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.
The drug being tested in this study is called TAK-536. TAK-536 is being tested in pediatric participants with hypertension aged 2 to less than 6 years. This study will look at the safety, efficacy, and pharmacokinetics of long-term administration of TAK-536. The study will enroll 10 participants. Participants will receive the study drug (TAK-536) 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 participants do not achieve the target blood pressure and no concerns are found in safety and tolerability. This multi-center trial will be conducted in Japan. The overall time to participate in this study is approximately 56 weeks. Participants will make multiple visits to the clinic.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
10
TAK-536 granule formulation
Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital
Nagoya, Aichi-ken, Japan
Aichi Children's Health and Medical Center
Ōbu, Aichi-ken, Japan
Hyogo Prefectural Kobe Children's Hospital
Kobe, Hyōgo, Japan
National Hospital Organization Kanazawa Medical Center
Kanazawa, Ishikawa-ken, Japan
Kitasato University Hospital
Sagamihara, Kanagawa, Japan
Miyagi Children's Hospital
Sendai, Miyagi, Japan
Tohoku University Hospital
Sendai, Miyagi, Japan
University of the Ryukyus Hospital
Nakagami-gun, Okinawa, Japan
Okinawa Prefectural Nanbu Medical Center & Children's Medical Center
Shimajiri-gun, Okinawa, Japan
Osaka University Hospital
Suita, Osaka, Japan
...and 9 more locations
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: From first dose of study drug up to end of follow-up period (Week 54)
Change From Baseline in Office Trough Sitting Diastolic Blood Pressure at Weeks 12 (Last Observation Carried Forward [LOCF]) and 52 (LOCF)
Office trough sitting diastolic blood pressure were measured in a sitting position. LOCF method was used to impute missing values.
Time frame: Baseline, Weeks 12 (LOCF) and 52 (LOCF)
Change From Baseline in Office Trough Sitting Systolic Blood Pressure at Weeks 12 (LOCF) and 52 (LOCF)
Office trough sitting systolic blood pressure were measured in a sitting position. LOCF method was used to impute missing values.
Time frame: Baseline, Weeks 12 (LOCF) and 52 (LOCF)
Percentage of Participants Who Achieved the Target Blood Pressure at Weeks 12 (LOCF) and 52 (LOCF)
The target blood pressure was defined as the normal reference range for blood pressure by age according to guidelines on the clinical examination for decision making of diagnosis and drug therapy in pediatric participants with cardiovascular diseases by the Japanese Circulation Society 2018 (JCS 2018). LOCF method was used to impute missing values.
Time frame: At Weeks 12 (LOCF) and 52 (LOCF)
Plasma Concentration of TAK-536
Plasma concentration of TAK-536 were reported.
Time frame: Weeks 2, 4, 8 and 12: Pre-dose and at 2 hours post-dose; Week 16: 2 hours post-dose
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