A Study of TAK-536 in Children From 2 to Less Than 6 Years Old With High Blood Pressure

NCT04668157 | Completed Phase 3 Results

• 3 other identifiers: Azilsartan-3004U1111-1259-9316jRCT2041200083
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 19

Brief Summary

The main aim of this study is to check the safety of TAK-536. This study will take place in Japan. At the first visit, the study doctor will check if each child can take part. For those who can take part, each participant will have a check-up by the study doctor. After this, each participant will take placebo. This might take 2 weeks. After this, parents or the caregivers of each participant will be given sachets that contain granules of TAK-536 to give to that participant. The participants will take the TAK-536 granules once a day for 52 weeks. After treatment has finished, participants will visit the study clinic for a final check-up.

Conditions

Hypertension

Outcome Measures

Primary Outcomes (5)

• Number of Participants Who Experienced At Least One Treatment-Emergent Adverse Event (TEAE)

  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.

  From first dose of study drug up to end of follow-up period (Week 54)

• Number of Participants With TEAE Related to Resting 12-lead Electrocardiogram (ECG)

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

  From first dose of study drug up to Week 52

• Number of Participants With TEAE Related to Anthropometric Measurement

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

  From first dose of study drug up to Week 52

• Number of Participants With TEAE Related to Clinical Laboratory Parameters

  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.

  From first dose of study drug up to Week 52

• Number of Participants With TEAE Related to Vital Sign Values

  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.

  From first dose of study drug up to end of follow-up period (Week 54)

Secondary Outcomes (4)

• 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)

• Plasma Concentration of TAK-536

  Weeks 2, 4, 8 and 12: Pre-dose and at 2 hours post-dose; Week 16: 2 hours post-dose

Study Arms (1)

TAK-536

EXPERIMENTAL

TAK-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.

Drug: TAK-536

Interventions

TAK-536 DRUG

TAK-536 granule formulation

TAK-536

Eligibility Criteria

• Age: 2 Years - 5 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• In the opinion of the investigator or subinvestigator, the participant's parent or legal guardian is capable of understanding and complying with protocol requirements.
• The participant's parent or the participant's legal guardian is capable of signing and dating a written informed consent form on behalf of the participant prior to the initiation of any study procedures.
• A Japanese participant who has a diagnosis of hypertension. A participant is eligible if he/she is deemed hypertensive according to the reference blood pressure values of children by gender and age; office sitting diastolic or systolic blood pressure \>=95th percentile for essential hypertension without concomitant hypertensive organ damage, and \>=90th percentile for secondary hypertension with concomitant CKD, diabetes mellitus, heart failure or hypertensive organ damage.
• In addition, participants need to meet the following criteria:
• If currently treated with any antihypertensive drugs at the start of the Run-in Period: Participant has a documented diagnosis of hypertension and an office sitting diastolic or systolic blood pressure meeting the above criteria at the end of the Run-in Period (Week 0).
• If currently untreated with any antihypertensive drugs at the start of the Run-in Period: Participant meets the above criteria for hypertension on 3 separate time points including screening and the end of the Run-in Period (Week 0). In addition, for a participant with essential hypertension without hypertensive organ damage, the participant does not respond to non-pharmacological therapy such as diet modification or exercises for at least 3 months within 1 year prior to the start of screening.
• The participant is male or female and aged 2 to less than 6 years at the time of informed consent.
• At screening, the participant has not less than minus 2 standard deviations from mean weight for age of reference population shown in the table of pediatric body weight by the Japanese Society for Pediatric Endocrinology.
• The participant is able to swallow the study drug.
• A participant who has undergone kidney transplantation is eligible if he/she underwent the transplantation, and the graft has been functionally stable (estimated glomerular filtration rate \[eGFR\] \>= 30 mL/min/1.73 m\^2) for at least 6 months with evidence (eg, Doppler echography, CT \[computed tomography\] scan or MRI \[magnetic resonance imaging\]) excluding dose at least 30 days prior to screening is eligible.
• The participant, judged by the investigator or subinvestigator, who can safely discontinue the therapy with RAS inhibitors for 2 weeks prior to the Treatment Period. This period may change to between 1 and 4 weeks depending on the participant's duration of Run-in Period.

You may not qualify if:

• The participant has received any investigational compound within 30 days prior to screening or is participating in another clinical study or a post-marketing clinical study.
• Note: This does not apply to participants participating in observational studies without interventional or surgical therapy.
• The participant previously received therapy with azilsartan.
• The participant has poorly controlled hypertension indicated by an office sitting systolic blood pressure higher by at least 22 mmHg and/or an office sitting diastolic blood pressure higher by at least 17 mmHg than the 95th percentiles of the reference blood pressure values of children by gender and age.
• The participant has a diagnosis of malignant or accelerated hypertension.
• The participant was noncompliant (compliance: \<70% or \>130%) with the study drug during the Run-in Period. The proportion of the number of the received the study drug to the number of the study drug which the participants should receive.
• The participant has severe renal dysfunction (eGFR \<30 mL/min/1.73 m\^2), is receiving dialysis, has a renovascular disease affecting one or both kidneys, severe nephrotic syndrome not in remission, or a serum albumin level \<2.5 g/dL.
• The participant has a history of, or the signs/symptoms of serious cardiovascular, hepatobiliary, gastrointestinal, endocrine (eg, hyperthyroidism, Cushing's syndrome), hematological, immunological, urogenital, psychiatric disease, cancer, or any other disease that adversely affects participant's health, or, in the opinion of the investigator or subinvestigator, potentially confounds the study results.
• The participant has hemodynamically significant left ventricular outflow obstruction due to aortic stenosis or uncorrected aortic valvular disease, or is scheduled to undergo a medical procedure affecting blood pressure during the study (eg, correction of arterial anomaly).
• Note: This does not apply to participants who received medical procedure(s) (eg, surgery for aortic coarctation) before the study and investigator or subinvestigator assess that participant's condition is stable at screening.
• The participant has a history of or concurrent clinically significant abnormality of 12-lead ECG that, in the opinion of the investigator or subinvestigator, disqualifies the participant for participation in the study.
• The participant has poorly controlled diabetes mellitus indicated by HbA1c \>9.0% at screening.
• The participant has an alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level \>=2.5 × the upper limit of normal (ULN), or a total bilirubin level \>=1.5 × ULN at screening, severely impaired hepatic function, any active liver disease (regardless of the cause), or jaundice.
• The participant has hyperkalemia exceeding ULN at screening.
• The participant has a history of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection at screening.

Sponsors & Collaborators

• Takeda: lead

Study Sites (19)

Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital

Nagoya, Aichi-ken, Japan

Location

Aichi Children's Health and Medical Center

Ōbu, Aichi-ken, Japan

Location

Hyogo Prefectural Kobe Children's Hospital

Kobe, Hyōgo, Japan

Location

National Hospital Organization Kanazawa Medical Center

Kanazawa, Ishikawa-ken, Japan

Location

Kitasato University Hospital

Sagamihara, Kanagawa, Japan

Location

Miyagi Children's Hospital

Sendai, Miyagi, Japan

Location

Tohoku University Hospital

Sendai, Miyagi, Japan

Location

University of the Ryukyus Hospital

Nakagami-gun, Okinawa, Japan

Location

Okinawa Prefectural Nanbu Medical Center & Children's Medical Center

Shimajiri-gun, Okinawa, Japan

Location

Osaka University Hospital

Suita, Osaka, Japan

Location

Shiga University of Medical Science Hospital

Ōtsu, Shiga, Japan

Location

Jichi Medical University Hospital

Shimotsuke, Tochigi, Japan

Location

Tokyo Metropolitan Hospital Organization Tokyo Metropolitan Children's Medical Center

Fuchū, Tokyo, Japan

Location

National Center for Child Health and Development

Setagaya-ku, Tokyo, Japan

Location

Tokyo Women's Medical University Hospital

Shinjuku-ku, Tokyo, Japan

Location

Hiroshima Prefectural Hospital

Hiroshima, Japan

Location

Local Independent Administrative Institution Saitama prefectural hospital organization Saitama Children's Medical Center

Saitama, Japan

Location

Shizuoka Childrens Hospital

Shizuoka, Japan

Location

Wakayama Medical University Hospital

Wakayama, Japan

Location

Related Links

• To obtain more information on the study, click here/on this link

MeSH Terms

Conditions

Hypertension

Interventions

azilsartan

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Study Director
• Organization: Takeda

TrialDisclosures@takeda.com

+1-877-825-3327

Study Officials

• Study Director

  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: December 10, 2020
• First Posted: December 16, 2020
• Study Start: May 17, 2021
• Primary Completion: December 28, 2023
• Study Completion: December 28, 2023
• Last Updated: December 9, 2024
• Results First Posted: December 9, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

JP (19)