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

Essential Hypertension Clinical Trial

Official title:

A Multi-center, Randomized, Double-blind, Phase II Clinical Trial to Evaluate the Efficacy and Safety of Combination Therapy vs. Monotherapy of Candesartan and Amlodipine for Dose-Finding in Patients With Essential Hypertension

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02944734
• Other study ID #: SP-AC-002
• Status: Completed
• Phase: Phase 2
• First received: October 24, 2016
• Last updated: November 21, 2016
• Start date: September 2014
• Est. completion date: December 2015

Study information

• Verified date: November 2016
• Source: Shin Poong Pharmaceutical Co. Ltd.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Korea: Korea Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 392
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 19 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Essential Hypertension
• Hypertension

Intervention

Drug:
• Candesartan Cilexetil 8mg
Candesartan Cilexetil 8mg Daily oral administration for 8 weeks
• Candesartan Cilexetil 16mg
Candesartan Cilexetil 16mg Daily oral administration for 8 weeks
• Amlodipine 5mg
Amlodipine 5mg Daily oral administration for 8 weeks
• Amlodipine 10mg
Amlodipine 10mg Daily oral administration for 8 weeks

Locations

Country	Name	City	State
Korea, Republic of	Inje University Busan Paik Hospital	Busanjin-gu	Busan
Korea, Republic of	Chonnam National University Hospital	Dong-Gu	Gwangju
Korea, Republic of	Ulsan University Hospital	Dong-gu	Ulsan
Korea, Republic of	Catholic University of Korea St. Paul's Hospital	Dongdaemun-gu	Seoul
Korea, Republic of	KyungHee University Medical Center	Dongdaemun-gu	Seoul
Korea, Republic of	Hallym University Kangdong Sacred Heart Hospital	Gangdong-gu	Seoul
Korea, Republic of	Kyung Hee University Hospital at Gangdong	Gangdong-Gu	Seoul
Korea, Republic of	VHS( Veterans Medical Service) Medical Center	Gangdong-gu	Seoul
Korea, Republic of	Konkuk University Medical Center	Gwangjin-gu	Seoul
Korea, Republic of	Dongguk University Ilsan Hospital	Ilsandong-gu	Goyang-si, Gyeoggi-do
Korea, Republic of	Seoul National University Hospital	Jongro-gu	Seoul
Korea, Republic of	Keimyung University Dongsan Medical Center	Joong-gu	Daegu
Korea, Republic of	Kyungpook National University Hospital	Joong-gu	Daegu
Korea, Republic of	Daegu Catholic University Medical Center	Nam- gu	Daegu
Korea, Republic of	Gachon University Gil Hospital	Namdong-gu	Incheon
Korea, Republic of	Pusan National University Hospital	Seo-gu	Busan
Korea, Republic of	Catholic University of Korea Seoul St. Mary's Hospital	Seocho-Gu	Seoul
Korea, Republic of	Korea University Anam Hospital	Seongbuk-Gu	Seoul
Korea, Republic of	St. Carollo General Hospital	Suncheon-si	Jeollanam-do
Korea, Republic of	Catholic University of Korea Uijeongbu St. Mary's hospital	Uijeongbu-si	Gyeoggi-do
Korea, Republic of	Wonju Severance Christian Hospital	Wonju	Kangwon-Do
Korea, Republic of	Catholic University of Korea Bucheon St. Mary's Hospital	Wonmi-gu	Bucheon
Korea, Republic of	Catholic University of Korea Yeouido St. Mary's Hospital	Yeongdeungpo-gu	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Shin Poong Pharmaceutical Co. Ltd.

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change mean sitting Diastolic Blood Pressure (msDBP) at week 8 compared to baseline		Week 8	No
Secondary	Change mean sitting Diastolic Blood Pressure (msDBP) at week 4 compared to baseline		Week 4	No
Secondary	Change mean sitting Systolic Blood Pressure (msSBP) at week 4 and 8 compared to baseline		Week 4 and 8	No
Secondary	Proportion of patients achieving treatment goal at week 4 and 8: < 140/90 mmHg	Joint National Committee VII Guideline Treatment goal: < 140/90 mmHg (< 130/80 mmHg, diabetic or chronic renal failure patient)	Week 4 and 8	No
Secondary	Blood Pressure Response rate at week 4 and 8: msSBP reduction = 20 mmHg and msDBP reduction = 10 mmHg		Week 4 and 8	No