AzTrials
AzTrials

Essential HypertensionPhase 3NCT02277691

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

A Phase 3 study testing TAK-536TCH tablet, TAK-536CCB tablet and HCTZ 12.5 mg tablet in people with Essential Hypertension, run by Takeda at 38 sites in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 20 years and older
Conditions the study is for
Essential Hypertension
What is being tested?
TAK-536TCH tablet, TAK-536CCB tablet and HCTZ 12.5 mg tablet
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
341 participants
Where
38 sitesJapan
Study dates
7 Nov 2014to 25 Apr 2016
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 20 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 12Show fewer
  • 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.

Who cannot join

  • 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.
Show all 28Show fewer
  • 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
  • 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 * Occurring or performed within 24 weeks of the start of the run-in period Observed within 24 weeks of the start of the run-in period
  • The participant has a clinically apparent hepatic disorder (e.g., aspartate aminotransferase (AST) or alanine aminotransferase (ALT) at Week -2 of the run-in period ≥ 2.5 times the upper limit of normal (ULN).
  • 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 m^2).
  • The participant's body fluid sodium or potassium level is markedly low* or high*.
  • Based on normal ranges
  • The participant has gout or a history of gout within 24 weeks of the start of the run-in period or has hyperuricemia requiring drug treatment.
  • The participant has uncontrolled diabetes (e.g., HbA1c ≥ 7.4% in laboratory tests performed at Week -2 of the run-in period).
  • The participant has a malignant tumor.
  • If female, the participant is pregnant or lactating or before giving informed consent, intending to become pregnant or donate ova during or within 1 month after participating in the study.
  • 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 run-in period.
  • The participant who, in the opinion of the investigator or subinvestigator, is unsuitable for any other reason.

Trial locations and contacts

38 sites in 1 country.

38 sites in 1 country

Japan38 sites

  • Study site

    Amagasaki-shi, Hyōgo

  • Study site

    Chiba, Chiba

  • Study site

    Chiyoda-ku, Tokyo

  • Study site

    Choufu-shi, Tokyo

  • Study site

    Choufu-shi

  • Study site

    Hirakata-shi, Osaka

  • Study site

    Itojima-shi, Fukuoka

  • Study site

    Kawasaki-shi, Kanagawa

  • Study site

    Kawasaki-shi

  • Study site

    Kodaira-shi, Tokyo

  • Study site

    Kouriyama-shi, Fukushima

  • Study site

    Koutou-ku, Tokyo

  • Study site

    Koutou-ku

  • Study site

    Kyoto, Kyoto

  • Study site

    Morioka, Iwate

  • Study site

    Morioka

  • Study site

    Nagoya, Aichi-ken

  • Study site

    Osaka, Osaka

  • Study site

    Saitama-shi, Saitama

  • Study site

    Sakaide-shi, Kagawa-ken

  • Study site

    Sakaide-shi

  • Study site

    Sapporo, Hokkaido

  • Study site

    Sendai, Miyagi

  • Study site

    Setagaya-ku, Tokyo

  • Study site

    Setagaya-ku

  • Study site

    Shinagawa-ku, Tokyo

  • Study site

    Shinagawa-ku

  • Study site

    Shinjuku-ku, Tokyo

  • Study site

    Shinjuku-ku

  • Study site

    Takamatsu, Kagawa-ken

  • Study site

    Takatsuki-shi, Osaka

  • Study site

    Tokorozawa-shi, Saitama

  • Study site

    Tsukuba, Ibaragi

  • Study site

    Tsukuba

  • Study site

    Uji-shi, Kyoto

  • Study site

    Uji-shi

  • Study site

    Yaizu-shi, Shizuoka

  • Study site

    Yaizu-shi

Other trials in Japan

About this study

Official title: A Phase 3, Open-label, Multicenter, Long-term Study to Evaluate the Safety and Efficacy of TAK-536, Amlodipine and Hydrochlorothiazide in Subjects With Essential Hypertension

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.

Read the detailed description

The drug being tested in this study is called TAK-536TCH. TAK-536TCH is being tested to treat people who have essential hypertension. The study looked at effectiveness and long-term safety of TAK-536TCH in people who took TAK-536CCB in addition to standard care.

The study enrolled 341 patients. Participants received:

  • TAK-536CCB (as TAK-536/AML, 20 mg/5 mg) in run-in period,
  • TAK-536TCH (as TAK-536/ AML/HCTZ, 20 mg/5 mg/12.5 mg) in treatment period
  • TAK-536CCB and HCTZ 12.5 mg in treatment period

All participants were asked to take tablets at the same time each day throughout the study.

This multi-center trial was conducted in Japan. The overall time to participate in this study was 56 weeks (4 weeks run-in period and 52 weeks treatment period). Participants made multiple visits to the clinic during the study.

Being tested
TAK-536TCH tablet, TAK-536CCB tablet, HCTZ 12.5 mg tablet
Keywords
Pharmacological therapy, Drug Therapy
Medical subject headings
Essential Hypertension

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TAK-536TCH tabletDrug

    TAK-536TCH tablets

  • TAK-536CCB tabletDrug

    TAK-536CCB tablets

  • HCTZ 12.5 mg tabletDrug

    HCTZ tablets

Study groups in NCT02277691
Study groupRoleWhat they receive
TAK-536TCHExperimentalFor 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.
Receives: Drug: TAK-536TCH tablet; Drug: TAK-536CCB tablet; Drug: HCTZ 12.5 mg tablet

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Baseline up to Week 52

  2. 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.

    Measured: Baseline up to Week 52

  3. 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.

    Measured: Baseline up to Week 52

  4. 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.

    Measured: Baseline up to Week 52

  5. 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.

    Measured: Baseline up to Week 52

Secondary outcomes (2)

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

    The change in office trough SBP and DBP measured at Weeks 12 last observation was carried forward (LOCF) and 52 (LOCF) relative to baseline. Sitting blood pressure was measured at least 3 times. Each measurement session ended once blood pressure was found stable at 2 consecutive measurements. The average of the last 2 measurements of office sitting blood pressure was used.

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

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

    The change in home morning SPB and DBP measured at End of Week 12, End of Treatment (Up to Week 52) relative to baseline.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Oct 2014 (estimated)
  2. Study start7 Nov 2014
  3. Primary completion25 Apr 2016
  4. Study completion25 Apr 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
341 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02277691
Sponsor's protocol ID
TAK-536TCH/OCT-001
Other IDs
U1111-1163-0169, JapicCTI-142689
Status last verified
Jun 2017
First submitted
27 Oct 2014
Last updated
2 Aug 2017
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 29235365

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing TAK-536TCH tablet, TAK-536CCB tablet and HCTZ 12.5 mg tablet in people with Essential Hypertension, run by Takeda at 38 sites in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 38 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Jun 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Who Experience at Least One Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) (time frame: Baseline up to Week 52). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02277691, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Aug 2017.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in