Comparison of Efficacy and Safety of Combination Therapy and Monotherapy of Candesartan and Amlodipine for Dose-Finding in Patients With Essential Hypertension

Shin Poong Pharmaceutical

Status and phase: Completed; Phase 2

Conditions: Essential Hypertension

Treatments: Drug: Candesartan Cilexetil 8mg; Drug: Amlodipine 5mg; Drug: Candesartan Cilexetil 16mg; Drug: Amlodipine 10mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT02944734

SP-AC-002

Details and patient eligibility

About

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.

Enrollment: 392 patients

Sex: All

Ages: 19+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Male or female patients greater than or equal to 19 years of age
2. Subject who was diagnosed with essential hypertension or after administer the antihypertensive drug (Subject who may temporarily suspend antihypertensive treatment based on doctor's decision)
3. Subject who have voluntarily agreed to participate in the trial and signed the written informed consent form

Exclusion criteria

1. Subject with severe hypertension (in a selected arm with msSBP ≥ 200 mmHg or msDBP ≥ 115 mmHg) during the Screening and Randomized Trial.

2. Subject with difference of the blood pressure of over 20 mmHg for SBP or 10 mmHg for diastolic blood pressure (DSP) between three consecutive measurements in a selected arm during the screening visit

3. Secondary hypertension (such as, coarctation of the aorta, primary hyperaldosteronism, renal artery stenosis, Cushing's disease, pheochromocytoma, polycystic kidney disease, etc.)

4. Symptomatic orthostatic hypotension

5. Severe heart failure( New York Heart Association(NYHA) Class III/IV)

6. Subject with acute coronary syndrome(myocardial infarction or unstable angina), peripheral vascular disease within the past 6 months

7. History of switching to another Antiarrhythmic drugs(not including electrolyte correction), or received Cardioversion or ICU treatment within the past 6 months

8. Type 1 diabetes mellitus or Uncontrolled Type 2 diabetes mellitus (HbA1c > 9.0%)

9. Subject with Haemodynamic disturbance, heart valve disease with structural defects

10. Severe cerebrovascular disease (stroke, cerebral infarction, or cerebral hemorrhage, etc. within the past 6 months)

11. Severe eye disease (retinal hemorrhage, visual impairment, retinal microaneurysm, etc. within the past 6 months)

12. Autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus, etc.)

13. Chronic inflammatory disease requiring continuous anti-inflammatory treatment

14. Clinically significant Renal or liver impairment, or laboratory abnormalities such as Ccr: below 30ml/min or Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) > 3 x Upper Limit Normal (ULN)

15. Hypokalaemia(Serum potassium < 3.5 mmol/L) or hyperkalaemia(Serum potassium > 5.5 mmol/L)

16. Subject with gastrointestinal disease(such as Crohn's disease, gastric ulcer, acute or chronic pancreatitis) or history of gastrointestinal surgery(not including appendectomy or hernia surgery) that might significantly alter the absorption of the drug

17. history of allergy or hypersensitivity to Angiotensin II Receptor Blockers(Candesartan) or Calcium Channel Blocker(amlodipine)

18. Subject with heredity defects such as galactose intolerance, Lapp lactose deficiency, or glucose-galactose malabsorption

19. Subject requiring concomitant use of other antihypertensive or contraindicated drugs( Tizanidine, dolasetron, Itraconazole, potassium, potassium-sparing diuretics, etc.) during the clinical trial

20. history of malignant tumors within the past 5 years

21. history of alcohol or drug abuse

22. Pregnant women and lactating mothers

23. Women who is planning to be pregnant during or 2 months after the study, or women or men who are not using medically acceptable methods of contraception *

    * progestin oral or implant contraceptive, intra-uterine device, condom, partner with surgical sterilization, etc.

24. Use of other investigational products within the past 1 month

25. Subject who are judged by the investigator unsuitable to participate in the study

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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392 participants in 8 patient groups

Candesartan Cilexetil (CC) 8mg

Experimental group

Description:

Candesartan Cilexetil 8mg, once a day for 8 weeks

Treatment:

Drug: Candesartan Cilexetil 8mg

CC 16mg

Experimental group

Description:

Candesartan Cilexetil 16mg, once a day for 8 weeks

Treatment:

Drug: Candesartan Cilexetil 16mg

Amlodipine(AML) 5mg

Experimental group

Description:

Amlodipine 5mg, once a day for 8 weeks

Treatment:

Drug: Amlodipine 5mg

AML 10mg

Experimental group

Description:

Amlodipine 10mg, once a day for 8 weeks

Treatment:

Drug: Amlodipine 10mg

CC 8mg / AML 5mg

Experimental group

Description:

Candesartan 8mg and Amlodipine 5mg, once a day for 8 weeks

Treatment:

Drug: Amlodipine 5mg

Drug: Candesartan Cilexetil 8mg

CC 8mg / AML 10mg

Experimental group

Description:

Candesartan 8mg and Amlodipine 10mg, once a day for 8 weeks

Treatment:

Drug: Amlodipine 10mg

Drug: Candesartan Cilexetil 8mg

CC 16mg / AML 5mg

Experimental group

Description:

Candesartan 16mg and Amlodipine 5mg, once a day for 8 weeks

Treatment:

Drug: Candesartan Cilexetil 16mg

Drug: Amlodipine 5mg

CC 16mg / AML 10mg

Experimental group

Description:

Candesartan 16mg and Amlodipine 10mg, once a day for 8 weeks

Treatment:

Drug: Amlodipine 10mg

Drug: Candesartan Cilexetil 16mg