Trial Outcomes & Findings for Safety, Tolerability and Pharmacokinetics of Escalating Single Doses of ENV8058 (TAK-058) in Healthy Participants (NCT NCT02153099)

NCT ID: NCT02153099

Last Updated: 2015-12-17

Results Overview

Treatment-emergent adverse events are defined as any unfavorable and unintended sign, symptom or disease temporally associated with the use of a medicinal product reported from first dose of study drug through 14 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 48 participants
• Primary outcome timeframe: Baseline up to Day 30
• Results posted on: 2015-12-17

Participant Flow

Participants took part in the study at 1 investigative site in the United States from 14 May 2014 (signing of informed consent) to 13 November 2014.

Healthy Volunteers were enrolled in 1 of 6 Dose Cohorts: (5 mg, 15 mg, 30 mg, 45 mg, 75 mg, 150 mg TAK-058) or placebo.

Participant milestones

Measure	Cohort 4: TAK-058 5 mg TAK-058 (ENV8058) 5 mg, 100 mL oral solution, once on Day 1.	Cohort 1: TAK-058 15 mg TAK-058 15 mg, 100 mL oral solution, once on Day 1.	Cohort 2: TAK-058 30 mg TAK-058 30 mg, 100 mL oral solution, once on Day 1.	Cohort 3: TAK-058 45 mg TAK-058 45 mg, 100 mL oral solution, once on Day 1.	Cohort 5: TAK-058 75 mg TAK-058 75 mg, 100 mL oral solution, once on Day 1.	Cohorts 6: TAK-058 150 mg TAK-058 150 mg, 100 mL oral solution, once on Day 1.	Cohort 1-6: Placebo TAK-058 placebo-matching, 100 mL oral solution, once on Day 1.
Overall Study STARTED	6	6	6	6	6	6	12
Overall Study COMPLETED	6	6	6	6	6	6	12
Overall Study NOT COMPLETED	0	0	0	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Safety, Tolerability and Pharmacokinetics of Escalating Single Doses of ENV8058 (TAK-058) in Healthy Participants

Baseline characteristics by cohort

Measure	Cohort 4: TAK-058 5 mg n=6 Participants TAK-058 5 mg, 100 mL oral solution, once on Day 1.	Cohort 1: TAK-058 15 mg n=6 Participants TAK-058 15 mg, 100 mL oral solution, once on Day 1.	Cohort 2: TAK-058 30 mg n=6 Participants TAK-058 30 mg, 100 mL oral solution, once on Day 1.	Cohort 3: TAK-058 45 mg n=6 Participants TAK-058 45 mg, 100 mL oral solution, once on Day 1.	Cohort 5: TAK-058 75 mg n=6 Participants TAK-058 75 mg, 100 mL oral solution, once on Day 1.	Cohorts 6: TAK-058 150 mg n=6 Participants TAK-058 150 mg, 100 mL oral solution, once on Day 1.	Cohort 1-6: Placebo n=12 Participants TAK-058 placebo-matching, 100 mL oral solution, once on Day 1.	Total n=48 Participants Total of all reporting groups
Age, Continuous	33.7 years STANDARD_DEVIATION 11.38 • n=93 Participants	37.0 years STANDARD_DEVIATION 14.01 • n=4 Participants	35.3 years STANDARD_DEVIATION 10.71 • n=27 Participants	34.2 years STANDARD_DEVIATION 7.78 • n=483 Participants	41.5 years STANDARD_DEVIATION 10.93 • n=36 Participants	30.8 years STANDARD_DEVIATION 8.54 • n=10 Participants	34.2 years STANDARD_DEVIATION 9.11 • n=115 Participants	35.1 years STANDARD_DEVIATION 10.09 • n=40 Participants
Sex: Female, Male Female	1 Participants n=93 Participants	1 Participants n=4 Participants	2 Participants n=27 Participants	2 Participants n=483 Participants	1 Participants n=36 Participants	0 Participants n=10 Participants	2 Participants n=115 Participants	9 Participants n=40 Participants
Sex: Female, Male Male	5 Participants n=93 Participants	5 Participants n=4 Participants	4 Participants n=27 Participants	4 Participants n=483 Participants	5 Participants n=36 Participants	6 Participants n=10 Participants	10 Participants n=115 Participants	39 Participants n=40 Participants
Race/Ethnicity, Customized Asian	1 participants n=93 Participants	0 participants n=4 Participants	0 participants n=27 Participants	1 participants n=483 Participants	0 participants n=36 Participants	0 participants n=10 Participants	1 participants n=115 Participants	3 participants n=40 Participants
Race/Ethnicity, Customized Black or African American	2 participants n=93 Participants	1 participants n=4 Participants	1 participants n=27 Participants	1 participants n=483 Participants	3 participants n=36 Participants	1 participants n=10 Participants	3 participants n=115 Participants	12 participants n=40 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	0 participants n=93 Participants	0 participants n=4 Participants	0 participants n=27 Participants	0 participants n=483 Participants	0 participants n=36 Participants	0 participants n=10 Participants	1 participants n=115 Participants	1 participants n=40 Participants
Race/Ethnicity, Customized White	3 participants n=93 Participants	5 participants n=4 Participants	5 participants n=27 Participants	4 participants n=483 Participants	3 participants n=36 Participants	5 participants n=10 Participants	7 participants n=115 Participants	32 participants n=40 Participants
Race/Ethnicity, Customized Hispanic or Latino	0 participants n=93 Participants	3 participants n=4 Participants	1 participants n=27 Participants	3 participants n=483 Participants	1 participants n=36 Participants	2 participants n=10 Participants	2 participants n=115 Participants	12 participants n=40 Participants
Race/Ethnicity, Customized Non-Hispanic or non-Latino	6 participants n=93 Participants	3 participants n=4 Participants	5 participants n=27 Participants	3 participants n=483 Participants	5 participants n=36 Participants	4 participants n=10 Participants	10 participants n=115 Participants	36 participants n=40 Participants
Region of Enrollment North America	6 participants n=93 Participants	6 participants n=4 Participants	6 participants n=27 Participants	6 participants n=483 Participants	6 participants n=36 Participants	6 participants n=10 Participants	12 participants n=115 Participants	48 participants n=40 Participants
Height	171.2 cm STANDARD_DEVIATION 4.40 • n=93 Participants	167.7 cm STANDARD_DEVIATION 6.44 • n=4 Participants	174.7 cm STANDARD_DEVIATION 15.20 • n=27 Participants	170.2 cm STANDARD_DEVIATION 10.42 • n=483 Participants	178.7 cm STANDARD_DEVIATION 8.78 • n=36 Participants	175.5 cm STANDARD_DEVIATION 8.69 • n=10 Participants	176.1 cm STANDARD_DEVIATION 12.91 • n=115 Participants	173.8 cm STANDARD_DEVIATION 10.49 • n=40 Participants
Weight	72.73 kg STANDARD_DEVIATION 10.683 • n=93 Participants	70.65 kg STANDARD_DEVIATION 6.763 • n=4 Participants	81.72 kg STANDARD_DEVIATION 20.142 • n=27 Participants	79.38 kg STANDARD_DEVIATION 10.860 • n=483 Participants	86.17 kg STANDARD_DEVIATION 12.796 • n=36 Participants	80.50 kg STANDARD_DEVIATION 16.471 • n=10 Participants	72.77 kg STANDARD_DEVIATION 12.359 • n=115 Participants	77.09 kg STANDARD_DEVIATION 13.514 • n=40 Participants
Body Mass Index (BMI)	24.79 kg/m^2 STANDARD_DEVIATION 3.110 • n=93 Participants	25.11 kg/m^2 STANDARD_DEVIATION 1.674 • n=4 Participants	26.35 kg/m^2 STANDARD_DEVIATION 3.086 • n=27 Participants	27.39 kg/m^2 STANDARD_DEVIATION 2.440 • n=483 Participants	26.86 kg/m^2 STANDARD_DEVIATION 1.989 • n=36 Participants	25.89 kg/m^2 STANDARD_DEVIATION 2.728 • n=10 Participants	23.42 kg/m^2 STANDARD_DEVIATION 2.533 • n=115 Participants	25.40 kg/m^2 STANDARD_DEVIATION 2.770 • n=40 Participants
Smoking Status Never smoked	5 participants n=93 Participants	5 participants n=4 Participants	5 participants n=27 Participants	6 participants n=483 Participants	5 participants n=36 Participants	5 participants n=10 Participants	11 participants n=115 Participants	42 participants n=40 Participants
Smoking Status Current smoker	0 participants n=93 Participants	0 participants n=4 Participants	0 participants n=27 Participants	0 participants n=483 Participants	0 participants n=36 Participants	0 participants n=10 Participants	0 participants n=115 Participants	0 participants n=40 Participants
Smoking Status Ex-smoker	1 participants n=93 Participants	1 participants n=4 Participants	1 participants n=27 Participants	0 participants n=483 Participants	1 participants n=36 Participants	1 participants n=10 Participants	1 participants n=115 Participants	6 participants n=40 Participants
Caffeine Consumption Yes	3 participants n=93 Participants	3 participants n=4 Participants	4 participants n=27 Participants	4 participants n=483 Participants	4 participants n=36 Participants	3 participants n=10 Participants	6 participants n=115 Participants	27 participants n=40 Participants
Caffeine Consumption No	3 participants n=93 Participants	3 participants n=4 Participants	2 participants n=27 Participants	2 participants n=483 Participants	2 participants n=36 Participants	3 participants n=10 Participants	6 participants n=115 Participants	21 participants n=40 Participants
Female Reproductive Status Postmenopausal	1 participants n=93 Participants	1 participants n=4 Participants	1 participants n=27 Participants	0 participants n=483 Participants	0 participants n=36 Participants	0 participants n=10 Participants	0 participants n=115 Participants	3 participants n=40 Participants
Female Reproductive Status Surgically Sterile	0 participants n=93 Participants	0 participants n=4 Participants	1 participants n=27 Participants	2 participants n=483 Participants	1 participants n=36 Participants	0 participants n=10 Participants	2 participants n=115 Participants	6 participants n=40 Participants
Female Reproductive Status Female of Childbearing Potential	0 participants n=93 Participants	0 participants n=4 Participants	0 participants n=27 Participants	0 participants n=483 Participants	0 participants n=36 Participants	0 participants n=10 Participants	0 participants n=115 Participants	0 participants n=40 Participants
Female Reproductive Status Subject is Male	5 participants n=93 Participants	5 participants n=4 Participants	4 participants n=27 Participants	4 participants n=483 Participants	5 participants n=36 Participants	6 participants n=10 Participants	10 participants n=115 Participants	39 participants n=40 Participants

PRIMARY outcome

Timeframe: Baseline up to Day 30

Population: Safety population included all enrolled participants who received at least 1 dose of study drug.

Treatment-emergent adverse events are defined as any unfavorable and unintended sign, symptom or disease temporally associated with the use of a medicinal product reported from first dose of study drug through 14 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug.

Outcome measures

Measure	Cohort 4: TAK-058 5 mg n=6 Participants TAK-058 5 mg, 100 mL oral solution, once on Day 1.	Cohort 1: TAK-058 15 mg n=6 Participants TAK-058 15 mg, 100 mL oral solution, once on Day 1.	Cohort 2: TAK-058 30 mg n=6 Participants TAK-058 30 mg, 100 mL oral solution, once on Day 1.	Cohort 3: TAK-058 45 mg n=6 Participants TAK-058 45 mg, 100 mL oral solution, once on Day 1.	Cohort 5: TAK-058 75 mg n=6 Participants TAK-058 75 mg, 100 mL oral solution, once on Day 1.	Cohorts 6: TAK-058 150 mg n=6 Participants TAK-058 150 mg, 100 mL oral solution, once on Day 1.	Cohort 1-6: Placebo n=12 Participants TAK-058 placebo-matching, 100 mL oral solution, once on Day 1.
Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE)	16.7 percentage of participants	0 percentage of participants	50.0 percentage of participants	0 percentage of participants	16.7 percentage of participants	0 percentage of participants	8.3 percentage of participants

PRIMARY outcome

Timeframe: Baseline up to Day 14

Population: Safety population included all enrolled participants who received at least 1 dose of study drug.

The percentage of participants with any markedly abnormal standard safety laboratory values, including hematology, serum chemistries, and urinalysis, during the treatment period.

Outcome measures

Measure	Cohort 4: TAK-058 5 mg n=6 Participants TAK-058 5 mg, 100 mL oral solution, once on Day 1.	Cohort 1: TAK-058 15 mg n=6 Participants TAK-058 15 mg, 100 mL oral solution, once on Day 1.	Cohort 2: TAK-058 30 mg n=6 Participants TAK-058 30 mg, 100 mL oral solution, once on Day 1.	Cohort 3: TAK-058 45 mg n=6 Participants TAK-058 45 mg, 100 mL oral solution, once on Day 1.	Cohort 5: TAK-058 75 mg n=6 Participants TAK-058 75 mg, 100 mL oral solution, once on Day 1.	Cohorts 6: TAK-058 150 mg n=6 Participants TAK-058 150 mg, 100 mL oral solution, once on Day 1.	Cohort 1-6: Placebo n=12 Participants TAK-058 placebo-matching, 100 mL oral solution, once on Day 1.
Percentage of Participants With Markedly Abnormal Safety Laboratory Tests	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants

PRIMARY outcome

Timeframe: Baseline up to Day 14

Population: Safety population included all enrolled participants who received at least 1 dose of study drug.

The percentage of participants who meet markedly abnormal criteria for vital signs, including oral body temperature, respiration rate, pulse [beats per minute (bpm)], and resting blood pressure and after standing.

Outcome measures

Measure	Cohort 4: TAK-058 5 mg n=6 Participants TAK-058 5 mg, 100 mL oral solution, once on Day 1.	Cohort 1: TAK-058 15 mg n=6 Participants TAK-058 15 mg, 100 mL oral solution, once on Day 1.	Cohort 2: TAK-058 30 mg n=6 Participants TAK-058 30 mg, 100 mL oral solution, once on Day 1.	Cohort 3: TAK-058 45 mg n=6 Participants TAK-058 45 mg, 100 mL oral solution, once on Day 1.	Cohort 5: TAK-058 75 mg n=6 Participants TAK-058 75 mg, 100 mL oral solution, once on Day 1.	Cohorts 6: TAK-058 150 mg n=6 Participants TAK-058 150 mg, 100 mL oral solution, once on Day 1.	Cohort 1-6: Placebo n=12 Participants TAK-058 placebo-matching, 100 mL oral solution, once on Day 1.
Percentage of Participants With Markedly Abnormal Vital Sign Measurements Any Vital Sign - Abnormal High	0 percentage of participants	16.7 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	16.7 percentage of participants	0 percentage of participants
Percentage of Participants With Markedly Abnormal Vital Sign Measurements Any Vital Sign - Any Abnormality	66.7 percentage of participants	33.3 percentage of participants	33.3 percentage of participants	33.3 percentage of participants	50.0 percentage of participants	33.3 percentage of participants	50.0 percentage of participants
Percentage of Participants With Markedly Abnormal Vital Sign Measurements Systolic Blood Pressure >180 mmHg	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants
Percentage of Participants With Markedly Abnormal Vital Sign Measurements Systolic Blood Pressure - Any Abnormality	16.7 percentage of participants	0 percentage of participants	33.3 percentage of participants	0 percentage of participants	0 percentage of participants	16.7 percentage of participants	0 percentage of participants
Percentage of Participants With Markedly Abnormal Vital Sign Measurements Diastolic Blood Pressure <50 mmHg	0 percentage of participants	0 percentage of participants	0 percentage of participants	16.7 percentage of participants	16.7 percentage of participants	0 percentage of participants	0 percentage of participants
Percentage of Participants With Markedly Abnormal Vital Sign Measurements Diastolic Blood Pressure - Any Abnormality	0 percentage of participants	0 percentage of participants	0 percentage of participants	16.7 percentage of participants	16.7 percentage of participants	0 percentage of participants	0 percentage of participants
Percentage of Participants With Markedly Abnormal Vital Sign Measurements Pulse <50 bpm	50.0 percentage of participants	16.7 percentage of participants	16.7 percentage of participants	16.7 percentage of participants	50.0 percentage of participants	0 percentage of participants	33.3 percentage of participants
Percentage of Participants With Markedly Abnormal Vital Sign Measurements Pulse >120 bpm	0 percentage of participants	16.7 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	16.7 percentage of participants	0 percentage of participants
Percentage of Participants With Markedly Abnormal Vital Sign Measurements Temperature <35.6 degrees Celsius	16.7 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	25.0 percentage of participants
Percentage of Participants With Markedly Abnormal Vital Sign Measurements Temperature - Any Abnormality	16.7 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	25.0 percentage of participants
Percentage of Participants With Markedly Abnormal Vital Sign Measurements Any Vital Sign - Abnormal Low	66.7 percentage of participants	16.7 percentage of participants	33.3 percentage of participants	33.3 percentage of participants	50.0 percentage of participants	16.7 percentage of participants	50.0 percentage of participants
Percentage of Participants With Markedly Abnormal Vital Sign Measurements Systolic Blood Pressure <85 mmHg	16.7 percentage of participants	0 percentage of participants	33.3 percentage of participants	0 percentage of participants	0 percentage of participants	16.7 percentage of participants	0 percentage of participants
Percentage of Participants With Markedly Abnormal Vital Sign Measurements Diastolic Blood Pressure >110 mmHg	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants
Percentage of Participants With Markedly Abnormal Vital Sign Measurements Pulse - Any Abnormality	50.0 percentage of participants	33.3 percentage of participants	16.7 percentage of participants	16.7 percentage of participants	50.0 percentage of participants	16.7 percentage of participants	33.3 percentage of participants
Percentage of Participants With Markedly Abnormal Vital Sign Measurements Temperature >37.7 degrees Celsius	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: Predose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, and 96 hours postdose

Population: Pharmacokinetic (PK) Population included all enrolled participants.

Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.

Outcome measures

Measure	Cohort 4: TAK-058 5 mg n=6 Participants TAK-058 5 mg, 100 mL oral solution, once on Day 1.	Cohort 1: TAK-058 15 mg n=6 Participants TAK-058 15 mg, 100 mL oral solution, once on Day 1.	Cohort 2: TAK-058 30 mg n=6 Participants TAK-058 30 mg, 100 mL oral solution, once on Day 1.	Cohort 3: TAK-058 45 mg n=6 Participants TAK-058 45 mg, 100 mL oral solution, once on Day 1.	Cohort 5: TAK-058 75 mg n=6 Participants TAK-058 75 mg, 100 mL oral solution, once on Day 1.	Cohorts 6: TAK-058 150 mg n=6 Participants TAK-058 150 mg, 100 mL oral solution, once on Day 1.	Cohort 1-6: Placebo TAK-058 placebo-matching, 100 mL oral solution, once on Day 1.
Cmax: Maximum Observed Plasma Concentration for ENV8058 (TAK-058)	142.4 ng/mL Standard Deviation 43.68	565.0 ng/mL Standard Deviation 112.07	824.7 ng/mL Standard Deviation 297.45	1248.2 ng/mL Standard Deviation 254.06	1563.3 ng/mL Standard Deviation 339.51	2136.7 ng/mL Standard Deviation 818.04	—

SECONDARY outcome

Timeframe: Predose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, and 96 hours postdose

Population: PK Population included all enrolled participants.

(AUC(0-tlqc) is a measure of total plasma exposure to the drug from time 0 to time of the last quantifiable concentration (AUC[0-tlqc]).

Outcome measures

Measure	Cohort 4: TAK-058 5 mg n=6 Participants TAK-058 5 mg, 100 mL oral solution, once on Day 1.	Cohort 1: TAK-058 15 mg n=6 Participants TAK-058 15 mg, 100 mL oral solution, once on Day 1.	Cohort 2: TAK-058 30 mg n=6 Participants TAK-058 30 mg, 100 mL oral solution, once on Day 1.	Cohort 3: TAK-058 45 mg n=6 Participants TAK-058 45 mg, 100 mL oral solution, once on Day 1.	Cohort 5: TAK-058 75 mg n=6 Participants TAK-058 75 mg, 100 mL oral solution, once on Day 1.	Cohorts 6: TAK-058 150 mg n=6 Participants TAK-058 150 mg, 100 mL oral solution, once on Day 1.	Cohort 1-6: Placebo TAK-058 placebo-matching, 100 mL oral solution, once on Day 1.
AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for ENV8058 (TAK-058)	617.8 ng*hr/mL Standard Deviation 334.31	2297.8 ng*hr/mL Standard Deviation 678.69	3243.9 ng*hr/mL Standard Deviation 1261.96	5027.3 ng*hr/mL Standard Deviation 1001.82	6275.4 ng*hr/mL Standard Deviation 1535.27	9385.8 ng*hr/mL Standard Deviation 3398.36	—

SECONDARY outcome

Timeframe: Predose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, and 96 hours postdose

Population: PK Population included all enrolled participants.

AUC(0-inf) is a measure of total plasma exposure to the drug from time zero extrapolated to infinity.

Outcome measures

Measure	Cohort 4: TAK-058 5 mg n=6 Participants TAK-058 5 mg, 100 mL oral solution, once on Day 1.	Cohort 1: TAK-058 15 mg n=6 Participants TAK-058 15 mg, 100 mL oral solution, once on Day 1.	Cohort 2: TAK-058 30 mg n=6 Participants TAK-058 30 mg, 100 mL oral solution, once on Day 1.	Cohort 3: TAK-058 45 mg n=6 Participants TAK-058 45 mg, 100 mL oral solution, once on Day 1.	Cohort 5: TAK-058 75 mg n=6 Participants TAK-058 75 mg, 100 mL oral solution, once on Day 1.	Cohorts 6: TAK-058 150 mg n=6 Participants TAK-058 150 mg, 100 mL oral solution, once on Day 1.	Cohort 1-6: Placebo TAK-058 placebo-matching, 100 mL oral solution, once on Day 1.
AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for ENV8058 (TAK-058)	620.5 ng*hr/mL Standard Deviation 334.86	2305.5 ng*hr/mL Standard Deviation 678.59	3252.1 ng*hr/mL Standard Deviation 1264.03	5038.9 ng*hr/mL Standard Deviation 998.48	6292.1 ng*hr/mL Standard Deviation 1546.90	9407.9 ng*hr/mL Standard Deviation 3402.50	—

SECONDARY outcome

Timeframe: Predose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, and 96 hours postdose

Population: PK population included all enrolled participants.

Terminal Phase Elimination Half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma.

Outcome measures

Measure	Cohort 4: TAK-058 5 mg n=6 Participants TAK-058 5 mg, 100 mL oral solution, once on Day 1.	Cohort 1: TAK-058 15 mg n=6 Participants TAK-058 15 mg, 100 mL oral solution, once on Day 1.	Cohort 2: TAK-058 30 mg n=6 Participants TAK-058 30 mg, 100 mL oral solution, once on Day 1.	Cohort 3: TAK-058 45 mg n=6 Participants TAK-058 45 mg, 100 mL oral solution, once on Day 1.	Cohort 5: TAK-058 75 mg n=6 Participants TAK-058 75 mg, 100 mL oral solution, once on Day 1.	Cohorts 6: TAK-058 150 mg n=6 Participants TAK-058 150 mg, 100 mL oral solution, once on Day 1.	Cohort 1-6: Placebo TAK-058 placebo-matching, 100 mL oral solution, once on Day 1.
Terminal Elimination Half-life (T1/2) Pharmacokinetic Parameter for ENV8058 (TAK-058)	2.814 hours Standard Deviation 1.0871	5.300 hours Standard Deviation 2.2727	5.925 hours Standard Deviation 4.5780	9.611 hours Standard Deviation 7.3329	10.486 hours Standard Deviation 7.1865	8.601 hours Standard Deviation 7.9332	—

Adverse Events

Cohort 4: TAK-058 5 mg

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Cohort 1: TAK-058 15 mg

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Cohort 2: TAK-058 30 mg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Cohort 3: TAK-058 45 mg

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Cohort 5: TAK-058 75 mg

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Cohorts 6: TAK-058 150 mg

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Cohort 1-6: Placebo

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	Cohort 4: TAK-058 5 mg n=6 participants at risk TAK-058 5 mg, 100 mL oral solution, once on Day 1.	Cohort 1: TAK-058 15 mg n=6 participants at risk TAK-058 15 mg, 100 mL oral solution, once on Day 1.	Cohort 2: TAK-058 30 mg n=6 participants at risk TAK-058 30 mg, 100 mL oral solution, once on Day 1.	Cohort 3: TAK-058 45 mg n=6 participants at risk TAK-058 45 mg, 100 mL oral solution, once on Day 1.	Cohort 5: TAK-058 75 mg n=6 participants at risk TAK-058 75 mg, 100 mL oral solution, once on Day 1.	Cohorts 6: TAK-058 150 mg n=6 participants at risk TAK-058 150 mg, 100 mL oral solution, once on Day 1.	Cohort 1-6: Placebo n=12 participants at risk TAK-058 placebo-matching, 100 mL oral solution, once on Day 1.
Gastrointestinal disorders Infrequent bowel movements	16.7% 1/6 • First dose of study drug to 14 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug. 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.	0.00% 0/6 • First dose of study drug to 14 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug. 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.	16.7% 1/6 • First dose of study drug to 14 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug. 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.	0.00% 0/6 • First dose of study drug to 14 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug. 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.	0.00% 0/6 • First dose of study drug to 14 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug. 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.	0.00% 0/6 • First dose of study drug to 14 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug. 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.	0.00% 0/12 • First dose of study drug to 14 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug. 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.
Gastrointestinal disorders Abdominal discomfort	0.00% 0/6 • First dose of study drug to 14 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug. 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.	0.00% 0/6 • First dose of study drug to 14 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug. 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.	16.7% 1/6 • First dose of study drug to 14 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug. 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.	0.00% 0/6 • First dose of study drug to 14 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug. 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.	0.00% 0/6 • First dose of study drug to 14 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug. 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.	0.00% 0/6 • First dose of study drug to 14 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug. 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.	0.00% 0/12 • First dose of study drug to 14 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug. 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.
Gastrointestinal disorders Constipation	0.00% 0/6 • First dose of study drug to 14 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug. 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.	0.00% 0/6 • First dose of study drug to 14 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug. 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.	0.00% 0/6 • First dose of study drug to 14 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug. 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.	0.00% 0/6 • First dose of study drug to 14 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug. 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.	16.7% 1/6 • First dose of study drug to 14 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug. 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.	0.00% 0/6 • First dose of study drug to 14 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug. 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.	0.00% 0/12 • First dose of study drug to 14 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug. 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.
General disorders Asthenia	0.00% 0/6 • First dose of study drug to 14 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug. 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.	0.00% 0/6 • First dose of study drug to 14 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug. 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.	16.7% 1/6 • First dose of study drug to 14 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug. 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.	0.00% 0/6 • First dose of study drug to 14 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug. 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.	0.00% 0/6 • First dose of study drug to 14 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug. 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.	0.00% 0/6 • First dose of study drug to 14 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug. 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.	0.00% 0/12 • First dose of study drug to 14 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug. 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.
Nervous system disorders Dizziness postural	0.00% 0/6 • First dose of study drug to 14 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug. 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.	0.00% 0/6 • First dose of study drug to 14 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug. 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.	33.3% 2/6 • First dose of study drug to 14 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug. 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.	0.00% 0/6 • First dose of study drug to 14 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug. 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.	0.00% 0/6 • First dose of study drug to 14 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug. 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.	0.00% 0/6 • First dose of study drug to 14 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug. 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.	0.00% 0/12 • First dose of study drug to 14 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug. 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.
Psychiatric disorders Euphoric mood	0.00% 0/6 • First dose of study drug to 14 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug. 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.	0.00% 0/6 • First dose of study drug to 14 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug. 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.	0.00% 0/6 • First dose of study drug to 14 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug. 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.	0.00% 0/6 • First dose of study drug to 14 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug. 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.	0.00% 0/6 • First dose of study drug to 14 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug. 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.	0.00% 0/6 • First dose of study drug to 14 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug. 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.	8.3% 1/12 • First dose of study drug to 14 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug. 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.

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