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

• Status: Withdrawn
• Trial end date: 2018-07-26
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Takeda
• Treatments: Amlodipine; Candesartan; Candesartan cilexetil

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.