Trial Outcomes & Findings for A Study of TAK-536 in Children From 2 to Less Than 6 Years Old With High Blood Pressure (NCT NCT04668157)

Last Updated: 2024-12-09

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

10 participants

Primary outcome timeframe

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

Results posted on

2024-12-09

Participant Flow

Participants took part in the study at 19 investigative sites in Japan from 17 May 2021 to 28 December 2023.

Participants with hypertension were enrolled in the study to receive TAK-536. The study consisted of a 2-week Run-in Period to receive placebo, followed by a 52-week Treatment Period to receive TAK-536, orally, once daily.

Participant milestones

Participant milestones
Measure	Run-in Period: Placebo TAK-536 matching-placebo, orally, once daily, before or after breakfast for up to 2 weeks.	Treatment Period: TAK-536 0.1 mg/kg - 0.8 mg/kg TAK-536 0.1 milligram per kilogram (mg/kg) (not exceeding 2.5 milligram per day \[mg/day\]), granules, orally, once daily, before or after breakfast on Day 1 for up to 52 weeks. The dose was titrated to the highest dose of 0.8 mg/kg (not exceeding 20 mg/day) as needed and based on body weight.
Run-in Period (2 Weeks) STARTED	10	0
Run-in Period (2 Weeks) COMPLETED	9	0
Run-in Period (2 Weeks) NOT COMPLETED	1	0
Treatment Period (52 Weeks) STARTED	0	9
Treatment Period (52 Weeks) COMPLETED	0	7
Treatment Period (52 Weeks) NOT COMPLETED	0	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Run-in Period: Placebo TAK-536 matching-placebo, orally, once daily, before or after breakfast for up to 2 weeks.	Treatment Period: TAK-536 0.1 mg/kg - 0.8 mg/kg TAK-536 0.1 milligram per kilogram (mg/kg) (not exceeding 2.5 milligram per day \[mg/day\]), granules, orally, once daily, before or after breakfast on Day 1 for up to 52 weeks. The dose was titrated to the highest dose of 0.8 mg/kg (not exceeding 20 mg/day) as needed and based on body weight.
Run-in Period (2 Weeks) Withdrawal by Subject	1	0
Treatment Period (52 Weeks) Other	0	2

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Run-in Period: Placebo n=10 Participants TAK-536 matching-placebo, orally, once daily, before or after breakfast for up to 2 weeks.
Age, Categorical <=18 years	10 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants
Race/Ethnicity, Customized Asian	10 Participants n=5 Participants
Region of Enrollment Japan	10 Participants n=5 Participants

PRIMARY outcome

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

Population: The safety analysis set included all participants who were enrolled and received at least 1 dose of study drug for the Treatment Period. As per planned analysis, outcomes in this study were analysed, collected and reported for treatment period only.

Outcome measures

Outcome measures
Measure	Treatment Period: TAK-536 0.1 mg/kg - 0.8 mg/kg n=9 Participants TAK-536 0.1 milligram per kilogram (mg/kg) (not exceeding 2.5 milligram per day \[mg/day\]), granules, orally, once daily, before or after breakfast on Day 1 for up to 52 weeks. The dose was titrated to the highest dose of 0.8 mg/kg (not exceeding 20 mg/day) as needed and based on body weight.
Number of Participants Who Experienced At Least One Treatment-Emergent Adverse Event (TEAE)	9 Participants

PRIMARY outcome

Timeframe: From first dose of study drug up to Week 52

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

Outcome measures

Outcome measures
Measure	Treatment Period: TAK-536 0.1 mg/kg - 0.8 mg/kg n=9 Participants TAK-536 0.1 milligram per kilogram (mg/kg) (not exceeding 2.5 milligram per day \[mg/day\]), granules, orally, once daily, before or after breakfast on Day 1 for up to 52 weeks. The dose was titrated to the highest dose of 0.8 mg/kg (not exceeding 20 mg/day) as needed and based on body weight.
Number of Participants With TEAE Related to Resting 12-lead Electrocardiogram (ECG)	0 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Treatment Period: TAK-536 0.1 mg/kg - 0.8 mg/kg n=9 Participants TAK-536 0.1 milligram per kilogram (mg/kg) (not exceeding 2.5 milligram per day \[mg/day\]), granules, orally, once daily, before or after breakfast on Day 1 for up to 52 weeks. The dose was titrated to the highest dose of 0.8 mg/kg (not exceeding 20 mg/day) as needed and based on body weight.
Number of Participants With TEAE Related to Anthropometric Measurement	0 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Treatment Period: TAK-536 0.1 mg/kg - 0.8 mg/kg n=9 Participants TAK-536 0.1 milligram per kilogram (mg/kg) (not exceeding 2.5 milligram per day \[mg/day\]), granules, orally, once daily, before or after breakfast on Day 1 for up to 52 weeks. The dose was titrated to the highest dose of 0.8 mg/kg (not exceeding 20 mg/day) as needed and based on body weight.
Number of Participants With TEAE Related to Clinical Laboratory Parameters	3 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Treatment Period: TAK-536 0.1 mg/kg - 0.8 mg/kg n=9 Participants TAK-536 0.1 milligram per kilogram (mg/kg) (not exceeding 2.5 milligram per day \[mg/day\]), granules, orally, once daily, before or after breakfast on Day 1 for up to 52 weeks. The dose was titrated to the highest dose of 0.8 mg/kg (not exceeding 20 mg/day) as needed and based on body weight.
Number of Participants With TEAE Related to Vital Sign Values	1 Participants

SECONDARY outcome

Timeframe: Baseline, Weeks 12 (LOCF) and 52 (LOCF)

Population: The full analysis set (FAS) included all participants who were enrolled and received at least 1 dose of study drug for the Treatment Period. As per planned analysis, outcomes in this study were analysed, collected and reported for treatment period only.

Office trough sitting diastolic blood pressure were measured in a sitting position. LOCF method was used to impute missing values.

Outcome measures

Outcome measures
Measure	Treatment Period: TAK-536 0.1 mg/kg - 0.8 mg/kg n=9 Participants TAK-536 0.1 milligram per kilogram (mg/kg) (not exceeding 2.5 milligram per day \[mg/day\]), granules, orally, once daily, before or after breakfast on Day 1 for up to 52 weeks. The dose was titrated to the highest dose of 0.8 mg/kg (not exceeding 20 mg/day) as needed and based on body weight.
Change From Baseline in Office Trough Sitting Diastolic Blood Pressure at Weeks 12 (Last Observation Carried Forward [LOCF]) and 52 (LOCF) Change from Baseline at Week 12 (LOCF)	-10.9 millimeters of mercury (mmHg) Standard Deviation 11.04
Change From Baseline in Office Trough Sitting Diastolic Blood Pressure at Weeks 12 (Last Observation Carried Forward [LOCF]) and 52 (LOCF) Change from Baseline at Week 52 (LOCF)	-14.8 millimeters of mercury (mmHg) Standard Deviation 8.39

SECONDARY outcome

Timeframe: Baseline, Weeks 12 (LOCF) and 52 (LOCF)

Population: The FAS included all participants who were enrolled and received at least 1 dose of study drug for the Treatment Period. As per planned analysis, outcomes in this study were analysed, collected and reported for treatment period only.

Office trough sitting systolic blood pressure were measured in a sitting position. LOCF method was used to impute missing values.

Outcome measures

Outcome measures
Measure	Treatment Period: TAK-536 0.1 mg/kg - 0.8 mg/kg n=9 Participants TAK-536 0.1 milligram per kilogram (mg/kg) (not exceeding 2.5 milligram per day \[mg/day\]), granules, orally, once daily, before or after breakfast on Day 1 for up to 52 weeks. The dose was titrated to the highest dose of 0.8 mg/kg (not exceeding 20 mg/day) as needed and based on body weight.
Change From Baseline in Office Trough Sitting Systolic Blood Pressure at Weeks 12 (LOCF) and 52 (LOCF) Change from Baseline at Week 12 (LOCF)	-8.0 mmHg Standard Deviation 6.73
Change From Baseline in Office Trough Sitting Systolic Blood Pressure at Weeks 12 (LOCF) and 52 (LOCF) Change from Baseline at Week 52 (LOCF)	-10.9 mmHg Standard Deviation 8.30

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Treatment Period: TAK-536 0.1 mg/kg - 0.8 mg/kg n=9 Participants TAK-536 0.1 milligram per kilogram (mg/kg) (not exceeding 2.5 milligram per day \[mg/day\]), granules, orally, once daily, before or after breakfast on Day 1 for up to 52 weeks. The dose was titrated to the highest dose of 0.8 mg/kg (not exceeding 20 mg/day) as needed and based on body weight.
Percentage of Participants Who Achieved the Target Blood Pressure at Weeks 12 (LOCF) and 52 (LOCF) At Week 12 (LOCF)	44.4 percentage of participants Interval 13.7 to 78.799
Percentage of Participants Who Achieved the Target Blood Pressure at Weeks 12 (LOCF) and 52 (LOCF) At Week 52 (LOCF)	44.4 percentage of participants Interval 13.7 to 78.799

SECONDARY outcome

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

Population: The FAS included all participants who were enrolled and received at least 1 dose of study drug for the Treatment Period. Here, 'Overall number of participants analyzed' signifies participants who were evaluable for this outcome measure and 'number of participants analyzed' refer to the participants evaluable for specified time points. As per planned analysis, outcomes in this study were analysed, collected and reported for treatment period only.

Plasma concentration of TAK-536 were reported.

Outcome measures

Outcome measures
Measure	Treatment Period: TAK-536 0.1 mg/kg - 0.8 mg/kg n=8 Participants TAK-536 0.1 milligram per kilogram (mg/kg) (not exceeding 2.5 milligram per day \[mg/day\]), granules, orally, once daily, before or after breakfast on Day 1 for up to 52 weeks. The dose was titrated to the highest dose of 0.8 mg/kg (not exceeding 20 mg/day) as needed and based on body weight.
Plasma Concentration of TAK-536 At Week 4 (Pre-dose)	42.5 nanogram per milliliter (ng/mL) Standard Deviation 25.77
Plasma Concentration of TAK-536 At Week 12 (Pre-dose)	170.0 nanogram per milliliter (ng/mL) Standard Deviation NA Standard deviation could not be calculated for 1 participant.
Plasma Concentration of TAK-536 At Week 2 (Pre-dose)	14.0 nanogram per milliliter (ng/mL) Standard Deviation 11.96
Plasma Concentration of TAK-536 At Week 2 (Post-dose)	356.0 nanogram per milliliter (ng/mL) Standard Deviation 435.58
Plasma Concentration of TAK-536 At Week 4 (Post-dose)	728.0 nanogram per milliliter (ng/mL) Standard Deviation NA Standard deviation could not be calculated for 1 participant.
Plasma Concentration of TAK-536 At Week 8 (Pre-dose)	50.0 nanogram per milliliter (ng/mL) Standard Deviation 8.49
Plasma Concentration of TAK-536 At Week 16 (Post-dose)	2374.5 nanogram per milliliter (ng/mL) Standard Deviation 1924.50

Adverse Events

Run-in Period: Placebo

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

TAK-536 0.1 mg/kg - 0.8 mg/kg

Serious events: 4 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Run-in Period: Placebo n=10 participants at risk TAK-536 matching-placebo, orally, once daily, before or after breakfast for up to 2 weeks.	TAK-536 0.1 mg/kg - 0.8 mg/kg n=9 participants at risk TAK-536 0.1 mg/kg (not exceeding 2.5 mg/day), granules, orally, once daily, before or after breakfast on Day 1 for up to 52 weeks in Treatment Period. The dose was titrated to the highest dose of 0.8 mg/kg (not exceeding 20 mg/day) as needed and based on body weight.
Renal and urinary disorders Acute kidney injury	0.00% 0/10 • Run-in Period: From first dose in Run-in Period up to 2 weeks; Treatment Period: From first dose in Treatment Period up to end of follow-up period (54 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. AEs were not collected by dose level. As planned, combined dose-wise data of all TAK-536 doses (0.1 mg/kg - 0.8 mg/kg) was collected, analyzed and reported for Treatment Period.	11.1% 1/9 • Run-in Period: From first dose in Run-in Period up to 2 weeks; Treatment Period: From first dose in Treatment Period up to end of follow-up period (54 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. AEs were not collected by dose level. As planned, combined dose-wise data of all TAK-536 doses (0.1 mg/kg - 0.8 mg/kg) was collected, analyzed and reported for Treatment Period.
Infections and infestations COVID-19	0.00% 0/10 • Run-in Period: From first dose in Run-in Period up to 2 weeks; Treatment Period: From first dose in Treatment Period up to end of follow-up period (54 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. AEs were not collected by dose level. As planned, combined dose-wise data of all TAK-536 doses (0.1 mg/kg - 0.8 mg/kg) was collected, analyzed and reported for Treatment Period.	22.2% 2/9 • Run-in Period: From first dose in Run-in Period up to 2 weeks; Treatment Period: From first dose in Treatment Period up to end of follow-up period (54 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. AEs were not collected by dose level. As planned, combined dose-wise data of all TAK-536 doses (0.1 mg/kg - 0.8 mg/kg) was collected, analyzed and reported for Treatment Period.
Gastrointestinal disorders Colitis	0.00% 0/10 • Run-in Period: From first dose in Run-in Period up to 2 weeks; Treatment Period: From first dose in Treatment Period up to end of follow-up period (54 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. AEs were not collected by dose level. As planned, combined dose-wise data of all TAK-536 doses (0.1 mg/kg - 0.8 mg/kg) was collected, analyzed and reported for Treatment Period.	11.1% 1/9 • Run-in Period: From first dose in Run-in Period up to 2 weeks; Treatment Period: From first dose in Treatment Period up to end of follow-up period (54 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. AEs were not collected by dose level. As planned, combined dose-wise data of all TAK-536 doses (0.1 mg/kg - 0.8 mg/kg) was collected, analyzed and reported for Treatment Period.
Infections and infestations Coronavirus infection	0.00% 0/10 • Run-in Period: From first dose in Run-in Period up to 2 weeks; Treatment Period: From first dose in Treatment Period up to end of follow-up period (54 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. AEs were not collected by dose level. As planned, combined dose-wise data of all TAK-536 doses (0.1 mg/kg - 0.8 mg/kg) was collected, analyzed and reported for Treatment Period.	11.1% 1/9 • Run-in Period: From first dose in Run-in Period up to 2 weeks; Treatment Period: From first dose in Treatment Period up to end of follow-up period (54 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. AEs were not collected by dose level. As planned, combined dose-wise data of all TAK-536 doses (0.1 mg/kg - 0.8 mg/kg) was collected, analyzed and reported for Treatment Period.
Renal and urinary disorders Proteinuria	0.00% 0/10 • Run-in Period: From first dose in Run-in Period up to 2 weeks; Treatment Period: From first dose in Treatment Period up to end of follow-up period (54 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. AEs were not collected by dose level. As planned, combined dose-wise data of all TAK-536 doses (0.1 mg/kg - 0.8 mg/kg) was collected, analyzed and reported for Treatment Period.	11.1% 1/9 • Run-in Period: From first dose in Run-in Period up to 2 weeks; Treatment Period: From first dose in Treatment Period up to end of follow-up period (54 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. AEs were not collected by dose level. As planned, combined dose-wise data of all TAK-536 doses (0.1 mg/kg - 0.8 mg/kg) was collected, analyzed and reported for Treatment Period.

Other adverse events

Additional Information

Study Director

Takeda

Phone: +1-877-825-3327

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Research Organization shall not publish any articles or papers nor make any presentations, nor assist any other person in publishing any articles or papers or in making any presentations relating or referring to the Study or any results, data or insights from or any data, information or materials obtained or generated in the performance of its obligations without the prior written consent of Takeda, which consent may be granted or withheld in Takeda's sole discretion.
Publication restrictions are in place

Restriction type: OTHER