Trial Outcomes & Findings for A Phase 1 Food Effect Study of Azilsartan (TAK-536) Pediatric Formulation (NCT NCT03434977)

NCT ID: NCT03434977

Last Updated: 2019-06-10

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 12 participants
• Primary outcome timeframe: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
• Results posted on: 2019-06-10

Participant Flow

Participants took part in the study at 1 investigative site in Japan from 14 February 2018 to 11 March 2018.

Healthy male participants were enrolled in 1 of the 2 treatment sequences of this 2-period cross-over study to receive pediatric formulation of TAK-536 10 milligram (mg) granules under fasted or fed condition.

Participant milestones

Measure	TAK-536 10 mg Granules Fasted + TAK-536 10 mg Granules Fed TAK-536 10 mg, granules (pediatric formulation), orally, under fasted condition, once on Day 1 of Period 1, followed by a washout period of at least 6 days, further followed by TAK-536 10 mg, granules (pediatric formulation), orally, under fed condition, once on Day 1 of Period 2.	TAK-536 10 mg Granules Fed + TAK-536 10 mg Granules Fasted TAK-536 10 mg, granules (pediatric formulation), orally, under fed condition, once on Day 1 of Period 1, followed by a washout period of at least 6 days, further followed by TAK-536 10 mg, granules (pediatric formulation), orally, under fasted condition, once on Day 1 of Period 2.
Intervention Period 1 (6 Days) STARTED	6	6
Intervention Period 1 (6 Days) COMPLETED	6	6
Intervention Period 1 (6 Days) NOT COMPLETED	0	0
Washout Period (at Least 6 Days) STARTED	6	6
Washout Period (at Least 6 Days) COMPLETED	6	5
Washout Period (at Least 6 Days) NOT COMPLETED	0	1
Intervention Period 2 (6 Days) STARTED	6	5
Intervention Period 2 (6 Days) COMPLETED	6	5
Intervention Period 2 (6 Days) NOT COMPLETED	0	0

Reasons for withdrawal

Measure	TAK-536 10 mg Granules Fasted + TAK-536 10 mg Granules Fed TAK-536 10 mg, granules (pediatric formulation), orally, under fasted condition, once on Day 1 of Period 1, followed by a washout period of at least 6 days, further followed by TAK-536 10 mg, granules (pediatric formulation), orally, under fed condition, once on Day 1 of Period 2.	TAK-536 10 mg Granules Fed + TAK-536 10 mg Granules Fasted TAK-536 10 mg, granules (pediatric formulation), orally, under fed condition, once on Day 1 of Period 1, followed by a washout period of at least 6 days, further followed by TAK-536 10 mg, granules (pediatric formulation), orally, under fasted condition, once on Day 1 of Period 2.
Washout Period (at Least 6 Days) Adverse Event	0	1

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	TAK-536 10 mg Granules Fasted + TAK-536 10 mg Granules Fed n=6 Participants TAK-536 10 mg, granules (pediatric formulation), orally, under fasted condition, once on Day 1 of Period 1, followed by a washout period of at least 6 days, further followed by TAK-536 10 mg, granules (pediatric formulation), orally, under fed condition, once on Day 1 of Period 2.	TAK-536 10 mg Granules Fed + TAK-536 10 mg Granules Fasted n=6 Participants TAK-536 10 mg, granules (pediatric formulation), orally, under fed condition, once on Day 1 of Period 1, followed by a washout period of at least 6 days, further followed by TAK-536 10 mg, granules (pediatric formulation), orally, under fasted condition, once on Day 1 of Period 2.	Total n=12 Participants Total of all reporting groups
Age, Continuous	22.7 years STANDARD_DEVIATION 2.73 • n=6 Participants	24.3 years STANDARD_DEVIATION 5.57 • n=6 Participants	23.5 years STANDARD_DEVIATION 4.27 • n=12 Participants
Sex: Female, Male Female	0 Participants n=6 Participants	0 Participants n=6 Participants	0 Participants n=12 Participants
Sex: Female, Male Male	6 Participants n=6 Participants	6 Participants n=6 Participants	12 Participants n=12 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment Japan	6 Participants n=6 Participants	6 Participants n=6 Participants	12 Participants n=12 Participants
Height	175.7 centimeter (cm) STANDARD_DEVIATION 7.31 • n=6 Participants	173.2 centimeter (cm) STANDARD_DEVIATION 5.71 • n=6 Participants	174.4 centimeter (cm) STANDARD_DEVIATION 6.39 • n=12 Participants
Weight	66.88 kilogram (kg) STANDARD_DEVIATION 5.712 • n=6 Participants	64.02 kilogram (kg) STANDARD_DEVIATION 11.129 • n=6 Participants	65.45 kilogram (kg) STANDARD_DEVIATION 8.566 • n=12 Participants
Body Mass Index (BMI)	21.72 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.036 • n=6 Participants	21.23 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.392 • n=6 Participants	21.47 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.133 • n=12 Participants
Smoking Classification Never smoked	4 Participants n=6 Participants	1 Participants n=6 Participants	5 Participants n=12 Participants
Smoking Classification Current smoker	1 Participants n=6 Participants	5 Participants n=6 Participants	6 Participants n=12 Participants
Smoking Classification Former smoker	1 Participants n=6 Participants	0 Participants n=6 Participants	1 Participants n=12 Participants
Alcohol Classification Drank a few times per month	5 Participants n=6 Participants	5 Participants n=6 Participants	10 Participants n=12 Participants
Alcohol Classification Never drank	1 Participants n=6 Participants	1 Participants n=6 Participants	2 Participants n=12 Participants
Caffeine Classification Had caffeine consumption	3 Participants n=6 Participants	0 Participants n=6 Participants	3 Participants n=12 Participants
Caffeine Classification Had no caffeine consumption	3 Participants n=6 Participants	6 Participants n=6 Participants	9 Participants n=12 Participants

PRIMARY outcome

Timeframe: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose

Population: The pharmacokinetic (PK) analysis set was defined as all participants who received the study drug, completed the minimum protocol-specified procedures without any major protocol deviations, and were evaluable for PK.

Outcome measures

Measure	TAK-536 10 mg Granules Fasted n=11 Participants TAK-536 10 mg, granules (pediatric formulation), orally, under fasted condition, once on Day 1 of either Period 1 or 2.	TAK-536 10 mg Granules Fed n=11 Participants TAK-536 10 mg, granules (pediatric formulation), orally, under fed condition, once on Day 1 of either Period 1 or 2.
Cmax: Maximum Observed Plasma Concentration for TAK-536	652.6 nanogram per milliliter (ng/mL) Standard Deviation 78.03	609.4 nanogram per milliliter (ng/mL) Standard Deviation 103.92

PRIMARY outcome

Timeframe: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose

Population: The PK analysis set was defined as all participants who received the study drug, completed the minimum protocol-specified procedures without any major protocol deviations, and were evaluable for PK.

Outcome measures

Measure	TAK-536 10 mg Granules Fasted n=11 Participants TAK-536 10 mg, granules (pediatric formulation), orally, under fasted condition, once on Day 1 of either Period 1 or 2.	TAK-536 10 mg Granules Fed n=11 Participants TAK-536 10 mg, granules (pediatric formulation), orally, under fed condition, once on Day 1 of either Period 1 or 2.
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-536	2.000 hours Interval 1.0 to 4.0	3.000 hours Interval 2.0 to 4.0

PRIMARY outcome

Timeframe: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose

Population: The PK analysis set was defined as all participants who received the study drug, completed the minimum protocol-specified procedures without any major protocol deviations, and were evaluable for PK.

Outcome measures

Measure	TAK-536 10 mg Granules Fasted n=11 Participants TAK-536 10 mg, granules (pediatric formulation), orally, under fasted condition, once on Day 1 of either Period 1 or 2.	TAK-536 10 mg Granules Fed n=11 Participants TAK-536 10 mg, granules (pediatric formulation), orally, under fed condition, once on Day 1 of either Period 1 or 2.
AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-536	5275.3 hour*nanogram per milliliter (h*ng/mL) Standard Deviation 1044.49	5220.7 hour*nanogram per milliliter (h*ng/mL) Standard Deviation 881.13

PRIMARY outcome

Timeframe: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose

Population: The PK analysis set was defined as all participants who received the study drug, completed the minimum protocol-specified procedures without any major protocol deviations, and were evaluable for PK.

Outcome measures

Measure	TAK-536 10 mg Granules Fasted n=11 Participants TAK-536 10 mg, granules (pediatric formulation), orally, under fasted condition, once on Day 1 of either Period 1 or 2.	TAK-536 10 mg Granules Fed n=11 Participants TAK-536 10 mg, granules (pediatric formulation), orally, under fed condition, once on Day 1 of either Period 1 or 2.
AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-536	5440.1 h*ng/mL Standard Deviation 1109.74	5377.8 h*ng/mL Standard Deviation 918.96

PRIMARY outcome

Timeframe: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose

Population: The PK analysis set was defined as all participants who received the study drug, completed the minimum protocol-specified procedures without any major protocol deviations, and were evaluable for PK.

Outcome measures

Measure	TAK-536 10 mg Granules Fasted n=11 Participants TAK-536 10 mg, granules (pediatric formulation), orally, under fasted condition, once on Day 1 of either Period 1 or 2.	TAK-536 10 mg Granules Fed n=11 Participants TAK-536 10 mg, granules (pediatric formulation), orally, under fed condition, once on Day 1 of either Period 1 or 2.
T1/2z: Terminal Disposition Phase Half-life for TAK-536	11.11 hours Standard Deviation 0.90050	10.96 hours Standard Deviation 0.85065

PRIMARY outcome

Timeframe: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose

Population: The PK analysis set was defined as all participants who received the study drug, completed the minimum protocol-specified procedures without any major protocol deviations, and were evaluable for PK.

Outcome measures

Measure	TAK-536 10 mg Granules Fasted n=11 Participants TAK-536 10 mg, granules (pediatric formulation), orally, under fasted condition, once on Day 1 of either Period 1 or 2.	TAK-536 10 mg Granules Fed n=11 Participants TAK-536 10 mg, granules (pediatric formulation), orally, under fed condition, once on Day 1 of either Period 1 or 2.
MRTlast, ev: Mean Residence Time From Time 0 to the Time of the Last Quantifiable Concentration for TAK-536	9.419 hours Standard Deviation 1.0233	9.836 hours Standard Deviation 0.61518

PRIMARY outcome

Timeframe: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose

Population: The PK analysis set was defined as all participants who received the study drug, completed the minimum protocol-specified procedures without any major protocol deviations, and were evaluable for PK.

Outcome measures

Measure	TAK-536 10 mg Granules Fasted n=11 Participants TAK-536 10 mg, granules (pediatric formulation), orally, under fasted condition, once on Day 1 of either Period 1 or 2.	TAK-536 10 mg Granules Fed n=11 Participants TAK-536 10 mg, granules (pediatric formulation), orally, under fed condition, once on Day 1 of either Period 1 or 2.
MRT∞, ev: Mean Residence Time From Time 0 to Infinity for TAK-536	11.02 hours Standard Deviation 1.3931	11.40 hours Standard Deviation 0.90089

PRIMARY outcome

Timeframe: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose

Population: The PK analysis set was defined as all participants who received the study drug, completed the minimum protocol-specified procedures without any major protocol deviations, and were evaluable for PK.

Outcome measures

Measure	TAK-536 10 mg Granules Fasted n=11 Participants TAK-536 10 mg, granules (pediatric formulation), orally, under fasted condition, once on Day 1 of either Period 1 or 2.	TAK-536 10 mg Granules Fed n=11 Participants TAK-536 10 mg, granules (pediatric formulation), orally, under fed condition, once on Day 1 of either Period 1 or 2.
λz: Terminal Disposition Phase Rate Constant for TAK-536	0.06285 1 per hour (1/h) Standard Deviation 0.0048845	0.06355 1 per hour (1/h) Standard Deviation 0.0047738

PRIMARY outcome

Timeframe: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose

Population: The PK analysis set was defined as all participants who received the study drug, completed the minimum protocol-specified procedures without any major protocol deviations, and were evaluable for PK.

Outcome measures

Measure	TAK-536 10 mg Granules Fasted n=11 Participants TAK-536 10 mg, granules (pediatric formulation), orally, under fasted condition, once on Day 1 of either Period 1 or 2.	TAK-536 10 mg Granules Fed n=11 Participants TAK-536 10 mg, granules (pediatric formulation), orally, under fed condition, once on Day 1 of either Period 1 or 2.
CL/F: Apparent Clearance for TAK-536	1.912 Liter per hour (L/h) Standard Deviation 0.40241	1.909 Liter per hour (L/h) Standard Deviation 0.31980

PRIMARY outcome

Timeframe: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose

Population: The PK analysis set was defined as all participants who received the study drug, completed the minimum protocol-specified procedures without any major protocol deviations, and were evaluable for PK.

Outcome measures

Measure	TAK-536 10 mg Granules Fasted n=11 Participants TAK-536 10 mg, granules (pediatric formulation), orally, under fasted condition, once on Day 1 of either Period 1 or 2.	TAK-536 10 mg Granules Fed n=11 Participants TAK-536 10 mg, granules (pediatric formulation), orally, under fed condition, once on Day 1 of either Period 1 or 2.
Vz/F: Apparent Volume of Distribution for TAK-536	30.35 liter Standard Deviation 5.5177	30.14 liter Standard Deviation 5.2637

SECONDARY outcome

Timeframe: Baseline up to Day 18 (End of Period 2)

Population: The safety analysis set was defined as all participants who received at least one dose of the study drug. Out of 12 participants, only 11 participants received study drug under fasted condition, since 1 participant discontinued the study due to adverse event (AE) before the start of Period 2.

Outcome measures

Measure	TAK-536 10 mg Granules Fasted n=11 Participants TAK-536 10 mg, granules (pediatric formulation), orally, under fasted condition, once on Day 1 of either Period 1 or 2.	TAK-536 10 mg Granules Fed n=12 Participants TAK-536 10 mg, granules (pediatric formulation), orally, under fed condition, once on Day 1 of either Period 1 or 2.
Number of Participants Who Experienced at Least One Treatment-emergent Adverse Event (TEAE)	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline up to Day 18 (End of Period 2)

Population: The safety analysis set was defined as all participants who received at least one dose of the study drug. Out of 12 participants, only 11 participants received study drug under fasted condition, since 1 participant discontinued the study due to AE before the start of Period 2.

Outcome measures

Measure	TAK-536 10 mg Granules Fasted n=11 Participants TAK-536 10 mg, granules (pediatric formulation), orally, under fasted condition, once on Day 1 of either Period 1 or 2.	TAK-536 10 mg Granules Fed n=12 Participants TAK-536 10 mg, granules (pediatric formulation), orally, under fed condition, once on Day 1 of either Period 1 or 2.
Number of Participants With TEAE Related to Vital Sign	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline up to Day 18 (End of Period 2)

Population: The safety analysis set was defined as all participants who received at least one dose of the study drug. Out of 12 participants, only 11 participants received study drug under fasted condition, since 1 participant discontinued the study due to AE before the start of Period 2.

Outcome measures

Measure	TAK-536 10 mg Granules Fasted n=11 Participants TAK-536 10 mg, granules (pediatric formulation), orally, under fasted condition, once on Day 1 of either Period 1 or 2.	TAK-536 10 mg Granules Fed n=12 Participants TAK-536 10 mg, granules (pediatric formulation), orally, under fed condition, once on Day 1 of either Period 1 or 2.
Number of Participants With TEAE Related to Body Weight	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline up to Day 18 (End of Period 2)

Population: The safety analysis set was defined as all participants who received at least one dose of the study drug. Out of 12 participants, only 11 participants received study drug under fasted condition, since 1 participant discontinued the study due to AE before the start of Period 2.

Outcome measures

Measure	TAK-536 10 mg Granules Fasted n=11 Participants TAK-536 10 mg, granules (pediatric formulation), orally, under fasted condition, once on Day 1 of either Period 1 or 2.	TAK-536 10 mg Granules Fed n=12 Participants TAK-536 10 mg, granules (pediatric formulation), orally, under fed condition, once on Day 1 of either Period 1 or 2.
Number of Participants With TEAE Related to Clinical Laboratory Tests (Eosinophil Count Increased)	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline up to Day 18 (End of Period 2)

Population: The safety analysis set was defined as all participants who received at least one dose of the study drug. Out of 12 participants, only 11 participants received study drug under fasted condition, since 1 participant discontinued the study due to AE before the start of Period 2.

Outcome measures

Measure	TAK-536 10 mg Granules Fasted n=11 Participants TAK-536 10 mg, granules (pediatric formulation), orally, under fasted condition, once on Day 1 of either Period 1 or 2.	TAK-536 10 mg Granules Fed n=12 Participants TAK-536 10 mg, granules (pediatric formulation), orally, under fed condition, once on Day 1 of either Period 1 or 2.
Number of Participants With TEAE Related to 12-lead Electrocardiograms (ECGs)	0 Participants	0 Participants

Adverse Events

TAK-536 10 mg Granules Fasted

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

TAK-536 10 mg Granules Fed

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	TAK-536 10 mg Granules Fasted n=11 participants at risk TAK-536 10 mg, granules (pediatric formulation), orally, under fasted condition, once on Day 1 of either Period 1 or 2.	TAK-536 10 mg Granules Fed n=12 participants at risk TAK-536 10 mg, granules (pediatric formulation), orally, under fed condition, once on Day 1 of either Period 1 or 2.
Investigations Eosinophil count increased	0.00% 0/11 • TEAEs are adverse events that started after the first dose of study drug until the follow up examination on Day 6 in Period 2 (Day 18) 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. Out of 12 participants, only 11 participants received study drug under fasted condition, since 1 participant discontinued the study due to AE before the start of Period 2.	8.3% 1/12 • TEAEs are adverse events that started after the first dose of study drug until the follow up examination on Day 6 in Period 2 (Day 18) 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. Out of 12 participants, only 11 participants received study drug under fasted condition, since 1 participant discontinued the study due to AE before the start of Period 2.

Additional Information

Medical Director

Takeda

Phone: +1-877-825-3327

Email: trialdisclosures@takeda.com

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