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

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

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

Conditions
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Hypertension

Intervention / Treatment
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* Drug: LCI699-matching placebo
* Drug: LCI699


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Blood Pressure, Hypertension, Cortisol