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

Hypertension Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00817414
• Other study ID #: CLCI699A2215
• Secondary ID: 2008-007337-49
• Status: Completed
• Phase: Phase 2
• Start date: January 14, 2009
• Est. completion date: August 12, 2009

Study information

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

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 63
• Est. completion date: August 12, 2009
• Est. primary completion date: August 12, 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hypertension

Intervention

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

Locations

Country	Name	City	State
Iceland	Encode Clinic	Reykjavik	SA
United States	Clinical Study Center of Asheville, LLC	Asheville	North Carolina
United States	Impact Clinical Trials	Beverly Hills	California
United States	Associated Pharmaceutical Research Center, Inc	Buena Park	California
United States	Punzi Medical Center	Carrollton	Texas
United States	Innovative Clinical Research, Inc	Harbor City	California
United States	Northstate Clinical Research	Lenoir	North Carolina
United States	Metro Clinical Research	Littleton	Colorado
United States	Long Beach Center for Clinical Research	Long Beach	California
United States	dgd Research, Inc	San Antonio	Texas
United States	Tipton Medical & Diagnostic Center	Tipton	Pennsylvania

Sponsors (3)

Lead Sponsor	Collaborator
Novartis	Great Lakes Drug Development, Inc., Integrium

Countries where clinical trial is conducted

United States,  Iceland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	LCI699 Plasma Concentration Post LCI699 Administration at Day 7		Predose and 3 hours post-dose on Day 7
Secondary	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
Secondary	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
Secondary	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
Secondary	Area Under the Concentration Time Curve Over the Dosing Interval (AUC0-t) 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
Secondary	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
Secondary	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
Secondary	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
Secondary	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