| 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 evaluate the long-term safety and tolerability of FDC of nifedipine GITS / candesartan cilexetil (primarily the highest dose) once daily in subjects with moderate to severe essential hypertension. |
|
| E.2.2 | Secondary objectives of the trial |
| The secondary objective is to evaluate the long-term efficacy of FDC nifedipine GITS / candesartan cilexetil (primarily the highest dose) once daily in subjects with moderate to severe essential hypertension. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Male and female subjects 18 years or older.
2. Subjects must have moderate to severe essential hypertension (Grade 2 or Grade 3, WHO classifications). At Visit 1, subjects not treated with
antihypertensive medications are to have MSSBP of ≥ 160 mmHg and < 200 mmHg, as measured by a calibrated electronic BP measuring device. For other subjects who are treated with antihypertensive medication before, they should have MSSBP ≥ 160 mmHg and <200 mmHg after wash out.
3. 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 informed consent (IC) form until the last study drug administration.
4. 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 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. 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 AST or ALT levels >3 x ULN at Screening Visit
- Renal insufficiency, defined as estimated glomerular filtration rate
(estimated GFR) of < 30 mL/min 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
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) |
Incidence of AEs and AEs of special interest, including the incidence of symptomatic hypotension and the incidence and severity of vasodilatory adverse events (such as edema, headache, and flushing)
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
At 28 and 52 weeks after randomization
|
|
| E.5.2 | Secondary end point(s) |
-Laboratory evaluations
-The change from baseline in MSSBP
-The change from baseline in MSDBP
-Control rate
-Response rate
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
At 28 and 52 weeks after randomization
|
|
| 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 | No |
| 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 | No |
| E.8.1.1 | Randomised | Information not present in EudraCT |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | Information not present in EudraCT |
| E.8.1.4 | Double blind | Information not present in EudraCT |
| E.8.1.5 | Parallel group | Information not present in EudraCT |
| 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) | Information not present in EudraCT |
| E.8.2.2 | Placebo | Information not present in EudraCT |
| E.8.2.3 | Other | Information not present in EudraCT |
| 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 | 12 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 28 |
| 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 |
| Belgium |
| Canada |
| Germany |
| Poland |
| United Kingdom |
| United States |
|
| 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 | 1 |
| E.8.9.1 | In the Member State concerned months | 8 |
| E.8.9.1 | In the Member State concerned days | 21 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 8 |
| E.8.9.2 | In all countries concerned by the trial days | 21 |
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