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

Sponsor

Daiichi Sankyo Korea Co., Ltd., a Daiichi Sankyo Company (Industry)

Overall Status

Completed

CT.gov ID

NCT01838850

Collaborator

(none)

344

Enrollment

Locations

Arms

Duration (Months)

8.8

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Essential Hypertension	Drug: CS8635 20/5/12.5mg and placebo Drug: Olmetec® Plus 20/12.5mg and placebo	Phase 3

Detailed Description

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

Study Design

Study Type:

Interventional

Actual Enrollment :

344 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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 Start Date :

Apr 1, 2013

Actual Primary Completion Date :

Aug 1, 2014

Actual Study Completion Date :

Aug 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CS8635 20/5/12.5mg and placebo 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 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.
Active Comparator: Olmetec® Plus 20/12.5mg and placebo 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 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.

Arm

Intervention/Treatment

Experimental: CS8635 20/5/12.5mg and placebo

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

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.

Active Comparator: Olmetec® Plus 20/12.5mg and placebo

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

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.

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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 Outcome Measures

Collection of safety data from Adverse event, Laboratory test, Physical examination, Vital signs with pulse and ECG [from screening to Week 16]

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Korea University Ansan Hospital	Ansan	Korea, Republic of	425-707
2	Hallym University Medical Center	Anyang	Korea, Republic of	431-796
3	Soonchunhyang University Hospital	Bucheon	Korea, Republic of	420-767
4	Dong-A University Hospital	Busan	Korea, Republic of	602-715
5	Pusan National University Hospital	Busan	Korea, Republic of	602-739
6	Daedong Hospital	Busan	Korea, Republic of	607-711
7	Inje University Haeundae Paik Hospital	Busan	Korea, Republic of	612-896
8	Inje University Busan Paik Hospital	Busan	Korea, Republic of	614-735
9	Chungbuk National University Hospital	Cheongju	Korea, Republic of	361-711,
10	Presbyterian Medical Center	Cheonju	Korea, Republic of	560-750
11	Chonbuk National University Hospital	Cheonju	Korea, Republic of	561-712
12	Keimyung University Dongsan Medical Center	Daegu	Korea, Republic of	700-712
13	Daegu Catholic University Medical Center	Daegu	Korea, Republic of	705-718
14	Chungnam National University Hospital	Daejeon	Korea, Republic of	301-721
15	Konyang University Hospital	Daejeon	Korea, Republic of	302-718
16	Health Insurance Service Ilsan Hospital	Goyang	Korea, Republic of	410-719
17	Hanyang University Guri Hospital	Guri	Korea, Republic of	471-701
18	Chonnam National University Hospital	Gwangju	Korea, Republic of	501-757
19	Gachon University Gil Medical Center	Incheon	Korea, Republic of	405-835
20	Seoul National University Bundang Hospital	Seongnam	Korea, Republic of	463-707
21	Seoul National University Hospital	Seoul	Korea, Republic of	110-744
22	Severance Hospital	Seoul	Korea, Republic of	120-752
23	Kyung Hee University Medical Center	Seoul	Korea, Republic of	130-702
24	Kyunghee University Hospital at Gandong	Seoul	Korea, Republic of	134-727
25	Seoul Veterans Hospital	Seoul	Korea, Republic of	134-791
26	Sanmsung Medical Center	Seoul	Korea, Republic of	135-710
27	Gangnam Severance Hospital	Seoul	Korea, Republic of	135-720
28	Korea University Anam Hospital	Seoul	Korea, Republic of	136-705
29	Seoul St. Mary's Hospital of the Catholic University of Korea	Seoul	Korea, Republic of	137-701
30	Asan Medical Center	Seoul	Korea, Republic of	138-736
31	Eulji General Hospital	Seoul	Korea, Republic of	139-711
32	Konkuk University Medical Center	Seoul	Korea, Republic of	143-729
33	Yeouido St. Mary's Hospital of the Catholic University of Korea	Seoul	Korea, Republic of	150-713
34	Korea University Guro Hospital	Seoul	Korea, Republic of	152-840
35	Chung-Ang University Hospital	Seoul	Korea, Republic of	156-755
36	St. Carollo Hospital	Suncheon	Korea, Republic of	540-719
37	Ajou University Hospital	Suwon	Korea, Republic of	443-380
38	Ulsan University hospital	Ulsan	Korea, Republic of	682-714
39	Wonju Severance Christian Hospital	Wonju	Korea, Republic of	220-701

Sponsors and Collaborators

Daiichi Sankyo Korea Co., Ltd., a Daiichi Sankyo Company

Investigators

Principal Investigator: 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
Study Chair: Byung-Hee Oh, Seoul National Univerisity Hospital
Principal Investigator: 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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Daiichi Sankyo Korea Co., Ltd., a Daiichi Sankyo Company

ClinicalTrials.gov Identifier:

NCT01838850

Other Study ID Numbers:

CS8635-SIT-11-01

First Posted:

Apr 24, 2013

Last Update Posted:

Dec 24, 2018

Last Verified:

Aug 1, 2017

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Additional relevant MeSH terms:

Hypertension

Essential Hypertension

Olmesartan Medoxomil

Study Results

No Results Posted as of Dec 24, 2018