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

Phase 3

Completed

Conditions: Essential hypertension
high blood pressure
10057166

Registration Number: NL-OMON35561

Lead Sponsor: Daiichi Pharmaceutical

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 22

Inclusion Criteria

Written informed consent obtained from male or female aged 18 years or older with a mean trough of >=SeBP 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, mean trough SeDBP >= 100mmHg, at the end of the taper-off period.

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: myocardial infarction (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)
•Alanine aminotransferase (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, phaeochromocytoma, 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 mean SeDBP > 115 mmHg or bradycardia (heart rate < 50 beats/min at rest documented by mean radial pulse rate [PR] or electrocardiogram [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

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary efficacy endpoint: The mean change in trough SeDBP from the<br /><br>randomisation visit (end of the OM/AML run-in period [Week 8]) to the end of<br /><br>the double-blind Period II (Week 16).</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary efficacy endpoints will include the following:<br /><br>1. Mean change from the double-blind randomisation visit (Week 8) to Week 12 in<br /><br>trough SeDBP.<br /><br>2. Mean change from the double-blind randomisation visit (Week 8) in trough<br /><br>SeSBP to Week 12 and Week 16.<br /><br>3. Mean changes from the double-blind randomisation visit (Week 8) to Week 16<br /><br>in daytime, night-time, and 24 hour DBP and SBP, assessed by 24 hour ABPM.<br /><br>4. Evaluation of the number (%) of subjects achieving BP goal and BP thresholds<br /><br>at Weeks 16, 24, and 32.<br /><br>5. Evaluation of the clinical benefit of up-titration from OM/AML/HCTZ<br /><br>40/10/12.5 mg to 40/10/25 mg during Period IV in terms of conventional BP and<br /><br>ABPM parameters.</p><br>

Related Trials