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

NCT02969265 | Withdrawn Phase 3

• 3 other identifiers: TCV-116CCB_302U1111-1184-7520CTR20160750
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 25

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.

Conditions

Hypertension

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Trough, Sitting, Clinic Systolic Blood Pressure (SBP) at Week 8

  The change between trough SBP measured at Week 8 relative to baseline. It is the arithmetic mean of the 3 trough sitting systolic blood pressure measurements.

  Baseline and Week 8

Secondary Outcomes (2)

• Change From Baseline in Trough, Sitting, Clinic Diastolic Blood Pressure (DBP) at Week 8

  Baseline and Week 8

• Percentage of Participants who Achieved Target Blood Pressure at Week 8

  Week 8

Study Arms (2)

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

EXPERIMENTAL

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.

Drug: Amlodipine; Drug: TCV-116CCB; Drug: Amlodipine Placebo; Drug: TCV-116CCB Placebo

Amlodipine 5 mg

EXPERIMENTAL

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.

Drug: Amlodipine; Drug: Amlodipine Placebo; Drug: TCV-116CCB Placebo

Interventions

Amlodipine DRUG

Amlodipine Capsules

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

TCV-116CCB DRUG

TCV-116CCB Tablets

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

Amlodipine Placebo DRUG

Amlodipine placebo-matching capsules

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

TCV-116CCB Placebo DRUG

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

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

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has grade 1 or 2 essential hypertension which is not adequately controlled, as defined by mean, trough, sitting, clinic systolic blood pressure (SBP):
• ≥155 to \<180 mm Hg in participants who have not received any antihypertensive medication in the 14 days prior to Visit 1.
• ≥145 to ≤170 mm Hg in participants taking 1 antihypertensive medication at Visit 1.
• ≥140 to \<160 mm Hg in participants taking 2 antihypertensive medications at Visit 1.
• Is willing to discontinue current antihypertensive medications.
• Entering amlodipine 5 mg monotherapy:
• 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:
• 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.

You may not qualify if:

• Has clinic SBP ≥180 mm Hg or DBP ≥110 mm Hg.
• The participant's 3 SBP measurements differ by more than 15 mm Hg (confirmed by a second set of three measurements).
• Has been randomized/enrolled in an amlodipine or candesartan or candesartan/amlodipine Fixed dose combination study.
• Has secondary hypertension of any etiology (e.g., renovascular disease documented as the cause of hypertension, pheochromocytoma, Cushing's syndrome).
• 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.
• Has clinically significant cardiac conduction defects (e.g., third-degree atrioventricular block, sick sinus syndrome).
• Has hemodynamically significant left ventricular outflow obstruction due to aortic valvular disease or hypertrophic cardiomyopathy.
• 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).
• Has poorly-controlled type 1 or 2 diabetes mellitus (hemoglobin A1c \[HbA1c\] \>8.0%) at Screening.
• Has severe renal dysfunction or disease (based on estimated Glomerular filtration rate \[GFR\] \<30 mL/min/1.73m\^2) at Screening.
• Has hypokalemia or hyperkalemia (defined as serum potassium outside of the normal reference range) at Screening.
• Has an alanine aminotransferase or aspartate aminotransferase level \>2.5 times the upper limit of normal, active liver disease, or jaundice at Screening.
• Works a night (third) shift (defined as 10 PM \[2200\] to 6 AM \[0600\]) (Only for participants with ambulatory blood pressure monitoring \[ABPM\]).
• Has an upper arm circumference \<24 cm or \>42 cm (Only for participants with ABPM).
• Entering amlodipine 5 mg monotherapy period:

Sponsors & Collaborators

• Takeda: lead

Study Sites (25)

Fuwai Hospital

Beijing, Beijing Municipality, 100037, China

Location

Beijing Friendship Hospital, Capital Medical University

Beijing, Beijing Municipality, 100050, China

Location

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100730, China

Location

The Second Hospital of Lanzhou University

Lanzhou, Gansu, 730030, China

Location

The Second Affiliated Hospital of Sun Yat-sen University

Guangzhou, Guangdong, 510120, China

Location

The Affiliated Hospital of Guizhou Medical University

Guiyang, Guizhou, 550004, China

Location

Fourth Hospital of Hebei Medical University

Shijiazhuang, Hebei, 050011, China

Location

Daqing first hospital

Daqing, Heilongjiang, 163001, China

Location

The First Affiliated Hospital of Harbin Medical University

Harbin, Heilongjiang, 150001, China

Location

People's Hospital of Wuhan University

Wuhan, Hubei, 430060, China

Location

The Xiangya Hospitalof Central South University

Changsha, Hunan, 410008, China

Location

The First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, 215006, China

Location

Jilin Siping Central Hospital

Siping, Jilin, China

Location

The Second Affiliated Hospital of Dalian Medical University

Dalian, Liaoning, 116027, China

Location

Shengjing Hospital of China Medical University

Shenyang, Liaoning, 110004, China

Location

People's Hospital of Liaoning Province

Shenyang, Liaoning, 110016, China

Location

General Hospital of Ningxia Medical University

Yinchuan, Ningxia, 750004, China

Location

Rui Jin Hospital Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200025, China

Location

the Central Hospital of Xuhui District, Shanghai

Shanghai, Shanghai Municipality, 200031, China

Location

Shanghai Putuo Center Hospital

Shanghai, Shanghai Municipality, 200062, China

Location

First Affiliated Hospital of Xian Jiaotong University

Xi’an, Shanxi, 710061, China

Location

West China Hospital, Sichuan Univeisity

Chengdu, Sichuan, 610041, China

Location

Sir Run Run Hospital of Zhejiang University

Hangzhou, Zhejiang, 310016, China

Location

Taizhou Hospital of Zhejiang Province

Linhai, Zhejiang, 317000, China

Location

Lishui Hospital of Zhejiang Province

Lishui, Zhejiang, 323000, China

Location

MeSH Terms

Conditions

Hypertension

Interventions

Amlodipine

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Medical Director Clinical Science

  Takeda

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2016
• First Posted: November 21, 2016
• Study Start: May 9, 2017
• Primary Completion: July 12, 2018
• Study Completion: July 26, 2018
• Last Updated: June 9, 2017

Record last verified: 2017-06

Locations

CN (25)