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

Essential Hypertension Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00758524
• Other study ID #: CLCI699A2201
• Status: Completed
• Phase: Phase 2
• Start date: September 11, 2008
• Est. completion date: July 2, 2009

Study information

• Verified date: June 2021
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 628
• Est. completion date: July 2, 2009
• Est. primary completion date: July 2, 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Essential Hypertension
• Hypertension

Intervention

Drug:
• LCI699
LCI699 oral capsules
• Eplerenone
Eplerenone oral capsules
• LCI699-matching Placebo
LCI699-matching placebo oral capsules
• Eplerenone-matching Placebo
Eplerenone-matching placebo oral capsules

Locations

Country	Name	City	State
United States	Novartis Pharmaceuticals	East Hanover	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline, Week 8
Secondary	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.	Baseline, Week 8
Secondary	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.	AEs: From start of the study drug treatment up to 8 weeks; SAE: From signing of the informed consent up to 8 weeks
Secondary	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.	Baseline, Week 8
Secondary	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.	Baseline, Week 8
Secondary	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.	Baseline, Week 8
Secondary	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.	Baseline, Week 8
Secondary	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.	Baseline, every hour up to 24 hours post-dose at Week 8
Secondary	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.	Baseline, every hour up to 24 hours post-dose at Week 8
Secondary	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.	Baseline, Week 8
Secondary	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.	Baseline, Week 8
Secondary	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.	Baseline, Week 8
Secondary	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.	Baseline, 1 hour post-dose at Week 8
Secondary	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.	From Week 8 to Week 9
Secondary	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.	From Week 8 to Week 9