Essential Hypertension MedDRA version: 9.1 Level: LLT Classification code 10015488 Term: Essential hypertension
Conditions
Interventions
Product Code: LCI699
Pharmaceutical Form: Capsule*
Current Sponsor code: LCI699
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.25-
Pharmaceutical form of the pla
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent to participate in the study. 2. Male, non-fertile female: a non-fertile female is defined as post menopausal (12 months of natural spontaneous amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or 6 months of spontaneous amenorrhea with serum FSH levels > 40 mIU/ml); 6 weeks post bilateral oophorectomy with or without hysterectomy (in case of oophrectomy only, non-fertile status is considered only when the reproductive status has been confirmed by hormone level assessment); post hysterectomy; or sterilized by tubal ligation. 3. Age from 18 up to 75 years inclusive. 4. Patients with mild-to-moderate uncomplicated essential hypertension, untreated including newly diagnosed and/or those with known hypertension history but who have not been treated for at least 4 weeks prior to Visit 1, or treated who are currently taking antihypertensive therapy (monotherapy or combination therapy of 2 drugs). Therapy with a fixed dose combination of two active substances is considered 2 drugs. 5. Untreated or treated patients must meet the following office BP criteria: • Untreated patients must have a MSDBP = 95 mm Hg and =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. All women of child bearing potential. 2. Pregnant or nursing women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test. 3. Female patients on hormone replacement therapy. 4. Severe hypertension. 5. History or evidence of a secondary form of hypertension. 6. Known moderate or malignant retinopathy. 7. History of angina pectoris, myocardial infarction, coronary bypass surgery, ischemic heart disease, surgical or percutaneous arterial intervention of any kind, troke, transient ischemic attack (TIA), carotid artery stenosis, aortic aneurysm or peripheral arterial disease. 8. Type 1 or type 2 diabetes mellitus. 9. Clinically significant valvular heart disease. 10. Previous or current diagnosis of congestive heart failure. 11. History or current diagnosis of the following cardiac electric abnormalities indicating significant risk of safety for patients participating in the study such as: • Second or third degree AV block without a pacemaker. • Concomitant clinically significant cardiac arrhythmias. • History of familial long QT syndrome or family history of torsade de pointe. 12. History of malignancy of any organ system, treated or untreated. 13. Liver disease such as cirrhosis or chronic active hepatitis. 14. Any surgical or medical conditions that may significantly alter the absorption, distribution, metabolism or excretion of any drug substance. 15. Any surgical or medical conditions, not identified in the protocol that in the opinion of the investigator or the Novartis monitor, place the patient at higher risk from his/her participation in the study. 16. Patients unwilling or not able to discontinue safely the use of current antihypertensive medications during the study period. 17. Any contraindication or history of hypersensitivity to any of the study drugs or to drugs with similar chemical structures. 18. Chronic oral or parenteral corticosteroid treatment within 4 weeks prior to Visit 1. 19. Treatment with potassium supplement or potassium sparing diuretics required during the course of study. 20. Treatment with potent CYP3A4 inhibitors during the study period. 21. Use of other investigational drugs at Visit 1, or within 30 days or 5 half-lives of Visit 1, whichever is longer, unless local health authority guidelines mandate a longer period. 22. Any of the significant laboratory abnormalities: 23. History of active substance abuse within the past 2 years and potentially unreliable patients. 24. Patients with night-shift employment. 25. Persons directly involved in the execution of this clinical study. 26. Arm circumference > 42 cm, due to ABPM assessment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of any of 4 dose regimens (0.25 mg QD, 0.5 mg QD, 1.0 mg QD and 0.5 mg BID) of LCI699 in patients with essential hypertension by testing the hypothesis that the reduction in mean sitting diastolic blood pressure (MSDBP) 23-26 hours post dose (11-14 hours post BID dosing ) with LCI699 is superior to that with placebo after 8 weeks treatment.;Secondary Objective: 1.To evaluate the efficacy of any of 4 dose regimens of LCI699 2.To evaluate the safety and tolerability of 4 dose regimens of LCI699 compared to placebo 3.To evaluate the dose-response relationship of LCI699 4.To evaluate whether the changes in mean 24 hours, mean daytime and mean nighttime SBP and DBP with 4 dose regimens of LCI699 are superior to those with placebo 5.To evaluate the trough/peak ratios of reduction in MSDBP and MSSBP with 4 dose regimens of LCI699 6.To assess the functional consequences of aldosterone inhibition by evaluating the efficacy and safety of LCI699 compared to eplerenone 50 mg bid 7.To evaluate the proportion of patients achieving a successful BP response and BP control in all treatment groups 8.To compare the efficacy and safety of two dose regimens of 1 mg LCI699. - see other objectives in the protocol page 15.;Primary end point(s): To evaluate the efficacy of any of 4 dose regimens (0.25 mg QD, 0.5 mg QD, 1.0 mg QD and 0.5 mg BID) of LCI699 in patients with essential hypertension by testing the hypothesis that the reduction in mean sitting diastolic blood pressure (MSDBP) 23-26 hours post dose (11-14 hours post BID dosing ) with LCI699 is superior to that with placebo after 8 weeks treatment. | — |
Countries
France, Germany, Netherlands, Sweden
Outcome results
None listed