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

Essential Hypertension Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01838850
• Other study ID #: CS8635-SIT-11-01
• Status: Completed
• Phase: Phase 3
• Start date: April 2013
• Est. completion date: August 2014

Study information

• Verified date: August 2017
• Source: Daiichi Sankyo, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 344
• Est. completion date: August 2014
• Est. primary completion date: August 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Essential Hypertension
• Hypertension

Intervention

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.
• 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.

Locations

Country	Name	City	State
Korea, Republic of	Korea University Ansan Hospital	Ansan
Korea, Republic of	Hallym University Medical Center	Anyang
Korea, Republic of	Soonchunhyang University Hospital	Bucheon
Korea, Republic of	Daedong Hospital	Busan
Korea, Republic of	Dong-A University Hospital	Busan
Korea, Republic of	Inje University Busan Paik Hospital	Busan
Korea, Republic of	Inje University Haeundae Paik Hospital	Busan
Korea, Republic of	Pusan National University Hospital	Busan
Korea, Republic of	Chungbuk National University Hospital	Cheongju
Korea, Republic of	Chonbuk National University Hospital	Cheonju
Korea, Republic of	Presbyterian Medical Center	Cheonju
Korea, Republic of	Daegu Catholic University Medical Center	Daegu
Korea, Republic of	Keimyung University Dongsan Medical Center	Daegu
Korea, Republic of	Chungnam National University Hospital	Daejeon
Korea, Republic of	Konyang University Hospital	Daejeon
Korea, Republic of	Health Insurance Service Ilsan Hospital	Goyang
Korea, Republic of	Hanyang University Guri Hospital	Guri
Korea, Republic of	Chonnam National University Hospital	Gwangju
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Chung-Ang University Hospital	Seoul
Korea, Republic of	Eulji General Hospital	Seoul
Korea, Republic of	Gangnam Severance Hospital	Seoul
Korea, Republic of	Konkuk University Medical Center	Seoul
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Korea University Guro Hospital	Seoul
Korea, Republic of	Kyung Hee University Medical Center	Seoul
Korea, Republic of	Kyunghee University Hospital at Gandong	Seoul
Korea, Republic of	Sanmsung Medical Center	Seoul
Korea, Republic of	Seoul National University 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	Severance Hospital	Seoul
Korea, Republic of	Yeouido St. Mary's Hospital of the Catholic University of Korea	Seoul
Korea, Republic of	St. Carollo Hospital	Suncheon
Korea, Republic of	Ajou University Hospital	Suwon
Korea, Republic of	Ulsan University hospital	Ulsan
Korea, Republic of	Wonju Severance Christian Hospital	Wonju

Sponsors (1)

Lead Sponsor	Collaborator
Daiichi Sankyo Korea Co., Ltd., a Daiichi Sankyo Company

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Collection of safety data from Adverse event, Laboratory test, Physical examination, Vital signs with pulse and ECG		from screening to Week 16
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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