| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
| High blood pressure of unknown cause |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10015488 |
| E.1.2 | Term | Essential hypertension |
| E.1.2 | System Organ Class | 10047065 - Vascular disorders |
|
| 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 |
| The primary objective is to demonstrate the superior efficacy of the FDC of nifedipine GITS and candesartan cilexetil compared to nifedipine GITS monotherapy in subjects with essential hypertension not adequately controlled on nifedipine GITS alone, based on reduction of MSSBP. |
|
| E.2.2 | Secondary objectives of the trial |
1. To demonstrate the efficacy of the FDCs of nifedipine GITS and candesartan cilexetil based on reduction of mean seated diastolic blood pressure (MSDBP), response rate, control rate.
2. To demonstrate the efficacy of the FDCs of Nifedipine GITS/ candesartan cilexetil based on reduction of mean diastolic blood pressure (DBP) and systolic blood pressure (SBP) on ABPM over a 24-h period, during both the daytime and night time.
2. To explore the safety and tolerability of the FDC treatments. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Male and female subjects 18 years or older are eligible.
2. At Visit 0, subjects not treated with antihypertensive medications are to have MSSBP ≥ 160 mmHg and < 200 mmHg, and 24 hours MASBP≥ 130 mmHg ; those subjects treated with antihypertensive medication are to have MSSBP ≥ 150 mmHg and <200 mmHg, as measured by a calibrated electronic BP measuring device.
3. At Visit 3, subject must have MSSBP ≥ 140 mmHg before
randomization.
4. Women of childbearing potential and men must agree to use adequate contraception other than hormonal contraceptives when sexually active. This applies since signing of the IC form until the last study drug administration.
5. Written informed consent.
|
|
| E.4 | Principal exclusion criteria |
1. MSSBP ≥200 mmHg and/or MSDBP ≥120 mmHg
2. MSDBP < 60 mmHg
3. If differences greater than 20 mmHg for SBP and 10 mmHg for DBP are present on 3 consecutive BP readings at Visit 0, the subject should be excluded from the study.
4. Any history of hypertensive emergency
5. Evidence of secondary hypertension such as coarctation of the aorta,
pheochromocytoma, hyperaldosteronism, etc.
6. Cerebrovascular ischemic event (stroke, transient ischemic attack
[TIA]) within the previous 12 months
7. History of intracerebral hemorrhage or subarachnoid hemorrhage
8. History of hypertensive retinopathy – known Keith-Wagener Grade III or IV
9. Any history of heart failure, New York Heart Association (NYHA) classification III or IV
10. Severe coronary heart disease as manifest by a history of myocardial infarction or unstable angina in the last 6 months prior to visit 0.
11. Clinically significant cardiac valvular disease
12. Subjects with an aortic aneurysm that, in the opinion of the investigator, will be unsuitable to be enrolled in the study.
13. Type 1 diabetes mellitus (DM) or poorly controlled Type 2 DM as evidenced by glycosylated hemoglobin (HbA1C) of greater than 9% on visit 0.
14. History of malignancy in the last 5 years, excluding treated basal or non-melanoma skin cancer, or treated cervical carcinoma in situ
15. Hyperkalemia: potassium above the upper limit of normal in the laboratory range
16. Present severe rhythm or conduction disorder, eg.:
- Atrial fibrillation
- Second or third degree heart block without a pacemaker.
17. Subjects who have night employment (night shift).
18. Surgical or medical conditions that might alter the metabolism, excretion or distribution or absorption of any drug
- Gastrointestinal disease or surgery resulting in the potential for malabsorption with the exception of lactose intolerance
- Severe gastro-intestinal tract narrowing; gastric banding; kock pouch (ileostomy after proctocolectomy)
- Cholestasis or biliary obstruction or history of pancreatic injury or disease.
- Liver disease or aspartate transaminase (AST) or alanine transaminase (ALT) levels >3 x upper limit of normal (ULN) at Screening Visit
- Renal insufficiency, defined as estimated glomerular filtration rate (estimated glomerular filtration rate [GFR]) of < 30 mL/min (see Section 7.6.2), or on hemodialysis
19. Investigational study participation with receipt of investigational study medication within the last month
20. Previous assignment to treatment in this study
21. Allergies or known intolerance to one of the investigational drugs/drug class or to one of their ingredients
22. Female subjects who are pregnant or lactating.
23. History of non-compliance, alcoholism, drug abuse or any other condition that in the opinion of the investigator will compromise successful completion of the study.
24. Subjects with pre-planned surgery during the course of the study
25. Inability to stop any of the medications listed in the prohibited concomitant medication list (see Section 6.9).
26. Subjects who are on treatment with any drug approved for the treatment of hypertension, when prescribed for any reason other than control of blood pressure.
27. Close affiliation with the investigational site; eg. a close relative of the investigator, dependent person (eg. employee or student of the investigational site) |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary efficacy variable will be change from baseline in MSSBP at Week 8. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
| As a secondary endpoint, this study will evaluate the change from baseline in MSDBP, as well as predefined response and control criteria at week 8. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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 | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| 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 | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| 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 | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| 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 | 6 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 12 |
| 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 | No |
| 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 |
| China |
| Germany |
| Italy |
| Korea, Republic of |
| Taiwan |
| United States |
| Vietnam |
|
| 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
|
|
| 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 | 9 |
| E.8.9.1 | In the Member State concerned days | 13 |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 9 |
| E.8.9.2 | In all countries concerned by the trial days | 13 |
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