Clinical trial NCT01838850: 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
Official title: A Randomized, Double-blind, Parallel Group Study to Evaluate the Efficacy and Safety of Triple Fixed Dose Combination Therapy With Olmesartan Medoxomil 20mg, Amlodipine 5mg and Hydrochlorothiazide 12.5mg in Patients With Hypertension Not Controlled With Dual Fixed Dose Combination Therapy With Olmesartan Medoxomil 20mg and Hydrochlorothiazide 12.5mg
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Essential Hypertension
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
First posted: 2013-04-24
Enrollment: 344
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria for Screening

* Male or female at the age of 20 to 75 years
* Voluntary written informed consent to participation in this study
* Patients with hypertension either newly diagnosed or without treatment of antihypertensive drugs within 4 weeks of screening, who have mean seated diastolic blood pressure (msDBP) ≥ 100 mmHg at screening, or
* Patients who have been on a stable dose of antihypertensive drugs for at least 4 weeks before run-in period and meet the following blood pressure criteria at screening: Monotherapy: msDBP ≥ 95 mmHg, or Dual combination therapy: msDBP ≥ 90 mmHg, or Triple combination therapy: 70 mmHg ≤ msDBP \< 90 mmHg

Inclusion criteria for randomization

* msSBP/DBP at randomization: msSBP ≥ 140 mmHg (msSBP ≥ 130 mmHg in subjects with diabetes or chronic renal disease), and msDBP ≥ 90 mmHg (msDBP ≥ 80 mmHg in subjects with diabetes or chronic renal disease)

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

Primary outcomes:
measure: The changes of seated diastolic blood pressure of the Triple Combinations OM/AML/HCTZ 20/5/12.5mg vs.OM/HCTZ 20/12.5mg
timeFrame: from baseline to week 8
Secondary outcomes:
measure: The changes of mean seated systolic blood pressure of the Triple Combinations OM/AML/HCTZ 20/5/12.5mg vs.OM/HCTZ 20/12.5mg
timeFrame: from baseline to Week 8
measure: The changes of mean seated systolic and diastolic blood pressure of the Triple Combinations OM/AML/HCTZ 20/5/12.5mg vs.OM/HCTZ 20/12.5mg
timeFrame: from baseline to week 4
measure: Percentage of subjects achieving blood pressure goal of the Triple Combinations OM/AML/HCTZ 20/5/12.5mg vs.OM/HCTZ 20/12.5mg
timeFrame: at Week 4, and Week 8
measure: Percentage of subjects achieving blood pressure goal of the Triple Combinations OM/AML/HCTZ 40/5/12.5mg vs.OM/AML/HCTZ 20/5/12.5mg
timeFrame: At week 16
measure: 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 20/5/12.5mg
timeFrame: from Week 8 to Week 16
Other outcomes:
measure: Collection of safety data from Adverse event, Laboratory test, Physical examination, Vital signs with pulse and ECG
timeFrame: from screening to Week 16
Locations:
city: Ansan
country: Korea, Republic of
facility: Korea University Ansan Hospital
city: Anyang
country: Korea, Republic of
facility: Hallym University Medical Center
city: Bucheon
country: Korea, Republic of
facility: Soonchunhyang University Hospital
city: Busan
country: Korea, Republic of
facility: Dong-A University Hospital
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Busan
country: Korea, Republic of
facility: Daedong Hospital
city: Busan
country: Korea, Republic of
facility: Inje University Haeundae Paik Hospital
city: Busan
country: Korea, Republic of
facility: Inje University Busan Paik Hospital
city: Cheongju
country: Korea, Republic of
facility: Chungbuk National University Hospital
city: Cheonju
country: Korea, Republic of
facility: Presbyterian Medical Center
city: Cheonju
country: Korea, Republic of
facility: Chonbuk National University Hospital
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Medical Center
city: Daegu
country: Korea, Republic of
facility: Daegu Catholic University Medical Center
city: Daejeon
country: Korea, Republic of
facility: Chungnam National University Hospital
city: Daejeon
country: Korea, Republic of
facility: Konyang University Hospital
city: Goyang
country: Korea, Republic of
facility: Health Insurance Service Ilsan Hospital
city: Guri
country: Korea, Republic of
facility: Hanyang University Guri Hospital
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hospital
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Kyung Hee University Medical Center
city: Seoul
country: Korea, Republic of
facility: Kyunghee University Hospital at Gandong
city: Seoul
country: Korea, Republic of
facility: Seoul Veterans Hospital
city: Seoul
country: Korea, Republic of
facility: Sanmsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Gangnam Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul St. Mary's Hospital of the Catholic University of Korea
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Eulji General Hospital
city: Seoul
country: Korea, Republic of
facility: Konkuk University Medical Center
city: Seoul
country: Korea, Republic of
facility: Yeouido St. Mary's Hospital of the Catholic University of Korea
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
city: Seoul
country: Korea, Republic of
facility: Chung-Ang University Hospital
city: Suncheon
country: Korea, Republic of
facility: St. Carollo Hospital
city: Suwon
country: Korea, Republic of
facility: Ajou University Hospital
city: Ulsan
country: Korea, Republic of
facility: Ulsan University hospital
city: Wonju
country: Korea, Republic of
facility: Wonju Severance Christian Hospital
Study officials:
affiliation: Keimyung University Dongsan Medical Center
name: Chang-Wook Nam
role: PRINCIPAL_INVESTIGATOR
affiliation: Seoul National University Bundang Hospital
name: Cheol-Ho Kim
role: PRINCIPAL_INVESTIGATOR
affiliation: Seoul St. Mary's Hospital of the Catholic University of Korea
name: Sang-Hong Baek
role: PRINCIPAL_INVESTIGATOR
affiliation: Yeouido St. Mary's Hospital of the Catholic University of Korea
name: Woo-Baek Chung
role: PRINCIPAL_INVESTIGATOR
affiliation: Kyunghee University Medical Center
name: Woo-Shik Kim
role: PRINCIPAL_INVESTIGATOR
affiliation: Gachon University Gil Medical Center
name: Tae-Hoon Ahn
role: PRINCIPAL_INVESTIGATOR
affiliation: St. Carollo Hospital
name: Jang-Hyun Cho
role: PRINCIPAL_INVESTIGATOR
affiliation: Seoul National Univerisity Hospital
name: Byung-Hee Oh
role: STUDY_CHAIR
affiliation: Konkuk University Medical Center
name: Hweung-Kon Hwang
role: PRINCIPAL_INVESTIGATOR
affiliation: Korea University Guro Hospital
name: Chang-Gyu Park
role: PRINCIPAL_INVESTIGATOR
affiliation: Ulsan University Hospital
name: Eun-Seok Shin
role: PRINCIPAL_INVESTIGATOR
affiliation: Seoul National University Bundang Hospital
name: Dong-Ju Choi
role: PRINCIPAL_INVESTIGATOR
affiliation: Ajou University School of Medicine
name: Joon-Han Shin
role: PRINCIPAL_INVESTIGATOR
affiliation: Chonnam National University Hospital
name: Myung-Ho Jeong
role: PRINCIPAL_INVESTIGATOR
affiliation: Chungnam National University Hospital
name: Jin-Ok Jeong
role: PRINCIPAL_INVESTIGATOR
affiliation: Kyunghee University Hospital at Gandong
name: Chong-Jin Kim
role: PRINCIPAL_INVESTIGATOR
affiliation: Konyang University Hospital
name: Jang-Ho Bae
role: PRINCIPAL_INVESTIGATOR
affiliation: Wonju Severance Christian Hospital
name: Seung-Hwan Lee
role: PRINCIPAL_INVESTIGATOR
affiliation: Gangnam Severance Hospital
name: Se-Joong Rim
role: PRINCIPAL_INVESTIGATOR
affiliation: Presbyterian medical center
name: Jay-Young Rhew
role: PRINCIPAL_INVESTIGATOR
affiliation: Inje University
name: Doo-Il Kim
role: PRINCIPAL_INVESTIGATOR
affiliation: Inje University
name: Dae-Kyeong Kim
role: PRINCIPAL_INVESTIGATOR
affiliation: Hanyang University
name: Soon-Kil Kim
role: PRINCIPAL_INVESTIGATOR
affiliation: Soonchunhyang University Hospital
name: Hye-Sun Seo
role: PRINCIPAL_INVESTIGATOR
affiliation: Asan Medical Center
name: Duk-Hyun Kang
role: PRINCIPAL_INVESTIGATOR
affiliation: Dong-A University Hospital
name: Young-Dae Kim
role: PRINCIPAL_INVESTIGATOR
affiliation: Chungbuk National University Hospital
name: Dong-Woon Kim
role: PRINCIPAL_INVESTIGATOR
affiliation: Pusan National University Hospital
name: Taek-Jong Hong
role: PRINCIPAL_INVESTIGATOR
affiliation: Severance Hospital
name: Jong-Won Ha
role: PRINCIPAL_INVESTIGATOR
affiliation: Hallym University Medical Center
name: Woo-Jung Park
role: PRINCIPAL_INVESTIGATOR
affiliation: Chung-Ang University Hosptial, Chung-Ang University College of Medicine
name: Tae Ho Kim
role: PRINCIPAL_INVESTIGATOR
affiliation: Daegu Catholic University Medical Center
name: Kee-Sik Kim
role: PRINCIPAL_INVESTIGATOR
affiliation: Sanmsung Medical Center
name: Seung-Woo Park
role: PRINCIPAL_INVESTIGATOR
affiliation: Korea University Anam Hospital
name: Wan-Joo Shim
role: PRINCIPAL_INVESTIGATOR
affiliation: Health Insurance Service Ilsan Hospital
name: Joo-Young Yang
role: PRINCIPAL_INVESTIGATOR
affiliation: Eulji General Hospital
name: Jae-Woong Choi
role: PRINCIPAL_INVESTIGATOR
affiliation: Chonbuk National University Hospital
name: Sun-Hwa Lee
role: PRINCIPAL_INVESTIGATOR
affiliation: Korea University
name: Jeong-Cheon Ahn
role: PRINCIPAL_INVESTIGATOR
affiliation: Seoul Veterans Hospital
name: Keun Lee
role: PRINCIPAL_INVESTIGATOR
affiliation: Daedong Hospital
name: Byung-Soo Kim
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sohn IS, Kim CJ, Oh BH, Hong TJ, Park CG, Kim BS, Chung WB; Investigators. 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: Results of a Randomized, Double-Blind, Multicenter Trial. Am J Cardiovasc Drugs. 2016 Apr;16(2):129-38. doi: 10.1007/s40256-015-0156-x.