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Parallel-Group Comparison of Olmesartan (OLM), Amlodipine (AML) and Hydrochlorothiazid (HCTZ) in Hypertension

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ClinicalTrials.gov Identifier: NCT00923091
Recruitment Status : Completed
First Posted : June 18, 2009
Results First Posted : April 6, 2012
Last Update Posted : January 10, 2019
Sponsor:
Information provided by (Responsible Party):
Daiichi Sankyo, Inc.

Brief Summary:
This study is to determine the change in blood pressure from the administration of Olmesartan/Amlodipine/Hydrochlorothiazide triple combinations compared to dual combinations with Olmesartan/Amlodipine.

Condition or disease Intervention/treatment Phase
Essential Hypertension Drug: olmesartan medoxomil + amlodipine + hydroclororthiazide + placebo Drug: Olmesartan medoxomil + amlodipine + hydrochlorothiazide + placebo Drug: olmesartan medoxomil + amlodipine + hydroclororthiazide Drug: olmesartan medoxomil + amlodipine Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2689 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Randomised, Double-Blind, Parallel-Group Study Evaluating Efficacy and Safety of Co-Administration of Triple Combinations of Olmesartan Medoxomil, Amlodipine Besylate, and Hydrochlorothiazide Compared With Corresponding Olmesartan - Amlodipine Combination in Subjects With Hypertension
Study Start Date : June 2009
Actual Primary Completion Date : January 2011
Actual Study Completion Date : March 2011

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: olmesartan/amlodipine/hydrochlorothiazide 20mg/5mg/12.5mg
olmesartan medoxomil 20mg / amlodipine besylate 5 mg / hydrochlorothiazide 12.5mg
Drug: olmesartan medoxomil + amlodipine + hydroclororthiazide + placebo
One olmesartan medoxomil 20 mg + amlodipine 5 mg combination oral tablet taken once per day. One hydrochlorothiazide 12.5 mg tablet + one hydrochlorothiazide 12.5 mg placebo tablet taken once per day.
Other Name: Azor

Experimental: olmesartan/amlodipine/hydrochlorothiazide 40mg/5mg/12.5mg Drug: Olmesartan medoxomil + amlodipine + hydrochlorothiazide + placebo
One olmesartan medoxomil 40 mg + amlodipine 5 mg combination oral tablet taken once per day. One hydrochlorothiazide 12.5 mg tablet + one hydrochlorothiazide 12.5 mg placebo tablet taken once per day.
Other Name: Azor

Experimental: olmesartan/amlodipine/hydrochlorothiazide 40mg/5mg/25mg Drug: olmesartan medoxomil + amlodipine + hydroclororthiazide
One olmesartan medoxomil 40 mg + amlodipine 5 mg combination oral tablet taken once per day. Two hydrochlorothiazide 12.5 mg tablets taken once per day.
Other Names:
  • Azor
  • Norvasc

Experimental: olmesartan/amlodipine/hydrochlorothiazide 40mg/10mg/12.5mg Drug: olmesartan medoxomil + amlodipine + hydroclororthiazide
One olmesartan medoxomil 40 mg + amlodipine 10 mg combination oral tablet taken once per day. One hydrochlorothiazide 12.5 mg tablet + one hydrochlorothiazide 12.5 mg placebo tablet taken once per day.
Other Name: Azor

Experimental: olmesartan/amlodipine/hydrochlorothiazide 40mg/10mg/25mg Drug: olmesartan medoxomil + amlodipine + hydroclororthiazide
One olmesartan medoxomil 40 mg + amlodipine 10 mg combination oral tablet taken once per day. Two hydrochlorothiazide 12.5 mg tablets taken once per day.
Other Name: Azor

Experimental: olmesartan/amlodipine 20mg/5mg
olmesartan medoxomil 20mg / amlodipine besylate 5mg
Drug: olmesartan medoxomil + amlodipine
One olmesartan medoxomil 20 mg + amlodipine 5 mg combination oral tablet taken once per day
Other Name: Azor

Experimental: olmesartan/amlodipine 40mg/5mg Drug: olmesartan medoxomil + amlodipine
One olmesartan medoxomil 40 mg + amlodipine 5 mg combination oral tablet taken once per day.

Experimental: olmesartan/amlodipine 40mg/10mg Drug: olmesartan medoxomil + amlodipine
One olmesartan medoxomil 40 mg + amlodipine 10 mg combination oral tablet taken once per day.
Other Name: Azor




Primary Outcome Measures :
  1. Change in Seated Diastolic Blood Pressure (SeDBP). [ Time Frame: Baseline to week 10 ]
    Baseline blood pressure was defined as the average values obtained at the randomization visit and at the visit prior to randomization


Secondary Outcome Measures :
  1. Change in Seated Systolic Blood Pressure (SeDBP). [ Time Frame: Baseline to week 10 ]
  2. Number of Subjects Reaching Blood Pressure Goal at Week 10 [ Time Frame: baseline to week 10 ]
    Blood pressure treatment goal was defined as blood pressure <140/90 mmHg or <130/80 mmHg for subjects with diabetes, chronic renal disease, or chronic cardiovascular disease.

  3. Change in Seated Diastolic Blood Pressure From Week 18 to Week 22 [ Time Frame: Week 18 to week 22 ]
  4. Change in Seated Systolic Blood Pressure From Week 18 to Week 22 [ Time Frame: Week 18 to week 22 ]
  5. Number of Subjects Reaching Blood Pressure Goal From Week 18 to Week 22 [ Time Frame: Week 18 to week 22 ]
    Blood pressure treatment goal was defined as blood pressure <140/90 mmHg or <130/80 mmHg for subjects with diabetes, chronic renal disease, or chronic cardiovascular disease.

  6. Change in Seated Diastolic Blood Pressure From Week 22 to Week 26 [ Time Frame: Week 22 to week 26 ]
  7. Change in Seated Systolic Blood Pressure From Week 22 to Week 26 [ Time Frame: Week 22 to week 26 ]
  8. Number of Subjects Reaching Blood Pressure Goal at Week 26 [ Time Frame: Week 22 to week 26 ]
    Blood pressure treatment goal was defined as blood pressure <140/90 mmHg or <130/80 mmHg for subjects with diabetes, chronic renal disease, or chronic cardiovascular disease.

  9. Change in Seated Systolic Blood Pressure (SeDBP) During Open-Label Period VI (Titration Effect From OM/AML/HCTZ 40/5/25 to 40/10/25. [ Time Frame: Week 26 to week 54 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female subjects aged 18 years or older.
  • Subjects with mean trough seated blood pressure (SeBP) ≥ 160/100 mmHg, (seated systolic blood pressure(SeSBP) ≥ 160 mmHg and seated diastolic blood pressure (SeDBP) ≥ 100 mmHg) at Screening if not currently on antihypertensive medication (newly diagnosed subjects or subjects who are not taking any antihypertensive medication for at least 3 weeks); Or Subjects with mean trough SeBP ≥ 160/100 mmHg, SeSBP ≥ 160 mmHg and SeDBP ≥ 100 mmHg) after washout of prior antihypertensive medication in subjects who discontinued their previous antihypertensive medication.

The difference in mean SeSBP/SeDBP between the visit prior to randomisation and the randomisation visit must be ≤ 20/10 mmHg. Subjects not currently on antihypertensive (HTN) medication may meet this requirement at the screening visit (Visit 1) and the randomization visit (Visit 3). Subjects washing out of HTN medication must meet this requirement at least by Visit 2 (or Visit 2.1, if needed) and Visit 3. All subjects undergoing washout of their prior antihypertensive medication will have the opportunity to re-visit the study sites for additional visits during washout (Visits 2 and 2.1) to assess eligibility for randomisation.

  • Subjects freely sign the informed consent form (ICF) after the nature of the study and the disclosure of his/her data has been explained.
  • 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]). 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.

Exclusion Criteria:

  • Female subjects of childbearing potential who are pregnant or lactating.
  • 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, haematologic or, neurologic, and psychiatric diseases. The same applies for immunocompromised and/or neutropenic subjects.
  • 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.
  • 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-glutamyl transferase (GGT) > 3 times ULN.
    • Potassium above ULN (unless high value is due to haemolytic blood sample).
  • Subjects with secondary hypertension of any aetiology such as renal disease, phaeochromocytoma, or Cushing's syndrome.
  • Subjects with contraindication to olmesartan, amlodipine, hydrochlorothiazide, or any of the tablet's excipients.
  • Newly diagnosed subjects with a mean trough SeSBP > 200 mmHg or mean trough SeDBP > 115 mmHg or any subjects with 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 3).
  • Subjects already taking four or more antihypertensive medications.
  • Subjects with a mean trough SeSBP > 145 mmHg or mean trough SeDBP > 95 mmHg while taking three antihypertensive medications.
  • Subjects with a mean trough SeSBP > 160 mmHg or mean trough SeDBP > 100 mmHg while taking two antihypertensive medications.
  • Subjects with a mean trough SeSBP > 180 mmHg or mean trough SeDBP > 110 mmHg while taking one antihypertensive medication.
  • Subjects with electrocardiogram evidence of 2nd or 3rd degree atrio ventricular (AV) block, atrial fibrillation, or other cardiac arrhythmia (requiring treatment).
  • 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.
  • Subjects with clinical evidence of renal disease including reno-vascular 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.
  • Subjects with clinically relevant hepatic impairment.
  • Subjects with biliary obstruction.
  • Subjects with uncontrolled Type 1 or Type 2 diabetes defined as HbA1c > 9.0%. Diabetics must have documentation of HbA1c within 6 months of the Screening Visit, or must have their HbA1c assessed prior to randomisation. Note: subjects with Type 1 or Type 2 diabetes controlled with insulin, diet or oral hypoglycaemic agents on a stable dose for at least 30 days may be included.
  • Subjects with a history of a wasting disease (e.g. cancer), autoimmune diseases, connective tissue diseases, major allergies or angioneurotic oedema.
  • Subjects who require or are taking any concomitant medication which may interfere with the objectives of the study.
  • Subjects on beta blockers or calcium channel blockers (CCBs) for both hypertension and either ischemia, post-MI prophylaxis or tachyarrhythmias.
  • Subjects with known malabsorption syndromes.
  • 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.
  • Subjects with a history of alcohol and/or drug abuse.
  • Subjects who have received any investigational agent within 30 days prior to Screening.
  • Subjects who are unwilling or unable to provide informed consent or to participate satisfactorily for the entire study.
  • Subjects with malignancy during the past 2 years excluding squamous cell or basal cell carcinoma of the skin.
  • Subjects with signs or symptoms which could exacerbate the occurrence of hypotension such as volume and salt depletion.
  • Subjects with any medical condition, which in the judgment of the Investigator would jeopardise the evaluation of efficacy or safety and/or constitute a significant safety risk to the subject.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00923091


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Sponsors and Collaborators
Daiichi Sankyo, Inc.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Daiichi Sankyo, Inc.
ClinicalTrials.gov Identifier: NCT00923091     History of Changes
Other Study ID Numbers: CS8635-A-E302
First Posted: June 18, 2009    Key Record Dates
Results First Posted: April 6, 2012
Last Update Posted: January 10, 2019
Last Verified: April 2012
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
URL: https://vivli.org/ourmember/daiichi-sankyo/
Keywords provided by Daiichi Sankyo, Inc.:
triple combination
parallel group
dual combination
Additional relevant MeSH terms:
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Olmesartan
Olmesartan Medoxomil
Hypertension
Essential Hypertension
Vascular Diseases
Cardiovascular Diseases
Amlodipine
Hydrochlorothiazide
Antihypertensive Agents
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs
Vasodilator Agents
Diuretics
Natriuretic Agents
Sodium Chloride Symporter Inhibitors
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists