Study to Confirm the Efficacy and Safety of Fixed-dose Combinations of Amlodipine and Candesartan (MACH)

HK inno.N

Status and phase

Unknown

Phase 4

Conditions

Hypertension

Treatments

Drug: Group II

Drug: Group I

Study type

Interventional

Funder types

Industry

Identifiers

NCT03231982

CJ_CCA_401

Details and patient eligibility

About

To evaluate the efficacy and safety of amlodipine besylate and candesartan cilexetil administered in a fixed-dose combination tablet versus co-administered as their separate formulations in patients with essential hypertension who have shown inadequate response on monotherapy of amlodipine or candesartan cilexetil or who are with blood pressure adequately controlled by co-administration of amlodipine besylate and candesartan cilexetil single agents

Enrollment

210 estimated patients

Sex

All

Ages

19 to 75 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Adult male and female aged 19 to 75 years
Diagnosed with essential hypertension

Patients with essential hypertension meeting one of the following two inclusion criteria:

2.1. Patients with essential hypertension who have shown inadequate response (mean siSBP ≥ 140 mmHg or mean siDBP ≥ 90 mmHg) to treatment with amlodipine or candesartan cilexetil.

2.2. Patients with essential hypertension with blood pressure adequately controlled by co-administration of amlodipine besylate and candesartan cilexetil (mean siSBP < 140 mmHg and mean siDBP < 90 mmHg).
Voluntarily consented to participate in the study and signed the informed consent form after receiving the explanation of the objectives, methods and effects of the study.

Exclusion criteria

The difference in blood pressure between the selected arm versus non-selected arm is ≥ 20 mmHg for siSBP and ≥ 10 mmHg for siDBP at Visit 1 (screening).
Blood pressure taken at screening and randomization is ≥ 180 mmHg for siSBP or ≥ 110 mmHg for siDBP.
Diagnosed with secondary hypertension or suspected of secondary hypertension [e.g., renovascular disease, adrenal medullary and cortical hyperfunction, coarctation of the aorta, hyperaldosteronism, unilateral or bilateral renal artery stenosis, Cushing's syndrome, pheochromocytoma, polycystic kidney disease, etc.]
Patients with symptomatic orthostatic hypertension (the difference in the blood pressures between measured at supine position and measured at standing position is ≥ 20 mmHg for siSBP and ≥ 10 mmHg for siDBP)
Diagnosis of type 1 diabetes mellitus (DM) or uncontrolled DM (patients on insulin therapy or with HbA1c > 9%)
Patients with severe cardiac conditions: heart failure (NYHA Class 3 or 4), history of ischemic cardiac disease (unstable angina, myocardial infarction), peripheral vascular diseases, percutaneous transluminal angioplasty or coronary artery bypass graft within recent 6 months.
Patients with clinically significant ventricular tachycardia, atrial fibrillation, atrial flutter or other clinically significant arrhythmia at the discretion of the investigator
Patients with hypertrophic occlusive myocardiopathy, severe occlusive coronary artery disease, aortic stenosis, hemodynamically significant aortic valve or mitral valve stenosis
History of cardiogenic shock
Presence of severe cerebrovascular disorders (diagnosis of stroke, cerebral infarction or cerebral hemorrhage within recent 6 months)
History or current evidence of wasting, autoimmune (such as rheumatoid arthritis and systemic lupus erythematosus) or connective tissue diseases
Known diagnosis of moderate or malignant retinopathy (including retinal hemorrhage, visual disturbance and retinal microaneurysm within 6 months)
Patients with surgical or medical intestinal diseases or having received surgeries that could interfere with drug absorption distribution, metabolism and elimination
History of malignancy including leukemia and lymphoma within recent 5 years except for localized basal cell carcinoma of the skin)
Patients with any inflammatory diseases requiring chronic anti-inflammatory therapy
Renal failure on dialysis
Laboratory abnormalities as follows:
- AST or ALT >2 x upper limit of normal (ULN)
- Serum creatinine > 1.5 x ULN
- Serum potassium < 3.5 mmol/L or >5.5 mmol/L
Needs for co-administration of non-study antihypertensive agents or contraindicated medications during the study
History of hypersensitivity to ARBs or dihydropyridines
History of angioedema to treatment with ACE inhibitors or ARBs
Pregnant or lactating women and female volunteers of childbearing potential (except for women who are surgically sterile) who are not willing to use an adequate method of contraception (oral contraceptives, intrauterine device, condom, etc.) during the study. Women of childbearing potential who are not surgically sterile will be allowed to participate in the study only if they have negative pregnancy test at Visit 1 (screening) and should continue to use medically acceptable method of contraception (basic body temperature method and rhythm method will not be allowed). Women with no menses for ≥ 12 months will be considered as postmenopausal state and method of contraception using hormonal contraception such as oral contraceptive should be initiated from or prior to the screening.
History of drug or alcohol abuse within recent 1 year
Patients having received any other investigational product within recent 12 weeks
Conditions which render a subject ineligible for the study at the discretion of the investigator

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Quadruple Blind

210 participants in 2 patient groups

Group I

Experimental group

Description:

Fixed-Dose combination of Candesartan cilexetil 8mg and Amlodipine 5mg(or Fixed-Dose combination of Candesartan cilexetil 16mg and Amlodipine 5mg), once a day for 8 weeks

Treatment:

Drug: Group I

Group II

Active Comparator group

Description:

Candesartan cilexetil 8mg and Amlodipine 5mg(or Candesartan cilexetil 16mg and Amlodipine 5mg), once a day for 8 weeks

Treatment:

Drug: Group II