An Efficacy and Safety Study Evaluating the Fixed-Dose Combination of Candesartan Plus Amlodipine in Participants With Mild/Moderate Essential Hypertension

NCT ID: NCT02969265

Last Updated: 2017-06-09

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-05-09
• Study Completion Date: 2018-07-26

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.

Conditions

Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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

Run-in Period: TCV-116CCB placebo-matching tablets, orally, once daily along with amlodipine placebo-matching capsules, orally, once daily up to 2 weeks.

Single-blind monotherapy treatment period: TCV-116CCB placebo-matching tablets, orally, once daily along with amlodipine 5 mg capsules, orally, once daily up to 4 weeks.

Double-blind treatment period: TCV-116CCB 8/5 mg tablets, orally, once daily along with amlodipine placebo-matching capsules, orally, once daily up to 8 weeks.

Group Type: EXPERIMENTAL

Amlodipine

Intervention Type: DRUG

Amlodipine Capsules

TCV-116CCB

Intervention Type: DRUG

TCV-116CCB Tablets

Amlodipine Placebo

Intervention Type: DRUG

Amlodipine placebo-matching capsules

TCV-116CCB Placebo

Intervention Type: DRUG

TCV-116CCB 8/5 mg placebo-matching tablets

Amlodipine 5 mg

Run-in Period: TCV-116CCB placebo-matching tablets, orally, once daily along with amlodipine placebo-matching capsules, orally, once daily up to 2 weeks.

Monotherapy treatment period: TCV-116CCB placebo-matching tablets, orally, once daily along with amlodipine 5 mg capsules, orally, once daily up to 4 weeks.

Double-blind treatment period: Amlodipine 5 mg capsules, orally, once daily along with TCV-116CCB placebo-matching tablets, orally, once daily up to 8 weeks.

Group Type: EXPERIMENTAL

Amlodipine

Intervention Type: DRUG

Amlodipine Capsules

Amlodipine Placebo

Intervention Type: DRUG

Amlodipine placebo-matching capsules

TCV-116CCB Placebo

Intervention Type: DRUG

TCV-116CCB 8/5 mg placebo-matching tablets

Interventions

Amlodipine

Amlodipine Capsules

Intervention Type: DRUG

TCV-116CCB

TCV-116CCB Tablets

Intervention Type: DRUG

Amlodipine Placebo

Amlodipine placebo-matching capsules

Intervention Type: DRUG

TCV-116CCB Placebo

TCV-116CCB 8/5 mg placebo-matching tablets

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Takeda

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director Clinical Science

Role: STUDY_DIRECTOR

Takeda

Locations

Fuwai Hospital

Beijing, Beijing Municipality, China

Beijing Friendship Hospital, Capital Medical University

Beijing, Beijing Municipality, China

Peking Union Medical College Hospital

Beijing, Beijing Municipality, China

The Second Hospital of Lanzhou University

Lanzhou, Gansu, China

The Second Affiliated Hospital of Sun Yat-sen University

Guangzhou, Guangdong, China

The Affiliated Hospital of Guizhou Medical University

Guiyang, Guizhou, China

Fourth Hospital of Hebei Medical University

Shijiazhuang, Hebei, China

Daqing first hospital

Daqing, Heilongjiang, China

The First Affiliated Hospital of Harbin Medical University

Harbin, Heilongjiang, China

People's Hospital of Wuhan University

Wuhan, Hubei, China

The Xiangya Hospitalof Central South University

Changsha, Hunan, China

The First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, China

Jilin Siping Central Hospital

Siping, Jilin, China

The Second Affiliated Hospital of Dalian Medical University

Dalian, Liaoning, China

Shengjing Hospital of China Medical University

Shenyang, Liaoning, China

People's Hospital of Liaoning Province

Shenyang, Liaoning, China

General Hospital of Ningxia Medical University

Yinchuan, Ningxia, China

Rui Jin Hospital Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, China

the Central Hospital of Xuhui District, Shanghai

Shanghai, Shanghai Municipality, China

Shanghai Putuo Center Hospital

Shanghai, Shanghai Municipality, China

First Affiliated Hospital of Xian Jiaotong University

Xi’an, Shanxi, China

West China Hospital, Sichuan Univeisity

Chengdu, Sichuan, China

Sir Run Run Hospital of Zhejiang University

Hangzhou, Zhejiang, China

Taizhou Hospital of Zhejiang Province

Linhai, Zhejiang, China

Lishui Hospital of Zhejiang Province

Lishui, Zhejiang, China

Countries

China

Other Identifiers

U1111-1184-7520

Identifier Type: REGISTRY

Identifier Source: secondary_id

CTR20160750

Identifier Type: REGISTRY

Identifier Source: secondary_id

TCV-116CCB_302

Identifier Type: -

Identifier Source: org_study_id