Clinical trial NCT02944734: Comparison of Efficacy and Safety of Combination Therapy and Monotherapy of Candesartan and Amlodipine for Dose-Finding in Patients With Essential Hypertension
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Essential Hypertension
Keywords: Candesartan
Amlodipine
Hypertension
Vascular Diseases
Cardiovascular Diseases
Antihypertensive Agents
Vasodilator Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Calcium Channel Blockers
Lead sponsor: Shin Poong Pharmaceutical Co. Ltd.
Sponsor class: INDUSTRY
First posted: 2016-10-26
Enrollment: 392
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Change mean sitting Diastolic Blood Pressure (msDBP) at week 8 compared to baseline
timeFrame: Week 8
Secondary outcomes:
measure: Change mean sitting Diastolic Blood Pressure (msDBP) at week 4 compared to baseline
timeFrame: Week 4
measure: Change mean sitting Systolic Blood Pressure (msSBP) at week 4 and 8 compared to baseline
timeFrame: Week 4 and 8
measure: Proportion of patients achieving treatment goal at week 4 and 8: < 140/90 mmHg
timeFrame: Week 4 and 8
measure: Blood Pressure Response rate at week 4 and 8: msSBP reduction ≥ 20 mmHg and msDBP reduction ≥ 10 mmHg
timeFrame: Week 4 and 8
Other outcomes:
Locations:
city: Wonmi-gu
country: Korea, Republic of
facility: Catholic University of Korea Bucheon St. Mary's Hospital
state: Bucheon
city: Busanjin-gu
country: Korea, Republic of
facility: Inje University Busan Paik Hospital
state: Busan
city: Seo-gu
country: Korea, Republic of
facility: Pusan National University Hospital
state: Busan
city: Joong-gu
country: Korea, Republic of
facility: Keimyung University Dongsan Medical Center
state: Daegu
city: Joong-gu
country: Korea, Republic of
facility: Kyungpook National University Hospital
state: Daegu
city: Nam- gu
country: Korea, Republic of
facility: Daegu Catholic University Medical Center
state: Daegu
city: Ilsandong-gu
country: Korea, Republic of
facility: Dongguk University Ilsan Hospital
state: Goyang-si, Gyeoggi-do
city: Dong-Gu
country: Korea, Republic of
facility: Chonnam National University Hospital
state: Gwangju
city: Uijeongbu-si
country: Korea, Republic of
facility: Catholic University of Korea Uijeongbu St. Mary's hospital
state: Gyeoggi-do
city: Namdong-gu
country: Korea, Republic of
facility: Gachon University Gil Hospital
state: Incheon
city: Suncheon-si
country: Korea, Republic of
facility: St. Carollo General Hospital
state: Jeollanam-do
city: Wonju
country: Korea, Republic of
facility: Wonju Severance Christian Hospital
state: Kangwon-Do
city: Dongdaemun-gu
country: Korea, Republic of
facility: Catholic University of Korea St. Paul's Hospital
state: Seoul
city: Dongdaemun-gu
country: Korea, Republic of
facility: KyungHee University Medical Center
state: Seoul
city: Gangdong-gu
country: Korea, Republic of
facility: Hallym University Kangdong Sacred Heart Hospital
state: Seoul
city: Gangdong-Gu
country: Korea, Republic of
facility: Kyung Hee University Hospital at Gangdong
state: Seoul
city: Gangdong-gu
country: Korea, Republic of
facility: VHS( Veterans Medical Service) Medical Center
state: Seoul
city: Gwangjin-gu
country: Korea, Republic of
facility: Konkuk University Medical Center
state: Seoul
city: Jongro-gu
country: Korea, Republic of
facility: Seoul National University Hospital
state: Seoul
city: Seocho-Gu
country: Korea, Republic of
facility: Catholic University of Korea Seoul St. Mary's Hospital
state: Seoul
city: Seongbuk-Gu
country: Korea, Republic of
facility: Korea University Anam Hospital
state: Seoul
city: Yeongdeungpo-gu
country: Korea, Republic of
facility: Catholic University of Korea Yeouido St. Mary's Hospital
state: Seoul
city: Dong-gu
country: Korea, Republic of
facility: Ulsan University Hospital
state: Ulsan
Study officials:
affiliation: KyungHee University Hospital at Gangdong
name: Chong-Jin Kim
role: STUDY_DIRECTOR
References:
citation: Sohn IS, Kim CJ, Ahn T, Youn HJ, Jeon HK, Ihm SH, Cho EJ, Chung WB, Chae SC, Kim WS, Nam CW, Park SM, Choi JY, Kim YK, Hong TJ, Lee HY, Cho JH, Shin ES, Yoon JH, Yang TH, Jeong MH, Lee JH, Park JI. Efficacy and Tolerability of Combination Therapy Versus Monotherapy with Candesartan and/or Amlodipine for Dose Finding in Essential Hypertension: A Phase II Multicenter, Randomized, Double-blind Clinical Trial. Clin Ther. 2017 Aug;39(8):1628-1638. doi: 10.1016/j.clinthera.2017.06.014. Epub 2017 Jul 19.