Clinical trial NCT00817414: A Study to Evaluate the Effects of LCI699 on Cortisol in Participants With Hypertension
Official title: A Phase II, Randomized, Double-blind, Placebo Controlled, Multi-center Study to Evaluate the Effects of LCI699 on Cortisol in Patients With Hypertension
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hypertension
Keywords: Blood Pressure
Hypertension
Cortisol
Lead sponsor: Novartis
Sponsor class: INDUSTRY
Collaborators: name: Great Lakes Drug Development, Inc.
name: Integrium
First posted: 2009-01-06
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) of LCI699 With Respect to Effect on the Adrenocorticotropic Hormone (ACTH)-Stimulated Cortisol Response Following ACTH Stimulation in Hypertensive Participants
timeFrame: Up to Week 6
Secondary outcomes:
measure: LCI699 Exposure-response Relationship on Cortisol Levels Following ACTH Stimulation in Hypertensive Participants
timeFrame: Up to Week 6
measure: LCI699 Plasma Concentration Post LCI699 Administration at Day 7
timeFrame: Predose and 3 hours post-dose on Day 7
measure: Maximum Plasma Concentration (Cmax) of LCI699
timeFrame: 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
measure: Time of Maximum Plasma Concentration (Tmax) of LCI699
timeFrame: 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
measure: Area Under the Concentration Time Curve From Time 0 to 8 Hours Post LCI699 Administration (AUC0-8)
timeFrame: Day 42: Pre-dose and 0.5, 1, 2, 3, 4, and 8-hours post-dose
measure: Area Under the Concentration Time Curve Over the Dosing Interval (AUC0-τ) for LCI699
timeFrame: 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
measure: Apparent Terminal Half-life (T1/2) of LCI699
timeFrame: 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
measure: Number of Participants With Adverse Event (AEs)
timeFrame: Up to 8 weeks
measure: 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)
timeFrame: Week 6
measure: Percentage of Participants With a Mean Sitting Diastolic Blood Pressure (MSDBP) Response and MSDBP Control at Week 6 LOCF, as Measured by OBP
timeFrame: Week 6
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: Impact Clinical Trials
state: California
city: Buena Park
country: United States
facility: Associated Pharmaceutical Research Center, Inc
state: California
city: Harbor City
country: United States
facility: Innovative Clinical Research, Inc
state: California
city: Long Beach
country: United States
facility: Long Beach Center for Clinical Research
state: California
city: Littleton
country: United States
facility: Metro Clinical Research
state: Colorado
city: Asheville
country: United States
facility: Clinical Study Center of Asheville, LLC
state: North Carolina
city: Lenoir
country: United States
facility: Northstate Clinical Research
state: North Carolina
city: Tipton
country: United States
facility: Tipton Medical & Diagnostic Center
state: Pennsylvania
city: Carrollton
country: United States
facility: Punzi Medical Center
state: Texas
city: San Antonio
country: United States
facility: dgd Research, Inc
state: Texas
city: Reykjavik
country: Iceland
facility: Encode Clinic
state: SA
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
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.