [millimeters of mercury (mmHg)] |
152.4
(11.21)
|
152.5
(9.79)
|
152.2
(7.58)
|
153.8
(8.92)
|
153.4
(9.61)
|
152.9
(9.39)
|
| Baseline Mean Sitting Diastolic Blood Pressure (MSDBP) (mmHg) [Mean (Standard Deviation) ] | ||||||
| Mean (Standard Deviation) [mmHg] |
91.8
(11.68)
|
89.2
(9.56)
|
88.9
(11.89)
|
89.1
(9.84)
|
90.1
(11.65)
|
89.8
(10.92)
|
Outcome Measures
| Title | Change From Baseline in MSSBP at Week 8 Last Observation Carried Forward (LOCF) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | LCI699 0.25 mg BID | LCI699 1 mg QD | LCI699 0.5 mg Followed by LCI699 1 mg BID | Eplerenone 50 mg BID | Placebo |
|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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 eplerenone 50 mg, capsules, orally, BID, with or without food for up to 8 weeks. | 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. |
| Measure Participants | 31 | 26 | 31 | 32 | 33 |
| Mean (Standard Error) [mmHg] |
-11.4
(2.96)
|
-13.1
(3.24)
|
-12.5
(2.96)
|
-18.7
(2.92)
|
-8.8
(2.87)
|
| Title | Change From Baseline in MSDBP at Week 8 LOCF |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | LCI699 0.25 mg BID | LCI699 1 mg QD | LCI699 0.5 mg Followed by LCI699 1 mg BID | Eplerenone 50 mg BID | Placebo |
|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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 eplerenone 50 mg, capsules, orally, BID, with or without food for up to 8 weeks. | 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. |
| Measure Participants | 31 | 26 | 31 | 32 | 33 |
| Mean (Standard Error) [mmHg] |
-4.5
(1.72)
|
-6.0
(1.88)
|
-6.1
(1.72)
|
-7.7
(1.69)
|
-4.8
(1.66)
|
| Title | Percentage of Participants With a MSSBP Response and MSSBP Control at Week 8, as Measured by Office Blood Pressure (OBP) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | LCI699 0.25 mg BID | LCI699 1 mg QD | LCI699 0.5 mg Followed by LCI699 1 mg BID | Eplerenone 50 mg BID | Placebo |
|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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 eplerenone 50 mg capsules, orally, BID, with or without food for up to 8 weeks. | 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. |
| Measure Participants | 31 | 26 | 31 | 32 | 33 |
| MSSBP Response |
54.8
171.3%
|
57.7
221.9%
|
41.9
135.2%
|
65.6
198.8%
|
42.4
128.5%
|
| MSSBP Control |
51.6
161.3%
|
50.0
192.3%
|
32.3
104.2%
|
53.1
160.9%
|
36.4
110.3%
|
| Title | Percentage of Participants With a MSDBP Response and MSDBP Control at Week 8, as Measured by OBP |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | LCI699 0.25 mg BID | LCI699 1 mg QD | LCI699 0.5 mg Followed by LCI699 1 mg BID | Eplerenone 50 mg BID | Placebo |
|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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 eplerenone 50 mg, capsules, orally, BID, with or without food for up to 8 weeks. | 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. |
| Measure Participants | 31 | 26 | 31 | 32 | 33 |
| MSDBP Response |
67.7
211.6%
|
73.1
281.2%
|
71.0
229%
|
71.9
217.9%
|
57.6
174.5%
|
| MSDBP Control |
54.8
171.3%
|
65.4
251.5%
|
58.1
187.4%
|
56.3
170.6%
|
54.5
165.2%
|
| Title | Dose/Exposure BP Response Relationship of LCI699, as Measured by Change From Baseline in MSSBP at Week 8 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | LCI699 0.25 mg BID | LCI699 1 mg QD | LCI699 0.5 mg Followed by LCI699 1 mg BID |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 31 | 26 | 31 |
| Mean (Standard Error) [mmHg] |
-11.4
(2.96)
|
-13.1
(3.24)
|
-12.5
(2.96)
|
| Title | Dose/Exposure BP Response Relationship of LCI699, as Measured by Change From Baseline in MSDBP at Week 8 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | LCI699 0.25 mg BID | LCI699 1 mg QD | LCI699 0.5 mg Followed by LCI699 1 mg BID |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 31 | 26 | 31 |
| Mean (Standard Error) [mmHg] |
-4.5
(1.72)
|
-6.0
(1.88)
|
-6.1
(1.72)
|
| Title | 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) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | LCI699 0.25 mg BID | LCI699 1 mg QD | LCI699 0.5 mg Followed by LCI699 1 mg BID | Eplerenone 50 mg BID | Placebo |
|---|---|---|---|---|---|
| Arm/Group Description | 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 | 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. | 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 eplerenone 50 mg, capsules, orally, BID, with or without food for up to 8 weeks. | 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. |
| Measure Participants | 15 | 19 | 26 | 23 | 23 |
| 24-hour Mean SBP |
-4.4
(3.22)
|
-5.7
(2.87)
|
-6.3
(2.47)
|
-15.7
(2.59)
|
-1.0
(2.59)
|
| Daytime Mean SBP |
-4.9
(3.29)
|
-6.0
(2.92)
|
-6.3
(2.52)
|
-15.7
(2.65)
|
-1.6
(2.65)
|
| Nighttime Mean SBP |
-3.2
(3.49)
|
-4.8
(3.13)
|
-7.0
(2.67)
|
-15.4
(2.81)
|
0.4
(2.81)
|
| Title | Change From Baseline in Mean 24 Hours, Mean Daytime and Mean Nighttime Diastolic Blood Pressure (DBP) at Week 8 LOCF, as Measured by ABPM |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | LCI699 0.25 mg BID | LCI699 1 mg QD | LCI699 0.5 mg Followed by LCI699 1 mg BID | Eplerenone 50 mg BID | Placebo |
|---|---|---|---|---|---|
| Arm/Group Description | 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 | 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. | 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 eplerenone 50 mg, capsules, orally, BID, with or without food for up to 8 weeks. | 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. |
| Measure Participants | 15 | 19 | 26 | 23 | 23 |
| 24-hour Mean DBP |
1.0
(2.15)
|
-3.4
(1.94)
|
-3.7
(1.67)
|
-9.6
(1.74)
|
-0.2
(1.74)
|
| Daytime Mean DBP |
0.6
(2.31)
|
-3.6
(2.06)
|
-3.4
(1.78)
|
-9.5
(1.86)
|
-0.8
(1.87)
|
| Nighttime Mean DBP |
1.9
(2.17)
|
-2.5
(1.98)
|
-4.6
(1.69)
|
-9.6
(1.75)
|
1.2
(1.76)
|
| Title | 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 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | LCI699 1 mg QD | LCI699 0.5 mg BID |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 18 | 26 |
| 24-hour Mean SBP |
-7.8
(2.72)
|
-4.7
(2.29)
|
| Daytime Mean SBP |
-8.1
(2.69)
|
-5.3
(2.27)
|
| Nighttime Mean SBP |
-6.8
(3.17)
|
-4.5
(2.70)
|
| Title | 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 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | LCI699 1 mg QD | LCI699 0.5 mg BID |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 18 | 26 |
| 24-hour Mean DBP |
-4.3
(1.98)
|
-2.5
(1.67)
|
| Daytime Mean DBP |
-3.9
(2.04)
|
-2.6
(1.73)
|
| Nighttime Mean DBP |
-4.5
(2.21)
|
-2.8
(1.87)
|
| Title | Number of Participants With Adverse Event (AEs), Serious Adverse Events (SAEs), Hyperkalemia, and Hyponatremia |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | LCI699 0.25 mg BID | LCI699 1 mg QD | LCI699 0.5 mg Followed by LCI699 1 mg BID | Eplerenone 50 mg BID | Placebo |
|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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 eplerenone 50 mg, capsules, orally, BID, with or without food for up to 8 weeks. | 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. |
| Measure Participants | 32 | 26 | 31 | 33 | 33 |
| AE(s) |
15
46.9%
|
15
57.7%
|
8
25.8%
|
13
39.4%
|
16
48.5%
|
| SAE(s) |
0
0%
|
0
0%
|
0
0%
|
1
3%
|
0
0%
|
| Hyperkalemia [potassium level >5.5 mmol/L] |
2
6.3%
|
0
0%
|
0
0%
|
0
0%
|
1
3%
|
| Hyperkalemia [potassium level ≥6.0 mmol/L] |
2
6.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Hyponatremia [sodium level <130 and ≥125 mmol/L] |
0
0%
|
0
0%
|
0
0%
|
1
3%
|
0
0%
|
| Hyponatremia [sodium level <135 mmol/L and ≥130mmol/L] |
3
9.4%
|
2
7.7%
|
7
22.6%
|
3
9.1%
|
2
6.1%
|
| Title | Number of Participants With Cortisol Levels Below 500 Nmol/L at 1 Hour After Adrenocorticotropic Hormone (ACTH) Injection at Week 8 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ACTH stimulation test subset population included all participants prior to treatment with LCI699 and at the end of the treatment interval (Week 8). |
| Arm/Group Title | LCI699 0.25 mg BID | LCI699 1 mg QD | LCI699 0.5 mg Followed by LCI699 1 mg BID | Eplerenone 50 mg BID | Placebo |
|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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 eplerenone 50 mg, capsules, orally, BID, with or without food for up to 8 weeks. | 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. |
| Measure Participants | 5 | 4 | 6 | 7 | 7 |
| Count of Participants [Participants] |
0
0%
|
1
3.8%
|
4
12.9%
|
0
0%
|
0
0%
|
| Title | 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 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | LCI699 0.25 mg BID | LCI699 1 mg QD | LCI699 0.5 mg Followed by LCI699 1 mg BID | Eplerenone 50 mg BID |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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 eplerenone 50 mg, capsules, orally, BID, with or without food for up to 8 weeks. |
| Measure Participants | 27 | 23 | 29 | 31 |
| Geometric Least Squares Mean (Standard Error) [percent change in aldosterone] |
-22.3
(0.16)
|
-30.4
(0.17)
|
-53.1
(0.15)
|
115.0
(0.15)
|
| Title | Percent Change From Baseline in RAAS Biomarker: Plasma Renin Activity (PRA) in LCI699 Compared to Eplerenone 50mg at Week 8 LOCF |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | LCI699 0.25 mg BID | LCI699 1 mg QD | LCI699 0.5 mg Followed by LCI699 1 mg BID | Eplerenone 50 mg BID |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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 eplerenone 50 mg, capsules, orally, BID, with or without food for up to 8 weeks. |
| Measure Participants | 27 | 20 | 27 | 31 |
| Geometric Least Squares Mean (Standard Error) [percent change in PRA] |
41.6
(0.24)
|
74.3
(0.28)
|
107.7
(0.24)
|
414.1
(0.22)
|
| Title | Percent Change From Baseline in RAAS Biomarker: Active Renin (ARC) in LCI699 Compared to Eplerenone 50mg at Week 8 LOCF |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | LCI699 0.25 mg BID | LCI699 1 mg QD | LCI699 0.5 mg Followed by LCI699 1 mg BID | Eplerenone 50 mg BID |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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 eplerenone 50 mg, capsules, orally, BID, with or without food for up to 8 weeks. |
| Measure Participants | 27 | 21 | 28 | 30 |
| Geometric Least Squares Mean (Standard Error) [percent change in ARC] |
73.1
(0.24)
|
72.8
(0.27)
|
156.4
(0.23)
|
430.6
(0.22)
|
| Title | Percent Change From Baseline in RAAS Biomarker: Ratio of PA to PRA in LCI699 Compared to Eplerenone 50mg at Week 8 LOCF |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | LCI699 0.25 mg BID | LCI699 1 mg QD | LCI699 0.5 mg Followed by LCI699 1 mg BID | Eplerenone 50 mg BID |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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 eplerenone 50 mg, capsules, orally, BID, with or without food for up to 8 weeks. |
| Measure Participants | 26 | 20 | 27 | 31 |
| Geometric Least Squares Mean (Standard Error) [percent change in ratio of PA to PRA] |
-46.7
(0.26)
|
-50.0
(0.29)
|
-78.3
(0.25)
|
-57.1
(0.23)
|
Adverse Events
| Time Frame | AEs: From start of the study drug treatment up to 10 weeks; SAE: From signing of the informed consent up to 10 weeks | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Safety set population included all participants who were randomized and received at least 1 dose of study drug. | |||||||||
| Arm/Group Title | LCI699 0.25 mg BID | LCI699 1.0 mg QD | LCI699 0.5 mg Followed by LCI699 1 mg BID | Eplerenone 50 mg BID | Placebo | |||||
| Arm/Group Description | 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. | 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. | 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 eplerenone 50 mg, capsules, orally, BID, with or without food for up to 8 weeks. | 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. | |||||
All Cause Mortality |
||||||||||
| LCI699 0.25 mg BID | LCI699 1.0 mg QD | LCI699 0.5 mg Followed by LCI699 1 mg BID | Eplerenone 50 mg BID | Placebo | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/32 (0%) | 0/26 (0%) | 0/31 (0%) | 0/33 (0%) | 0/33 (0%) | |||||
Serious Adverse Events |
||||||||||
| LCI699 0.25 mg BID | LCI699 1.0 mg QD | LCI699 0.5 mg Followed by LCI699 1 mg BID | Eplerenone 50 mg BID | Placebo | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/32 (0%) | 0/26 (0%) | 0/31 (0%) | 1/33 (3%) | 0/33 (0%) | |||||
| Nervous system disorders | ||||||||||
| Cerebrovascular accident | 0/32 (0%) | 0/26 (0%) | 0/31 (0%) | 1/33 (3%) | 0/33 (0%) | |||||
Other (Not Including Serious) Adverse Events |
||||||||||
| LCI699 0.25 mg BID | LCI699 1.0 mg QD | LCI699 0.5 mg Followed by LCI699 1 mg BID | Eplerenone 50 mg BID | Placebo | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 15/32 (46.9%) | 15/26 (57.7%) | 8/31 (25.8%) | 13/33 (39.4%) | 16/33 (48.5%) | |||||
| Cardiac disorders | ||||||||||
| Palpitations | 0/32 (0%) | 0/26 (0%) | 0/31 (0%) | 1/33 (3%) | 0/33 (0%) | |||||
| Ear and labyrinth disorders | ||||||||||
| Inner ear inflammation | 0/32 (0%) | 0/26 (0%) | 0/31 (0%) | 0/33 (0%) | 1/33 (3%) | |||||
| Endocrine disorders | ||||||||||
| Goitre | 0/32 (0%) | 1/26 (3.8%) | 0/31 (0%) | 0/33 (0%) | 0/33 (0%) | |||||
| Eye disorders | ||||||||||
| Conjunctival haemorrhage | 1/32 (3.1%) | 0/26 (0%) | 0/31 (0%) | 0/33 (0%) | 0/33 (0%) | |||||
| Gastrointestinal disorders | ||||||||||
| Abdominal pain | 0/32 (0%) | 0/26 (0%) | 0/31 (0%) | 1/33 (3%) | 2/33 (6.1%) | |||||
| Abdominal pain upper | 1/32 (3.1%) | 1/26 (3.8%) | 0/31 (0%) | 0/33 (0%) | 0/33 (0%) | |||||
| Constipation | 0/32 (0%) | 1/26 (3.8%) | 0/31 (0%) | 0/33 (0%) | 0/33 (0%) | |||||
| Diarrhoea | 3/32 (9.4%) | 0/26 (0%) | 0/31 (0%) | 2/33 (6.1%) | 1/33 (3%) | |||||
| Dry mouth | 1/32 (3.1%) | 0/26 (0%) | 0/31 (0%) | 0/33 (0%) | 0/33 (0%) | |||||
| Dyspepsia | 1/32 (3.1%) | 0/26 (0%) | 1/31 (3.2%) | 0/33 (0%) | 1/33 (3%) | |||||
| Food poisoning | 0/32 (0%) | 0/26 (0%) | 0/31 (0%) | 0/33 (0%) | 1/33 (3%) | |||||
| Frequent bowel movements | 1/32 (3.1%) | 0/26 (0%) | 0/31 (0%) | 0/33 (0%) | 0/33 (0%) | |||||
| Haematochezia | 0/32 (0%) | 0/26 (0%) | 0/31 (0%) | 0/33 (0%) | 1/33 (3%) | |||||
| Nausea | 1/32 (3.1%) | 1/26 (3.8%) | 1/31 (3.2%) | 0/33 (0%) | 1/33 (3%) | |||||
| Vomiting | 0/32 (0%) | 0/26 (0%) | 0/31 (0%) | 1/33 (3%) | 0/33 (0%) | |||||
| General disorders | ||||||||||
| Asthenia | 0/32 (0%) | 0/26 (0%) | 0/31 (0%) | 0/33 (0%) | 1/33 (3%) | |||||
| Chest pain | 0/32 (0%) | 0/26 (0%) | 0/31 (0%) | 1/33 (3%) | 1/33 (3%) | |||||
| Fatigue | 0/32 (0%) | 1/26 (3.8%) | 1/31 (3.2%) | 3/33 (9.1%) | 2/33 (6.1%) | |||||
| Oedema | 0/32 (0%) | 0/26 (0%) | 0/31 (0%) | 0/33 (0%) | 1/33 (3%) | |||||
| Oedema peripheral | 1/32 (3.1%) | 1/26 (3.8%) | 0/31 (0%) | 0/33 (0%) | 0/33 (0%) | |||||
| Pain | 1/32 (3.1%) | 0/26 (0%) | 0/31 (0%) | 0/33 (0%) | 0/33 (0%) | |||||
| Immune system disorders | ||||||||||
| Multiple allergies | 0/32 (0%) | 1/26 (3.8%) | 0/31 (0%) | 0/33 (0%) | 0/33 (0%) | |||||
| Infections and infestations | ||||||||||
| Bronchitis | 0/32 (0%) | 0/26 (0%) | 0/31 (0%) | 1/33 (3%) | 0/33 (0%) | |||||
| Nasopharyngitis | 0/32 (0%) | 1/26 (3.8%) | 0/31 (0%) | 0/33 (0%) | 1/33 (3%) | |||||
| Tooth infection | 0/32 (0%) | 1/26 (3.8%) | 0/31 (0%) | 0/33 (0%) | 0/33 (0%) | |||||
| Injury, poisoning and procedural complications | ||||||||||
| Arthropod bite | 0/32 (0%) | 0/26 (0%) | 0/31 (0%) | 0/33 (0%) | 1/33 (3%) | |||||
| Chest injury | 0/32 (0%) | 1/26 (3.8%) | 0/31 (0%) | 0/33 (0%) | 0/33 (0%) | |||||
| Contusion | 0/32 (0%) | 0/26 (0%) | 0/31 (0%) | 0/33 (0%) | 1/33 (3%) | |||||
| Joint sprain | 0/32 (0%) | 0/26 (0%) | 0/31 (0%) | 0/33 (0%) | 1/33 (3%) | |||||
| Muscle strain | 1/32 (3.1%) | 0/26 (0%) | 0/31 (0%) | 0/33 (0%) | 0/33 (0%) | |||||
| Scratch | 1/32 (3.1%) | 0/26 (0%) | 0/31 (0%) | 0/33 (0%) | 0/33 (0%) | |||||
| Investigations | ||||||||||
| Alanine aminotransferase increased | 0/32 (0%) | 0/26 (0%) | 1/31 (3.2%) | 0/33 (0%) | 0/33 (0%) | |||||
| Aspartate aminotransferase increased | 0/32 (0%) | 0/26 (0%) | 1/31 (3.2%) | 0/33 (0%) | 0/33 (0%) | |||||
| Blood chloride increased | 1/32 (3.1%) | 0/26 (0%) | 0/31 (0%) | 0/33 (0%) | 0/33 (0%) | |||||
| Blood cortisol decreased | 2/32 (6.3%) | 1/26 (3.8%) | 1/31 (3.2%) | 0/33 (0%) | 1/33 (3%) | |||||
| Blood creatinine increased | 2/32 (6.3%) | 0/26 (0%) | 0/31 (0%) | 0/33 (0%) | 0/33 (0%) | |||||
| Blood glucose increased | 0/32 (0%) | 1/26 (3.8%) | 1/31 (3.2%) | 0/33 (0%) | 0/33 (0%) | |||||
| Blood potassium increased | 1/32 (3.1%) | 0/26 (0%) | 0/31 (0%) | 0/33 (0%) | 0/33 (0%) | |||||
| Blood sodium decreased | 1/32 (3.1%) | 0/26 (0%) | 1/31 (3.2%) | 0/33 (0%) | 0/33 (0%) | |||||
| Blood sodium increased | 1/32 (3.1%) | 0/26 (0%) | 0/31 (0%) | 0/33 (0%) | 0/33 (0%) | |||||
| Blood urea increased | 1/32 (3.1%) | 0/26 (0%) | 0/31 (0%) | 0/33 (0%) | 0/33 (0%) | |||||
| Blood uric acid increased | 1/32 (3.1%) | 0/26 (0%) | 0/31 (0%) | 0/33 (0%) | 0/33 (0%) | |||||
| Eosinophil count increased | 0/32 (0%) | 0/26 (0%) | 1/31 (3.2%) | 0/33 (0%) | 0/33 (0%) | |||||
| Glucose urine present | 0/32 (0%) | 0/26 (0%) | 1/31 (3.2%) | 0/33 (0%) | 0/33 (0%) | |||||
| Heart rate irregular | 0/32 (0%) | 0/26 (0%) | 0/31 (0%) | 1/33 (3%) | 0/33 (0%) | |||||
| Metabolism and nutrition disorders | ||||||||||
| Anorexia | 0/32 (0%) | 0/26 (0%) | 0/31 (0%) | 1/33 (3%) | 0/33 (0%) | |||||
| Decreased appetite | 0/32 (0%) | 0/26 (0%) | 0/31 (0%) | 0/33 (0%) | 1/33 (3%) | |||||
| Hypoglycaemia | 0/32 (0%) | 0/26 (0%) | 0/31 (0%) | 0/33 (0%) | 1/33 (3%) | |||||
| Hypokalaemia | 0/32 (0%) | 0/26 (0%) | 0/31 (0%) | 0/33 (0%) | 1/33 (3%) | |||||
| Hyponatraemia | 1/32 (3.1%) | 0/26 (0%) | 2/31 (6.5%) | 2/33 (6.1%) | 0/33 (0%) | |||||
| Type 2 diabetes mellitus | 0/32 (0%) | 1/26 (3.8%) | 0/31 (0%) | 0/33 (0%) | 0/33 (0%) | |||||
| Musculoskeletal and connective tissue disorders | ||||||||||
| Arthralgia | 0/32 (0%) | 0/26 (0%) | 1/31 (3.2%) | 0/33 (0%) | 0/33 (0%) | |||||
| Arthritis | 0/32 (0%) | 1/26 (3.8%) | 0/31 (0%) | 0/33 (0%) | 0/33 (0%) | |||||
| Back pain | 0/32 (0%) | 1/26 (3.8%) | 0/31 (0%) | 0/33 (0%) | 1/33 (3%) | |||||
| Costochondritis | 0/32 (0%) | 0/26 (0%) | 0/31 (0%) | 1/33 (3%) | 0/33 (0%) | |||||
| Joint swelling | 0/32 (0%) | 0/26 (0%) | 0/31 (0%) | 0/33 (0%) | 1/33 (3%) | |||||
| Muscle spasms | 1/32 (3.1%) | 2/26 (7.7%) | 0/31 (0%) | 4/33 (12.1%) | 0/33 (0%) | |||||
| Musculoskeletal pain | 0/32 (0%) | 1/26 (3.8%) | 0/31 (0%) | 0/33 (0%) | 0/33 (0%) | |||||
| Myalgia | 0/32 (0%) | 0/26 (0%) | 1/31 (3.2%) | 0/33 (0%) | 0/33 (0%) | |||||
| Pain in extremity | 1/32 (3.1%) | 0/26 (0%) | 0/31 (0%) | 0/33 (0%) | 0/33 (0%) | |||||
| Nervous system disorders | ||||||||||
| Dizziness | 1/32 (3.1%) | 1/26 (3.8%) | 0/31 (0%) | 4/33 (12.1%) | 1/33 (3%) | |||||
| Headache | 0/32 (0%) | 1/26 (3.8%) | 1/31 (3.2%) | 0/33 (0%) | 2/33 (6.1%) | |||||
| Hypoaesthesia | 0/32 (0%) | 1/26 (3.8%) | 0/31 (0%) | 0/33 (0%) | 0/33 (0%) | |||||
| Paraesthesia | 1/32 (3.1%) | 0/26 (0%) | 0/31 (0%) | 0/33 (0%) | 0/33 (0%) | |||||
| Somnolence | 0/32 (0%) | 0/26 (0%) | 1/31 (3.2%) | 0/33 (0%) | 0/33 (0%) | |||||
| Speech disorder | 0/32 (0%) | 0/26 (0%) | 0/31 (0%) | 1/33 (3%) | 0/33 (0%) | |||||
| Tremor | 0/32 (0%) | 0/26 (0%) | 0/31 (0%) | 0/33 (0%) | 1/33 (3%) | |||||
| Psychiatric disorders | ||||||||||
| Anxiety | 0/32 (0%) | 0/26 (0%) | 1/31 (3.2%) | 0/33 (0%) | 0/33 (0%) | |||||
| Anxiety disorder | 1/32 (3.1%) | 0/26 (0%) | 0/31 (0%) | 0/33 (0%) | 0/33 (0%) | |||||
| Depression | 0/32 (0%) | 0/26 (0%) | 0/31 (0%) | 1/33 (3%) | 0/33 (0%) | |||||
| Disorientation | 0/32 (0%) | 0/26 (0%) | 0/31 (0%) | 1/33 (3%) | 0/33 (0%) | |||||
| Mood altered | 0/32 (0%) | 1/26 (3.8%) | 0/31 (0%) | 0/33 (0%) | 0/33 (0%) | |||||
| Renal and urinary disorders | ||||||||||
| Dysuria | 0/32 (0%) | 0/26 (0%) | 0/31 (0%) | 0/33 (0%) | 1/33 (3%) | |||||
| Haematuria | 1/32 (3.1%) | 0/26 (0%) | 0/31 (0%) | 0/33 (0%) | 1/33 (3%) | |||||
| Polyuria | 0/32 (0%) | 0/26 (0%) | 0/31 (0%) | 1/33 (3%) | 0/33 (0%) | |||||
| Pyuria | 1/32 (3.1%) | 0/26 (0%) | 0/31 (0%) | 0/33 (0%) | 0/33 (0%) | |||||
| Urine odour abnormal | 0/32 (0%) | 0/26 (0%) | 0/31 (0%) | 0/33 (0%) | 1/33 (3%) | |||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Asthma | 1/32 (3.1%) | 0/26 (0%) | 0/31 (0%) | 0/33 (0%) | 0/33 (0%) | |||||
| Dyspnoea exertional | 0/32 (0%) | 0/26 (0%) | 0/31 (0%) | 1/33 (3%) | 0/33 (0%) | |||||
| Oropharyngeal pain | 1/32 (3.1%) | 0/26 (0%) | 0/31 (0%) | 0/33 (0%) | 1/33 (3%) | |||||
| Rhinitis allergic | 0/32 (0%) | 1/26 (3.8%) | 0/31 (0%) | 0/33 (0%) | 0/33 (0%) | |||||
| Upper respiratory tract congestion | 1/32 (3.1%) | 0/26 (0%) | 0/31 (0%) | 0/33 (0%) | 0/33 (0%) | |||||
| Skin and subcutaneous tissue disorders | ||||||||||
| Dermatitis contact | 0/32 (0%) | 1/26 (3.8%) | 0/31 (0%) | 0/33 (0%) | 0/33 (0%) | |||||
| Erythema | 0/32 (0%) | 0/26 (0%) | 0/31 (0%) | 1/33 (3%) | 1/33 (3%) | |||||
| Hyperhidrosis | 0/32 (0%) | 0/26 (0%) | 2/31 (6.5%) | 0/33 (0%) | 0/33 (0%) | |||||
| Petechiae | 1/32 (3.1%) | 0/26 (0%) | 0/31 (0%) | 0/33 (0%) | 0/33 (0%) | |||||
| Pruritus | 0/32 (0%) | 1/26 (3.8%) | 0/31 (0%) | 0/33 (0%) | 0/33 (0%) | |||||
| Vascular disorders | ||||||||||
| Flushing | 0/32 (0%) | 0/26 (0%) | 1/31 (3.2%) | 0/33 (0%) | 0/33 (0%) | |||||
| Venous thrombosis | 0/32 (0%) | 1/26 (3.8%) | 0/31 (0%) | 0/33 (0%) | 0/33 (0%) | |||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Novartis Pharmaceuticals |
| Phone | 862-778-8300 |
| Novartis.email@novartis.com |
Responsible Party:
Novartis
ClinicalTrials.gov Identifier:
NCT00817635
Other Study ID Numbers:
- CLCI699A2216
- 2008-007338-23
First Posted:
Jan 6, 2009
Last Update Posted:
Jun 2, 2021
Last Verified:
May 1, 2021