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Azilsartan

Phase 3

Pediatric Hypertension | Small molecule | Cardiovascular |Takeda Pharmaceutical Company Limited|Last Updated: Feb 7, 2020

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
CONTROLLEDBiomarker
Total Trials2
Total Enrollment33
FDA Designations
No designations recorded
Clinical Trials (2)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT02791438A Phase 3 Long-term Study of TAK-536 in Pediatric Patients 6 to Less Than 16 Years With HypertensionPHASE3 COMPLETED 27Aug 18, 2016Jun 4, 2019Feb 7, 202030 Japan
NCT02451150A Phase 3 Pharmacokinetic Study of TAK-536 (Azilsartan) in Pediatric Patients 6 to Less Than 16 Years With HypertensionPHASE3 COMPLETED 6Aug 1, 2015Sep 1, 2015Apr 7, 20163 Japan
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Study Endpoints
Primary Endpoints
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
Up to Week 54

An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs or worsens after receiving study drug.

Number of Participants With TEAEs Related to Anthropometric Measurement (Weight, Height and Body Mass Index (BMI))
Up to Week 54

An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs or worsens after receiving study drug.

Number Of Participants With Markedly Abnormal Values of Laboratory Parameters
Up to Week 54

The laboratory values outside the range (Blood Urea Nitrogen (BUN) (mg/dL) \>30, Creatinine (mg/dL) \>2.0, eGFR (mL/min/1.73m\^2) \<30, Creatine Kinase (U/L) \>5×ULN) are considered markedly abnormal.

Number Of Participants With TEAEs Related To Resting 12-Lead Electrocardiogram (ECG)
Up to Week 54

A standard 12-lead ECG was performed while the participant was at rest. Any abnormal ECG findings determined by the investigator to be clinically significant were reported as adverse events.

Number Of Participants With TEAEs Related To Vital Signs (Hypotension)
Up to Week 54

A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. Vital signs included office standing blood pressure, office sitting pulse rate, office standing pulse rate, and home sitting blood pressure. Any abnormal vital signs findings determined by the investigator to be clinically significant were reported as adverse events.

AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to Time 24 Hours of TAK-536 (Azilsartan)
Pre-dose and at multiple time points (up to 24 hours) post-dose

AUC(0-24) is a measure of total plasma exposure to the drug from time 0 to 24 hours post-dose, calculated using the linear trapezoidal rule.

Cmax: Maximum Observed Plasma Concentration of TAK-536 (Azilsartan)
Pre-dose and at multiple time points (up to 24 hours) post-dose

Cmax is the maximum observed plasma concentration (actual measurement value) of a drug after administration, obtained directly from the plasma concentration-time curve.

AUC(0-inf): Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity of TAK-536 (Azilsartan)
Pre-dose and at multiple time points (up to 24 hours) post-dose

AUC(0-inf) is a measure of total plasma exposure to the drug from time zero extrapolated to infinity, calculated as AUC(0-inf)=AUC(0-tlqc)+lqc/λz

Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of TAK-536 (Azilsartan)
Pre-dose and at multiple time points (up to 24 hours) post-dose

Tmax is the time to reach Cmax (actual measurement value), equal to time (hours) to Cmax.

T1/2: Terminal Elimination Half-Life of TAK-536 (Azilsartan)
Pre-dose and at multiple time points (up to 24 hours) post-dose

T1/2 is the terminal elimination half-life (time required for half of the drug to be eliminated from the plasma), calculated as T1/2=ln(2)/λz.

AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to Time 24 Hours of TAK-536 (Azilsartan) Metabolite M-I
Pre-dose and at multiple time points (up to 24 hours) post-dose

AUC(0-24) is a measure of total plasma exposure to the drug from time 0 to 24 hours post-dose, calculated using the linear trapezoidal rule.

Cmax: Maximum Observed Plasma Concentration of TAK-536 (Azilsartan) Metabolite M-I
Pre-dose and at multiple time points (up to 24 hours) post-dose

Cmax is the maximum observed plasma concentration (actual measurement value) of a drug after administration, obtained directly from the plasma concentration-time curve.

AUC(0-inf) Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity of TAK-536 (Azilsartan) Metabolite M-I
Pre-dose and at multiple time points (up to 24 hours) post-dose

AUC(0-inf) is a measure of total plasma exposure to the drug from time zero extrapolated to infinity, calculated as AUC(0-inf)=AUC(0-tlqc)+lqc/λz.

Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of TAK-536 (Azilsartan) Metabolite M-I
Pre-dose and at multiple time points (up to 24 hours) post-dose

Tmax is the time to reach Cmax (actual measurement value), equal to time (hours) to Cmax.

T1/2: Terminal Elimination Half-Life of TAK-536 (Azilsartan) Metabolite M-I
Pre-dose and at multiple time points (up to 24 hours) post-dose

T1/2 is the terminal elimination half-life (time required for half of the drug to be eliminated from the plasma), calculated as T1/2=ln(2)/λz.

AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to Time 24 Hours of TAK-536 (Azilsartan) Metabolite M-II
Pre-dose and at multiple time points (up to 24 hours) post-dose

AUC(0-24) is a measure of total plasma exposure to the drug from time 0 to 24 hours post-dose, calculated using the linear trapezoidal rule.

Cmax: Maximum Observed Plasma Concentration of TAK-536 (Azilsartan) Metabolite M-II
Pre-dose and at multiple time points (up to 24 hours) post-dose

Cmax is the maximum observed plasma concentration (actual measurement value) of a drug after administration, obtained directly from the plasma concentration-time curve.

AUC(0-inf) Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity of TAK-536 (Azilsartan) Metabolite M-II
Pre-dose and at multiple time points (up to 24 hours) post-dose

AUC(0-inf) is a measure of total plasma exposure to the drug from time zero extrapolated to infinity, calculated as AUC(0-inf)=AUC(0-tlqc)+lqc/λz.

Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of TAK-536 (Azilsartan) Metabolite M-II
Pre-dose and at multiple time points (up to 24 hours) post-dose

Tmax is the time to reach Cmax (actual measurement value), equal to time (hours) to Cmax.

T1/2: Terminal Elimination Half-Life of TAK-536 (Azilsartan) Metabolite M-II
Pre-dose and at multiple time points (up to 24 hours) post-dose

T1/2 is the terminal elimination half-life (time required for half of the drug to be eliminated from the plasma), calculated as T1/2=ln(2)/λz.

Cumulative Urinary Excretion Ratio of TAK-536 (Azilsartan)
Day 1 from 0 to 24 hours post-dose

The cumulative urinary excretion ratio (% of dose \[TAK-536-equivalent\]) of TAK-536 will be calculated from the urinary concentration and volume of each participant.

Cumulative Urinary Excretion Ratio of TAK-536 (Azilsartan) Metabolite M-I
Day 1 from 0 to 24 hours post-dose

The cumulative urinary excretion ratio (% of dose \[TAK-536-equivalent\]) of TAK-536 metabolite M-I will be calculated from the urinary concentration and volume of each participant.

Cumulative Urinary Excretion Ratio of TAK-536 (Azilsartan) Metabolite M-II
Day 1 from 0 to 24 hours post-dose

The cumulative urinary excretion ratio (% of dose \[TAK-536-equivalent\]) of TAK-536 metabolite M-II will be calculated from the urinary concentration and volume of each participant.

Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
Up to 15 Days

An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. Treatment emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; or congenital anomaly; or a medically important event.

Percentage of Participants With Remarkable Findings of Clinical Concern From Baseline in Vital Signs
Baseline and Day 2

Vital signs are defined as sitting blood pressure, sitting pulse rate and temperature.

Percentage of Participants With Remarkable Findings of Clinical Concern From Baseline in Body Weight
Baseline and Day 2
Percentage of Participants With Remarkable Findings of Clinical Concern From Baseline in Resting 12-Lead Electrocardiogram (ECG)
Baseline and Day 2

A resting 12-lead ECG was recorded. The investigator or subinvestigator (or a qualified physician at the study site) interpreted the ECG results.

Percentage of Participants With Remarkable Findings of Clinical Concern From Baseline in Laboratory Test Results
Baseline and Day 2

Laboratory test results are defined as serum chemistry, hematology and urinalysis.

Secondary Endpoints
Change From Baseline in Office Trough Sitting Systolic Blood Pressure
Baseline (Day 0), Weeks 2, 4, 8, 12,16, 20, 24, 32, 40, 52, Week 54 (Follow-up), End-of-treatment (EOT) 1 (Up to Week 12), EOT 2 (Up to Week 52)
Change From Baseline in Office Trough Sitting Diastolic Blood Pressure
Baseline (Day 0), Weeks 2, 4, 8, 12,16, 20, 24, 32, 40, 52, Week 54 (Follow-up), EOT 1 (Up to Week 12), EOT 2 (Up to Week 52)
Percentage Of Participants Who Achieve The Target Blood Pressure
Weeks 2, 4, 8, 12,16, 20, 24, 32, 40, 52, Week 54 (Follow-up), EOT 1 (Up to Week 12), EOT 2 (Up to Week 52)
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Study Design & Arms
AllocationNON_RANDOMIZED
MaskingNONE
ModelSINGLE_GROUP
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
Azilsartan 2.5 - 20 mg (Weight < 50 kg)EXPERIMENTALFollowing a 2-week placebo run-in period, azilsartan 2.5 mg (titrated as needed to the highest dose of 20 mg) was administered orally once daily before or after breakfast, for the participants weighing \< 50 kg.
Azilsartan 5 - 40 mg (Weight ≥ 50 kg)EXPERIMENTALFollowing a 2-week placebo run-in period, azilsartan 5 mg (titrated as needed to the highest dose of 40 mg) was administered orally once daily before or after breakfast, for the participants weighing ≥ 50 kg.
Azilsartan 5 mgEXPERIMENTALWeight \<50 kg: azilsartan 5 mg, tablets, orally, once, after breakfast on Day 1.
Azilsartan 10 mgEXPERIMENTALWeight ≥50 kg: azilsartan 10 mg, tablets, orally, once, after breakfast on Day 1.
Interventions
NameTypeDescription
AzilsartanDRUGAzilsartan granules and tablets
PlaceboDRUGPlacebo-matching azilsartan granules and tablets
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Eligibility Criteria
Age Range6 Years — 15 Years
SexALL
Healthy VolunteersNo
Study Sites30

Inclusion Criteria: 1. In the opinion of the investigator or subinvestigator, the participant's parent or the participant's 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 ...

Countries:Japan
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