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

NCT02277691 | Completed Phase 3 Results

• 3 other identifiers: TAK-536TCH/OCT-001U1111-1163-0169JapicCTI-142689
• Study Type: interventional
• Target: 341
• Locations: 1 country
• Sites: 38

Brief Summary

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

Conditions

Essential Hypertension

Keywords

Pharmacological therapy; Drug Therapy

Outcome Measures

Primary Outcomes (5)

• Number of Participants Who Experience at Least One Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

  An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. A Serious Adverse Event (SAE) A serious is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.

  Baseline up to Week 52

• Number of Participants With Markedly Abnormal Vital Signs Values

  Vital signs included supine and standing systolic and diastolic blood pressure (SBP and DBP) respectively and office sitting pulse. Vital signs were considered abnormal if they were beyond the values defined in categories.

  Baseline up to Week 52

• Number of Participants With Treatment Emergent Adverse Event (TEAE) Related to Body Weight

  Reported TEAE is categorized into investigations System Organ Class (SOC) related to body weight.

  Baseline up to Week 52

• Number of Participants With Treatment Emergent Adverse Event (TEAE) Related to Electrocardiogram (ECG)

  Reported TEAE is categorized into cardiac disorders and investigations system organ class (SOC) related to ECG.

  Baseline up to Week 52

• Number of Participants With Markedly Abnormal Clinical Laboratory Tests

  The number of participants with any markedly abnormal clinical laboratory test values collected throughout study. RBC = Red blood cells, ALT = alanine aminotransferase, AST = aspartate aminotransferase, GGT = gamma-glutamyl transferase, LLN = lower limit of normal or lower reference limit, ULN = upper limit of normal or upper reference limit. Laboratory vallues were considered abnormal if they were beyond the values defined in categories.

  Baseline up to Week 52

Secondary Outcomes (2)

• Change From Baseline in Office Trough Sitting Clinic Systolic and Diastolic Blood Pressure at Each Visit

  Baseline (End of Run-in Period, Week 0) and Weeks 12 (LOCF) and 52 (LOCF)

• Change From Baseline in Home Sitting Clinic Systolic and Diastolic Blood Pressure at Each Visit

  Baseline (End of Run-in Period, Week 0), End of Week 12 and End of Treatment (Up to Week 52)

Study Arms (1)

TAK-536TCH

EXPERIMENTAL

For 4 weeks during the run-in period, one tablet of TAK-536CCB (as TAK-536/AML, 20 mg/5 mg, respectively) orally, once daily, before or after breakfast. For 48 weeks during 52 weeks of the treatment period, one tablet of TAK-536TCH (as TAK-536/AML/HCTZ, 20 mg/5 mg/12.5 mg, respectively) orally, once daily, before or after breakfast. For the remaining 4 weeks of the treatment period, one tablet each of TAK-536CCB and HCTZ 12.5 mg orally, once daily, before or after breakfast.

Drug: TAK-536TCH tablet; Drug: TAK-536CCB tablet; Drug: HCTZ 12.5 mg tablet

Interventions

TAK-536TCH tablet DRUG

TAK-536TCH tablets

TAK-536TCH

TAK-536CCB tablet DRUG

TAK-536CCB tablets

TAK-536TCH

HCTZ 12.5 mg tablet DRUG

HCTZ tablets

TAK-536TCH

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• In the opinion of the investigator or subinvestigator, the participant is capable of understanding and complying with protocol requirements.
• The participant signs and dates a written informed consent form prior to the initiation of any study procedures.
• The participant has essential hypertension.
• The participant has an office sitting systolic blood pressure (SBP) of \<180 mmHg and office sitting diastolic blood pressure (DBP) of \< 110 mmHg at the start of the run-in period (Week -4). Participants receiving combined therapy with a 3-drug antihypertensive within 4 weeks prior to the start of the run-in period is required to have an office sitting SBP of \< 160 mmHg and an office sitting DBP of \< 100 mmHg.
• The participant's office sitting blood pressure at Week -2 and at the end of the run-in period (Week 0) need to be either:
• Participants without concurrent diabetes mellitus or chronic kidney disease (CKD)\*: Sitting SBP of ≥ 140 mmHg or sitting DBP of ≥ 90 mmHg
• Participants with concurrent diabetes mellitus or CKD\*: Sitting SBP of ≥ 130 mmHg or sitting DBP of ≥ 80 mmHg.
• Estimate glomerular filtration rate according to creatinine (eGFRcreat) of \<60 mL/min/1.73 m\^2, or urinary albumin (spot urine) of ≥30 μg/mL in laboratory tests performed at Week -2 of the run-in period, and diagnosed with CKD by the investigator or subinvestigator.
• The participant has an office sitting SBP of \< 160 mmHg and office sitting DBP of \< 100 mmHg at the end of the run-in period (Week 0).
• The participant is male or female, aged 20 years or older at the time of providing informed consent.
• The participant is an outpatient.
• A female participant of childbearing potential who is sexually active with a nonsterilized male partner agree to use routinely adequate contraception from signing of informed consent through 1 month following the end of the study.

You may not qualify if:

• The participant has received any study drugs within 12 weeks prior to the start of the run-in period.
• The participant has participated in another clinical study or a post-marketing study within 30 days prior to the start of the run-in period.
• The participant is an immediate family member, study site employee, or is in a dependent 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.
• The participant requires taking prohibited concomitant drugs during the study.
• 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.
• The participant is judged by the investigator or subinvestigator to be in danger of experiencing an excessive increase in blood pressure when changing or discontinuing premedication.
• The participant received combination therapy with antihypertensive drugs of the 3 ingredients contained in TAK-536TCH.
• The participant received combined therapy with antihypertensive drugs, including 4 or more components, within 4 weeks prior to the start of the run-in period.
• The participant has secondary or malignant hypertension.
• The participant has a difference of ≥ 20 mmHg between left and right arms in office sitting SBP at the start of the run-in period (Week -4).
• The participant has apparent white coat hypertension or exhibits a white coat effect.
• The participant has a day-night reversed lifestyle, such as those working during the night.
• The participant has sleep apnea syndrome requiring treatment.
• 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 conditions requiring treatment: angina pectoris, congestive heart failure, arrhythmia

Sponsors & Collaborators

• Takeda: lead

Study Sites (38)

Unknown Facility

Nagoya, Aichi-ken, Japan

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Unknown Facility

Chiba, Chiba, Japan

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Itojima-shi, Fukuoka, Japan

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Kouriyama-shi, Fukushima, Japan

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Sapporo, Hokkaido, Japan

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Amagasaki-shi, Hyōgo, Japan

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Tsukuba, Ibaragi, Japan

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Morioka, Iwate, Japan

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Sakaide-shi, Kagawa-ken, Japan

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Takamatsu, Kagawa-ken, Japan

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Kawasaki-shi, Kanagawa, Japan

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Kyoto, Kyoto, Japan

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Uji-shi, Kyoto, Japan

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Sendai, Miyagi, Japan

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Hirakata-shi, Osaka, Japan

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Osaka, Osaka, Japan

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Takatsuki-shi, Osaka, Japan

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Saitama-shi, Saitama, Japan

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Tokorozawa-shi, Saitama, Japan

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Yaizu-shi, Shizuoka, Japan

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Chiyoda-ku, Tokyo, Japan

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Choufu-shi, Tokyo, Japan

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Kodaira-shi, Tokyo, Japan

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Koutou-ku, Tokyo, Japan

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Setagaya-ku, Tokyo, Japan

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Shinagawa-ku, Tokyo, Japan

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Shinjuku-ku, Tokyo, Japan

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Choufu-shi, Japan

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Kawasaki-shi, Japan

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Koutou-ku, Japan

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Morioka, Japan

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Sakaide-shi, Japan

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Setagaya-ku, Japan

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Shinagawa-ku, Japan

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Shinjuku-ku, Japan

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Tsukuba, Japan

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Uji-shi, Japan

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Unknown Facility

Yaizu-shi, Japan

Location

Related Publications (1)

• Rakugi H, Shimizu K, Nishiyama Y, Sano Y, Umeda Y. A phase III, open-label, multicenter study to evaluate the safety and efficacy of long-term triple combination therapy with azilsartan, amlodipine, and hydrochlorothiazide in patients with essential hypertension. Blood Press. 2018 Jun;27(3):125-133. doi: 10.1080/08037051.2017.1412797. Epub 2017 Dec 13.

  PMID: 29235365 DERIVED

MeSH Terms

Conditions

Essential Hypertension

Interventions

Hydrochlorothiazide; Tablets

Condition Hierarchy (Ancestors)

Hypertension; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Chlorothiazide; Benzothiadiazines; Sulfonamides; Sulfones; Sulfur Compounds; Organic Chemicals; Thiazides; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Dosage Forms; Pharmaceutical Preparations

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director Clinical Science

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2014
• First Posted: October 29, 2014
• Study Start: November 7, 2014
• Primary Completion: April 25, 2016
• Study Completion: April 25, 2016
• Last Updated: August 2, 2017
• Results First Posted: June 26, 2017

Record last verified: 2017-06

Locations

JP (38)