Clinical trial NCT04668157: A Study of TAK-536 in Children From 2 to Less Than 6 Years Old With High Blood Pressure
Official title: A Phase 3, Open-label, Multicenter, Long-term Study to Evaluate the Safety, Efficacy and Pharmacokinetics of TAK-536 in Pediatric Subjects From 2 to Less Than 6 Years of Age With Hypertension
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypertension
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2020-12-16
Enrollment: 10
Sex: ALL
Minimum age (years): 2
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: 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.

Eligibility criteria: 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 informed consent form on behalf of the participant prior to the initiation of any study procedures.
3. 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.
4. The participant is male or female and aged 2 to less than 6 years at the time of informed consent.
5. 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.
6. The participant is able to swallow the study drug.
7. 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.
8. 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.

Exclusion Criteria:

1. 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.
2. The participant previously received therapy with azilsartan.
3. 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.
4. The participant has a diagnosis of malignant or accelerated hypertension.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.
10. The participant has poorly controlled diabetes mellitus indicated by HbA1c \>9.0% at screening.
11. 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.
12. The participant has hyperkalemia exceeding ULN at screening.
13. The participant has a history of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection at screening.
14. The participant has a known hypersensitivity or allergy to any ARBs.
15. The participant needs treatment with any of the excluded medication.

Primary outcomes:
measure: Number of Participants Who Experienced At Least One Treatment-Emergent Adverse Event (TEAE)
timeFrame: From first dose of study drug up to end of follow-up period (Week 54)
measure: Number of Participants With TEAE Related to Resting 12-lead Electrocardiogram (ECG)
timeFrame: From first dose of study drug up to Week 52
measure: Number of Participants With TEAE Related to Anthropometric Measurement
timeFrame: From first dose of study drug up to Week 52
measure: Number of Participants With TEAE Related to Clinical Laboratory Parameters
timeFrame: From first dose of study drug up to Week 52
measure: Number of Participants With TEAE Related to Vital Sign Values
timeFrame: From first dose of study drug up to end of follow-up period (Week 54)
Secondary outcomes:
measure: Change From Baseline in Office Trough Sitting Diastolic Blood Pressure at Weeks 12 (Last Observation Carried Forward [LOCF]) and 52 (LOCF)
timeFrame: Baseline, Weeks 12 (LOCF) and 52 (LOCF)
measure: Change From Baseline in Office Trough Sitting Systolic Blood Pressure at Weeks 12 (LOCF) and 52 (LOCF)
timeFrame: Baseline, Weeks 12 (LOCF) and 52 (LOCF)
measure: Percentage of Participants Who Achieved the Target Blood Pressure at Weeks 12 (LOCF) and 52 (LOCF)
timeFrame: At Weeks 12 (LOCF) and 52 (LOCF)
measure: Plasma Concentration of TAK-536
timeFrame: Weeks 2, 4, 8 and 12: Pre-dose and at 2 hours post-dose; Week 16: 2 hours post-dose
Other outcomes:
Locations:
city: Nagoya
country: Japan
facility: Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital
state: Aichi
city: Obu
country: Japan
facility: Aichi Children's Health and Medical Center
state: Aichi
city: Kobe
country: Japan
facility: Hyogo Prefectural Kobe Children's Hospital
state: Hyogo
city: Kanazawa
country: Japan
facility: National Hospital Organization Kanazawa Medical Center
state: Ishikawa
city: Sagamihara
country: Japan
facility: Kitasato University Hospital
state: Kanagawa
city: Sendai
country: Japan
facility: Miyagi Children's Hospital
state: Miyagi
city: Sendai
country: Japan
facility: Tohoku University Hospital
state: Miyagi
city: Nakagami-gun
country: Japan
facility: University of the Ryukyus Hospital
state: Okinawa
city: Shimajiri-gun
country: Japan
facility: Okinawa Prefectural Nanbu Medical Center & Children's Medical Center
state: Okinawa
city: Suita
country: Japan
facility: Osaka University Hospital
state: Osaka
city: Otsu
country: Japan
facility: Shiga University of Medical Science Hospital
state: Shiga
city: Shimotsuke
country: Japan
facility: Jichi Medical University Hospital
state: Tochigi
city: Fuchu
country: Japan
facility: Tokyo Metropolitan Hospital Organization Tokyo Metropolitan Children's Medical Center
state: Tokyo
city: Setagaya-ku
country: Japan
facility: National Center for Child Health and Development
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Tokyo Women's Medical University Hospital
state: Tokyo
city: Hiroshima
country: Japan
facility: Hiroshima Prefectural Hospital
city: Saitama
country: Japan
facility: Local Independent Administrative Institution Saitama prefectural hospital organization Saitama Children's Medical Center
city: Shizuoka
country: Japan
facility: Shizuoka Childrens Hospital
city: Wakayama
country: Japan
facility: Wakayama Medical University Hospital
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: