Clinical trial NCT02969265: An Efficacy and Safety Study Evaluating the Fixed-Dose Combination of Candesartan Plus Amlodipine in Participants With Mild/Moderate Essential Hypertension
Official title: A Phase-3 Randomized, Double-Blind, Parallel-Group Efficacy and Safety Study Evaluating the Fixed-Dose Combination of Candesartan Plus Amlodipine (8/5 mg) in Chinese Subjects With Mild/Moderate Essential Hypertension, Who Do Not Achieve Target Blood Pressure Following Treatment With Amlodipine 5 mg Monotherapy
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Hypertension
Keywords: Drug therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2016-11-21
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
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 evaluate the efficacy and safety of TCV-116CCB (candesartan cilexetil and amlodipine besylate fixed-dose combination) in Chinese participants with mild to moderate hypertension who do not reach target blood pressure following 4 weeks of treatment with amlodipine monotherapy.

Detailed description: The drug being tested in this study is called TCV-116CCB (candesartan cilexetil and amlodipine besylate fixed-dose combination). This study will look at blood pressure in Chinese participants with grade 1 or 2 essential hypertension.

The study will enroll approximately 370 patients. Prior to the start of study treatment, participants will undergo run-in period of 2 weeks followed by single-blind treatment period of 4 weeks. Upon completion of single-blind treatment period, participants will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups-which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need):

* Amlodipine 5 mg
* TCV-116CCB (Candesartan 8 mg Plus Amlodipine 5 mg)

All participants will be asked to take one tablet/capsule at the same time each day throughout the study up to 8 weeks.

This multicenter trial will be conducted China. The overall time to participate in this study is 19 weeks. Participants will make multiple visits to the clinic, and will be contacted by telephone plus a final visit 14 days after receiving their last dose of drug for a follow-up assessment.

Eligibility criteria: Inclusion Criteria:

1. Has grade 1 or 2 essential hypertension which is not adequately controlled, as defined by mean, trough, sitting, clinic systolic blood pressure (SBP):

   1. ≥155 to \<180 mm Hg in participants who have not received any antihypertensive medication in the 14 days prior to Visit 1.
   2. ≥145 to ≤170 mm Hg in participants taking 1 antihypertensive medication at Visit 1.
   3. ≥140 to \<160 mm Hg in participants taking 2 antihypertensive medications at Visit 1.
2. Is willing to discontinue current antihypertensive medications.

   Entering amlodipine 5 mg monotherapy:
3. Must have a clinic SBP measurement of 155 to 179 mm Hg inclusive (determined by the mean of 3 sitting, trough, measurements on Day -28, using same arm throughout study) to qualify for entry in to the 4 week single-blind amlodipine 5 mg monotherapy treatment period.

   At double-blind randomization:
4. Has not achieved target blood pressure (defined as clinic SBP ≥140 mm Hg as determined by the mean of 3 sitting, trough, measurements) following 4 weeks single-blind treatment with amlodipine 5 mg monotherapy at Day 1 prior to randomization to double-blind treatment.

Exclusion Criteria:

1. Has clinic SBP ≥180 mm Hg or DBP ≥110 mm Hg.
2. The participant's 3 SBP measurements differ by more than 15 mm Hg (confirmed by a second set of three measurements).
3. Has been randomized/enrolled in an amlodipine or candesartan or candesartan/amlodipine Fixed dose combination study.
4. Has secondary hypertension of any etiology (e.g., renovascular disease documented as the cause of hypertension, pheochromocytoma, Cushing's syndrome).
5. Has any history of myocardial infarction, heart failure, unstable angina, coronary artery bypass graft, percutaneous coronary intervention, hypertensive encephalopathy, cerebrovascular accident, persistent or permanent atrial fibrillation or transient ischemic attack.
6. Has clinically significant cardiac conduction defects (e.g., third-degree atrioventricular block, sick sinus syndrome).
7. Has hemodynamically significant left ventricular outflow obstruction due to aortic valvular disease or hypertrophic cardiomyopathy.
8. Has a history of cancer that has not been in remission for at least 5 years prior to the first dose of single-blind amlodipine monotherapy study drug. (This criterion does not apply to those participants with basal cell or Stage 1 squamous cell carcinoma of the skin).
9. Has poorly-controlled type 1 or 2 diabetes mellitus (hemoglobin A1c \[HbA1c\] \>8.0%) at Screening.
10. Has severe renal dysfunction or disease (based on estimated Glomerular filtration rate \[GFR\] \<30 mL/min/1.73m\^2) at Screening.
11. Has hypokalemia or hyperkalemia (defined as serum potassium outside of the normal reference range) at Screening.
12. Has an alanine aminotransferase or aspartate aminotransferase level \>2.5 times the upper limit of normal, active liver disease, or jaundice at Screening.
13. Works a night (third) shift (defined as 10 PM \[2200\] to 6 AM \[0600\]) (Only for participants with ambulatory blood pressure monitoring \[ABPM\]).
14. Has an upper arm circumference \<24 cm or \>42 cm (Only for participants with ABPM).

    Entering amlodipine 5 mg monotherapy period:
15. Has a clinic SBP ≥180 mm Hg or DBP ≥110 mm Hg.
16. Is non-compliant (\<80% or \>120%) with study medication during the placebo run-in period.

    Post-single-blind amlodipine 5 mg treatment period:
17. Achieves target blood pressure (defined as clinic SBP\<140 mm Hg as determined by the mean of 3 sitting, trough measurements) following 4 weeks single-blind treatment with amlodipine 5 mg monotherapy at Day 1, prior to randomization to double-blind treatment.
18. Has a clinic SBP ≥180 mm Hg or/and DBP ≥110 mm Hg.
19. Is non-compliant (\<80% or \>120%) with study medication during the amlodipine 5 mg single-blind treatment period.

Primary outcomes:
measure: Change From Baseline in Trough, Sitting, Clinic Systolic Blood Pressure (SBP) at Week 8
timeFrame: Baseline and Week 8
Secondary outcomes:
measure: Change From Baseline in Trough, Sitting, Clinic Diastolic Blood Pressure (DBP) at Week 8
timeFrame: Baseline and Week 8
measure: Percentage of Participants who Achieved Target Blood Pressure at Week 8
timeFrame: Week 8
Other outcomes:
Locations:
city: Beijing
country: China
facility: Fuwai Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Friendship Hospital, Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
city: Lanzhou
country: China
facility: The Second Hospital of Lanzhou University
state: Gansu
city: Guangzhou
country: China
facility: The Second Affiliated Hospital of Sun Yat-sen University
state: Guangdong
city: Guiyang
country: China
facility: The Affiliated Hospital of Guizhou Medical University
state: Guizhou
city: Shijiazhuang
country: China
facility: Fourth Hospital of Hebei Medical University
state: Hebei
city: Daqing
country: China
facility: Daqing first hospital
state: Heilongjiang
city: Harbin
country: China
facility: The First Affiliated Hospital of Harbin Medical University
state: Heilongjiang
city: Wuhan
country: China
facility: People's Hospital of Wuhan University
state: Hubei
city: Changsha
country: China
facility: The Xiangya Hospitalof Central South University
state: Hunan
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
state: Jiangsu
city: Siping
country: China
facility: Jilin Siping Central Hospital
state: Jilin
city: Dalian
country: China
facility: The Second Affiliated Hospital of Dalian Medical University
state: Liaoning
city: Shenyang
country: China
facility: Shengjing Hospital of China Medical University
state: Liaoning
city: Shenyang
country: China
facility: People's Hospital of Liaoning Province
state: Liaoning
city: Yinchuan
country: China
facility: General Hospital of Ningxia Medical University
state: Ningxia
city: Shanghai
country: China
facility: Rui Jin Hospital Shanghai Jiao Tong University School of Medicine
state: Shanghai
city: Shanghai
country: China
facility: the Central Hospital of Xuhui District, Shanghai
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Putuo Center Hospital
state: Shanghai
city: Xi'an
country: China
facility: First Affiliated Hospital of Xian Jiaotong University
state: Shanxi
city: Chengdu
country: China
facility: West China Hospital, Sichuan Univeisity
state: Sichuan
city: Hangzhou
country: China
facility: Sir Run Run Hospital of Zhejiang University
state: Zhejiang
city: Linhai
country: China
facility: Taizhou Hospital of Zhejiang Province
state: Zhejiang
city: Lishui
country: China
facility: Lishui Hospital of Zhejiang Province
state: Zhejiang
Study officials:
affiliation: Takeda
name: Medical Director Clinical Science
role: STUDY_DIRECTOR
References: