hypertension artérielle par hyperaldostéronisme primaire MedDRA version: 9.1 Level: LLT Classification code 10039834 Term: Secondary hypertension
Conditions
Interventions
Product Code: LCI699
Pharmaceutical Form: Capsule*
Current Sponsor code: LCI699
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.5-
Pharmaceutical form of the plac
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male and/or female subjects 18 to 70 years of age (inclusive) • Female subjects must have been surgically sterilized (oophorectomy with or without hysterectomy) at least 6 months prior to screening. Surgical sterilization procedures must be supported with clinical documentation made available to sponsor and noted in the Relevant Medical History / Current Medical Conditions section of the CRF. OR: • Postmenopausal women must have no regular menstrual bleeding for at least 1 year prior to inclusion. Menopause will be confirmed by a plasma FSH level of =40 IU/L OR: • Male subjects must be using a double-barrier local contraception, i.e., spermicidal gel plus condom, for the entire duration of the study, up to Study Completion visit, and refrain from fathering a child or donating sperm in the three (3) months following last study drug administration. 2. Body mass index of 18 to 34 kg/m2 at Screening. Subjects must weigh at least 50 kg to participate in the study. 3. Diagnosis of primary hyperaldosteronism (PH) within the last 3 years, either with or without an aldosterone producing adenoma (APA). PH will be defined by aldosterone/renin ratio (ARR) = 64 pmol/mU twice and an elevated aldosterone concentration (plasma = 500 pmol/L or urinary =63 nmol/day) after 2-6 week washout of drugs interfering with the renin/ angiotensin / aldosterone system (RAAS). 4. Diagnosis of hypertension at screening (systolic and/or diastolic OBP> 140/90 mmHg or on current antihypertensive treatment) 5. Morning plasma cortisol (sampled between 08:00 and 09:00) > 200 nmol/l at screening and 60 min post-ACTH plasma cortisol should be > 500 nmol/l at baseline (Day -15). 6. Able to provide written informed consent prior to study participation. Patient information and consent forms generated by the Investigator must be approved by the sponsor prior to submission to the Institutional Review Board (IRB). A copy of the patient information and consent forms approved by the IRB must be forwarded to the sponsor prior to study initiation. 7. Able to communicate well with the investigator and comply with the requirements of the study. 8. Registration to the French national welfare system Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Patients with persistent hypokalemia ( 500 mg/dl at Screening • ALT and AST > 2X upper limit of normal (ULN) • Total bilirubin > 2X ULN • Conjugated bilirubin > 1X ULN • A positive hepatitis B surface antigen (HBsAg) or Hepatitis C test result. 12. History of active substance abuse (including alcohol) within the past 2 years 13. History of hypersensitivity to any of the study drugs or to drugs with similar chemical structures 14. Chronic use of NSAID or COX2 inhibitors or heparin. Aspirin up to 80 mg/day is allowed 15. Chronic use of corticosteroids in any formulation (oral, topical, eye drops, inhaled) 16. Known Keith-Wagener grade III or IV hypertensive retinopathy. 17. History of hypertensive encephalopathy or cerebrovascular accident at any time prior to eligibility visit. 18. Transient ischemic cerebral attack during the 3 months prior to eligibility visit. 19. History of heart failure (NYHA Class I-IV). 20. Unstable angina pectoris or myocardial infarction, or revascularization during the six months prior screening. Stable coronary heart disease patients treated with beta-blockers which cannot be interrupted. 21. Second or third degree heart block without a pacemaker. 22. Concurrent potentially life threatening arrhythmia or symptomatic arrhythmia. Patients with chronic atrial fibrillation (because of the difficulty to measure BP ) 23. Clinically significant valvular heart disease. 24. Type 1 diabetes. 25. Type 2 diabetes mellitus with poor glucose control as defined by HbA1c >8% 26. Any surgic
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: • To examine the safety and tolerability of LCI699 • To explore the effects of LCI699 on plasma and urine hormone levels and electrolytes • To determine the effects of LCI699 on mean 24-hour diastolic blood pressure (DBP) • To determine the effects of LCI699 on mean day time and night time SBP and DBP • To determine the pharmacokinetics of LCI699 following bid dosing ;Main Objective: To determine the effects of LCI699 on mean 24-hour systolic blood pressure (SBP) as measured by ambulatory blood pressure monitoring (ABPM) ;Primary end point(s): to explore the pharmacodynamics (blood pressure, electrolyte and hormonal changes) and safety and tolerability of LCI699 following bid dosing. ABPM will be used to evaluate the primary endpoint of the study | — |
Countries
France
Outcome results
None listed