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A Study to Evaluate Efficacy and Safety of LCI699 in Participants With Essential Hypertension

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00758524
Recruitment Status : Completed
First Posted : September 25, 2008
Results First Posted : July 6, 2021
Last Update Posted : July 6, 2021
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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.

Condition or disease Intervention/treatment Phase
Essential Hypertension Drug: LCI699 Drug: Eplerenone Drug: LCI699-matching Placebo Drug: Eplerenone-matching Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 628 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : September 11, 2008
Actual Primary Completion Date : July 2, 2009
Actual Study Completion Date : July 2, 2009

Resource links provided by the National Library of Medicine

Drug Information available for: Eplerenone

Arm Intervention/treatment
Experimental: Core Period: LCI699 0.25 mg QD
Participants received LCI699 0.25 mg capsules, orally, once daily (QD), with or without food for up to 8 weeks.
Drug: LCI699
LCI699 oral capsules

Experimental: Core Period: LCI699 0.5 mg QD
Participants received LCI699 0.5 mg capsules, orally, QD, with or without food for up to 8 weeks.
Drug: LCI699
LCI699 oral capsules

Experimental: Core Period: LCI699 1.0 mg QD
Participants received LCI699 1 mg capsules, orally, QD, with or without food for up to 8 weeks.
Drug: LCI699
LCI699 oral capsules

Experimental: Core Period: LCI699 0.5 mg BID
Participants received LCI699 0.5 mg capsules, orally, twice daily (BID), with or without food for up to 8 weeks.
Drug: LCI699
LCI699 oral capsules

Active Comparator: Core Period: Eplerenone 50 mg BID
Participants received eplerenone 50 mg capsules, orally, BID, with or without food for up to 8 weeks.
Drug: Eplerenone
Eplerenone oral capsules

Placebo Comparator: Core Period: Placebo
Participants received LCI699-matching placebo or eplerenone-matching placebo, capsules, orally, QD or BID, with or without food for up to 8 weeks.
Drug: LCI699-matching Placebo
LCI699-matching placebo oral capsules

Drug: Eplerenone-matching Placebo
Eplerenone-matching placebo oral capsules

Experimental: Withdrawal Period: LCI699 0.25 mg QD
Participants received LCI699 0.25 mg capsules, orally, QD, with or without food for up to 1 week (Week 8 to Week 9).
Drug: LCI699
LCI699 oral capsules

Placebo Comparator: Withdrawal Period: LCI699 0.25 mg QD Placebo
Participants received LCI699 matching placebo capsules, orally, QD, with or without food for up to 1 week (Week 8 to Week 9).
Drug: LCI699-matching Placebo
LCI699-matching placebo oral capsules

Experimental: Withdrawal Period: LCI699 0.5 mg QD
Participants received LCI699 0.5 mg capsules, orally, QD, with or without food for up to 1 week (Week 8 to Week 9).
Drug: LCI699
LCI699 oral capsules

Placebo Comparator: Withdrawal Period: LCI699 0.5 mg QD Placebo
Participants received LCI699 matching placebo capsules, orally, QD, with or without food for up to 1 week (Week 8 to Week 9).
Drug: LCI699-matching Placebo
LCI699-matching placebo oral capsules

Experimental: Withdrawal Period: LCI699 1.0 mg QD
Participants received LCI699 1 mg capsules, orally, QD, with or without food for up to 1 week (Week 8 to Week 9).
Drug: LCI699
LCI699 oral capsules

Placebo Comparator: Withdrawal Period: LCI699 1.0 mg QD Placebo
Participants received LCI699 matching placebo capsules, orally, QD, with or without food for up to 1 week (Week 8 to Week 9).
Drug: LCI699-matching Placebo
LCI699-matching placebo oral capsules

Experimental: Withdrawal Period: LCI699 0.5 mg BID
Participants received LCI699 0.5 mg capsules, orally, BID, with or without food for up to 1 week (Week 8 to Week 9).
Drug: LCI699
LCI699 oral capsules

Placebo Comparator: Withdrawal Period: LCI699 0.5 mg BID Placebo
Participants received LCI699 matching placebo capsules, orally, BID, with or without food for up to 1 week (Week 8 to Week 9).
Drug: LCI699-matching Placebo
LCI699-matching placebo oral capsules

Active Comparator: Withdrawal Period: Eplerenone 50 mg BID
Participants received eplerenone 50 mg capsules, orally, BID, with or without food for up to 1 week (Week 8 to Week 9).
Drug: Eplerenone
Eplerenone oral capsules

Placebo Comparator: Withdrawal Period: Eplerenone 50 mg BID Placebo
Participants received eplerenone matching placebo capsules, orally, BID, with or without food for up to 1 week (Week 8 to Week 9).
Drug: Eplerenone-matching Placebo
Eplerenone-matching placebo oral capsules

Placebo Comparator: Withdrawal Period: Placebo
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).
Drug: LCI699-matching Placebo
LCI699-matching placebo oral capsules

Drug: Eplerenone-matching Placebo
Eplerenone-matching placebo oral capsules




Primary Outcome Measures :
  1. 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) [ Time Frame: Baseline, 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.


Secondary Outcome Measures :
  1. Core Period: Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP) at Week 8 LOCF, as Measured by OBP [ Time Frame: Baseline, 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.

  2. Core Period: Number of Participants With Adverse Event (AEs), Serious Adverse Events (SAEs), and Deaths [ 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 ]
    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.

  3. Core Period: Dose Response Relationship of LCI699 as Measured by Change From Baseline in MSDBP at Week 8 [ Time Frame: Baseline, 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.

  4. Core Period: Dose Response Relationship of LCI699 as Measured by Change From Baseline in MSSBP at Week 8 [ Time Frame: Baseline, 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.

  5. Core Period: Change From Baseline in Mean 24 Hour Ambulatory SBP at Week 8 as Measured by Ambulatory Blood Pressure Monitoring (ABPM) [ Time Frame: Baseline, Week 8 ]
    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.

  6. Core Period: Change From Baseline in Mean 24 Hour Ambulatory DBP at Week 8, as Measured by ABPM [ Time Frame: Baseline, Week 8 ]
    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.

  7. Core Period: Trough to Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory DBP at Week 8 [ Time Frame: Baseline, every hour up to 24 hours post-dose 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.

  8. Core Period: Trough to Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory SBP at Week 8 [ Time Frame: Baseline, every hour up to 24 hours post-dose 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.

  9. Core Period: Change From Baseline in Plasma Aldosterone Levels at Week 8 [ Time Frame: Baseline, Week 8 ]
    Change from baseline was analyzed using plasma aldosterone values measured at Baseline and Week 8.

  10. Core Period: Percentage of Participants With a MSDBP Response and MSDBP Control at Week 8 LOCF [ Time Frame: Baseline, 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.

  11. Core Period: Percentage of Participants With a MSSBP Response and MSSBP Control at Week 8 LOCF [ Time Frame: Baseline, 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.

  12. Core Period: Change From Baseline in Plasma Cortisol Levels by Adrenocorticotropic Hormone (ACTH) Stimulation Test [ Time Frame: Baseline, 1 hour post-dose at Week 8 ]
    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.

  13. Withdrawal Period: Change From Week 8 to Week 9 in MSDBP at Week 9, as Measured by OBP [ Time Frame: From Week 8 to Week 9 ]
    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.

  14. Withdrawal Period: Change From Week 8 to Week 9 in MSSBP at Week 9 as Measured by OBP [ Time Frame: From Week 8 to Week 9 ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00758524


Locations
Layout table for location information
United States, New Jersey
Novartis Pharmaceuticals
East Hanover, New Jersey, United States
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00758524    
Other Study ID Numbers: CLCI699A2201
First Posted: September 25, 2008    Key Record Dates
Results First Posted: July 6, 2021
Last Update Posted: July 6, 2021
Last Verified: June 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Essential hypertension
Phase 2 study
Antihypertensive agent
Additional relevant MeSH terms:
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Hypertension
Essential Hypertension
Vascular Diseases
Cardiovascular Diseases
Eplerenone
Mineralocorticoid Receptor Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Diuretics, Potassium Sparing
Diuretics
Natriuretic Agents
Antihypertensive Agents