A RANDOMISED, DOUBLE-BLIND, ADD-ON STUDY OF HYDROCHLOROTHIAZIDE IN SUBJECTS WITH MODERATE TO SEVERE HYPERTENSION NOT ACHIEVING TARGET BLOOD PRESSURE ON OLMESARTAN MEDOXOMIL/AMLODIPINE FIXED DOSE COMBINATION 40/10 MG ALONE

• Conditions: Essential hypertension; MedDRA version: 9.1Level: LLTClassification code 10020772Term: Hypertension

• Registration Number: EUCTR2008-003535-20-AT
• Lead Sponsor: DAIICHI SANKYO EUROPE GmbH

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-03-31
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 1965

Inclusion Criteria

1.Male or female aged 18 years or older.
2.Mean trough SeBP of = 160/100 mmHg (SeSBP of = 160 mmHg and SeDBP = 100 mmHg) at Screening if not currently on antihypertensive medication (e.g. newly
diagnosed subjects).
OR:
For subjects on monotherapy: mean trough SeBP of = 150/95 mmHg (SeSBP of = 150 mmHg and SeDBP = 95 mmHg) at Screening.
OR:
For subjects on any combination of antihypertensive medications that includes either HCTZ, OM or AML for a duration of at least four weeks: mean trough SeBP of = 140/90 mmHg (SeSBP of = 140 mmHg and SeDBP = 90 mmHg) at Screening.
OR:
For subjects on any other combination of antihypertensive medications that includes neither HCTZ, OM nor AML: mean trough SeSBP = 160 mmHg and mean trough SeDBP = 100mmHg, at the end of the taper-off period.
3.Subject freely signs ICF after the nature of the study and the disclosure of his/her data has been explained.
4.Female subjects of childbearing potential must be using adequate contraception (female of childbearing potential is defined as one who has not been postmenopausal for at least one year, or has not been surgically sterilised, or has not had a hysterectomy at least three months prior to the start of this study [Visit 1]). Females taking oral contraceptives should have been on therapy for at least three months. Adequate contraceptives include hormonal intra-uterine devices, hormonal contraceptives (oral, depot, patch or injectable), and double barrier methods such as condoms or diaphragms with spermicidal gel or foam. If a female becomes pregnant during the study, she has to be withdrawn immediately.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.Female subjects of childbearing potential who are pregnant or lactating.
2.Subjects with serious disorders which may limit the ability to evaluate the efficacy or safety of the investigational products, including cerebrovascular, cardiovascular, renal, respiratory, hepatic, gastrointestinal, endocrine or metabolic, haematological or oncological, neurological, and psychiatric diseases. The same applies for immunocompromised and/or neutropenic subjects.
3.Subjects having a history of the following within the last six months: MI, unstable angina pectoris, percutaneous coronary intervention, heart failure, hypertensive encephalopathy, cerebrovascular accident (stroke), or transient ischaemic attack.
4.Subjects with clinically significant abnormal laboratory values at Screening, including subjects with one or more of the following:
•Aspartate aminotransferase (AST) > 3 times upper limit of normal (ULN)
•ALT > 3 times ULN
•Gamma-glutamyltransferase (GGT) > 3 times ULN
•Potassium above ULN (unless high value is due to haemolytic blood sample)
5.Subjects with secondary HTN of any aetiology such as renal disease, phaechromocytoma, or Cushing’s syndrome.
6.Subjects with contraindication to OM, AML, HCTZ, or any of the excipients.
7.Subjects with a mean SeSBP > 200 mmHg or SeDBP > 115 mmHg or bradycardia (heart rate < 50 beats/min at rest documented by mean radial PR or ECG at Screening (Visit 1) or immediately before taking Period I study medication (Visit 2).
8.Subjects already taking four or more antihypertensive medications.
9.Subjects with ECG evidence of 2nd or 3rd degree atrio-ventricular (AV) block, atrial fibrillation, or other cardiac arrhythmia (requiring treatment).
10.Subjects with severe heart failure (New York Heart Association stage III IV), clinically significant aortic or mitral valve stenosis, uncorrected coarctation of the aorta, obstruction of cardiac outflow (obstructive, hypertrophic cardiomyopathy) or symptomatic coronary disease.
11.Subjects with clinical evidence of renal disease including renovascular occlusive disease, nephrectomy and/or renal transplant, bilateral renal artery stenosis, unilateral renal artery stenosis in a solitary kidney, or severe renal impairment as evidenced by CrCl of < 30 mL/min calculated using the Cockcroft and Gault formula.
12.Subjects with clinically relevant hepatic impairment.
13.Subjects with biliary obstruction.
14.Subjects with a history of a wasting disease (e.g. cancer), autoimmune diseases, connective tissue diseases, major allergies or angioneurotic oedema.
15.Subjects who require or are taking any concomitant medication which may interfere with the objectives of the study.
16.Subjects with known malabsorption syndromes.
17.Subjects with psychiatric or emotional problems, which would invalidate the giving of Informed Consent or limit the ability of the subject to comply with study requirements.
18.Subjects with a current history of alcohol and/or drug abuse.
19.Subjects who have received any investigational drug within 30 days prior to Screening.
20.Subjects who are unwilling or unable to provide informed consent or to participate satisfactorily for the entire study.
21.Signs or symptoms which could exacerbate the occurrence of hypotension such as volume and salt depletion.
22.Uncontrolled Type 1 or Type 2 diabetes defined as an HbA1c > 9.0%. Diabetics must have documentation of an HbA1c level within 6 months of the Screening Visit, or must have their

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified