A Phase II, Randomized, Double-blind, Placebo Controlled, Multi-center Study to Evaluate the Effects of LCI699 on Cortisol in Patients With Hypertension
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Novartis
- Enrollment
- 63
- Locations
- 11
- Primary Endpoint
- Maximum Tolerated Dose (MTD) of LCI699 With Respect to Effect on the Adrenocorticotropic Hormone (ACTH)-Stimulated Cortisol Response Following ACTH Stimulation in Hypertensive Participants
Study Overview
Brief Summary
This study determined the maximum dose of LCI6999 with respect to effect on the ACTH-stimulated cortisol response in participants with hypertension.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
Arms & Interventions
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.
Intervention: LCI699 (Drug)
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.
Intervention: LCI699 (Drug)
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.
Intervention: LCI699 (Drug)
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.
Intervention: LCI699 (Drug)
Placebo
Participants received LCI699-matching placebo, capsules, orally, QD or BID, with or without food for up to 6 weeks.
Intervention: LCI699-matching placebo (Drug)
Outcomes
Primary Outcomes
Maximum Tolerated Dose (MTD) of LCI699 With Respect to Effect on the Adrenocorticotropic Hormone (ACTH)-Stimulated Cortisol Response Following ACTH Stimulation in Hypertensive Participants
Time Frame: 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 Outcomes
- 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)
- 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)
- 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)
- 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)