| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| 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 |
|
| 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 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. |
|
| E.2.2 | Secondary objectives of the trial |
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.
3.To evaluate the dose-response relationship of LCI699 in the reduction in MSDBP and MSSBP.
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.
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.
9.To evaluate the potential off-target effect of 4 dose regimens of LCI699 on cortisol synthesis. |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
| Pharmacogenetic Study CLCI699A2201; Protocol Post Text Supplement 1 (18. Nov-2008) |
|
| E.3 | Principal 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 < 110 mmHg at Visits 1-3.
• Treated patients must have a MSDBP ≥ 90 mmHg and < 110 mmHg at Visits 1.
(screening) & 2 (after washout) and a MSDBP ≥ 95 mmHg and < 110 mmHg at Visit 3.
6. Ability to communicate and comply with all study requirements and demonstrating a good medication compliance (≥ 80% compliance rate) during the run-in period. |
|
| E.4 | Principal 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. |
|
| E.5 End points |
| E.5.1 | 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. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| 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) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| 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
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 16 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 54 |
| 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 |
|
| 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
|
| The trial will end when the last subject has their last study visit as defined in the protocol. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 9 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 9 |
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