Clinical trial NCT03847506: Evaluate Efficacy and Safety of Ezetimibe/Rosuvastatin and Candesartan Cilexetil/Amlodipine Besylate Combination Tablets
Official title: A Randomized, Double-blind, Multi-center Clinical Trial to Evaluate Efficacy and Safety of Ezetimibe/Rosuvastatin Combination Tablets and Candesartan Cilexetil/Amlodipine Besylate Combination Tablets
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hypertension, Hyperlipidemia
Lead sponsor: HK inno.N Corporation
Sponsor class: INDUSTRY
First posted: 2019-02-20
Enrollment: 127
Sex: ALL
Minimum age (years): 19
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel Assignment
Primary purpose: TREATMENT

Brief summary: To evaluate the efficacy and the safety of concomitant use of Ezetimibe/Rosuvastatin combination tablets and Candesartan cilexetil/Amlodipine besylate combination tablets compared to each combination tablet alone in patients with essential hypertension (HTN) and hyperlipidemia.

Detailed description: To improve the ease of use of high blood pressure and hyperlipidemia to improve patient compliance and reduce the risk of cardiovascular disease.

And It is recommended to identify the need to develop a combination of Candesartan cilexetil/Amlodipine besylate combination tablets , and Ezetimibe/Rosuvastatin combination tablets.

Eligibility criteria: \[ Inclusion Criteria \]

1. Adults aged 19 to \<75 years.
2. Diagnosed with essential HTN accompanied by hyperlipidemia (average siSBP ≥140 mmHg and LDL-C ≥100 mg/dL) or being treated for the condition after the diagnosis, at Visit 1 (screening).
3. Provided the signed informed consent form voluntarily after receiving explanation of the objectives, methods and effects of the study.
4. Medically sterile or agreed to use medically acceptable contraceptive method during the study.

\[ Exclusion Criteria \]

\* Criteria Related to HTN and Dyslipidemia

1. Severe HTN defined as average siDBP ≥110 mmHg or average siSBP ≥180 mmHg at Visit 1 (screening).
2. The difference in BPs between those measured at both arms at Visit 1 (screening) is ≥10 mmHg for siDBP or ≥20 mmHg for siSBP.
3. LDL-C \>250 mg/dL or TG ≥400 mg/dL at Visit 1 (screening).
4. Diagnosed with or suspected of secondary HTN (e.g., renovascular disease, coarctation of the aorta, hyperaldosteronism, unilateral or bilateral renal artery stenosis, Cushing's syndrome, pheochromo-cytoma, polycystic kidney disease, etc.).
5. Patients with symptomatic orthostatic HTN (difference in BPs between the value measured in supine position and the value measured in standing position is ≥20 mmHg for siSBP or ≥10 mmHg for siDBP).

   \* Criteria Related to Medical History
6. Diagnosis with type 1 diabetes mellitus (DM) or uncontrolled DM (patients on insulin therapy or patients with HbA1C ≥9%).
7. Patients with severe heart disease - heart failure (NYHA Classes 3 and 4), history of ischemic cardiac disease (unstable angina, myocardial infarction), peripheral vascular diseases, percutaneous transluminal angioplasty, or coronary artery bypass graft within the recent 3 months.
8. Patients with clinically significant ventricular tachycardia, atrial fibrillation, atrial flutter, or other clinically significant arrhythmia at the discretion of the investigator.
9. History of muscular toxicity while on treatment with other HMG-CoA reductase inhibitors or fibrates.
10. History of angioedema while on treatment with ACE inhibitors or ARBs.
11. History of hypersensitivity to ARBs, dihydropyridines, or HMG-CoA reductase inhibitors.
12. Patients with hypertrophic occlusive myocardiopathy, severe occlusive coronary artery disease, aortic stenosis, hemodynamically significant aortic, or mitral valve stenosis.
13. Presence of severe cerebrovascular disorders (diagnosis of stroke, cerebral infarction, or cerebral hemorrhage within the recent 6 months).
14. History or current evidence of wasting diseases, autoimmune diseases (such as rheumatoid arthritis and systemic lupus erythematosus), or connective tissue diseases.
15. Known diagnosis of moderate or malignant retinopathy (including retinal hemorrhage, visual disturbance, and retinal microaneurysm within the recent 6 months).
16. Patients with surgical or medical gastrointestinal diseases or having received surgery that could interfere with drug absorption, distribution, metabolism, and elimination and patients with active gastritis, gastrointestinal/rectal bleeding, or diagnosed with active inflammatory bowel disease within the recent 12 months.
17. History of malignancy including leukemia and lymphoma within the recent 5 years (except for localized basal cell carcinoma of the skin).
18. Patients with any inflammatory diseases requiring chronic anti-inflammatory therapy.
19. Patients who received kidney transplant or with only one kidney.
20. Presence of biliary obstruction or cholestasis.
21. Presence of hereditary conditions such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption.
22. Patients with shock.

    \* Criteria Related to Clinical Laboratory Tests
23. Laboratory abnormalities as follows:

    * AST or ALT \>3 x upper limit of normal (ULN);
    * Serum creatinine \>1.5 x ULN.
24. History of myopathy or rhabdomyolysis (e.g., serum CK ≥5 x ULN).
25. Uncontrolled abnormal thyroid function (e.g., TSH ≥1.5 x ULN).
26. Persistent abnormal serum potassium level (e.g., serum potassium level \<3.5 mmol/L or \>5.5 mmol/L).
27. Patients with conditions of body fluid depletion or laboratory findings indicating clinically significant electrolyte abnormality.

    \* Others
28. Needs for concomitant administration of non-study antihypertensive agents or prohibited medications during the study.
29. Pregnant or lactating women.
30. History of drug or alcohol abuse within the recent 1 year.
31. Having received other investigational product within 4 weeks prior to screening.
32. Patients considered ineligible for the study at the discretion of the principal investigator (PI) or study staff.

Primary outcomes:
measure: Change in sitting Systolic Blood Pressure(siSBP) from baseline after 6 weeks of study treatment
timeFrame: week 6
measure: Percentage change in LDL-C levels from baseline after 6 weeks of study treatment
timeFrame: week 6
Secondary outcomes:
measure: Change in siSBP from baseline after 3 weeks of study treatment
timeFrame: week 3
measure: Percentage changes in LDL-C levels from baseline after 3 and 6 weeks of study treatment
timeFrame: week 3 and week 6
measure: Percentage change in LDL-C levels from baseline after 3 weeks of study treatment
timeFrame: week 3
measure: Changes in siSBPs from baseline after 3 and 6 weeks of study treatment
timeFrame: week 3 and week 6
measure: Percentage changes in LDL-C/HDL-C and TC/HDL-C from baseline after 3 and 6 weeks of study treatment
timeFrame: week 3 and week 6
measure: Changes in siDBPs from baseline after 3 and 6 weeks of study treatment
timeFrame: week 3 and week 6
measure: Proportions of subjects who achieve the treatment goal based on JNC VIII Guideline from baseline after 3 and 6 weeks of study treatment
timeFrame: week 3 and week 6
measure: Proportions of subjects who achieve the treatment goal based on NCEP ATP III Guideline from baseline after 3 and 6 weeks of study treatment
timeFrame: week 3 and week 6
measure: Percentage changes in TC, TG, HDL-C, apolipoprotein B, and CRP levels from baseline after 3 and 6 weeks of study treatment
timeFrame: week 3 and week 6
Other outcomes:
measure: Adverse events
timeFrame: Baseline, week 3 and week 6
Locations:
city: Gyeonggi-do
country: Korea, Republic of
facility: Bundang Seoul National University Hospital
state: Seongnam-si, Bundang-gu
Study officials:
affiliation: Seoul National University Bundang Hospital
name: In-Ho Chae, Ph.D
role: PRINCIPAL_INVESTIGATOR
References: