Title
A Study to Evaluate the Effects of LCI699 on Cortisol in Participants With Hypertension
A Phase II, Randomized, Double-blind, Placebo Controlled, Multi-center Study to Evaluate the Effects of LCI699 on Cortisol in Patients With Hypertension
Phase
Phase 2Lead Sponsor
NovartisStudy Type
InterventionalStatus
Completed Results PostedIndication/Condition
HypertensionIntervention/Treatment
osilodrostat ...Study Participants
63This study determined the maximum dose of LCI6999 with respect to effect on the ACTH-stimulated cortisol response in participants with hypertension.
LCI699-matching placebo oral capsules
LCI699 oral capsules
Participants received LCI699 0.5 mg, capsules, orally, once daily (QD), with or without food for up to 6 weeks.
Participants received LCI699 1.0 mg, capsules, orally, QD, with or without food for up to 6 weeks.
Participants received LCI699 1.0 mg, capsules, orally, twice daily (BID), with or without food for up to 6 weeks.
Participants received LCI699 2.0 mg, capsules, orally, QD, with or without food for up to 6 weeks.
Participants received LCI699-matching placebo, capsules, orally, QD or BID, with or without food for up to 6 weeks.
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.
| Event Type | Organ System | Event Term | Cohort A: LCI699 0.5 mg QD | Cohort A: LCI699 1.0 mg QD | Cohort B1: LCI699 1.0 mg BID | Cohort B1: LCI699 2.0 mg QD | Placebo |
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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.
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.
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.
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.
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.
