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

NCT00758524 | Completed Phase 2 Results FDA Drug

• 1 other identifier: CLCI699A2201
• Study Type: interventional
• Target: 628
• Locations: 1 country
• Sites: 1

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.

Conditions

Essential Hypertension

Keywords

Essential hypertension; Phase 2 study; Antihypertensive agent

Outcome Measures

Primary Outcomes (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)

  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 Outcomes (14)

• Core Period: Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP) at Week 8 LOCF, as Measured by OBP

  Baseline, Week 8

• Core Period: Number of Participants With Adverse Event (AEs), Serious Adverse Events (SAEs), and Deaths

  AEs: From start of the study drug treatment up to 8 weeks; SAE: From signing of the informed consent up to 8 weeks

• Core Period: Dose Response Relationship of LCI699 as Measured by Change From Baseline in MSDBP at Week 8

  Baseline, Week 8

• Core Period: Dose Response Relationship of LCI699 as Measured by Change From Baseline in MSSBP at Week 8

  Baseline, Week 8

• Core Period: Change From Baseline in Mean 24 Hour Ambulatory SBP at Week 8 as Measured by Ambulatory Blood Pressure Monitoring (ABPM)

  Baseline, Week 8

Study Arms (17)

Core Period: LCI699 0.25 mg QD

EXPERIMENTAL

Participants received LCI699 0.25 mg capsules, orally, once daily (QD), with or without food for up to 8 weeks.

Drug: LCI699

Core Period: LCI699 0.5 mg QD

EXPERIMENTAL

Participants received LCI699 0.5 mg capsules, orally, QD, with or without food for up to 8 weeks.

Drug: LCI699

Core Period: LCI699 1.0 mg QD

EXPERIMENTAL

Participants received LCI699 1 mg capsules, orally, QD, with or without food for up to 8 weeks.

Drug: LCI699

Core Period: LCI699 0.5 mg BID

EXPERIMENTAL

Participants received LCI699 0.5 mg capsules, orally, twice daily (BID), with or without food for up to 8 weeks.

Drug: LCI699

Core Period: Eplerenone 50 mg BID

ACTIVE COMPARATOR

Participants received eplerenone 50 mg capsules, orally, BID, with or without food for up to 8 weeks.

Drug: Eplerenone

Core Period: Placebo

PLACEBO COMPARATOR

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; Drug: Eplerenone-matching Placebo

Withdrawal Period: LCI699 0.25 mg QD

EXPERIMENTAL

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

Withdrawal Period: LCI699 0.25 mg QD Placebo

PLACEBO COMPARATOR

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

Withdrawal Period: LCI699 0.5 mg QD

EXPERIMENTAL

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

Withdrawal Period: LCI699 0.5 mg QD Placebo

PLACEBO COMPARATOR

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

Withdrawal Period: LCI699 1.0 mg QD

EXPERIMENTAL

Participants received LCI699 1 mg capsules, orally, QD, with or without food for up to 1 week (Week 8 to Week 9).

Drug: LCI699

Withdrawal Period: LCI699 1.0 mg QD Placebo

PLACEBO COMPARATOR

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

Withdrawal Period: LCI699 0.5 mg BID

EXPERIMENTAL

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

Withdrawal Period: LCI699 0.5 mg BID Placebo

PLACEBO COMPARATOR

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

Withdrawal Period: Eplerenone 50 mg BID

ACTIVE COMPARATOR

Participants received eplerenone 50 mg capsules, orally, BID, with or without food for up to 1 week (Week 8 to Week 9).

Drug: Eplerenone

Withdrawal Period: Eplerenone 50 mg BID Placebo

PLACEBO COMPARATOR

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

Withdrawal Period: Placebo

PLACEBO COMPARATOR

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; Drug: Eplerenone-matching Placebo

Interventions

LCI699 DRUG

LCI699 oral capsules

Core Period: LCI699 0.25 mg QD; Core Period: LCI699 0.5 mg BID; Core Period: LCI699 0.5 mg QD; Core Period: LCI699 1.0 mg QD; Withdrawal Period: LCI699 0.25 mg QD; Withdrawal Period: LCI699 0.5 mg BID; Withdrawal Period: LCI699 0.5 mg QD; Withdrawal Period: LCI699 1.0 mg QD

Eplerenone DRUG

Eplerenone oral capsules

Core Period: Eplerenone 50 mg BID; Withdrawal Period: Eplerenone 50 mg BID

LCI699-matching Placebo DRUG

LCI699-matching placebo oral capsules

Core Period: Placebo; Withdrawal Period: LCI699 0.25 mg QD Placebo; Withdrawal Period: LCI699 0.5 mg BID Placebo; Withdrawal Period: LCI699 0.5 mg QD Placebo; Withdrawal Period: LCI699 1.0 mg QD Placebo; Withdrawal Period: Placebo

Eplerenone-matching Placebo DRUG

Eplerenone-matching placebo oral capsules

Core Period: Placebo; Withdrawal Period: Eplerenone 50 mg BID Placebo; Withdrawal Period: Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and non-fertile females.
• years inclusive.
• Participants with mild-to-moderate uncomplicated essential hypertension.

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (1)

Novartis Pharmaceuticals

East Hanover, New Jersey, United States

Location

Related Publications (2)

• 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.

  PMID: 24107737 DERIVED

• 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.

  PMID: 21986283 DERIVED

MeSH Terms

Conditions

Essential Hypertension

Interventions

Osilodrostat; Eplerenone

Condition Hierarchy (Ancestors)

Hypertension; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

8627788300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2008
• First Posted: September 25, 2008
• Study Start: September 11, 2008
• Primary Completion: July 2, 2009
• Study Completion: July 2, 2009
• Last Updated: July 6, 2021
• Results First Posted: July 6, 2021

Record last verified: 2021-06

Locations

US (1)