A Phase 2 Dose Selection Trial of Candesartan Cilexetil and Amlodipine Besylate to Treat Essential Hypertension

Sponsor

HK inno.N Corporation (Industry)

Overall Status

Unknown status

CT.gov ID

NCT02059616

Collaborator

(none)

384

Enrollment

Locations

Arms

21.9

Duration (Months)

19.2

Patients Per Site

0.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to explore the optimal dose of fixed-dose combination of candesartan cilexetil and amlodipine besylate by examining the safety and efficacy of the combination therapy compared to each of the monotherapy in patients with essential hypertension.

Condition or Disease	Intervention/Treatment	Phase
Essential Hypertension	Drug: Amlodipine 5mg Drug: Amlodipine 10mg Drug: Candesartan Cilexetil 8mg Drug: Candesartan cilexetil 16mg	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

384 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

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

Primary Purpose:

Treatment

Official Title:

A Randomized, Double-blind, Multi-center, PhaseⅡ Clinical Trial to Evaluate the Antihypertensive Efficacy and Safety of Candesartan Cilexetil and Amlodipine Besylate for the Dose Selection in Patients With Essential Hypertension

Study Start Date :

Feb 1, 2014

Anticipated Primary Completion Date :

Jun 1, 2015

Anticipated Study Completion Date :

Dec 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AML 5mg Amlodipine 5 mg, once a day for 8 weeks	Drug: Amlodipine 5mg Daily oral administration for 8 weeks Other Names: Norvasc 5mg
Experimental: AML 10mg Amlodipine 10 mg, once a day for 8 weeks	Drug: Amlodipine 10mg Daily oral administration for 8 weeks Other Names: Norvasc 10mg
Experimental: CC 8mg Candesartan Cilexetil 8 mg, once a day for 8 weeks	Drug: Candesartan Cilexetil 8mg Daily oral administration for 8 weeks Other Names: Atacand 8mg
Experimental: CC 16mg Candesartan Cilexetil 16 mg, once a day for 8 weeks	Drug: Candesartan cilexetil 16mg Daily oral administration for 8 weeks Other Names: Atacand 16mg
Experimental: AML 5mg/CC 8mg Amlodipine 5 mg and Candesartan 8 mg, once a day for 8 weeks	Drug: Amlodipine 5mg Daily oral administration for 8 weeks Other Names: Norvasc 5mg Drug: Candesartan Cilexetil 8mg Daily oral administration for 8 weeks Other Names: Atacand 8mg
Experimental: AML 5mg/CC16mg Amlodipine 5 mg and Candesartan Cilexetil 16 mg, once a day for 8 weeks	Drug: Amlodipine 5mg Daily oral administration for 8 weeks Other Names: Norvasc 5mg Drug: Candesartan cilexetil 16mg Daily oral administration for 8 weeks Other Names: Atacand 16mg
Experimental: AML 10mg/CC 8mg Amlodipine 10 mg and Candesartan Cilexetil 8 mg, once a day for 8 weeks	Drug: Amlodipine 10mg Daily oral administration for 8 weeks Other Names: Norvasc 10mg Drug: Candesartan Cilexetil 8mg Daily oral administration for 8 weeks Other Names: Atacand 8mg
Experimental: AML 10mg/CC 16mg Amlodipine 10 mg and Candesartan Cilexetil 16 mg, once a day for 8 weeks	Drug: Amlodipine 10mg Daily oral administration for 8 weeks Other Names: Norvasc 10mg Drug: Candesartan cilexetil 16mg Daily oral administration for 8 weeks Other Names: Atacand 16mg

Outcome Measures

Primary Outcome Measures

Change in sitting Diastolic Blood Pressure (siDBP) at week 8 compared to baseline [Week 8]

Secondary Outcome Measures

Change in sitting Systolic Blood Pressure (siSBP) at week 4 and 8 [Week 4 and 8]
Change in siDBP at week 4 [Week 4]
Proportion of patients achieving ΔsiDBP > 10 mmHg and ΔsiSBP < 20 mmHg after 8 weeks [Week 8]
Proportion of patients achieving siDBP < 90 mmHg and siSBP < 120 mmHg after 8 weeks [Week 8]

Eligibility Criteria

Criteria

Ages Eligible for Study:

19 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male or female aged ≥ 19 and ≤ 75 years old
Subject with mild-to-moderate uncomplicated essential hypertension
Subject who have voluntarily agreed to participate in the trial and signed the written informed consent form, after having listened to the purpose, method, and effect of the clinical trial

Exclusion Criteria:

Subject with severe hypertension (siDBP ≥ 115 mmHg or siSBP ≥ 185 mmHg)
Subject with difference in the mean blood pressure of over 10mmHg for siDBP or 20mmHg for siSBP between both arms at the screening visit
Subject with known or suspected secondary hypertension [including but not limited to any of the following: renovascular hypertension, adrenal medullary and cortical hyperfunction, coarctation of the aorta, primary hyperaldosteronism, unilateral or bilateral renal artery stenosis, Cushing's disease, pheochromocytoma, polycystic kidney disease, etc.]
Subject with symptomatic orthostatic hypotension (a sudden fall in siDBP of at least 10 mmHg or siSBP of at least 20 mmHg after standing compared with blood pressure from the sitting or supine position)
Subject with Type 1 diabetes mellitus OR Type 2 diabetes mellitus with poor glucose control (defined as subject on insulin treatment, with HbA1c > 9.0%, or with a modification in the oral anti-hyperglycemic medication regiment within the past 12 weeks prior to Visit 1)
Subject with severe heart disease (Congestive heart failure (NYHA Class III-IV), ischemic heart disease within the past 6 months (unstable angina, myocardial infarction), peripheral vascular disease, history of Percutaneous Transluminal Coronary Angioplasty or Coronary Artery Bypass Grafting)
Subject with clinically significant ventricular tachycardia, atrial fibrillation, atrial flutter or other clinically significant arrhythmia
Subject with hypertrophic obstructive cardiomyopathy, severe obstructive coronary artery disease, aortic stenosis, haemodynamically relevant stenosis of the aortic or mitral valve
Subject with severe cerebrovascular disease (history of stroke, cerebral infarction, or cerebral hemorrhage within the past 6 months)
Subject with or with a history of wasting disease, autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus), or connective tissue disease
Subject with known moderate or malignant retinopathy (history of retinal signs of hemorrhage, visual impairment, retinal microaneurysm, etc. within the past 6 months)
Subject with the following clinically significant laboratory abnormalities:
AST or ALT > 3 x Upper Limit Normal (ULN)
Serum Creatinine > 1.5 ULN
Serum potassium < 3.5 mmol/L or > 5.5 mmol/L
Subject with any surgical or medical condition of the gastrointestinal tract that might significantly alter the absorption, distribution, metabolism or excretion of the drug
Subject with a history of malignant tumors including leukemia and lymphoma within the past 5 years (except for localized basal cell carcinoma of the skin)
Subject with any chronic inflammatory condition needing chronic anti-inflammatory therapy
Subject with chronic kidney disease on dialysis
Subject with cardiogenic shock
Subject requiring concomitant use of other antihypertensive or contraindicated drugs during the entire study period
Subject with known or suspected contraindications, including history of allergy or hypersensitivity to ARB or dihydropyridine derivatives
Subject who have previously experienced symptoms characteristic of angioedema during treatment with ACE inhibitors or ARB
Pregnant women, lactating mothers, women suspected of being pregnant, women who wish to be pregnant during the study, or women of child-bearing potential who are not using medically acceptable methods of contraception (oral contraceptive, intra-uterine device, condom, etc.), except for women with surgical sterilization. Pre-menopausal women who are not surgically sterilized must have a negative pregnancy test result at Visit 1 and maintain acceptable methods of contraception throughout the study. Periodic abstinence (eg, symptothermal, calendar, post-ovulation methods), or hormonal contraceptive are not acceptable methods of contraception
History of drug or alcohol abuse within the past 1 year
Use of other investigational products within the past 4 weeks
Subject who are judged unsuitable to participate in the study in the opinion of the investigator

Contacts and Locations

Locations

	Site	City	Country
1	Seoul National University Bundang Hospital	Bundang	Korea, Republic of
2	Dong-A University Hospital	Busan	Korea, Republic of
3	Yeungnam University Medical Center	Daegu	Korea, Republic of
4	Konyang University Hospital	Daejeon	Korea, Republic of
5	Chonnam National University Hospital	Gwangju	Korea, Republic of
6	Inje University Ilsan Paik Hospital	Ilsan	Korea, Republic of
7	Inha University Hospital	Incheon	Korea, Republic of
8	Hallym University Sacred Heart hospital	Kyungki-do	Korea, Republic of
9	Inje University Haeundae Baik Hospital	Pusan	Korea, Republic of
10	Pusan National University Hospital	Pusan	Korea, Republic of
11	Asan Medical Center	Seoul	Korea, Republic of
12	Ewha Womans University Mokdong Hospital	Seoul	Korea, Republic of
13	Korea University Guro Hospital	Seoul	Korea, Republic of
14	Seoul Medical Center	Seoul	Korea, Republic of
15	Seoul St. Mary's hospital	Seoul	Korea, Republic of
16	Severance Hospital	Seoul	Korea, Republic of
17	Soonchunhyang University Hospital	Seoul	Korea, Republic of
18	Yonsei University Gangnam Severance Hospital	Seoul	Korea, Republic of
19	Ajou University Hospital	Suwon	Korea, Republic of
20	Wonju Severance Christian Hospital	Wonju	Korea, Republic of