| 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 | 10015488 |
| E.1.2 | Term | Essential 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 assess the anti-hypertensive effect of Olmesartan Medoxomil/
Hydrochlorothiazide (OM/HCTZ) 40/12.5 mg combination therapy
compared to Olmesartan Medoxomil (OM) 40 mg monotherapy in lowering
sitting diastolic blood pressure (dBP) in hypertensive patients after 8 weeks
of double-blind treatment (from baseline to the end of the first double-blind
treatment phase of the study). |
|
| E.2.2 | Secondary objectives of the trial |
1. Assess anti-hypertensive effect of OM/HCTZ 40/12.5 mg combination therapy compared to OM 40 mg monotherapy in lowering sitting systolic blood pressure in hypertensive patients after 8 weeks of double-blind treatment
2. Evaluate percentage of responders in each treatment group after the first 8 weeks of treatment and in up-titrated patients after 16 weeks of treatment.
3. Compare the efficacy in lowering sitting dBP and sBP between patients up-titrated from OM/HCTZ 40/12.5 mg to OM/HCTZ 40/25 mg and patients continuing on OM/HCTZ 40/12.5 mg after 16 weeks of treatment compared to week 8.
4. Compare the efficacy in lowering sitting dBP and sBP between patients up-titrated from OM 40 mg monotherapy to OM/HCTZ 40/12.5 mg and patients continuing on OM 40 mg after 16 weeks of treatment compared to week 8.
5. Evaluate the safety and tolerability of the combinations OM/HCTZ 40/12.5 mg and OM/HCTZ 40/25 mg versus OM 40 mg monotherapy. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Male or female Caucasian patients ≥ 18 years of age. A female of childbearing potential may be enrolled providing she:
- has a negative pregnancy test at screening/enrolment and
randomisation, and
- is routinely using a highly effective method of birth control resulting
in a low failure rate (i.e. less than 1% per year) when used
consistently and correctly, e.g. implants, injectables, combined oral
contraceptives, hormone containing intra uterine devices (IUDs).
2. Patients with a diagnosis of essential hypertension, either treatment-naive
or currently on anti-hypertensive medication in whom it is medically
justifiable to withdraw treatment, and who are likely to meet the required
BP inclusion criteria at randomisation (see inclusion criteria No. 3
below).
3. BP criteria at randomisation:
a) Mean sitting dBP ≥ 100 mmHg and ≤ 120 mmHg.
b) Mean sitting sBP ≥ 160 mmHg and ≤ 200 mmHg.
4. Patients who have freely given written informed consent. |
|
| E.4 | Principal exclusion criteria |
1. Patients with mean sitting sBP values > 200 mmHg and/or dBP
> 120 mmHg.
2. Pregnant or nursing women.
3. Patients with serious disorders which may limit the ability to evaluate the
efficacy or safety of the tested medication, including cerebrovascular,
cardiovascular, renal, respiratory, hepatic, gastrointestinal, endocrine or
metabolic, haematological, oncological, neurological, and psychiatric
diseases. The same applies for immunocompromised and/or neutropenic
patients.
4. Patients having a history of the following within the last six months:
Myocardial infarction, unstable angina pectoris, percutaneous coronary
intervention, hypertensive encephalopathy, cerebrovascular accident
(stroke), or transient ischaemic attack.
5. Patients with clinically relevant significant abnormal laboratory values at
screening/enrolment, including patients with:
- aspartate aminotransferase/serum glutamic-oxaloacetic-transaminase
(ASAT/SGOT) and alanine aminotransferase/serum glutamic –
pyruvate - transaminase (ALAT/SGPT) greater than twice the upper
limit and/or gamma-glutamyltransferase (γ-GT) greater than three times
the upper limit of laboratory reference range
and/or
- potassium above the upper limit of laboratory reference range (unless
high value is due to haemolytic blood sample).
6. Patients with secondary hypertension of any aetiology such as renal
disease, pheochromocytoma, or Cushing’s syndrome.
7. Patients with contraindication to Hydrochlorothiazide (HCTZ) and/or
OM.
8. Patients with electrocardiographic evidence of 2nd or 3rd degree
atrioventricular (AV)-block, atrial fibrillation or other cardiac arrhythmia
(requiring treatment), or bradycardia (< 50 beats/min as measured by
mean radial heart rate).
9. Patients with severe heart failure (New York Heart Association stage IIIIV),
a narrowing of the aortic or bicuspid valve, an obstruction of cardiac
outflow (obstructive, hypertrophic cardiomyopathy) or symptomatic
coronary disease.
10. Patients with clinical evidence of a renal disease (including renovascular
occlusive disease, nephrectomy and/or renal transplant, bilateral renal
artery stenosis or unilateral renal artery stenosis in a solitary kidney, or
severe renal impairment as evidenced by creatinine clearance (CLCR) < 30
mL/min).
11. Patients with uncorrected coarctation of aorta and higher grades of
acquired aortic stenosis.
12. Patients with clinically relevant hepatic impairment.
13. Patients with biliary obstruction.
14. Poorly controlled diabetic patients, defined as Type 1 or Type 2 patients
with a fasting glucose >12.21 mmol/L [>220 mg/dL].
15. Patients with a history of a wasting disease (e.g. cancer), autoimmune
diseases, connective tissue diseases, major allergies, or angioneurotic
oedema.
16. Patients being treated for other diseases with drugs or medication which
may influence BP or interfere with the objectives of the study and which
cannot be withdrawn during the period of the study (e.g. alpha-blockers
for the treatment of benign prostatic hypertrophy or intra-ocular betablockers
for the treatment of glaucoma).
17. Patients being treated at randomisation with any antihypertensive
medication (e.g. calcium channel-blockers, angiotensin II receptor
blocker, diuretics, α- and β-blocking agents, angiotensin converting
enzyme [ACE] inhibitors, reserpine).
18. Patients with known malabsorption syndromes.
19. Patients who have shown non-compliance with medication and study
procedures during the single-blind placebo run-in phase.
20. Patients with psychiatric or emotional problems, which would invalidate
the giving of informed consent or limit the ability of the patient to comply
with study requirements.
21. Patients with a history of alcohol and/or drug abuse.
22. Patients unwilling or unable to tolerate discontinuation of their previous
medication.
23. Patients who have donated 450 ml or more blood during the last three
months before screening/enrolment.
24. Patients who have received an investigational drug within 30 days prior
to screening/enrolment.
25. Patients who are unwilling or unable to provide informed consent or to
participate satisfactorily for the entire study period. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Change in mean trough sitting dBP between baseline and week 8 or last
observation carried forward (LOCF). |
|
| 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 | 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 | Yes |
| E.8.1.7.1 | Other trial design description |
| 2 week single-blind placebo run-in phase prior to randomisation |
|
| 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.8.3 |
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 | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 52 |
| 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
| |
| 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 | 10 |
| E.8.9.1 | In the Member State concerned days | 0 |
| 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 | 10 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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