Trial Outcomes & Findings for A Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Escalating Multiple Doses of TAK-831 in Healthy Participants (NCT NCT03224325)

Last Updated: 2021-06-14

Results Overview

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. A TEAE is defined as an AE with an onset that occurs after receiving study drug.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

50 participants

Primary outcome timeframe

Baseline up to 30 days after the last dose (Up to 48 days)

Results posted on

2021-06-14

Participant Flow

Participants took part in the study at 1 investigative site in the United States from 21-Jul-2017 to 9-Sep-2018.

Healthy volunteers were enrolled in a 1:3 ratio to receive placebo or TAK-831 in 6 cohorts.

Participant milestones

Participant milestones
Measure	Placebo (Pooled) TAK-831 placebo-matching suspension, orally, once daily (QD) on Days 1 and 3 to 16.	TAK-831 100 mg TAK-831 100 mg, tablets, orally, QD on Days 1 and 3 to 16.	TAK-831 300 mg TAK-831 300 mg, tablets, orally, QD on Days 1 and 3 to 16.	TAK-831 600 mg TAK-831 600 mg, tablets, orally, QD on Days 1 and 3 to 16.	TAK-831 15 mg TAK-831 15 mg, suspension, orally, multiple doses (MD) daily, on Days 1 and 3 to 16.	TAK-831 800 mg TAK-831 800 mg, suspension, orally, QD on Day 1, MD on Days 3 to 16.	TAK-831 1200 mg TAK-831 1200 mg, suspension, orally, QD on Day 1, MD on Days 3 to 16.
Overall Study STARTED	13	6	6	6	6	6	7
Overall Study COMPLETED	12	6	6	5	6	6	6
Overall Study NOT COMPLETED	1	0	0	1	0	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo (Pooled) TAK-831 placebo-matching suspension, orally, once daily (QD) on Days 1 and 3 to 16.	TAK-831 100 mg TAK-831 100 mg, tablets, orally, QD on Days 1 and 3 to 16.	TAK-831 300 mg TAK-831 300 mg, tablets, orally, QD on Days 1 and 3 to 16.	TAK-831 600 mg TAK-831 600 mg, tablets, orally, QD on Days 1 and 3 to 16.	TAK-831 15 mg TAK-831 15 mg, suspension, orally, multiple doses (MD) daily, on Days 1 and 3 to 16.	TAK-831 800 mg TAK-831 800 mg, suspension, orally, QD on Day 1, MD on Days 3 to 16.	TAK-831 1200 mg TAK-831 1200 mg, suspension, orally, QD on Day 1, MD on Days 3 to 16.
Overall Study Adverse Event	1	0	0	0	0	0	1
Overall Study Withdrawal by Subject	0	0	0	1	0	0	0

Baseline Characteristics

A Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Escalating Multiple Doses of TAK-831 in Healthy Participants

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo (Pooled) n=13 Participants TAK-831 placebo-matching suspension, orally, QD on Days 1 and 3 to 16.	TAK-831 100 mg n=6 Participants TAK-831 100 mg, tablets, orally, QD on Days 1 and 3 to 16.	TAK-831 300 mg n=6 Participants TAK-831 300 mg, tablets, orally, QD on Days 1 and 3 to 16.	TAK-831 600 mg n=6 Participants TAK-831 600 mg, tablets, orally, QD on Days 1 and 3 to 16.	TAK-831 15 mg n=6 Participants TAK-831 15 mg, suspension, orally, multiple doses (MD) daily, on Days 1 and 3 to 16.	TAK-831 800 mg n=6 Participants TAK-831 800 mg, suspension, orally, QD on Day 1, MD on Days 3 to 16.	TAK-831 1200 mg n=7 Participants TAK-831 1200 mg, suspension, orally, QD on Day 1, MD on Days 3 to 16.	Total n=50 Participants Total of all reporting groups
Age, Continuous	38.8 years STANDARD_DEVIATION 10.96 • n=93 Participants	35.7 years STANDARD_DEVIATION 7.61 • n=4 Participants	30.0 years STANDARD_DEVIATION 6.99 • n=27 Participants	42.8 years STANDARD_DEVIATION 7.63 • n=483 Participants	45.2 years STANDARD_DEVIATION 5.56 • n=36 Participants	35.5 years STANDARD_DEVIATION 6.63 • n=10 Participants	37.0 years STANDARD_DEVIATION 9.09 • n=115 Participants	38.0 years STANDARD_DEVIATION 9.09 • n=40 Participants
Sex: Female, Male Female	1 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants	1 Participants n=36 Participants	2 Participants n=10 Participants	1 Participants n=115 Participants	6 Participants n=40 Participants
Sex: Female, Male Male	12 Participants n=93 Participants	6 Participants n=4 Participants	6 Participants n=27 Participants	5 Participants n=483 Participants	5 Participants n=36 Participants	4 Participants n=10 Participants	6 Participants n=115 Participants	44 Participants n=40 Participants
Race/Ethnicity, Customized Hispanic or Latino	2 Participants n=93 Participants	3 Participants n=4 Participants	2 Participants n=27 Participants	1 Participants n=483 Participants	2 Participants n=36 Participants	2 Participants n=10 Participants	4 Participants n=115 Participants	16 Participants n=40 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	11 Participants n=93 Participants	3 Participants n=4 Participants	4 Participants n=27 Participants	5 Participants n=483 Participants	4 Participants n=36 Participants	4 Participants n=10 Participants	3 Participants n=115 Participants	34 Participants n=40 Participants
Race/Ethnicity, Customized Asian	1 Participants n=93 Participants	0 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	2 Participants n=40 Participants
Race/Ethnicity, Customized Black or African American	5 Participants n=93 Participants	3 Participants n=4 Participants	0 Participants n=27 Participants	2 Participants n=483 Participants	0 Participants n=36 Participants	2 Participants n=10 Participants	0 Participants n=115 Participants	12 Participants n=40 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	1 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	1 Participants n=10 Participants	0 Participants n=115 Participants	2 Participants n=40 Participants
Race/Ethnicity, Customized White	5 Participants n=93 Participants	3 Participants n=4 Participants	5 Participants n=27 Participants	4 Participants n=483 Participants	6 Participants n=36 Participants	3 Participants n=10 Participants	7 Participants n=115 Participants	33 Participants n=40 Participants
Race/Ethnicity, Customized Multiracial	1 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	1 Participants n=40 Participants
Region of Enrollment United States	13 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	7 Participants n=115 Participants	50 Participants n=40 Participants
Weight	81.21 kg STANDARD_DEVIATION 12.06 • n=93 Participants	82.58 kg STANDARD_DEVIATION 8.443 • n=4 Participants	77.40 kg STANDARD_DEVIATION 10.22 • n=27 Participants	84.95 kg STANDARD_DEVIATION 11.85 • n=483 Participants	77.67 kg STANDARD_DEVIATION 8.823 • n=36 Participants	82.07 kg STANDARD_DEVIATION 13.18 • n=10 Participants	75.56 kg STANDARD_DEVIATION 10.78 • n=115 Participants	80.25 kg STANDARD_DEVIATION 10.81 • n=40 Participants
Height	176.8 cm STANDARD_DEVIATION 7.87 • n=93 Participants	177.3 cm STANDARD_DEVIATION 7.47 • n=4 Participants	176.8 cm STANDARD_DEVIATION 9.66 • n=27 Participants	175.8 cm STANDARD_DEVIATION 6.85 • n=483 Participants	173.3 cm STANDARD_DEVIATION 10.42 • n=36 Participants	173.2 cm STANDARD_DEVIATION 10.03 • n=10 Participants	171.1 cm STANDARD_DEVIATION 8.30 • n=115 Participants	175.1 cm STANDARD_DEVIATION 8.36 • n=40 Participants
Body Mass Index (BMI)	26.00 kg/m^2 STANDARD_DEVIATION 3.028 • n=93 Participants	26.50 kg/m^2 STANDARD_DEVIATION 1.761 • n=4 Participants	24.83 kg/m^2 STANDARD_DEVIATION 3.312 • n=27 Participants	27.33 kg/m^2 STANDARD_DEVIATION 2.338 • n=483 Participants	25.67 kg/m^2 STANDARD_DEVIATION 2.066 • n=36 Participants	27.17 kg/m^2 STANDARD_DEVIATION 2.483 • n=10 Participants	25.86 kg/m^2 STANDARD_DEVIATION 3.388 • n=115 Participants	26.16 kg/m^2 STANDARD_DEVIATION 2.691 • n=40 Participants

PRIMARY outcome

Timeframe: Baseline up to 30 days after the last dose (Up to 48 days)

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

Outcome measures

Outcome measures
Measure	Placebo (Pooled) n=13 Participants TAK-831 placebo-matching suspension, orally, QD on Days 1 and 3 to 16.	TAK-831 100 mg n=6 Participants TAK-831 100 mg, tablets, orally, QD on Days 1 and 3 to 16.	TAK-831 300 mg n=6 Participants TAK-831 300 mg, tablets, orally, QD on Days 1 and 3 to 16.	TAK-831 600 mg n=6 Participants TAK-831 600 mg, tablets, orally, QD on Days 1 and 3 to 16.	TAK-831 15 mg n=6 Participants TAK-831 15 mg, suspension, orally, multiple doses (MD) daily, on Days 1 and 3 to 16.	TAK-831 800 mg n=6 Participants TAK-831 800 mg, suspension, orally, QD on Day 1, MD on Days 3 to 16.	TAK-831 1200 mg n=7 Participants TAK-831 1200 mg, suspension, orally, QD on Day 1, MD on Days 3 to 16.
Percentage of Participants Who Experienced at Least 1 Treatment-Emergent Adverse Event (TEAE)	69.2 percentage of participants	83.3 percentage of participants	100.0 percentage of participants	66.7 percentage of participants	100.0 percentage of participants	100.0 percentage of participants	42.9 percentage of participants

PRIMARY outcome

Timeframe: Baseline up to 30 days after the last dose (Up to 48 days)

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

Clinical Laboratory parameters included tests for chemistry, hematology and urinalysis. Markedly abnormal values during treatment period were categorized as: alanine aminotransferase (ALT)\>3.0 U/L\*upper limit of normal(ULN), albumin\<25 g/L, alkaline phosphatase \>3.0 U/L\*ULN, aspartate aminotransferase \>3.0 U/L\*ULN, bilirubin \>3.42 umol/L creatinine \>177umol/L, gamma glutamyl transferase (GGT) \>3 U/L\*ULN, glucose \<2.8 mmol/L, \>19.4 mmol/L, potassium\<3 mmol/L, \>6 mmol/L, sodium \<130 mmol/L, \>150 mmol/L, protein \<0.8 g/L,\* lower limit of normal (LLN), \>1.2 g/L\*ULN, erythrocytes \<0.8 (10\^12/L)\*LLN, \>1.2 (10\^12/L)\*ULN, hematocrit (%) \<0.8\*LLN, \>1.2\*ULN, hemoglobin \<0.8 g/L\*LLN, \>1.2 g/L\*ULN, leukocytes \<0.5 (10\^9/L)\*LLN, \>1.5 (10\^9/L)\*ULN, platelets \<75(10\^9/L), \>600(10\^9/L). Only categories with values have been reported.

Outcome measures

Outcome measures
Measure	Placebo (Pooled) n=13 Participants TAK-831 placebo-matching suspension, orally, QD on Days 1 and 3 to 16.	TAK-831 100 mg n=6 Participants TAK-831 100 mg, tablets, orally, QD on Days 1 and 3 to 16.	TAK-831 300 mg n=6 Participants TAK-831 300 mg, tablets, orally, QD on Days 1 and 3 to 16.	TAK-831 600 mg n=6 Participants TAK-831 600 mg, tablets, orally, QD on Days 1 and 3 to 16.	TAK-831 15 mg n=6 Participants TAK-831 15 mg, suspension, orally, multiple doses (MD) daily, on Days 1 and 3 to 16.	TAK-831 800 mg n=6 Participants TAK-831 800 mg, suspension, orally, QD on Day 1, MD on Days 3 to 16.	TAK-831 1200 mg n=7 Participants TAK-831 1200 mg, suspension, orally, QD on Day 1, MD on Days 3 to 16.
Percentage of Participants Who Met the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Postdose	0 percentage of participants	0 percentage of participants	16.7 percentage of participants	0 percentage of participants	16.7 percentage of participants	0 percentage of participants	0 percentage of participants

PRIMARY outcome

Timeframe: Baseline up to 30 days after the last dose (Up to 48 days)

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

Vital signs included temperature, pulse rate and blood pressure. Markedly abnormal values during treatment period were categorized as: Pulse Rate (beats/min) \<50-\>120, Systolic Blood Pressure (SBP) (mmHg) \<85-\>180, Diastolic Blood Pressure (DBP) (mmHg) \<50-\>110 and Temperature (degree centigrades) \<35.6- \>37.7.

Outcome measures

Outcome measures
Measure	Placebo (Pooled) n=13 Participants TAK-831 placebo-matching suspension, orally, QD on Days 1 and 3 to 16.	TAK-831 100 mg n=6 Participants TAK-831 100 mg, tablets, orally, QD on Days 1 and 3 to 16.	TAK-831 300 mg n=6 Participants TAK-831 300 mg, tablets, orally, QD on Days 1 and 3 to 16.	TAK-831 600 mg n=6 Participants TAK-831 600 mg, tablets, orally, QD on Days 1 and 3 to 16.	TAK-831 15 mg n=6 Participants TAK-831 15 mg, suspension, orally, multiple doses (MD) daily, on Days 1 and 3 to 16.	TAK-831 800 mg n=6 Participants TAK-831 800 mg, suspension, orally, QD on Day 1, MD on Days 3 to 16.	TAK-831 1200 mg n=7 Participants TAK-831 1200 mg, suspension, orally, QD on Day 1, MD on Days 3 to 16.
Percentage of Participants Who Met the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Postdose	92.3 percentage of participants	83.3 percentage of participants	100 percentage of participants	66.7 percentage of participants	83.3 percentage of participants	66.7 percentage of participants	42.9 percentage of participants

PRIMARY outcome

Timeframe: Baseline up to 30 days after the last dose (Up to 48 days)

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

A 12-lead ECG was performed. Markedly abnormal values during treatment period were categorized as: ECG Mean Heart Rate (beats/min) \<50-\>120, PR Interval, Aggregate (msec) \<=80-\>=200, QRS Duration, Aggregate (msec) \<=80-\>=180, QT Interval, Aggregate (msec) \<=300-\>=460, QTcF Interval, Aggregate (msec) \<=300-\>=500 OR \>=30 change from baseline and \>=450 milliseconds.

Outcome measures

Outcome measures
Measure	Placebo (Pooled) n=13 Participants TAK-831 placebo-matching suspension, orally, QD on Days 1 and 3 to 16.	TAK-831 100 mg n=6 Participants TAK-831 100 mg, tablets, orally, QD on Days 1 and 3 to 16.	TAK-831 300 mg n=6 Participants TAK-831 300 mg, tablets, orally, QD on Days 1 and 3 to 16.	TAK-831 600 mg n=6 Participants TAK-831 600 mg, tablets, orally, QD on Days 1 and 3 to 16.	TAK-831 15 mg n=6 Participants TAK-831 15 mg, suspension, orally, multiple doses (MD) daily, on Days 1 and 3 to 16.	TAK-831 800 mg n=6 Participants TAK-831 800 mg, suspension, orally, QD on Day 1, MD on Days 3 to 16.	TAK-831 1200 mg n=7 Participants TAK-831 1200 mg, suspension, orally, QD on Day 1, MD on Days 3 to 16.
Percentage of Participants Who Met the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Postdose	38.5 percentage of participants	83.3 percentage of participants	66.7 percentage of participants	16.7 percentage of participants	66.7 percentage of participants	66.7 percentage of participants	42.9 percentage of participants

SECONDARY outcome

Timeframe: 0.5 hours pre-dose and at multiple timepoint (Up to 24 hours) post-dose on Day 1

Population: The PK set included all participants from the safety set who had at least 1 measurable post dose TAK-831 plasma concentration.

Outcome measures

Outcome measures
Measure	Placebo (Pooled) n=6 Participants TAK-831 placebo-matching suspension, orally, QD on Days 1 and 3 to 16.	TAK-831 100 mg n=6 Participants TAK-831 100 mg, tablets, orally, QD on Days 1 and 3 to 16.	TAK-831 300 mg n=6 Participants TAK-831 300 mg, tablets, orally, QD on Days 1 and 3 to 16.	TAK-831 600 mg n=6 Participants TAK-831 600 mg, tablets, orally, QD on Days 1 and 3 to 16.	TAK-831 15 mg n=6 Participants TAK-831 15 mg, suspension, orally, multiple doses (MD) daily, on Days 1 and 3 to 16.	TAK-831 800 mg n=7 Participants TAK-831 800 mg, suspension, orally, QD on Day 1, MD on Days 3 to 16.	TAK-831 1200 mg TAK-831 1200 mg, suspension, orally, QD on Day 1, MD on Days 3 to 16.
Cmax: Maximum Observed Plasma Concentration for TAK-831	242.2 ng/mL Standard Deviation 101.98	566.7 ng/mL Standard Deviation 233.48	1008.8 ng/mL Standard Deviation 387.83	140.0 ng/mL Standard Deviation 58.43	1721.2 ng/mL Standard Deviation 558.38	2682.9 ng/mL Standard Deviation 945.83	—

SECONDARY outcome

Timeframe: 0.5 hours pre-dose and at multiple timepoint (Up to 24 hours) post-dose on Day 16

Population: The PK set included all participants from the safety set who had at least 1 measurable post dose TAK-831 plasma concentration with data available for this outcome measure.

Outcome measures

Outcome measures
Measure	Placebo (Pooled) n=5 Participants TAK-831 placebo-matching suspension, orally, QD on Days 1 and 3 to 16.	TAK-831 100 mg n=6 Participants TAK-831 100 mg, tablets, orally, QD on Days 1 and 3 to 16.	TAK-831 300 mg n=5 Participants TAK-831 300 mg, tablets, orally, QD on Days 1 and 3 to 16.	TAK-831 600 mg n=6 Participants TAK-831 600 mg, tablets, orally, QD on Days 1 and 3 to 16.	TAK-831 15 mg n=6 Participants TAK-831 15 mg, suspension, orally, multiple doses (MD) daily, on Days 1 and 3 to 16.	TAK-831 800 mg n=7 Participants TAK-831 800 mg, suspension, orally, QD on Day 1, MD on Days 3 to 16.	TAK-831 1200 mg TAK-831 1200 mg, suspension, orally, QD on Day 1, MD on Days 3 to 16.
Cmax ss: Maximum Observed Steady-state Plasma Concentration During a Dosing Interval for TAK-831	220.8 ng/mL Standard Deviation 99.52	528.2 ng/mL Standard Deviation 125.48	1494.0 ng/mL Standard Deviation 325.78	165.0 ng/mL Standard Deviation 51.26	2048.3 ng/mL Standard Deviation 610.39	3351.7 ng/mL Standard Deviation 1125.62	—

SECONDARY outcome

Timeframe: 0.5 hours pre-dose and at multiple timepoint (Up to 24 hours) post-dose on Days 1 and 16

Population: The PK set included all participants from the safety set who had at least 1 measurable post dose TAK-831 plasma concentration. Number analyzed is the number of participants with data available for analysis for the given timepoint.

Outcome measures

Outcome measures
Measure	Placebo (Pooled) n=6 Participants TAK-831 placebo-matching suspension, orally, QD on Days 1 and 3 to 16.	TAK-831 100 mg n=6 Participants TAK-831 100 mg, tablets, orally, QD on Days 1 and 3 to 16.	TAK-831 300 mg n=6 Participants TAK-831 300 mg, tablets, orally, QD on Days 1 and 3 to 16.	TAK-831 600 mg n=6 Participants TAK-831 600 mg, tablets, orally, QD on Days 1 and 3 to 16.	TAK-831 15 mg n=6 Participants TAK-831 15 mg, suspension, orally, multiple doses (MD) daily, on Days 1 and 3 to 16.	TAK-831 800 mg n=7 Participants TAK-831 800 mg, suspension, orally, QD on Day 1, MD on Days 3 to 16.	TAK-831 1200 mg TAK-831 1200 mg, suspension, orally, QD on Day 1, MD on Days 3 to 16.
Tmax: Time of First Occurrence of Cmax for TAK-831 Day 1	0.760 hours (hr) Interval 0.5 to 1.5	1.265 hours (hr) Interval 1.02 to 1.63	1.775 hours (hr) Interval 1.0 to 4.0	0.500 hours (hr) Interval 0.5 to 0.5	2.000 hours (hr) Interval 1.92 to 4.03	2.020 hours (hr) Interval 0.52 to 2.07	—
Tmax: Time of First Occurrence of Cmax for TAK-831 Day 16	0.500 hours (hr) Interval 0.5 to 2.15	1.475 hours (hr) Interval 0.98 to 2.0	2.000 hours (hr) Interval 1.0 to 2.07	0.500 hours (hr) Interval 0.48 to 0.5	2.000 hours (hr) Interval 1.0 to 2.0	2.000 hours (hr) Interval 1.0 to 2.02	—

SECONDARY outcome

Timeframe: 0.5 hours pre-dose and at multiple timepoint (Up to 24 hours) post-dose on Days 1 and 16

Population: The PK set included all participants from the safety set who had at least 1 measurable post dose TAK-831 plasma concentration with data available for this outcome measure.