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Efficacy and Safety Study of Olmesartan Medoxomil, Amlodipine and Hydrochlorothiazide Combination Therapy in Patients With Hypertension Not Controlled With Olmesartan Medoxomil and Hydrochlorothiazide Combination Therapy

Phase 3
Completed
Conditions
Essential Hypertension
Interventions
Drug: CS8635 20/5/12.5mg and placebo
Registration Number
NCT01838850
Lead Sponsor
Daiichi Sankyo Korea Co., Ltd., a Daiichi Sankyo Company
Brief Summary

CS-8635 combines three widely prescribed antihypertensive medications, olmesartan medoxomil(OM), amlodipine (AML), and hydrochlorothiazide (HCTZ), to lower blood pressure. The purpose of the study is to evaluate the efficacy and safety of triple therapy with CS-8635 compared with dual therapy in Korean patients with hypertension not controlled with dual fixed dose combination therapy (Olmetec® Plus). The treatments that will be used in this study are as follows: Run-in period -OM/HCTZ 20/12.5 mg (Olmetec® Plus 20/12.5 mg) ; Double blind treatment period - OM/AML/HCTZ 20/5/12.5mg (CS8635 20/5/12.5mg) + its matching placebo vs.OM/HCTZ 20/12.5mg (Olmetec® Plus 20/12.5 mg) + its matching placebo; Open label extension period - OM/AML/HCTZ 40/5/12.5mg (CS8635 40/5/12.5mg) or OM/AML/HCTZ 20/5/12.5mg (CS8635 20/5/12.5mg).

Detailed Description

Please refer to arms, outcome measures and eligibility criteria for details.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
344
Inclusion Criteria

Not provided

Exclusion Criteria
  • msDBP ≥ 115mmHg or msSBP ≥ 200 mmHg measured at screening and randomization
  • Patients with mini-max blood pressure difference of SeSBP ≥ 20 mmHg or SeDBP ≥ 10 mmHg in the chosen arm at screening
  • Patients with blood pressure difference of SeSBP ≥ 20 mmHg and SeDBP ≥ 10 mmHg in both arms at screening
  • Patients with hypersensitivity to the investigational product or any of its components
  • Patients with medical history or hypersensitivity to sulfonamide, dihydropyridine, or thiazide diuretics
  • History of secondary hypertension or history of any of the diseases suspected of secondary hypertension
  • Symptomatic orthostatic hypotension
  • Uncontrolled diabetes mellitus
  • Severe heart disease, or ischemic heart disease, peripheral vascular disease
  • Clinically significant ventricular tachycardia, atrial fibrillation, atrial flutter, or other arrhythmia considered clinically significant
  • Hypertrophic obstructive cardiomyopathy, severe obstructive coronary artery disease, aortic stenosis, or hemodynamically significant stenosis on aortic valve or mitral valve.
  • Severe cerebrovascular disorder
  • Known moderate or malignant retinopathy
  • Consumption disease , autoimmune disease, or connective tissue disease
  • Patients requiring chronic anti-inflammatory treatment
  • Anuria or severe renal failure
  • Severe hepatic failure, AST or ALT > 3 times the upper limit of normal, biliary obstruction, biliary cirrhosis, or cholestasis
  • Patients who have been treated for hyponatremia, hypokalemia, hyperkalemia, hypercalcemia, or symptomatic hyperuricemia
  • Addison's disease
  • Glucose-galactose malabsorption, galactose intolerance, or Lapp lactase deficiency
  • Gastrointestinal tract disease or surgical operation that may affect absorption, distribution, metabolism, and excretion of drugs, presence of active gastritis or gastrointestinal/rectal bleeding considered clinical significant by the investigator, active inflammatory bowel syndrome within the last 12 months, etc
  • Patients with history of or suspected of drug or alcohol abuse
  • Pregnant or lactating women, or women of childbearing potential who do not agree to use appropriate contraceptive methods such as progestin hormone therapy (Oral, implant), intrauterine device, barrier methods of contraception (condom or occlusive cap (diaphragm or cervical/vault caps) with spermicide), male sterilisation or true abstinence
  • Patients who participated in other clinical study within 1 month prior to screening
  • Patients considered to be incapable of complying with the protocol

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Olmetec® Plus 20/12.5mg and placeboOlmetec® Plus 20/12.5mg and placeboParticipants receiving Olmetec® Plus 20/12.5mg (OM/HCTZ 20/12.5 mg) for the 4-week, Run-in Period but who do not meet their blood pressure goals(Non-responders) could start receiving this dual fixed dose combination therapy (Olmetec® Plus 20/12.5mg (OM/HCTZ 20/12.5mg) + Placebo) in randomized, 8-week, double-blind Period. The non-responders finishing double-blind treatment could continue the 8-week Open-label Period with CS8635 20/5/12.5mg (OM/AML/HCTZ 20/5/12.5 mg).
CS8635 20/5/12.5mg and placeboCS8635 20/5/12.5mg and placeboParticipants receiving Olmetec® Plus 20/12.5mg (OM/HCTZ 20/12.5 mg) for the 4-week, Run-in Period but who do not meet their blood pressure goals(Non-responders) could start receiving this triple fixed dose combination therapy (CS8635 20/5/12.5mg (OM/AML/HCTZ 20/5/12.5mg) + placebo) in randomized, 8-week, double-blind Period. The non-responders finishing double-blind treatment could continue the 8-week Open-label Period with CS8635 40/5/12.5mg (OM/AML/HCTZ 40/5/12.5 mg).
Primary Outcome Measures
NameTimeMethod
The changes of seated diastolic blood pressure of the Triple Combinations OM/AML/HCTZ 20/5/12.5mg vs.OM/HCTZ 20/12.5mgfrom baseline to week 8
Secondary Outcome Measures
NameTimeMethod
Percentage of subjects achieving blood pressure goal of the Triple Combinations OM/AML/HCTZ 20/5/12.5mg vs.OM/HCTZ 20/12.5mgat Week 4, and Week 8
The changes of mean seated systolic blood pressure of the Triple Combinations OM/AML/HCTZ 20/5/12.5mg vs.OM/HCTZ 20/12.5mgfrom baseline to Week 8
The changes of mean seated systolic and diastolic blood pressure of the Triple Combinations OM/AML/HCTZ 20/5/12.5mg vs.OM/HCTZ 20/12.5mgfrom baseline to week 4
Percentage of subjects achieving blood pressure goal of the Triple Combinations OM/AML/HCTZ 40/5/12.5mg vs.OM/AML/HCTZ 20/5/12.5mgAt week 16
The changes of mean seated systolic and diastolic blood pressure of the Triple Combinations OM/AML/HCTZ 40/5/12.5mg vs.OM/AML/HCTZ 20/5/12.5mgfrom Week 8 to Week 16

Trial Locations

Locations (39)

Daegu Catholic University Medical Center

🇰🇷

Daegu, Korea, Republic of

Konyang University Hospital

🇰🇷

Daejeon, Korea, Republic of

Ajou University Hospital

🇰🇷

Suwon, Korea, Republic of

Daedong Hospital

🇰🇷

Busan, Korea, Republic of

Korea University Ansan Hospital

🇰🇷

Ansan, Korea, Republic of

Hallym University Medical Center

🇰🇷

Anyang, Korea, Republic of

Dong-A University Hospital

🇰🇷

Busan, Korea, Republic of

Soonchunhyang University Hospital

🇰🇷

Bucheon, Korea, Republic of

Inje University Haeundae Paik Hospital

🇰🇷

Busan, Korea, Republic of

Presbyterian Medical Center

🇰🇷

Cheonju, Korea, Republic of

Pusan National University Hospital

🇰🇷

Busan, Korea, Republic of

Chonbuk National University Hospital

🇰🇷

Cheonju, Korea, Republic of

Hanyang University Guri Hospital

🇰🇷

Guri, Korea, Republic of

Seoul National University Bundang Hospital

🇰🇷

Seongnam, Korea, Republic of

Kyunghee University Hospital at Gandong

🇰🇷

Seoul, Korea, Republic of

Inje University Busan Paik Hospital

🇰🇷

Busan, Korea, Republic of

Chonnam National University Hospital

🇰🇷

Gwangju, Korea, Republic of

Seoul National University Hospital

🇰🇷

Seoul, Korea, Republic of

Chungbuk National University Hospital

🇰🇷

Cheongju, Korea, Republic of

Keimyung University Dongsan Medical Center

🇰🇷

Daegu, Korea, Republic of

Health Insurance Service Ilsan Hospital

🇰🇷

Goyang, Korea, Republic of

Chungnam National University Hospital

🇰🇷

Daejeon, Korea, Republic of

Gachon University Gil Medical Center

🇰🇷

Incheon, Korea, Republic of

Severance Hospital

🇰🇷

Seoul, Korea, Republic of

Kyung Hee University Medical Center

🇰🇷

Seoul, Korea, Republic of

Korea University Anam Hospital

🇰🇷

Seoul, Korea, Republic of

Seoul St. Mary's Hospital of the Catholic University of Korea

🇰🇷

Seoul, Korea, Republic of

Seoul Veterans Hospital

🇰🇷

Seoul, Korea, Republic of

Sanmsung Medical Center

🇰🇷

Seoul, Korea, Republic of

Gangnam Severance Hospital

🇰🇷

Seoul, Korea, Republic of

Asan Medical Center

🇰🇷

Seoul, Korea, Republic of

Konkuk University Medical Center

🇰🇷

Seoul, Korea, Republic of

Yeouido St. Mary's Hospital of the Catholic University of Korea

🇰🇷

Seoul, Korea, Republic of

Korea University Guro Hospital

🇰🇷

Seoul, Korea, Republic of

Wonju Severance Christian Hospital

🇰🇷

Wonju, Korea, Republic of

Chung-Ang University Hospital

🇰🇷

Seoul, Korea, Republic of

St. Carollo Hospital

🇰🇷

Suncheon, Korea, Republic of

Ulsan University hospital

🇰🇷

Ulsan, Korea, Republic of

Eulji General Hospital

🇰🇷

Seoul, Korea, Republic of

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