A Phase III Long-term Study of TAK-536TCH in Patients With Essential Hypertension

Essential Hypertension Clinical Trial

Official title:

A Phase III, Open-label, Multicenter Study to Evaluate the Safety and Efficacy of Long-term Administration of TAK-536, Amlodipine (AML), and Hydrochlorothiazide (HCTZ) in Patients With Essential Hypertension

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02277691
• Other study ID #: TAK-536TCH/OCT-001
• Secondary ID: U1111-1163-0169
• Status: Completed
• Phase: Phase 3
• First received: October 27, 2014
• Last updated: July 13, 2016
• Start date: November 2014
• Est. completion date: April 2016

Study information

• Verified date: July 2016
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Ministry of Health, Labor and Welfare
• Study type: Interventional

Clinical Trial Summary

Primary objective of this study is to evaluate the safety of long-term administration of TAK-536, amlodipine (AML), and hydrochlorothiazide (HCTZ) in patients with essential hypertension.

Description:

This is a Phase III, open-label, multicenter study to evaluate the safety and efficacy of long-term administration of TAK-536 20 mg, amlodipine (AML) 5 mg, and hydrochlorothiazide (HCTZ) 12.5 mg once daily for 52 weeks in patients with essential hypertension that is poorly controlled with TAK-536CCB.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 341
• Est. completion date: April 2016
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years and older

Eligibility

Inclusion Criteria:

• 1. In the opinion of the investigator or subinvestigator, the participant is capable of understanding and complying with protocol requirements.

2. The participant signs and dates an informed consent form prior to the initiation of any study procedures.

3. The participant has essential hypertension. 4. The participant's clinic sitting systolic blood pressure (SBP) is < 180 mmHg and clinic sitting diastolic blood pressure (DBP) is < 110 mmHg at the start of the run-in period (Week -4). Patients receiving treatment with a three-drug antihypertensive within 4 weeks prior to the start of the run-in period must have a clinic sitting SBP of < 160 mmHg and clinic sitting DBP of < 100 mmHg.

5. The participant's clinic sitting blood pressure at Week -2 and the end of the run-in period (Week 0) is: <Patients without concurrent diabetes mellitus or chronic kidney disease (CKD)> Sitting SBP is = 140 mmHg or sitting DBP is = 90 mmHg <Patients with concurrent diabetes mellitus or CKD> Sitting SBP is = 130 mmHg or sitting DBP is = 80 mmHg 6. The participant's clinic sitting SBP is < 160 mmHg and clinic sitting DBP is < 100 mmHg at the end of the run-in period (Week 0).

7. Sex: male and/or female; Aged 20 years or older at the time when informed consent is obtained.

8. Hospitalization status: Outpatient 9. A female participant of childbearing potential who are sexually active with a nonsterilized male partner agree to use routinely adequate contraception from signing of informed consent to 1 month after the end of the study.

Exclusion Criteria:

• 1. The participant has received any investigational compounds within 12 weeks prior to the start of the run-in period.

2. The participant has participated in other clinical trials or post-marketing studies within 30 days prior to the start of the run-in period.

3. The participant is an immediate family member, study site employee, or is in a dependant relationship with a study site employee who is involved in conduct of this study (e.g. spouse, parent, child, sibling), or may consent under duress.

4. The participant requires treatment with a prohibited concomitant drug during the study.

5. The participant has a history of hypersensitivity or allergies to TAK-536, AML, HCTZ, any thiazide diuretic or analog, any dihydropyridine drug, or any analog of TAK-536TCH.

6. The participant may, in the opinion of the investigator or subinvestigator, experience an excessive increase in blood pressure when changing or discontinuing premedication.

7. The participant previously received treatment with a three-ingredient antihypertensive drug with the same three ingredients found in TAK-536TCH.

8. The participant received therapy with 4 or more different antihypertensive agents within 4 weeks prior to the start of the run-in period.

9. The participant has secondary or malignant hypertension. 10. The participant's clinic sitting SBP at Week -4 differs between left and right arms by = 20 mmHg.

11. The participant has apparent white coat hypertension or shows a white coat effect.

12. The participant leads a nocturnal lifestyle due to working a night shift or for another reason.

13. The participant has sleep apnea syndrome requiring treatment. 14. The participant has any of the following cardiovascular diseases:

• Cardiac disease: Myocardial infarction, coronary arterial revascularization, severe valvular disorder, atrial fibrillation, any of the following disorders when drug treatment is required: angina pectoris, congestive heart failure, arrhythmia

• Cerebrovascular disorders: Cerebral infarction/cerebral hemorrhage, transient ischemic attack

• Vascular disease: Peripheral artery disease with intermittent claudication, artery dissection, aneurysm

• Advanced hypertensive retinopathy: With bleeding or exudate/papilledema 15. The participant has a clinically apparent hepatic disorder (e.g., alanine aminotransferase (AST) or aspartate aminotransferase (ALT) at Week -2 of the run-in period = 2.5 times the upper limit of normal).

16. The participant has a clinically apparent hepatic disorder (e.g., alanine aminotransferase (AST) or aspartate aminotransferase (ALT) at Week -2 of the run-in period = 2.5 times the upper limit of normal).

17. The participant has a clinically severe renal disorder (e.g., eGFRcreat in laboratory tests performed at Week -2 of run-in period < 30 mL/minute/1.73 m2).

18. The participant's body fluid sodium or potassium level is markedly low or high.

19. The participant has gout or had gout within 24 weeks prior to the start of the run-in period or has hyperuricemia requiring drug treatment.

20. The participant has poorly controlled diabetes (e.g., HbA1c = 7.4% in laboratory tests performed at Week -2 of run-in period).

21. The participant has a malignancy. 22. If female, the participant is pregnant or lactating or intending to become pregnant before, during, or within 1 month after participating in this study; or intending to donate ova during such time period..

23. The participant has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 2 years prior to the start of the run-in period.

24. The participant is otherwise found ineligible by the investigator or subinvestigator.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Essential Hypertension
• Hypertension

Intervention

Drug:
• TAK-536TCH tablet, TAK-536CCB tablet, and HCTZ 12.5 mg tablet

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency of Adverse events	The frequencies of all adverse events will be tabulated. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a drug whether or not it is considered related to the drug.	52 weeks	Yes
Secondary	Clinic sitting SBP and DBP at trough	The change in clinic trough sitting systolic and diastolic blood pressure from baseline to each evaluation point of treatment period.	52 weeks	No
Secondary	Home sitting SBP and DBP on awakening and at bedtime	The change in home sitting systolic and diastolic blood pressure on awakening and at bedtime from baseline to each evaluation point of treatment period.	52 weeks	No