E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020772 |
E.1.2 | Term | Hypertension |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of the 3 dose regimens (0.25 mg BID, 1 mg QD, and 0.5 mg BID titrated to 1 mg BID) of LCI699 in patients with resistant hypertension by testing the hypotheses that the change from baseline in mean sitting systolic blood pressure (MSSBP) 23-26 hours post dose (11 -14 hours post BID dosing) with each dose/regimen of LCI699 is superior to that of placebo after 8 weeks of treatment. |
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E.2.2 | Secondary objectives of the trial |
Key secondary objectives have been listed below. For full list, please refer to the protocol.
o To evaluate the efficacy of the 3 dose regimens (0.25 mg BID, 1 mg QD, and 0.5 mg BID titrated to 1 mg BID) of LCI699 in patients with resistant hypertension by testing the hypotheses that the change from baseline in mean sitting diastolic blood pressure (MSDBP) 23-26 hours post dose (11 -14 hours post BID dosing) with each dose/regimen of LCI699 is superior to that of placebo after 8 weeks of treatment. o To evaluate the safety and tolerability of LCI699 including, but not limited to: • Cortisol levels following ACTH stimulation testing • Hyperkalemia • Hyponatremia o To assess the functional consequences of aldosterone inhibition by evaluating the efficacy and safety of LCI699 compared to eplerenone 50 mg BID after 8 weeks of treatment. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. An established diagnosis of hypertension with MSSBP > 140mmHg and < 180 mmHg on current antihypertensive treatment measured within two (2) weeks of randomization. This includes subjects with diabetes and/or chronic kidney disease. 2. Resistant hypertension as defined by the failure to achieve goal blood pressure in patients who are adhering to optimal doses of a stable three-drug regimen that includes a diuretic for a period of at least 4 weeks. 3. Male or non-fertile female patients 18 to 75 years of age (inclusive) o 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. o 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 o 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. 4. Morning plasma cortisol (sampled between 08:00 and 09:00) > 250 nM 5. Able to provide written informed consent prior to study participation. 6. Able to communicate with the investigator and willing to comply with the requirements of the study. |
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E.4 | Principal exclusion criteria |
For full list, please refer to the protocol.
1. Severe hypertension (MSSBP > 180 mmHg or MSDBP > 110 mmHg) at screening. 2. Pregnant or nursing (lactating) women, where pregnancy confirmed by a positive hCG laboratory test (>5 mIU/ml). 3. Recent history (within last 6 months) of myocardial infarction, heart failure, unstable angina, coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI), hypertensive encephalopathy, cerebrovascular accident, or transient ischemic attack (TIA). 4. Clinically significant cardiac conduction defects (eg, 3rd degree atrioventricular [AV] block, left bundle branch block [LBBB], sick sinus syndrome, atrial fibrillation or flutter). 5. Implanted cardioverter defibrillator (ICD) that has fired for any arrhythmia within 3 months of screening or implanted pacemakers. 6. Clinically significant valvular heart disease. 7. A history of secondary hypertension of any etiology (eg, renal parenchymal hypertension, renovascular hypertension, coarctation of the aorta, primary hyperaldosteronism, unilateral or bilateral renal artery stenosis, Cushing’s disease, pheochromocytoma, polycystic kidney disease, and drug-induced hypertension, obstructive sleep apnea, etc). 8. Known moderate or maliganant retinopathy defined as: moderate (retinal signs of hemorrahage, microaneurysm, cotton-wool spots, hard exudates, or a combination thereof) or maliganant (signs of moderate retinopathy plus swelling of the optic disk). 9. Type 1 diabetes. 10. Type 2 diabetes mellitus with poor glucose control as defined by HbA1c >9%. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary objective of the study is to evaluate the efficacy of the 3 dose regimens (0.25 mg QD, 1 mg QD, and 0.5 mg BID titrated to 1 mg BID) of LCI699 in patients with resistant hypertension by testing the hypotheses that the reduction in mean sitting systolic blood pressure (MSSBP) 23-26 hours post dose (11 -14 hours post BID dosing) with each dose/regimen of LCI699 is superior to that of placebo after 8 weeks of treatment. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 12 |
E.8.9.1 | In the Member State concerned days | 0 |