A Study to Evaluate the Effects of LCI699 on Cortisol in Participants With Hypertension

A Phase II, Randomized, Double-blind, Placebo Controlled, Multi-center Study to Evaluate the Effects of LCI699 on Cortisol in Patients With Hypertension

This study determined the maximum dose of LCI6999 with respect to effect on the ACTH-stimulated cortisol response in participants with hypertension.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: LCI699; Drug: LCI699-matching placebo

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 2

Contacts and Locations

Study Locations

• Iceland
  • SA
    • Reykjavik, SA, Iceland
      • Encode Clinic
• United States
  • California
    • Beverly Hills, California, United States, 90211
      • Impact Clinical Trials
    • Buena Park, California, United States, 90620
      • Associated Pharmaceutical Research Center, Inc
    • Harbor City, California, United States, 90710
      • Innovative Clinical Research, INC
    • Long Beach, California, United States, 90806
      • Long Beach Center For Clinical Research
  • Colorado
    • Littleton, Colorado, United States, 80120
      • Metro Clinical Research
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Clinical Study Center of Asheville, LLC
    • Lenoir, North Carolina, United States, 28645
      • Northstate Clinical Research
  • Pennsylvania
    • Tipton, Pennsylvania, United States, 16684
      • Tipton Medical & Diagnostic Center
  • Texas
    • Carrollton, Texas, United States, 75006
      • Punzi Medical Center
    • San Antonio, Texas, United States, 78229
      • dgd Research, Inc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of hypertension with blood pressure ≥ 140/90 millimeters of mercury (mmHg) and < 180/110 mmHg on current antihypertensive treatment
• Male and female participants 18-75 years of age
• Participants must weigh at least 50 kilograms (kg)

Exclusion Criteria:

• Recent history of myocardial infarction, heart failure, unstable angina, coronary artery bypass graft, percutaneous coronary intervention, hypertensive encephalopathy, cerebral 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)
• Liver disease

Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A: LCI699 0.5 mg QD; Participants received LCI699 0.5 mg, capsules, orally, once daily (QD), with or without food for up to 6 weeks.	Drug: LCI699; LCI699 oral capsules
Experimental: Cohort A: LCI699 1.0 mg QD; Participants received LCI699 1.0 mg, capsules, orally, QD, with or without food for up to 6 weeks.	Drug: LCI699; LCI699 oral capsules
Experimental: Cohort B1: LCI699 1.0 mg BID; Participants received LCI699 1.0 mg, capsules, orally, twice daily (BID), with or without food for up to 6 weeks.	Drug: LCI699; LCI699 oral capsules
Experimental: Cohort B1: LCI699 2.0 mg QD; Participants received LCI699 2.0 mg, capsules, orally, QD, with or without food for up to 6 weeks.	Drug: LCI699; LCI699 oral capsules
Placebo Comparator: Placebo; Participants received LCI699-matching placebo, capsules, orally, QD or BID, with or without food for up to 6 weeks.	Drug: LCI699-matching placebo; LCI699-matching placebo oral capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Tolerated Dose (MTD) of LCI699 With Respect to Effect on the Adrenocorticotropic Hormone (ACTH)-Stimulated Cortisol Response Following ACTH Stimulation in Hypertensive Participants	As per the protocol, MTD is the dose at which 4 participants exhibited ACTH-stimulated cortisol results <400 nanomoles per liter (nmol/L). The change in the distribution across the treatments were analyzed using 1- way analysis of variance (ANOVA) for continuous variables.	Up to Week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
LCI699 Exposure-response Relationship on Cortisol Levels Following ACTH Stimulation in Hypertensive Participants	Exposure-response relationship was assessed using ACTH stimulation test. Tests were done 2 hours after study drug administration (i.e., at peak LCI699 concentrations). An increase in cortisol greater than >500 nmol at 60 minutes after ACTH administration was expected.	Up to Week 6
LCI699 Plasma Concentration Post LCI699 Administration at Day 7		Predose and 3 hours post-dose on Day 7
Maximum Plasma Concentration (Cmax) of LCI699		Days 7, 28: Pre-dose and 3 hours post-dose; Day 30: Pre-dose; Day 42: Pre-dose and 0.5, 1, 2, 3, 4, and 8-hours post-dose
Time of Maximum Plasma Concentration (Tmax) of LCI699		Days 7, 28: Pre-dose and 3 hours post-dose; Day 30: Pre-dose; Day 42: Pre-dose and 0.5, 1, 2, 3, 4, and 8-hours post-dose
Area Under the Concentration Time Curve From Time 0 to 8 Hours Post LCI699 Administration (AUC0-8)		Day 42: Pre-dose and 0.5, 1, 2, 3, 4, and 8-hours post-dose
Area Under the Concentration Time Curve Over the Dosing Interval (AUC0-τ) for LCI699		Days 7, 28: Pre-dose and 3 hours post-dose; Day 30: Pre-dose; Day 42: Pre-dose and 0.5, 1, 2, 3, 4, and 8-hours post-dose
Apparent Terminal Half-life (T1/2) of LCI699		Days 7, 28: Pre-dose and 3 hours post-dose; Day 30: Pre-dose; Day 42: Pre-dose and 0.5, 1, 2, 3, 4, and 8-hours post-dose
Number of Participants With Adverse Event (AEs)	An AE is 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.	Up to 8 weeks
Percentage of Participants With a Mean Sitting Systolic Blood Pressure (MSSBP) Response and MSSBP Control at Week 6 Last Observation Carried Forward (LOCF), as Measured by Office Blood Pressure (OBP)	Automated arterial BP determinations was made with an automated BP device (such as the Omron BP monitor) in accordance with the Guidelines for management of hypertension: report of the 4th working party of the British Hypertension Society, 2004-BHS IV. Sitting and standing blood pressure (BP) and heart rate (HR) measurements were performed. MSSBP response was defined as the percentage of participants with a MSSBP <140 mmHg or a >=20 mmHg 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.	Week 6
Percentage of Participants With a Mean Sitting Diastolic Blood Pressure (MSDBP) Response and MSDBP Control at Week 6 LOCF, as Measured by OBP	Automated arterial BP determinations was made with an automated BP device (such as the Omron BP monitor) in accordance with the Guidelines for management of hypertension: report of the 4th working party of the British Hypertension Society, 2004-BHS IV. Sitting and standing BP and HR measurements were performed. 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.	Week 6

Collaborators and Investigators

• Sponsor: Novartis
• Collaborators: Integrium; Great Lakes Drug Development, Inc.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 14, 2009
• Primary Completion (Actual): August 12, 2009
• Study Completion (Actual): August 12, 2009

Study Registration Dates

• First Submitted: January 5, 2009
• First Submitted That Met QC Criteria: January 5, 2009
• First Posted (Estimate): January 6, 2009

Study Record Updates

• Last Update Posted (Actual): June 2, 2021
• Last Update Submitted That Met QC Criteria: May 6, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Hypertension; Cortisol; Blood Pressure
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension
• Other Study ID Numbers: CLCI699A2215; 2008-007337-49 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No