Back to resultsA Study to Evaluate Efficacy and Safety of LCI699 in Participants With Essential Hypertension
Primary Purpose
Essential Hypertension
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
LCI699
Eplerenone
LCI699-matching Placebo
Eplerenone-matching Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Essential Hypertension focused on measuring Essential hypertension, Phase 2 study, Antihypertensive agent
Eligibility Criteria
Inclusion Criteria:
- Males and non-fertile females.
- 18-75 years inclusive.
- Participants with mild-to-moderate uncomplicated essential hypertension.
Exclusion Criteria:
- All women of child bearing potential.
- Female participants on hormone replacement therapy.
- Severe hypertension.
- History or evidence of a secondary form of hypertension.
- Known moderate or malignant retinopathy.
- History of angina pectoris, myocardial infarction, coronary bypass surgery,ischemic heart disease, surgical or percutaneous arterial intervention of any kind (coronary, carotid or peripheral vessels), stroke, transient ischemic attack (TIA), carotid artery stenosis, aortic aneurysm or peripheral arterial disease.
- Type 1 or type 2 diabetes mellitus.
- Clinically significant valvular heart disease.
- Congestive heart failure (New York Heart Association [NYHA] class II-IV).
- Cardiac electrical abnormalities indicating significant risk of safety for participant taking part in the study.
- History of malignancy of any organ system, treated or untreated, within the past 5 years.
- Liver disease such as cirrhosis or chronic active hepatitis.
- Any surgical or medical conditions that may significantly alter the absorption, distribution, metabolism or excretion of any drug substance
- Any surgical or medical conditions, not identified in the protocol that in the opinion of the investigator or the monitor, place the participant at higher risk from his/her participation in the study, or is likely to prevent the participant from complying with the requirements of the study or completing the trial period.
- Participant unwilling or not able to discontinue safely the use of current antihypertensive medications during the study period
- Any contraindication or history of hypersensitivity to any of the study drugs or to drugs with similar chemical structures.
- Chronic oral or parenteral corticosteroid treatment.
- Treatment with potassium supplement or potassium sparing diuretics.
- Treatment with potent cytochrome P450 3A4 (CYP3A4) inhibitors during the study period.
- Use of other investigational drugs at Visit 1, or within 30 days or 5 half-lives of Visit 1, whichever is longer, unless local health authority guidelines mandate a longer period.
- Serum potassium > 5.2 milliequivalents per liter (mEq/L) or < 3.5 mEq/L at Visit 1.
- Serum sodium < 132 mEq/L at Visit 1.
- Aspartate aminotransferase (ALT) or alanine aminotransferase (AST) > 2 times the upper limit of the normal range (ULN) at Visit 1.
- Bilirubin (total) > 1.5 x ULN at Visit 1.
- Modification of diet in renal disease estimated glomerular filtration rate (MDRD eGFR) < 60 milliliters per minute (ml/min)/1.73 m^2 at Visit 1.
- Other clinically significant laboratory abnormalities, confirmed by repeat measurements, at Visit 1.
- History of active substance abuse (including alcohol).
- Participants with night-shift employment.
Sites / Locations
- Novartis Pharmaceuticals
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm 9
Arm 10
Arm 11
Arm 12
Arm 13
Arm 14
Arm 15
Arm 16
Arm 17
Arm Type
Experimental
Experimental
Experimental
Experimental
Active Comparator
Placebo Comparator
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Active Comparator
Placebo Comparator
Placebo Comparator
Arm Label
Core Period: LCI699 0.25 mg QD
Core Period: LCI699 0.5 mg QD
Core Period: LCI699 1.0 mg QD
Core Period: LCI699 0.5 mg BID
Core Period: Eplerenone 50 mg BID
Core Period: Placebo
Withdrawal Period: LCI699 0.25 mg QD
Withdrawal Period: LCI699 0.25 mg QD Placebo
Withdrawal Period: LCI699 0.5 mg QD
Withdrawal Period: LCI699 0.5 mg QD Placebo
Withdrawal Period: LCI699 1.0 mg QD
Withdrawal Period: LCI699 1.0 mg QD Placebo
Withdrawal Period: LCI699 0.5 mg BID
Withdrawal Period: LCI699 0.5 mg BID Placebo
Withdrawal Period: Eplerenone 50 mg BID
Withdrawal Period: Eplerenone 50 mg BID Placebo
Withdrawal Period: Placebo
Arm Description
Participants received LCI699 0.25 mg capsules, orally, once daily (QD), with or without food for up to 8 weeks.
Participants received LCI699 0.5 mg capsules, orally, QD, with or without food for up to 8 weeks.
Participants received LCI699 1 mg capsules, orally, QD, with or without food for up to 8 weeks.
Participants received LCI699 0.5 mg capsules, orally, twice daily (BID), with or without food for up to 8 weeks.
Participants received eplerenone 50 mg capsules, orally, BID, with or without food for up to 8 weeks.
Participants received LCI699-matching placebo or eplerenone-matching placebo, capsules, orally, QD or BID, with or without food for up to 8 weeks.
Participants received LCI699 0.25 mg capsules, orally, QD, with or without food for up to 1 week (Week 8 to Week 9).
Participants received LCI699 matching placebo capsules, orally, QD, with or without food for up to 1 week (Week 8 to Week 9).
Participants received LCI699 0.5 mg capsules, orally, QD, with or without food for up to 1 week (Week 8 to Week 9).
Participants received LCI699 matching placebo capsules, orally, QD, with or without food for up to 1 week (Week 8 to Week 9).
Participants received LCI699 1 mg capsules, orally, QD, with or without food for up to 1 week (Week 8 to Week 9).
Participants received LCI699 matching placebo capsules, orally, QD, with or without food for up to 1 week (Week 8 to Week 9).
Participants received LCI699 0.5 mg capsules, orally, BID, with or without food for up to 1 week (Week 8 to Week 9).
Participants received LCI699 matching placebo capsules, orally, BID, with or without food for up to 1 week (Week 8 to Week 9).
Participants received eplerenone 50 mg capsules, orally, BID, with or without food for up to 1 week (Week 8 to Week 9).
Participants received eplerenone matching placebo capsules, orally, BID, with or without food for up to 1 week (Week 8 to Week 9).
Participants received LCI699-matching placebo or eplerenone-matching placebo, capsules, orally, QD or BID, with or without food for up to 1 week (Week 8 to Week 9).
Outcomes
Primary Outcome Measures
Core Period: Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP) at Week 8 Last Observation Carried Forward (LOCF), as Measured by Office Blood Pressure (OBP)
Automated arterial BP determinations were made after the participant was in the sitting position for 5 minutes according to the Guidelines for management of hypertension: report of the 4th working party of the British Hypertension Society, 2004-BHS IV, using an automated BP device (such as the Omron BP monitor). 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 analysis of covariance model (ANCOVA) with treatment and region as factors and baseline MSDBP level as a covariate.
Secondary Outcome Measures
Core Period: Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP) at Week 8 LOCF, as Measured by OBP
Automated arterial BP determinations were made after the participant was in the sitting position for 5 minutes according to the Guidelines for management of hypertension: report of the 4th working party of the British Hypertension Society, 2004-BHS IV, using an automated BP device (such as the Omron BP monitor). 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 region as factors and baseline MSSBP levels as a covariate.
Core Period: Number of Participants With Adverse Event (AEs), Serious Adverse Events (SAEs), and Deaths
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.
Core Period: Dose Response Relationship of LCI699 as Measured by Change From Baseline in MSDBP at Week 8
Automated arterial BP determinations were made after the participant was in the sitting position for 5 minutes according to the Guidelines for management of hypertension: report of the 4th working party of the British Hypertension Society, 2004-BHS IV, using an automated BP device (such as the Omron BP monitor). 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 analysis of covariance model (ANCOVA) with treatment and region as factors and baseline MSDBP level as a covariate.
Core Period: Dose Response Relationship of LCI699 as Measured by Change From Baseline in MSSBP at Week 8
Automated arterial BP determinations were made after the participant was in the sitting position for 5 minutes according to the Guidelines for management of hypertension: report of the 4th working party of the British Hypertension Society, 2004-BHS IV, using an automated BP device (such as the Omron BP monitor). 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 region as factors and baseline MSSBP levels as a covariate.
Core Period: Change From Baseline in Mean 24 Hour Ambulatory SBP at Week 8 as Measured by Ambulatory Blood Pressure Monitoring (ABPM)
An ABPM measured a participant's BP over a 24-hour period 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 SBP readings for the 24-hour period.
Core Period: Change From Baseline in Mean 24 Hour Ambulatory DBP at Week 8, as Measured by ABPM
An ABPM measured a participant's BP over a 24-hour period 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 DBP readings for the 24-hour period.
Core Period: Trough to Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory DBP at Week 8
Trough to peak ratios were derived from an ANCOVA model containing treatment, region, hour, treatment by hour interaction as factors with Baseline as a covariate.
Core Period: Trough to Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory SBP at Week 8
Trough to peak ratios were derived from an ANCOVA model containing treatment, region, hour, treatment by hour interaction as factors with Baseline as a covariate.
Core Period: Change From Baseline in Plasma Aldosterone Levels at Week 8
Change from baseline was analyzed using plasma aldosterone values measured at Baseline and Week 8.
Core Period: Percentage of Participants With a MSDBP Response and MSDBP Control at Week 8 LOCF
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.
Core Period: Percentage of Participants With a MSSBP Response and MSSBP Control at Week 8 LOCF
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.
Core Period: Change From Baseline in Plasma Cortisol Levels by Adrenocorticotropic Hormone (ACTH) Stimulation Test
The ACTH stimulation cortisol test was a standard procedure to measure the ability of adrenal cortex to respond to exogenous ACTH and directly assess the adrenal reserve. 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.
Withdrawal Period: Change From Week 8 to Week 9 in MSDBP at Week 9, as Measured by OBP
Automated arterial BP determinations were made after the participant was in the sitting position for 5 minutes according to the Guidelines for management of hypertension: report of the 4th working party of the British Hypertension Society, 2004-BHS IV, using an automated BP device (such as the Omron BP monitor). The change in the MSDBP was calculated comparing the Week 9 readings to the readings taken at Week 8 (Baseline). The change from Week 8 to week 9 in MSDBP was analyzed using an ANCOVA with treatment and region as factors and Week 8 MSDBP level as a covariate.
Withdrawal Period: Change From Week 8 to Week 9 in MSSBP at Week 9 as Measured by OBP
Automated arterial BP determinations were made after the participant was in the sitting position for 5 minutes according to the Guidelines for management of hypertension: report of the 4th working party of the British Hypertension Society, 2004-BHS IV, using an automated BP device (such as the Omron BP monitor). The change in the MSSBP was calculated comparing the Week 9 readings to the readings taken at Week 8 (Baseline). The change from Week 8 to week 9 in MSSBP was analyzed using an ANCOVA with treatment and region as factors and Week 8 MSSBP level as a covariate.
Full Information
NCT ID
NCT00758524
First Posted
September 23, 2008
Last Updated
June 11, 2021
Sponsor
Novartis Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT00758524
Brief Title
A Study to Evaluate Efficacy and Safety of LCI699 in Participants With Essential Hypertension
Official Title
A Multi-center, Randomized, Double-blind, Placebo and Active Controlled, Parallel Group, Dose Finding Study to Evaluate the Efficacy and Safety of LCI699 Compared to Placebo After 8 Weeks Treatment in Patients With Essential Hypertension
Study Type
Interventional
2. Study Status
Record Verification Date
June 2021
Overall Recruitment Status
Completed
Study Start Date
September 11, 2008 (Actual)
Primary Completion Date
July 2, 2009 (Actual)
Study Completion Date
July 2, 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study was a proof-of-efficacy, dose finding study of LCI699 in participants with mild-to-moderate uncomplicated essential hypertension in order to assess the blood pressure (BP) lowering effect, safety and tolerability of LCI699 as compared to placebo and eplerenone.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Essential Hypertension
Keywords
Essential hypertension, Phase 2 study, Antihypertensive agent
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
628 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Core Period: LCI699 0.25 mg QD
Arm Type
Experimental
Arm Description
Participants received LCI699 0.25 mg capsules, orally, once daily (QD), with or without food for up to 8 weeks.
Arm Title
Core Period: LCI699 0.5 mg QD
Arm Type
Experimental
Arm Description
Participants received LCI699 0.5 mg capsules, orally, QD, with or without food for up to 8 weeks.
Arm Title
Core Period: LCI699 1.0 mg QD
Arm Type
Experimental
Arm Description
Participants received LCI699 1 mg capsules, orally, QD, with or without food for up to 8 weeks.
Arm Title
Core Period: LCI699 0.5 mg BID
Arm Type
Experimental
Arm Description
Participants received LCI699 0.5 mg capsules, orally, twice daily (BID), with or without food for up to 8 weeks.
Arm Title
Core Period: Eplerenone 50 mg BID
Arm Type
Active Comparator
Arm Description
Participants received eplerenone 50 mg capsules, orally, BID, with or without food for up to 8 weeks.
Arm Title
Core Period: Placebo
Arm Type
Placebo Comparator
Arm Description
Participants received LCI699-matching placebo or eplerenone-matching placebo, capsules, orally, QD or BID, with or without food for up to 8 weeks.
Arm Title
Withdrawal Period: LCI699 0.25 mg QD
Arm Type
Experimental
Arm Description
Participants received LCI699 0.25 mg capsules, orally, QD, with or without food for up to 1 week (Week 8 to Week 9).
Arm Title
Withdrawal Period: LCI699 0.25 mg QD Placebo
Arm Type
Placebo Comparator
Arm Description
Participants received LCI699 matching placebo capsules, orally, QD, with or without food for up to 1 week (Week 8 to Week 9).
Arm Title
Withdrawal Period: LCI699 0.5 mg QD
Arm Type
Experimental
Arm Description
Participants received LCI699 0.5 mg capsules, orally, QD, with or without food for up to 1 week (Week 8 to Week 9).
Arm Title
Withdrawal Period: LCI699 0.5 mg QD Placebo
Arm Type
Placebo Comparator
Arm Description
Participants received LCI699 matching placebo capsules, orally, QD, with or without food for up to 1 week (Week 8 to Week 9).
Arm Title
Withdrawal Period: LCI699 1.0 mg QD
Arm Type
Experimental
Arm Description
Participants received LCI699 1 mg capsules, orally, QD, with or without food for up to 1 week (Week 8 to Week 9).
Arm Title
Withdrawal Period: LCI699 1.0 mg QD Placebo
Arm Type
Placebo Comparator
Arm Description
Participants received LCI699 matching placebo capsules, orally, QD, with or without food for up to 1 week (Week 8 to Week 9).
Arm Title
Withdrawal Period: LCI699 0.5 mg BID
Arm Type
Experimental
Arm Description
Participants received LCI699 0.5 mg capsules, orally, BID, with or without food for up to 1 week (Week 8 to Week 9).
Arm Title
Withdrawal Period: LCI699 0.5 mg BID Placebo
Arm Type
Placebo Comparator
Arm Description
Participants received LCI699 matching placebo capsules, orally, BID, with or without food for up to 1 week (Week 8 to Week 9).
Arm Title
Withdrawal Period: Eplerenone 50 mg BID
Arm Type
Active Comparator
Arm Description
Participants received eplerenone 50 mg capsules, orally, BID, with or without food for up to 1 week (Week 8 to Week 9).
Arm Title
Withdrawal Period: Eplerenone 50 mg BID Placebo
Arm Type
Placebo Comparator
Arm Description
Participants received eplerenone matching placebo capsules, orally, BID, with or without food for up to 1 week (Week 8 to Week 9).
Arm Title
Withdrawal Period: Placebo
Arm Type
Placebo Comparator
Arm Description
Participants received LCI699-matching placebo or eplerenone-matching placebo, capsules, orally, QD or BID, with or without food for up to 1 week (Week 8 to Week 9).
Intervention Type
Drug
Intervention Name(s)
LCI699
Intervention Description
LCI699 oral capsules
Intervention Type
Drug
Intervention Name(s)
Eplerenone
Intervention Description
Eplerenone oral capsules
Intervention Type
Drug
Intervention Name(s)
LCI699-matching Placebo
Intervention Description
LCI699-matching placebo oral capsules
Intervention Type
Drug
Intervention Name(s)
Eplerenone-matching Placebo
Intervention Description
Eplerenone-matching placebo oral capsules
Primary Outcome Measure Information:
Title
Core Period: Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP) at Week 8 Last Observation Carried Forward (LOCF), as Measured by Office Blood Pressure (OBP)
Description
Automated arterial BP determinations were made after the participant was in the sitting position for 5 minutes according to the Guidelines for management of hypertension: report of the 4th working party of the British Hypertension Society, 2004-BHS IV, using an automated BP device (such as the Omron BP monitor). 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 analysis of covariance model (ANCOVA) with treatment and region as factors and baseline MSDBP level as a covariate.
Time Frame
Baseline, Week 8
Secondary Outcome Measure Information:
Title
Core Period: Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP) at Week 8 LOCF, as Measured by OBP
Description
Automated arterial BP determinations were made after the participant was in the sitting position for 5 minutes according to the Guidelines for management of hypertension: report of the 4th working party of the British Hypertension Society, 2004-BHS IV, using an automated BP device (such as the Omron BP monitor). 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 region as factors and baseline MSSBP levels as a covariate.
Time Frame
Baseline, Week 8
Title
Core Period: Number of Participants With Adverse Event (AEs), Serious Adverse Events (SAEs), and Deaths
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.
Time Frame
AEs: From start of the study drug treatment up to 8 weeks; SAE: From signing of the informed consent up to 8 weeks
Title
Core Period: Dose Response Relationship of LCI699 as Measured by Change From Baseline in MSDBP at Week 8
Description
Automated arterial BP determinations were made after the participant was in the sitting position for 5 minutes according to the Guidelines for management of hypertension: report of the 4th working party of the British Hypertension Society, 2004-BHS IV, using an automated BP device (such as the Omron BP monitor). 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 analysis of covariance model (ANCOVA) with treatment and region as factors and baseline MSDBP level as a covariate.
Time Frame
Baseline, Week 8
Title
Core Period: Dose Response Relationship of LCI699 as Measured by Change From Baseline in MSSBP at Week 8
Description
Automated arterial BP determinations were made after the participant was in the sitting position for 5 minutes according to the Guidelines for management of hypertension: report of the 4th working party of the British Hypertension Society, 2004-BHS IV, using an automated BP device (such as the Omron BP monitor). 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 region as factors and baseline MSSBP levels as a covariate.
Time Frame
Baseline, Week 8
Title
Core Period: Change From Baseline in Mean 24 Hour Ambulatory SBP at Week 8 as Measured by Ambulatory Blood Pressure Monitoring (ABPM)
Description
An ABPM measured a participant's BP over a 24-hour period 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 SBP readings for the 24-hour period.
Time Frame
Baseline, Week 8
Title
Core Period: Change From Baseline in Mean 24 Hour Ambulatory DBP at Week 8, as Measured by ABPM
Description
An ABPM measured a participant's BP over a 24-hour period 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 DBP readings for the 24-hour period.
Time Frame
Baseline, Week 8
Title
Core Period: Trough to Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory DBP at Week 8
Description
Trough to peak ratios were derived from an ANCOVA model containing treatment, region, hour, treatment by hour interaction as factors with Baseline as a covariate.
Time Frame
Baseline, every hour up to 24 hours post-dose at Week 8
Title
Core Period: Trough to Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory SBP at Week 8
Description
Trough to peak ratios were derived from an ANCOVA model containing treatment, region, hour, treatment by hour interaction as factors with Baseline as a covariate.
Time Frame
Baseline, every hour up to 24 hours post-dose at Week 8
Title
Core Period: Change From Baseline in Plasma Aldosterone Levels at Week 8
Description
Change from baseline was analyzed using plasma aldosterone values measured at Baseline and Week 8.
Time Frame
Baseline, Week 8
Title
Core Period: Percentage of Participants With a MSDBP Response and MSDBP Control at Week 8 LOCF
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.
Time Frame
Baseline, Week 8
Title
Core Period: Percentage of Participants With a MSSBP Response and MSSBP Control at Week 8 LOCF
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.
Time Frame
Baseline, Week 8
Title
Core Period: Change From Baseline in Plasma Cortisol Levels by Adrenocorticotropic Hormone (ACTH) Stimulation Test
Description
The ACTH stimulation cortisol test was a standard procedure to measure the ability of adrenal cortex to respond to exogenous ACTH and directly assess the adrenal reserve. 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
Baseline, 1 hour post-dose at Week 8
Title
Withdrawal Period: Change From Week 8 to Week 9 in MSDBP at Week 9, as Measured by OBP
Description
Automated arterial BP determinations were made after the participant was in the sitting position for 5 minutes according to the Guidelines for management of hypertension: report of the 4th working party of the British Hypertension Society, 2004-BHS IV, using an automated BP device (such as the Omron BP monitor). The change in the MSDBP was calculated comparing the Week 9 readings to the readings taken at Week 8 (Baseline). The change from Week 8 to week 9 in MSDBP was analyzed using an ANCOVA with treatment and region as factors and Week 8 MSDBP level as a covariate.
Time Frame
From Week 8 to Week 9
Title
Withdrawal Period: Change From Week 8 to Week 9 in MSSBP at Week 9 as Measured by OBP
Description
Automated arterial BP determinations were made after the participant was in the sitting position for 5 minutes according to the Guidelines for management of hypertension: report of the 4th working party of the British Hypertension Society, 2004-BHS IV, using an automated BP device (such as the Omron BP monitor). The change in the MSSBP was calculated comparing the Week 9 readings to the readings taken at Week 8 (Baseline). The change from Week 8 to week 9 in MSSBP was analyzed using an ANCOVA with treatment and region as factors and Week 8 MSSBP level as a covariate.
Time Frame
From Week 8 to Week 9
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Males and non-fertile females.
18-75 years inclusive.
Participants with mild-to-moderate uncomplicated essential hypertension.
Exclusion Criteria:
All women of child bearing potential.
Female participants on hormone replacement therapy.
Severe hypertension.
History or evidence of a secondary form of hypertension.
Known moderate or malignant retinopathy.
History of angina pectoris, myocardial infarction, coronary bypass surgery,ischemic heart disease, surgical or percutaneous arterial intervention of any kind (coronary, carotid or peripheral vessels), stroke, transient ischemic attack (TIA), carotid artery stenosis, aortic aneurysm or peripheral arterial disease.
Type 1 or type 2 diabetes mellitus.
Clinically significant valvular heart disease.
Congestive heart failure (New York Heart Association [NYHA] class II-IV).
Cardiac electrical abnormalities indicating significant risk of safety for participant taking part in the study.
History of malignancy of any organ system, treated or untreated, within the past 5 years.
Liver disease such as cirrhosis or chronic active hepatitis.
Any surgical or medical conditions that may significantly alter the absorption, distribution, metabolism or excretion of any drug substance
Any surgical or medical conditions, not identified in the protocol that in the opinion of the investigator or the monitor, place the participant at higher risk from his/her participation in the study, or is likely to prevent the participant from complying with the requirements of the study or completing the trial period.
Participant unwilling or not able to discontinue safely the use of current antihypertensive medications during the study period
Any contraindication or history of hypersensitivity to any of the study drugs or to drugs with similar chemical structures.
Chronic oral or parenteral corticosteroid treatment.
Treatment with potassium supplement or potassium sparing diuretics.
Treatment with potent cytochrome P450 3A4 (CYP3A4) inhibitors during the study period.
Use of other investigational drugs at Visit 1, or within 30 days or 5 half-lives of Visit 1, whichever is longer, unless local health authority guidelines mandate a longer period.
Serum potassium > 5.2 milliequivalents per liter (mEq/L) or < 3.5 mEq/L at Visit 1.
Serum sodium < 132 mEq/L at Visit 1.
Aspartate aminotransferase (ALT) or alanine aminotransferase (AST) > 2 times the upper limit of the normal range (ULN) at Visit 1.
Bilirubin (total) > 1.5 x ULN at Visit 1.
Modification of diet in renal disease estimated glomerular filtration rate (MDRD eGFR) < 60 milliliters per minute (ml/min)/1.73 m^2 at Visit 1.
Other clinically significant laboratory abnormalities, confirmed by repeat measurements, at Visit 1.
History of active substance abuse (including alcohol).
Participants with night-shift employment.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Pharmaceuticals
City
East Hanover
State/Province
New Jersey
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
24107737
Citation
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.
Results Reference
derived
PubMed Identifier
21986283
Citation
Calhoun DA, White WB, Krum H, Guo W, Bermann G, Trapani A, Lefkowitz MP, Menard J. Effects of a novel aldosterone synthase inhibitor for treatment of primary hypertension: results of a randomized, double-blind, placebo- and active-controlled phase 2 trial. Circulation. 2011 Nov 1;124(18):1945-55. doi: 10.1161/CIRCULATIONAHA.111.029892. Epub 2011 Oct 10.
Results Reference
derived
Learn more about this trial
A Study to Evaluate Efficacy and Safety of LCI699 in Participants With Essential Hypertension
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