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

NCT01838850 | Completed Phase 3

• 1 other identifier: CS8635-SIT-11-01
• Study Type: interventional
• Target: 344
• Locations: 1 country
• Sites: 39

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).

Conditions

Essential Hypertension

Outcome Measures

Primary Outcomes (1)

• The changes of seated diastolic blood pressure of the Triple Combinations OM/AML/HCTZ 20/5/12.5mg vs.OM/HCTZ 20/12.5mg

  from baseline to week 8

Secondary Outcomes (5)

• 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

  from 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 20/12.5mg

  from baseline to week 4

• Percentage of subjects achieving blood pressure goal of the Triple Combinations OM/AML/HCTZ 20/5/12.5mg vs.OM/HCTZ 20/12.5mg

  at Week 4, and Week 8

• 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

  At 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 20/5/12.5mg

  from Week 8 to Week 16

Other Outcomes (1)

• Collection of safety data from Adverse event, Laboratory test, Physical examination, Vital signs with pulse and ECG

  from screening to Week 16

Study Arms (2)

CS8635 20/5/12.5mg and placebo

EXPERIMENTAL

Participants 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).

Drug: CS8635 20/5/12.5mg and placebo

Olmetec® Plus 20/12.5mg and placebo

ACTIVE COMPARATOR

Participants 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).

Drug: Olmetec® Plus 20/12.5mg and placebo

Interventions

CS8635 20/5/12.5mg and placebo DRUG

Run-in period: Coated, Oral tablet containing Olmesartan medoxomil(OM)-Hydrochlorothiazide(HCTZ) 20-12.5mg, given once a day. Double-blind period: Coated, Oral tablet containing Olmesartan medoxomil(OM)-Amlodipine (AML)-Hydrochlorothiazide(HCTZ) 20-5-12.5mg, oral placebo tablet. All tablets are given once a day. Open-label period: Coated, Oral tablet containing Olmesartan medoxomil(OM)-Amlodipine(AML)-Hydrochlorothiazide(HCTZ) 40-5-12.5mg, given once a day.

CS8635 20/5/12.5mg and placebo

Olmetec® Plus 20/12.5mg and placebo DRUG

Run-in period: Coated, Oral tablet containing Olmesartan medoxomil(OM)-Hydrochlorothiazide(HCTZ) 20-12.5mg, given once a day. Double-blind period: Coated, Oral tablet containing Olmesartan medoxomil(OM)-Hydrochlorothiazide(HCTZ) 20-12.5mg, oral placebo tablet. All tablets are given once a day. Open-label period: Coated, Oral tablet containing Olmesartan medoxomil(OM)-Amlodipine(AML)-Hydrochlorothiazide(HCTZ) 20-5-12.5mg, given once a day.

Olmetec® Plus 20/12.5mg and placebo

Eligibility Criteria

• Age: 20 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Daiichi Sankyo Korea Co., Ltd., a Daiichi Sankyo Company: lead

Study Sites (39)

Korea University Ansan Hospital

Ansan, 425-707, South Korea

Location

Hallym University Medical Center

Anyang, 431-796, South Korea

Location

Soonchunhyang University Hospital

Bucheon-si, 420-767, South Korea

Location

Dong-A University Hospital

Busan, 602-715, South Korea

Location

Pusan National University Hospital

Busan, 602-739, South Korea

Location

Daedong Hospital

Busan, 607-711, South Korea

Location

Inje University Haeundae Paik Hospital

Busan, 612-896, South Korea

Location

Inje University Busan Paik Hospital

Busan, 614-735, South Korea

Location

Chungbuk National University Hospital

Cheongju-si, 361-711,, South Korea

Location

Presbyterian Medical Center

Cheonju, 560-750, South Korea

Location

Chonbuk National University Hospital

Cheonju, 561-712, South Korea

Location

Keimyung University Dongsan Medical Center

Daegu, 700-712, South Korea

Location

Daegu Catholic University Medical Center

Daegu, 705-718, South Korea

Location

Chungnam National University Hospital

Daejeon, 301-721, South Korea

Location

Konyang University Hospital

Daejeon, 302-718, South Korea

Location

Health Insurance Service Ilsan Hospital

Goyang, 410-719, South Korea

Location

Hanyang University Guri Hospital

Guri-si, 471-701, South Korea

Location

Chonnam National University Hospital

Gwangju, 501-757, South Korea

Location

Gachon University Gil Medical Center

Incheon, 405-835, South Korea

Location

Seoul National University Bundang Hospital

Seongnam, 463-707, South Korea

Location

Seoul National University Hospital

Seoul, 110-744, South Korea

Location

Severance Hospital

Seoul, 120-752, South Korea

Location

Kyung Hee University Medical Center

Seoul, 130-702, South Korea

Location

Kyunghee University Hospital at Gandong

Seoul, 134-727, South Korea

Location

Seoul Veterans Hospital

Seoul, 134-791, South Korea

Location

Sanmsung Medical Center

Seoul, 135-710, South Korea

Location

Gangnam Severance Hospital

Seoul, 135-720, South Korea

Location

Korea University Anam Hospital

Seoul, 136-705, South Korea

Location

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

Seoul, 137-701, South Korea

Location

Asan Medical Center

Seoul, 138-736, South Korea

Location

Eulji General Hospital

Seoul, 139-711, South Korea

Location

Konkuk University Medical Center

Seoul, 143-729, South Korea

Location

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

Seoul, 150-713, South Korea

Location

Korea University Guro Hospital

Seoul, 152-840, South Korea

Location

Chung-Ang University Hospital

Seoul, 156-755, South Korea

Location

St. Carollo Hospital

Suncheon, 540-719, South Korea

Location

Ajou University Hospital

Suwon, 443-380, South Korea

Location

Ulsan University hospital

Ulsan, 682-714, South Korea

Location

Wonju Severance Christian Hospital

Wŏnju, 220-701, South Korea

Location

Related Publications (1)

• 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.

  PMID: 26691333 DERIVED

MeSH Terms

Conditions

Essential Hypertension

Interventions

Olmesartan Medoxomil

Condition Hierarchy (Ancestors)

Hypertension; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrazoles

Study Officials

• Chang-Wook Nam

  Keimyung University Dongsan Medical Center

  PRINCIPAL INVESTIGATOR

• Cheol-Ho Kim

  Seoul National University Bundang Hospital

  PRINCIPAL INVESTIGATOR

• Sang-Hong Baek

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

  PRINCIPAL INVESTIGATOR

• Woo-Baek Chung

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

  PRINCIPAL INVESTIGATOR

• Woo-Shik Kim

  Kyunghee University Medical Center

  PRINCIPAL INVESTIGATOR

• Tae-Hoon Ahn

  Gachon University Gil Medical Center

  PRINCIPAL INVESTIGATOR

• Jang-Hyun Cho

  St. Carollo Hospital

  PRINCIPAL INVESTIGATOR

• Byung-Hee Oh

  Seoul National Univerisity Hospital

  STUDY CHAIR

• Hweung-Kon Hwang

  Konkuk University Medical Center

  PRINCIPAL INVESTIGATOR

• Chang-Gyu Park

  Korea University Guro Hospital

  PRINCIPAL INVESTIGATOR

• Eun-Seok Shin

  Ulsan University Hospital

  PRINCIPAL INVESTIGATOR

• Dong-Ju Choi

  Seoul National University Bundang Hospital

  PRINCIPAL INVESTIGATOR

• Joon-Han Shin

  Ajou University School of Medicine

  PRINCIPAL INVESTIGATOR

• Myung-Ho Jeong

  Chonnam National University Hospital

  PRINCIPAL INVESTIGATOR

• Jin-Ok Jeong

  Chungnam National University Hospital

  PRINCIPAL INVESTIGATOR

• Chong-Jin Kim

  Kyunghee University Hospital at Gandong

  PRINCIPAL INVESTIGATOR

• Jang-Ho Bae

  Konyang University Hospital

  PRINCIPAL INVESTIGATOR

• Seung-Hwan Lee

  Wonju Severance Christian Hospital

  PRINCIPAL INVESTIGATOR

• Se-Joong Rim

  Gangnam Severance Hospital

  PRINCIPAL INVESTIGATOR

• Jay-Young Rhew

  Presbyterian medical center

  PRINCIPAL INVESTIGATOR

• Doo-Il Kim

  Inje University

  PRINCIPAL INVESTIGATOR

• Dae-Kyeong Kim

  Inje University

  PRINCIPAL INVESTIGATOR

• Soon-Kil Kim

  Hanyang University

  PRINCIPAL INVESTIGATOR

• Hye-Sun Seo

  Soonchunhyang University Hospital

  PRINCIPAL INVESTIGATOR

• Duk-Hyun Kang

  Asan Medical Center

  PRINCIPAL INVESTIGATOR

• Young-Dae Kim

  Dong-A University Hospital

  PRINCIPAL INVESTIGATOR

• Dong-Woon Kim

  Chungbuk National University Hospital

  PRINCIPAL INVESTIGATOR

• Taek-Jong Hong

  Pusan National University Hospital

  PRINCIPAL INVESTIGATOR

• Jong-Won Ha

  Severance Hospital

  PRINCIPAL INVESTIGATOR

• Woo-Jung Park

  Hallym University Medical Center

  PRINCIPAL INVESTIGATOR

• Tae Ho Kim

  Chung-Ang University Hosptial, Chung-Ang University College of Medicine

  PRINCIPAL INVESTIGATOR

• Kee-Sik Kim

  Daegu Catholic University Medical Center

  PRINCIPAL INVESTIGATOR

• Seung-Woo Park

  Sanmsung Medical Center

  PRINCIPAL INVESTIGATOR

• Wan-Joo Shim

  Korea University Anam Hospital

  PRINCIPAL INVESTIGATOR

• Joo-Young Yang

  Health Insurance Service Ilsan Hospital

  PRINCIPAL INVESTIGATOR

• Jae-Woong Choi

  Eulji General Hospital

  PRINCIPAL INVESTIGATOR

• Sun-Hwa Lee

  Chonbuk National University Hospital

  PRINCIPAL INVESTIGATOR

• Jeong-Cheon Ahn

  Korea University

  PRINCIPAL INVESTIGATOR

• Keun Lee

  Seoul Veterans Hospital

  PRINCIPAL INVESTIGATOR

• Byung-Soo Kim

  Daedong Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2013
• First Posted: April 24, 2013
• Study Start: April 1, 2013
• Primary Completion: August 1, 2014
• Study Completion: August 1, 2014
• Last Updated: December 24, 2018

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, 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.

Locations

KR (39)