Clinical trial NCT03231982: Study to Confirm the Efficacy and Safety of Fixed-dose Combinations of Amlodipine and Candesartan
Official title: A Randomized, Double-blind, Multi-center, Phase Ⅳ Clinical Trial to Evaluate the Antihypertensive Efficacy and Safety Between Amlodipine Besylate/Candesartan Cilexetil Combination Tablets and Co-administration of Amlodipine Besylate and Candesartan Cilexetil in Patients With Essential Hypertension
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Hypertension
Lead sponsor: HK inno.N Corporation
Sponsor class: INDUSTRY
First posted: 2017-07-27
Enrollment: 210
Sex: ALL
Minimum age (years): 19
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: Inclusion Criteria:

1. Adult male and female aged 19 to 75 years
2. 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).
3. 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:

1. 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).
2. Blood pressure taken at screening and randomization is ≥ 180 mmHg for siSBP or ≥ 110 mmHg for siDBP.
3. Diagnosed with secondary hypertension or suspected of secondary hypertension \[e.g., renovascular disease, adrenal medullary and cortical hyperfunction, coarctation of the aorta, hyperaldosteronism, unilateral or bilateral renal artery stenosis, Cushing's syndrome, pheochromocytoma, polycystic kidney disease, etc.\]
4. 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)
5. Diagnosis of type 1 diabetes mellitus (DM) or uncontrolled DM (patients on insulin therapy or with HbA1c \> 9%)
6. 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.
7. Patients with clinically significant ventricular tachycardia, atrial fibrillation, atrial flutter or other clinically significant arrhythmia at the discretion of the investigator
8. Patients with hypertrophic occlusive myocardiopathy, severe occlusive coronary artery disease, aortic stenosis, hemodynamically significant aortic valve or mitral valve stenosis
9. History of cardiogenic shock
10. Presence of severe cerebrovascular disorders (diagnosis of stroke, cerebral infarction or cerebral hemorrhage within recent 6 months)
11. History or current evidence of wasting, autoimmune (such as rheumatoid arthritis and systemic lupus erythematosus) or connective tissue diseases
12. Known diagnosis of moderate or malignant retinopathy (including retinal hemorrhage, visual disturbance and retinal microaneurysm within 6 months)
13. Patients with surgical or medical intestinal diseases or having received surgeries that could interfere with drug absorption distribution, metabolism and elimination
14. History of malignancy including leukemia and lymphoma within recent 5 years except for localized basal cell carcinoma of the skin)
15. Patients with any inflammatory diseases requiring chronic anti-inflammatory therapy
16. Renal failure on dialysis
17. 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
18. Needs for co-administration of non-study antihypertensive agents or contraindicated medications during the study
19. History of hypersensitivity to ARBs or dihydropyridines
20. History of angioedema to treatment with ACE inhibitors or ARBs
21. 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.
22. History of drug or alcohol abuse within recent 1 year
23. Patients having received any other investigational product within recent 12 weeks
24. Conditions which render a subject ineligible for the study at the discretion of the investigator

Primary outcomes:
measure: Change in sitting Systolic Blood Pressure(siSBP) from baseline after 8 weeks of treatment
timeFrame: Week 8
Secondary outcomes:
measure: Change in siSBP from baseline after 4 weeks of treatment
timeFrame: Week 4
measure: Change in siDBP from baseline after 4 and 8 weeks of treatment
timeFrame: Week 4 and Week 8
measure: Proportion of subjects with siDBP < 90 mmHg and siSBP <140 mmHg after 8 weeks of treatment
timeFrame: Week8
Other outcomes:
measure: Adverse events
timeFrame: Baseline, Week 4 and Week 8
measure: Clinical laboratory tests
timeFrame: Baseline, Wee4 and Week 8
measure: Electrocardiogram (ECG)
timeFrame: Screening and Week 8
Locations:
city: Seoul
country: Korea, Republic of
facility: Yonsei University Severance Cardiovascular Hospital
Study officials:
References: