Mild-to-moderate Essential Hypertensive MedDRA version: 24.0 Level: PT Classification code 10020823 Term: Hypertensive heart disease System Organ Class: 10007541 - Cardiac disorders
Conditions
Interventions
Trade Name: Edarbi
Product Name: Azilsartan Medoxomil
Product Code: AZM/AR14/TAK-491
Pharmaceutical Form: Tablet
INN or Proposed INN: Azilsartan medoxomil
CAS Number: 863031-21-4
Current Sponsor code:
Sponsors
Celltrion Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subject eligibility is determined according to the following criteria: At screening: 1. Subjects voluntarily agree to participate in the trial and sign the written ICF, after listening to the purpose, method, and effect of clinical trial 2. Male or female adult subjects below the age of 75 years, inclusive Note: Legal minimum age of adult requirement is country specific, and requirement of current country specific regulations will be applied. The current legal ages of adult in Korea, Taiwan, and Poland are = 19, =18, and =18 respectively. 3. Subjects with mild-to-moderate essential hypertension: a. Previously untreated subjects who have not received any antihypertensive medication in the 28 days prior to Visit 1 with msitSBP =140 mmHg and =180 mmHg OR b. Subjects with msitSBP =130 mmHg and =180 mmHg who have not been controlled with antihypertensive drugs 4. Subjects who are capable of understanding and complying with protocol requirements Post-4 week, Azilsartan medoxomil or Amlodipine besylate monotherapy treatment: 5. Subjects who do not achieve target BP (defined as clinic SBP 70% and =65 years) yes F.1.3.1 Number of subjects for this age range 150
Exclusion criteria
Exclusion criteria: At screening: 1. Subjects who have msitSBP >180 mmHg or msitDBP >110 mmHg 2. The differences of msitSBP > 20 mmHg or msitDBP > 10 mmHg between 2 arms 3. A history or any suspected history of secondary hypertension (including but not limited to any of the following): coarctation of the aorta, primary hyperaldosteronism, unilateral or bilateral renal artery stenosis, Cushing’s syndrome, pheochromocytoma, polycystic kidney disease, chronic kidney disease on dialysis, etc. 4. Symptomatic orthostatic hypotension (a sudden fall in standing SBP of at least 20 mmHg or standing DBP of at least 10 mmHg after standing compared with BP from the sitting or supine position) 5. Type 1 or 2 diabetes mellitus with poor glucose control which is defined as history of poorly controlled diabetes mellitus (fasting blood glucose > 11.1 mmol/L [200 mg/dL]); excluding subjects who do not need diabetes medication control during the study period 6. Severe heart disease (congestive heart failure [NYHA Class 3 or 4]); ischemic heart disease (unstable angina, myocardial infarction), peripheral arterial vascular disease/endovascular intervention for peripheral artery disease, history of Percutaneous Transluminal Coronary Angioplasty or coronary artery bypass grafting within the past 6 months 7. Clinically significant ventricular tachycardia, atrial fibrillation, atrial flutter or other clinically significant arrhythmia, or clinically significant QT interval corrected using Fridericia formula (QTcF) for heart rate interval > 450 milliseconds (male) and >470 milliseconds (female), or symptomatic bradycardia 8. Clinically significant electrocardiogram (ECG) abnormalities including third-degree atrioventricular block, sick sinus syndrome, sinus-atrial block 9. Hypertrophic obstructive cardiomyopathy, severe obstructive coronary artery disease, aortic stenosis, hemodynamically relevant stenosis of the aortic or mitral valve 10. Severe cerebrovascular disease (history of stroke, cerebral infarction, or cerebral hemorrhage) within the past 6 months 11. Known moderate or malignant retinopathy (history of retinal signs of hemorrhage, visual impairment, retinal microaneurysm, etc.) within the past 6 months 12. A history of or ongoing: wasting disease, autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus, etc.), hepatic impairment defined as Child- Pugh Class A and above or connective tissue disease 13. Subjects who have the following clinically significant laboratory abnormalities: either creatinine clearance 2 mg/dL or > 200 µmol/L, serum potassium > 5.5mmol/L, alanine aminotransferase or aspartate aminotransferase > 3 × upper limit normal (ULN) 14. Significant thyroid disease (thyroid stimulating hormone > 1.5 × ULN) 15. History of unexplained syncope within the prior 2 years, or a known syncopal disorder 16. Any surgical or medical condition of the gastrointestinal tract that might significantly alter the absorption, distribution, metabolism, or excretion of the drug; current active gastritis, gastrointestinal/rectal bleeding, active inflammatory bowel disease within the last 12 months, etc. 17. Positive for human immunodeficiency virus (HIV), Hepatitis C antibody (HCV Ab), and/or positive for Hepatitis B surface antigen (HBsAg) that requires antiviral treatment 18. History of drug or alcohol abuse within the past 1 year 19. Subjects who are pregnant or lactating women, women suspected of being pregnant, women who wish t
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate antihypertensive efficacy of a combination of Azilsartan medoxomil and Amlodipine besylate, in mild-to-moderate essential hypertensive subjects not adequately controlled by Azilsartan medoxomil monotherapy or Amlodipine besylate monotherapy;Secondary Objective: • To evaluate the safety and tolerability of a combination of Azilsartan medoxomil and Amlodipine besylate, in mild-to-moderate essential hypertensive subjects not adequately controlled by Azilsartan medoxomil monotherapy or Amlodipine besylate monotherapy • To determine the dose-response relationship of Azilsartan medoxomil and Amlodipine besylate monotherapy and Azilsartan medoxomil/ Amlodipine besylate combination therapy in subjects with mild-to-moderate essential hypertension.;Primary end point(s): The primary efficacy endpoint is: • Change from baseline in mean sitting systolic BP (msitSBP) after 8 weeks of treatment;Timepoint(s) of evaluation of this end point: After 8 weeks of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Key secondary efficacy endpoint: • Change from baseline in mean sitting diastolic BP (msitDBP) after 8 weeks of treatment 2) Other secondary efficacy endpoints: • Change from baseline in msitSBP after 4 weeks of treatment • Change from baseline in msitDBP after 4 weeks of treatment • Proportion of subjects who achieve below response criteria: a. Clinic msitSBP <140 mmHg (but, subjects having diabetes mellitus or CVD or CKD with albuminuria (or proteinuria) <130 mmHg) and/or reduction of =20 mmHg from baseline after 4 and 8 weeks of treatment. b. Clinic msitDBP <90 mmHg (but, subjects having diabetes mellitus or CVD or CKD with albuminuria (or proteinuria) <80 mmHg) and/or reduction of =10 mmHg from baseline after 4 and 8 weeks of treatment c. (a) and (b);Timepoint(s) of evaluation of this end point: After 4 and 8 weeks of treatment. | — |
Countries
Korea, Republic of, Poland, Taiwan
Contacts
Public ContactGlobal Clinical Development 2 Team
Celltrion Inc.
Outcome results
None listed