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TAK-536

Phase 3

Hypertension | Small molecule | Cardiovascular |Takeda Pharmaceutical Company Limited|Last Updated: Dec 9, 2024

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Trial Design

UNCONTROLLED
Total Trials1
Total Enrollment10

FDA Designations

No designations recorded

Clinical trial landscape

TAK-536 · 4 trials · 4 indications

Phase 3 1Phase 1 3
NCT04668157A Study of TAK-536 in Children From 2 to Less Than 6 Years Old With High Blood PressureHypertension
COMPLETED10 Analytics
PHASE3COMPLETED
A Study of TAK-536 in Children From 2 to Less Than 6 Years Old With High Blood Pressure
HypertensionUnlock trial analytics

Study Endpoints

Primary Endpoints

Number of Participants Who Experienced At Least One Treatment-Emergent Adverse Event (TEAE)
From first dose of study drug up to end of follow-up period (Week 54)

An Adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant whose parent or legal guardian had signed informed consent form to participate in a study; it did not necessarily have to have a causal relationship with this treatment or study participation. An AE could therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the study participation whether or not it was considered related to the drug or study procedures. A TEAE was defined as any AE occurring after the start of TAK-536 administration, and until the end of follow-up period of 2 weeks.

Number of Participants With TEAE Related to Resting 12-lead Electrocardiogram (ECG)
From first dose of study drug up to Week 52

The relatedness of TEAEs with resting 12-lead ECG was based upon investigator discretion.

Number of Participants With TEAE Related to Anthropometric Measurement
From first dose of study drug up to Week 52

The anthropometric measurements included weight, height and body mass index (BMI). The relatedness of TEAEs to anthropometric measurements was based upon investigator discretion.

Number of Participants With TEAE Related to Clinical Laboratory Parameters
From first dose of study drug up to Week 52

The laboratory values outside the range (triglycerides greater than \[\>\] 2.5\*upper limit of normal \[ULN\], blood urea nitrogen \[BUN\] \>30 milligram per deciliter \[mg/dL\], estimated glomerular filtration rate \[eGFR\] less than \[\<\] 30 milliliter per minute per 1.73 square meter \[mL/min/1.73m\^2\], and glucose \<50 mg/dL were considered markedly abnormal for TEAEs. The relatedness of TEAEs to clinical laboratory parameters was based upon investigator discretion.

Number of Participants With TEAE Related to Vital Sign Values
From first dose of study drug up to end of follow-up period (Week 54)

Vital signs included home sitting blood pressure (diastolic and systolic) and office sitting pulse rate (pulse rate per 1 minute). The pulse rate measured at the last measurement of the sitting blood pressure was used as the sitting pulse rate value. The relatedness of TEAEs to vital signs was based upon investigator discretion.

Cmax: Maximum Observed Plasma Concentration for TAK-536
Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-536
Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-536
Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-536
Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
T1/2z: Terminal Disposition Phase Half-life for TAK-536
Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
MRTlast, ev: Mean Residence Time From Time 0 to the Time of the Last Quantifiable Concentration for TAK-536
Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
MRT∞, ev: Mean Residence Time From Time 0 to Infinity for TAK-536
Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
λz: Terminal Disposition Phase Rate Constant for TAK-536
Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
CL/F: Apparent Clearance for TAK-536
Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
Vz/F: Apparent Volume of Distribution for TAK-536
Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
AUC(0-48): Area Under the Plasma Concentration-time Curve From Time 0 to 48 Hours Postdose for TAK-536
Day 1 pre-dose and at multiple time points post-dose (0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, and 48 hours post-dose; up to 48 hours)
AUC(0-48): Area Under the Plasma Concentration-Time Curve From Time 0 to 48 Hours Postdose for TAK-536 in Dry Syrup Cohort
Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose
Cmax: Maximum Observed Plasma Concentration for TAK-536 in Dry Syrup Cohort
Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose
AUC(0-48): Area Under the Plasma Concentration-Time Curve From Time 0 to 48 Hours Postdose for TAK-536 in Granule Cohort
Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose
Cmax: Maximum Observed Plasma Concentration for TAK-536 in Granule Cohort
Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose

Secondary Endpoints

Change From Baseline in Office Trough Sitting Diastolic Blood Pressure at Weeks 12 (Last Observation Carried Forward [LOCF]) and 52 (LOCF)
Baseline, Weeks 12 (LOCF) and 52 (LOCF)
Change From Baseline in Office Trough Sitting Systolic Blood Pressure at Weeks 12 (LOCF) and 52 (LOCF)
Baseline, Weeks 12 (LOCF) and 52 (LOCF)
Percentage of Participants Who Achieved the Target Blood Pressure at Weeks 12 (LOCF) and 52 (LOCF)
At Weeks 12 (LOCF) and 52 (LOCF)
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Study Design & Arms

AllocationNA
MaskingNONE
ModelSINGLE_GROUP
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
TAK-536EXPERIMENTALTAK-536 granule formulation, orally once daily before or after breakfast. The initial dose of TAK-536 will be 0.1 mg/kg (not exceeding 2.5 mg/day). After the initial dose, TAK-536 will be titrated to 0.2 mg/kg (not exceeding 5 mg/day), 0.4 mg/kg (not exceeding 10 mg/day), and 0.8 mg/kg (not exceeding 20 mg/day) if the subjects do not achieve the target blood pressure and no concerns are found in safety and tolerability.
TAK-536 10 mg (fasted) + TAK-536 10 mg (fed)EXPERIMENTALTAK-536 10 milligram (mg) granule formulation (pediatric formulation), once daily on Day 1 of Period 1 (6 days) in the morning under fasted condition, followed by wash-out (6 days), followed by TAK-536 10 mg granule formulation (pediatric formulation), once daily on Day 1 of Period 2 (6 days) after starting breakfast.
TAK-536 10 mg (fed) + TAK-536 10 mg (fasted)EXPERIMENTALTAK-536 10 mg granule formulation (pediatric formulation), once daily on Day 1 of Period 1 (6 days) after starting breakfast, followed by wash-out (6 days), followed by TAK-536 10 mg granule formulation (pediatric formulation), once daily on Day 1 of Period 2 (6 days) in the morning under fasted condition.
TAK-536 Granules + TAK-536 TabletEXPERIMENTALTAK-536 10 milligram (mg), granules (pediatric formulation), under fasted condition, orally, once on Day 1 of Intervention Period 1, followed by a Washout Period of at least 6 days, further followed by TAK-536 10 mg, tablet (commercial formulation), under fasted condition, orally, once on Day 1 of Intervention Period 2.
TAK-536 Tablet + TAK-536 GranulesEXPERIMENTALTAK-536 10 mg, tablet (commercial formulation), under fasted condition, orally, once on Day 1 of Intervention Period 1, followed by a Washout Period of at least 6 days, further followed by TAK-536 10 mg, granules (pediatric formulation), under fasted condition, orally, once on Day 1 of Intervention Period 2.
Dry syrup formulation (Group a)EXPERIMENTALOne pack of the dry syrup formulation of TAK-536, containing 10 milligram (mg) of TAK-536, will be orally administered with water (200 milliliter \[mL\]) at breakfast to fasting participants who have fasted for 10 hours or longer since the night prior to the administration of study medication in Period 1 and, after a washout period of 6 days or more, one 10 mg tablet of TAK-536 will be orally administered with water (200 mL) at breakfast to fasting participants who have fasted for 10 hours or longer since the night prior to the administration of study medication in Period 2.
Dry syrup formulation (Group b)EXPERIMENTALOne 10 mg tablet of TAK-536 will be orally administered with water (200 mL) at breakfast to fasting participants who have fasted for 10 hours or longer since the night prior to the administration of study medication in Period 1 and, after a washout period of 6 days or more, one pack of the dry syrup formulation of TAK-536, containing 10 mg of TAK-536, will be orally administered with water (200 mL) at breakfast to fasting participants who have fasted for 10 hours or longer since the night prior to the administration of study medication in Period 2.
Granule formulation (Group a)EXPERIMENTALOne pack of the granule formulation of TAK-536, containing 10 mg of TAK-536,will be orally administered with water (200 mL) at breakfast to fasting participants who have fasted for 10 hours or longer since the night prior to the administration of study medication in Period 1 and, after a washout period of 6 days or more, one 10 mg tablet of TAK-536 will be orally administered with water (200 mL) at breakfast to fasting participants who have fasted for 10 hours or longer since the night prior to the administration of study medication in Period 2.
Granule formulation (Group b)EXPERIMENTALOne 10 mg tablet of TAK-536 will be orally administered with water (200 mL) at breakfast to fasting participants who have fasted for 10 hours or longer since the night prior to the administration of study medication in Period 1 and, after a washout period of 6 days or more, one pack of the granule formulation of TAK-536, containing 10 mg of TAK-536, will be orally administered with water (200 mL) at breakfast to fasting participants who have fasted for 10 hours or longer since the night prior to the administration of study medication in Period 2.

Interventions

NameTypeDescription
TAK-536DRUGTAK-536 granule formulation
TAK-536 TabletDRUGTAK-536 10 mg tablet
TAK-536 Dry Syrup FormulationDRUGTAK-536 dry syrup formulation
TAK-536 Ganule FormulationDRUGTAK-536 granule formulation
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Eligibility Criteria

Age Range2 Years to 5 Years
SexALL
Healthy VolunteersNo
Study Sites19

Inclusion Criteria: 1. In the opinion of the investigator or subinvestigator, the participant's parent or legal guardian is capable of understanding and complying with protocol requirements. 2. The participant's parent or the participant's legal guardian is capable of signing and dating a written i...

Countries:Japan
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Frequently asked questions about TAK-536

What is TAK-536 used for?

TAK-536, also known as azilsartan, is an investigational small molecule being studied for hypertension (high blood pressure). It is also being evaluated in healthy volunteers and Japanese healthy adult males in early-phase trials. The drug is in clinical development for use in children aged 2 to less than 6 years with high blood pressure.

Who makes TAK-536?

TAK-536 is being developed by Takeda Pharmaceutical Company Limited, which trades under the ticker TAK. The company is conducting clinical trials of this investigational small molecule in Japan, focusing on hypertension and related studies in healthy volunteers.

What phase is TAK-536 in?

TAK-536 is in Phase 1 clinical development, with completed bioequivalence and food effect studies in healthy Japanese adult males. A Phase 3 study in children aged 2 to less than 6 years with high blood pressure has also been completed. The drug remains investigational and is not yet approved.

What clinical trials is TAK-536 in?

TAK-536 has completed several clinical trials in Japan, including NCT02401464 and NCT03042299, which are Phase 1 bioequivalence studies of the pediatric formulation in Japanese healthy adult males. NCT03434977 is a Phase 1 food effect study in healthy volunteers, and NCT04668157 is a Phase 3 study in children with high blood pressure.

Is TAK-536 the same as azilsartan?

Yes, TAK-536 is also known as azilsartan. Clinical trials such as NCT03434977, titled 'A Phase 1 Food Effect Study of Azilsartan (TAK-536) Pediatric Formulation,' use both names interchangeably. This investigational small molecule is being studied for hypertension and related conditions.

What does TAK-536 target?

TAK-536 is an angiotensin II receptor blocker (ARB) that targets the angiotensin II type 1 (AT1) receptor. By blocking this receptor, it is intended to lower blood pressure in patients with hypertension. The drug is being studied in pediatric populations with high blood pressure.