A Study to Evaluate the Effects of LCI699 on Cortisol in Participants With Hypertension
- Registration Number
- NCT00817414
- Lead Sponsor
- Novartis
- Brief Summary
This study determined the maximum dose of LCI6999 with respect to effect on the ACTH-stimulated cortisol response in participants with hypertension.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 63
- 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)
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cohort A: LCI699 1.0 mg QD LCI699 Participants received LCI699 1.0 mg, capsules, orally, QD, with or without food for up to 6 weeks. Placebo LCI699-matching placebo Participants received LCI699-matching placebo, capsules, orally, QD or BID, with or without food for up to 6 weeks. Cohort A: LCI699 0.5 mg QD LCI699 Participants received LCI699 0.5 mg, capsules, orally, once daily (QD), with or without food for up to 6 weeks. Cohort B1: LCI699 1.0 mg BID LCI699 Participants received LCI699 1.0 mg, capsules, orally, twice daily (BID), with or without food for up to 6 weeks. Cohort B1: LCI699 2.0 mg QD LCI699 Participants received LCI699 2.0 mg, capsules, orally, QD, with or without food for up to 6 weeks.
- Primary Outcome Measures
Name Time Method Maximum Tolerated Dose (MTD) of LCI699 With Respect to Effect on the Adrenocorticotropic Hormone (ACTH)-Stimulated Cortisol Response Following ACTH Stimulation in Hypertensive Participants Up to Week 6 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.
- Secondary Outcome Measures
Name Time Method 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 LCI699 Exposure-response Relationship on Cortisol Levels Following ACTH Stimulation in Hypertensive Participants Up to Week 6 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.
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 Number of Participants With Adverse Event (AEs) Up to 8 weeks 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.
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 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 LCI699 Plasma Concentration Post LCI699 Administration at Day 7 Predose and 3 hours post-dose on Day 7 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) Week 6 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.
Percentage of Participants With a Mean Sitting Diastolic Blood Pressure (MSDBP) Response and MSDBP Control at Week 6 LOCF, as Measured by OBP Week 6 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.
Trial Locations
- Locations (11)
Impact Clinical Trials
🇺🇸Beverly Hills, California, United States
Long Beach Center for Clinical Research
🇺🇸Long Beach, California, United States
Innovative Clinical Research, Inc
🇺🇸Harbor City, California, United States
Metro Clinical Research
🇺🇸Littleton, Colorado, United States
Punzi Medical Center
🇺🇸Carrollton, Texas, United States
Associated Pharmaceutical Research Center, Inc
🇺🇸Buena Park, California, United States
Northstate Clinical Research
🇺🇸Lenoir, North Carolina, United States
Tipton Medical & Diagnostic Center
🇺🇸Tipton, Pennsylvania, United States
Encode Clinic
🇮🇸Reykjavik, SA, Iceland
Clinical Study Center of Asheville, LLC
🇺🇸Asheville, North Carolina, United States
dgd Research, Inc
🇺🇸San Antonio, Texas, United States