Trial Outcomes & Findings for Effects of TAK-063 on Preventing Ketamine-Induced Brain Activity Changes as Well as Psychotic-Like Symptoms in Healthy Male Adults (NCT NCT01892189)

NCT ID: NCT01892189

Last Updated: 2017-01-12

Results Overview

Ketamine model was used to enhance the sensitivity to detect an effect of phosphodiesterase 10a (PDE10a) inhibition by TAK-063 by ketamine using neuroimaging battery tests. Ketamine induced robust blood oxygen level-dependent(BOLD) functional magnetic resonance imaging(fMRI) response while maintaining minimal accompanying psychotomimetic symptoms. The regions of interest include:left anterior cingulate cortex,right anterior cingulate cortex,left posterior cingulate cortex,right posterior cingulate cortex,left striatum,right striatum,left amygdala,right amygdala,left substantia nigra,right substantia nigra,left thalamus,right thalamus,left ventrolateral prefrontal cortex,right ventrolateral prefrontal cortex,left dorsolateral prefrontal cortex,right dorsolateral prefrontal cortex,left hippocampus,right hippocampus,left subgenual cingulate/Ba25,right subgenual cingulate/Ba25,left paracingulate gyrus/Ba32, and right paracingulate gyrus/Ba32.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 27 participants
• Primary outcome timeframe: Day 1: 4 hours post TAK-063 dose or placebo
• Results posted on: 2017-01-12

Participant Flow

Participants took part in the study at 1 investigative site in the United States from 27 June 2013 to 28 August 2014.

Healthy male participants were enrolled in this 3 period study and randomized in 1 of 9 administration sequences to receive TAK-063 3 mg, TAK-063 10 mg, TAK-063 30 mg and TAK-063 matching placebo. Due to predicted exposures being higher than likely clinically relevant, the dose of 300 mg was removed and replaced by 10 mg in protocol amendment 3.

Participant milestones

Measure	Placebo + TAK-063 3 mg + TAK-063 30 mg TAK-063 placebo-matching tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of first intervention period (1 day), followed by 7 days washout period, further followed by TAK-063 3 mg, tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of second intervention period (1 day), followed by 7 days washout period, further followed by TAK-063 30 mg, tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of third intervention period (1 day).	TAK-063 3 mg + TAK-063 30 mg + Placebo TAK-063 3 mg, tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of first intervention period (1 day), followed by 7 days washout period, further followed by TAK-063 30 mg, tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of second intervention period (1 day), followed by 7 days washout period, further followed by TAK-063 placebo-matching tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of third intervention period (1 day).	TAK-063 30 mg + Placebo + TAK-063 3 mg TAK-063 30 mg, tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of first intervention period (1 day), followed by 7 days washout period, further followed by TAK-063 placebo-matching tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of second intervention period (1 day), followed by 7 days washout period, further followed by TAK-063 3 mg, tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of third intervention period (1 day).	Placebo + TAK-063 3 mg + TAK-063 300 mg/10 mg TAK-063 placebo-matching tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of first intervention period (1 day), followed by 7 days washout period, further followed by TAK-063 3 mg, tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of second intervention period (1 day), followed by 7 days washout period, further followed by TAK-063 300 mg (participants enrolled before protocol amendment 3) or 10 mg (participants enrolled after protocol amendment 3), tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of third intervention period (1 day).	TAK-063 3 mg + TAK-063 300 mg/10 mg + Placebo TAK-063 3 mg, tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of first intervention period (1 day), followed by 7 days washout period, further followed by TAK-063 300 mg (participants enrolled before protocol amendment 3) or 10 mg (participants enrolled after protocol amendment 3), mg, tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of second intervention period (1 day), followed by 7 days washout period, further followed by TAK-063 placebo-matching tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of third intervention period (1 day).	TAK-063 300 mg/10 mg + Placebo + TAK-063 3 mg TAK-063 300 mg (participants enrolled before protocol amendment 3) or 10 mg (participants enrolled after protocol amendment 3), tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of first intervention period (1 day), followed by 7 days washout period, further followed by TAK-063 placebo-matching tablets orally along with ketamine, infusion, intravenously once only on Day 1 of second intervention period (1 day), followed by 7 days washout period, further followed by TAK-063 3 mg, tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of third intervention period (1 day).	Placebo + TAK-063 30 mg + TAK-063 300 mg/10 mg TAK-063 placebo-matching tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of first intervention period (1 day), followed by 7 days washout period, further followed by TAK-063 30 mg, tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of second intervention period (1 day), followed by 7 days washout period, further followed by TAK-063 300 mg (participants enrolled before protocol amendment 3) or 10 mg (participants enrolled after protocol amendment 3), tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of third intervention period (1 day).	TAK-063 30 mg + TAK-063 300 mg/10 mg + Placebo TAK-063 30 mg, tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of first intervention period (1 day), followed by 7 days washout period, further followed by TAK-063 300 mg (participants enrolled before protocol amendment 3) or 10 mg (participants enrolled after protocol amendment 3), tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of second intervention period (1 day), followed by 7 days washout period, further followed by TAK-063 placebo-matching tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of third intervention period (1 day).	TAK-063 300 mg/10 mg + Placebo + TAK-063 30 mg TAK-063 300 mg (participants enrolled before protocol amendment 3) or 10 mg (participants enrolled after protocol amendment 3), , tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of first intervention period (1 day), followed by 7 days washout period, further followed by TAK-063 placebo-matching tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of second intervention period (1 day), followed by 7 days washout period, further followed by TAK-063 30 mg, tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of third intervention period (1 day).
First Intervention Period (1 Day) STARTED	3	3	3	3	3	3	3	3	3
First Intervention Period (1 Day) COMPLETED	3	3	3	3	3	3	3	3	3
First Intervention Period (1 Day) NOT COMPLETED	0	0	0	0	0	0	0	0	0
Washout Period 1 (7 Days) STARTED	3	3	3	3	3	3	3	3	3
Washout Period 1 (7 Days) COMPLETED	3	3	1	2	3	2	2	3	1
Washout Period 1 (7 Days) NOT COMPLETED	0	0	2	1	0	1	1	0	2
Second Intervention Period (1 Day) STARTED	3	3	1	2	3	2	2	3	1
Second Intervention Period (1 Day) COMPLETED	3	3	1	2	3	2	2	3	1
Second Intervention Period (1 Day) NOT COMPLETED	0	0	0	0	0	0	0	0	0
Washout Period 2 (7 Days) STARTED	3	3	1	2	3	2	2	3	1
Washout Period 2 (7 Days) COMPLETED	3	3	1	2	3	2	2	3	1
Washout Period 2 (7 Days) NOT COMPLETED	0	0	0	0	0	0	0	0	0
Third Intervention Period (1 Day) STARTED	3	3	1	2	3	2	2	3	1
Third Intervention Period (1 Day) COMPLETED	3	3	1	2	3	2	2	3	1
Third Intervention Period (1 Day) NOT COMPLETED	0	0	0	0	0	0	0	0	0

Reasons for withdrawal

Measure	Placebo + TAK-063 3 mg + TAK-063 30 mg TAK-063 placebo-matching tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of first intervention period (1 day), followed by 7 days washout period, further followed by TAK-063 3 mg, tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of second intervention period (1 day), followed by 7 days washout period, further followed by TAK-063 30 mg, tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of third intervention period (1 day).	TAK-063 3 mg + TAK-063 30 mg + Placebo TAK-063 3 mg, tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of first intervention period (1 day), followed by 7 days washout period, further followed by TAK-063 30 mg, tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of second intervention period (1 day), followed by 7 days washout period, further followed by TAK-063 placebo-matching tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of third intervention period (1 day).	TAK-063 30 mg + Placebo + TAK-063 3 mg TAK-063 30 mg, tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of first intervention period (1 day), followed by 7 days washout period, further followed by TAK-063 placebo-matching tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of second intervention period (1 day), followed by 7 days washout period, further followed by TAK-063 3 mg, tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of third intervention period (1 day).	Placebo + TAK-063 3 mg + TAK-063 300 mg/10 mg TAK-063 placebo-matching tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of first intervention period (1 day), followed by 7 days washout period, further followed by TAK-063 3 mg, tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of second intervention period (1 day), followed by 7 days washout period, further followed by TAK-063 300 mg (participants enrolled before protocol amendment 3) or 10 mg (participants enrolled after protocol amendment 3), tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of third intervention period (1 day).	TAK-063 3 mg + TAK-063 300 mg/10 mg + Placebo TAK-063 3 mg, tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of first intervention period (1 day), followed by 7 days washout period, further followed by TAK-063 300 mg (participants enrolled before protocol amendment 3) or 10 mg (participants enrolled after protocol amendment 3), mg, tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of second intervention period (1 day), followed by 7 days washout period, further followed by TAK-063 placebo-matching tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of third intervention period (1 day).	TAK-063 300 mg/10 mg + Placebo + TAK-063 3 mg TAK-063 300 mg (participants enrolled before protocol amendment 3) or 10 mg (participants enrolled after protocol amendment 3), tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of first intervention period (1 day), followed by 7 days washout period, further followed by TAK-063 placebo-matching tablets orally along with ketamine, infusion, intravenously once only on Day 1 of second intervention period (1 day), followed by 7 days washout period, further followed by TAK-063 3 mg, tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of third intervention period (1 day).	Placebo + TAK-063 30 mg + TAK-063 300 mg/10 mg TAK-063 placebo-matching tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of first intervention period (1 day), followed by 7 days washout period, further followed by TAK-063 30 mg, tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of second intervention period (1 day), followed by 7 days washout period, further followed by TAK-063 300 mg (participants enrolled before protocol amendment 3) or 10 mg (participants enrolled after protocol amendment 3), tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of third intervention period (1 day).	TAK-063 30 mg + TAK-063 300 mg/10 mg + Placebo TAK-063 30 mg, tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of first intervention period (1 day), followed by 7 days washout period, further followed by TAK-063 300 mg (participants enrolled before protocol amendment 3) or 10 mg (participants enrolled after protocol amendment 3), tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of second intervention period (1 day), followed by 7 days washout period, further followed by TAK-063 placebo-matching tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of third intervention period (1 day).	TAK-063 300 mg/10 mg + Placebo + TAK-063 30 mg TAK-063 300 mg (participants enrolled before protocol amendment 3) or 10 mg (participants enrolled after protocol amendment 3), , tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of first intervention period (1 day), followed by 7 days washout period, further followed by TAK-063 placebo-matching tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of second intervention period (1 day), followed by 7 days washout period, further followed by TAK-063 30 mg, tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of third intervention period (1 day).
Washout Period 1 (7 Days) Adverse Event	0	0	0	0	0	0	0	0	1
Washout Period 1 (7 Days) Withdrawal by Subject	0	0	2	1	0	0	1	0	1
Washout Period 1 (7 Days) Noncompliance, Irritability	0	0	0	0	0	1	0	0	0

Baseline Characteristics

Effects of TAK-063 on Preventing Ketamine-Induced Brain Activity Changes as Well as Psychotic-Like Symptoms in Healthy Male Adults

Baseline characteristics by cohort

Measure	Placebo + TAK-063 3 mg + TAK-063 30 mg n=3 Participants TAK-063 placebo-matching tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of first intervention period (1 day), followed by 7 days washout period, further followed by TAK-063 3 mg, tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of second intervention period (1 day), followed by 7 days washout period, further followed by TAK-063 30 mg, tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of third intervention period (1 day).	TAK-063 3 mg + TAK-063 30 mg + Placebo n=3 Participants TAK-063 3 mg, tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of first intervention period (1 day), followed by 7 days washout period, further followed by TAK-063 30 mg, tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of second intervention period (1 day), followed by 7 days washout period, further followed by TAK-063 placebo-matching tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of third intervention period (1 day).	TAK-063 30 mg + Placebo + TAK-063 3 mg n=3 Participants TAK-063 30 mg, tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of first intervention period (1 day), followed by 7 days washout period, further followed by TAK-063 placebo-matching tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of second intervention period (1 day), followed by 7 days washout period, further followed by TAK-063 3 mg, tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of third intervention period (1 day).	Placebo + TAK-063 3 mg + TAK-063 300 mg/10 mg n=3 Participants TAK-063 placebo-matching tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of first intervention period (1 day), followed by 7 days washout period, further followed by TAK-063 3 mg, tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of second intervention period (1 day), followed by 7 days washout period, further followed by TAK-063 300 mg (participants enrolled before protocol amendment 3) or 10 mg (participants enrolled after protocol amendment 3), tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of third intervention period (1 day).	TAK-063 3 mg + TAK-063 300 mg/10 mg + Placebo n=3 Participants TAK-063 3 mg, tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of first intervention period (1 day), followed by 7 days washout period, further followed by TAK-063 300 mg (participants enrolled before protocol amendment 3) or 10 mg (participants enrolled after protocol amendment 3), mg, tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of second intervention period (1 day), followed by 7 days washout period, further followed by TAK-063 placebo-matching tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of third intervention period (1 day).	TAK-063 300 mg/10 mg + Placebo + TAK-063 3 mg n=3 Participants TAK-063 300 mg (participants enrolled before protocol amendment 3) or 10 mg (participants enrolled after protocol amendment 3), tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of first intervention period (1 day), followed by 7 days washout period, further followed by TAK-063 placebo-matching tablets orally along with ketamine, infusion, intravenously once only on Day 1 of second intervention period (1 day), followed by 7 days washout period, further followed by TAK-063 3 mg, tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of third intervention period (1 day).	Placebo + TAK-063 30 mg + TAK-063 300 mg/10 mg n=3 Participants TAK-063 placebo-matching tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of first intervention period (1 day), followed by 7 days washout period, further followed by TAK-063 30 mg, tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of second intervention period (1 day), followed by 7 days washout period, further followed by TAK-063 300 mg (participants enrolled before protocol amendment 3) or 10 mg (participants enrolled after protocol amendment 3), tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of third intervention period (1 day).	TAK-063 30 mg + TAK-063 300 mg/10 mg + Placebo n=3 Participants TAK-063 30 mg, tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of first intervention period (1 day), followed by 7 days washout period, further followed by TAK-063 300 mg (participants enrolled before protocol amendment 3) or 10 mg (participants enrolled after protocol amendment 3), tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of second intervention period (1 day), followed by 7 days washout period, further followed by TAK-063 placebo-matching tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of third intervention period (1 day).	TAK-063 300 mg/10 mg + Placebo + TAK-063 30 mg n=3 Participants TAK-063 300 mg (participants enrolled before protocol amendment 3) or 10 mg (participants enrolled after protocol amendment 3), , tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of first intervention period (1 day), followed by 7 days washout period, further followed by TAK-063 placebo-matching tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of second intervention period (1 day), followed by 7 days washout period, further followed by TAK-063 30 mg, tablets, orally along with ketamine, infusion, intravenously once only on Day 1 of third intervention period (1 day).	Total n=27 Participants Total of all reporting groups
Age, Continuous	27.7 years STANDARD_DEVIATION 3.21 • n=5 Participants	28.7 years STANDARD_DEVIATION 7.64 • n=7 Participants	23.7 years STANDARD_DEVIATION 6.66 • n=5 Participants	32.3 years STANDARD_DEVIATION 5.13 • n=4 Participants	23 years STANDARD_DEVIATION 5.20 • n=21 Participants	22.3 years STANDARD_DEVIATION 3.51 • n=10 Participants	27 years STANDARD_DEVIATION 7.94 • n=115 Participants	24.7 years STANDARD_DEVIATION 2.08 • n=24 Participants	23.7 years STANDARD_DEVIATION 5.69 • n=42 Participants	25.9 years STANDARD_DEVIATION 5.60 • n=42 Participants
Sex/Gender, Customized Female	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	0 participants n=21 Participants	0 participants n=10 Participants	0 participants n=115 Participants	0 participants n=24 Participants	0 participants n=42 Participants	0 participants n=42 Participants
Sex/Gender, Customized Male	3 participants n=5 Participants	3 participants n=7 Participants	3 participants n=5 Participants	3 participants n=4 Participants	3 participants n=21 Participants	3 participants n=10 Participants	3 participants n=115 Participants	3 participants n=24 Participants	3 participants n=42 Participants	27 participants n=42 Participants
Race/Ethnicity, Customized Hispanic or Latino	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	0 participants n=21 Participants	0 participants n=10 Participants	1 participants n=115 Participants	0 participants n=24 Participants	0 participants n=42 Participants	1 participants n=42 Participants
Race/Ethnicity, Customized Non Hispanic or Latino	3 participants n=5 Participants	3 participants n=7 Participants	3 participants n=5 Participants	3 participants n=4 Participants	3 participants n=21 Participants	3 participants n=10 Participants	2 participants n=115 Participants	3 participants n=24 Participants	3 participants n=42 Participants	26 participants n=42 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	1 participants n=21 Participants	0 participants n=10 Participants	0 participants n=115 Participants	0 participants n=24 Participants	0 participants n=42 Participants	1 participants n=42 Participants
Race/Ethnicity, Customized Asian	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	0 participants n=21 Participants	0 participants n=10 Participants	1 participants n=115 Participants	0 participants n=24 Participants	0 participants n=42 Participants	1 participants n=42 Participants
Race/Ethnicity, Customized Multiracial	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	0 participants n=21 Participants	0 participants n=10 Participants	0 participants n=115 Participants	1 participants n=24 Participants	0 participants n=42 Participants	1 participants n=42 Participants
Race/Ethnicity, Customized Pacific Islander-White	3 participants n=5 Participants	3 participants n=7 Participants	3 participants n=5 Participants	3 participants n=4 Participants	2 participants n=21 Participants	3 participants n=10 Participants	2 participants n=115 Participants	2 participants n=24 Participants	3 participants n=42 Participants	24 participants n=42 Participants
Region of Enrollment United States	3 participants n=5 Participants	3 participants n=7 Participants	3 participants n=5 Participants	3 participants n=4 Participants	3 participants n=21 Participants	3 participants n=10 Participants	3 participants n=115 Participants	3 participants n=24 Participants	3 participants n=42 Participants	27 participants n=42 Participants
Height	179 centimeters (cm) STANDARD_DEVIATION 2.65 • n=5 Participants	182 centimeters (cm) STANDARD_DEVIATION 4.58 • n=7 Participants	177 centimeters (cm) STANDARD_DEVIATION 8.19 • n=5 Participants	187.7 centimeters (cm) STANDARD_DEVIATION 3.79 • n=4 Participants	179.7 centimeters (cm) STANDARD_DEVIATION 10.79 • n=21 Participants	182.3 centimeters (cm) STANDARD_DEVIATION 3.06 • n=10 Participants	183.3 centimeters (cm) STANDARD_DEVIATION 8.14 • n=115 Participants	183.3 centimeters (cm) STANDARD_DEVIATION 6.51 • n=24 Participants	182.7 centimeters (cm) STANDARD_DEVIATION 4.51 • n=42 Participants	181.9 centimeters (cm) STANDARD_DEVIATION 6.06 • n=42 Participants
Weight	83.23 kilogram (kg) STANDARD_DEVIATION 11.981 • n=5 Participants	93.80 kilogram (kg) STANDARD_DEVIATION 4.784 • n=7 Participants	79.87 kilogram (kg) STANDARD_DEVIATION 16.910 • n=5 Participants	82.3 kilogram (kg) STANDARD_DEVIATION 12.643 • n=4 Participants	87.47 kilogram (kg) STANDARD_DEVIATION 13.955 • n=21 Participants	77.33 kilogram (kg) STANDARD_DEVIATION 8.107 • n=10 Participants	81.10 kilogram (kg) STANDARD_DEVIATION 5.821 • n=115 Participants	86.40 kilogram (kg) STANDARD_DEVIATION 4.939 • n=24 Participants	79.07 kilogram (kg) STANDARD_DEVIATION 11.716 • n=42 Participants	83.40 kilogram (kg) STANDARD_DEVIATION 10.306 • n=42 Participants
Body Mass Index	26.06 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 4.430 • n=5 Participants	28.38 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.557 • n=7 Participants	25.30 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.190 • n=5 Participants	23.39 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.844 • n=4 Participants	26.99 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.108 • n=21 Participants	23.28 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.611 • n=10 Participants	24.20 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.417 • n=115 Participants	25.71 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 1.011 • n=24 Participants	23.69 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.269 • n=42 Participants	25.22 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.997 • n=42 Participants
Smoking Classification Never smoked	3 participants n=5 Participants	2 participants n=7 Participants	3 participants n=5 Participants	2 participants n=4 Participants	3 participants n=21 Participants	3 participants n=10 Participants	2 participants n=115 Participants	3 participants n=24 Participants	2 participants n=42 Participants	23 participants n=42 Participants
Smoking Classification Ex-smoker	0 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants	0 participants n=21 Participants	0 participants n=10 Participants	1 participants n=115 Participants	0 participants n=24 Participants	1 participants n=42 Participants	4 participants n=42 Participants
Caffeine Consumption Consumes Caffiene	2 participants n=5 Participants	3 participants n=7 Participants	3 participants n=5 Participants	3 participants n=4 Participants	2 participants n=21 Participants	2 participants n=10 Participants	3 participants n=115 Participants	3 participants n=24 Participants	3 participants n=42 Participants	24 participants n=42 Participants
Caffeine Consumption Not consumes Caffiene	1 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	1 participants n=21 Participants	1 participants n=10 Participants	0 participants n=115 Participants	0 participants n=24 Participants	0 participants n=42 Participants	3 participants n=42 Participants

PRIMARY outcome

Timeframe: Day 1: 4 hours post TAK-063 dose or placebo

Population: The pharmacodynamic (PD) analysis set included all participants in the safety set and with at least 1 valid PD assessment. PD analysis set did not include 2 participants treated with TAK-063 300 mg.

Ketamine model was used to enhance the sensitivity to detect an effect of phosphodiesterase 10a (PDE10a) inhibition by TAK-063 by ketamine using neuroimaging battery tests. Ketamine induced robust blood oxygen level-dependent(BOLD) functional magnetic resonance imaging(fMRI) response while maintaining minimal accompanying psychotomimetic symptoms. The regions of interest include:left anterior cingulate cortex,right anterior cingulate cortex,left posterior cingulate cortex,right posterior cingulate cortex,left striatum,right striatum,left amygdala,right amygdala,left substantia nigra,right substantia nigra,left thalamus,right thalamus,left ventrolateral prefrontal cortex,right ventrolateral prefrontal cortex,left dorsolateral prefrontal cortex,right dorsolateral prefrontal cortex,left hippocampus,right hippocampus,left subgenual cingulate/Ba25,right subgenual cingulate/Ba25,left paracingulate gyrus/Ba32, and right paracingulate gyrus/Ba32.

Outcome measures

Measure	Placebo n=22 Participants TAK-063 placebo-matching tablets, orally and ketamine, infusion, intravenously on Day 1 in either intervention period 1, 2 or 3.	TAK-063 3 mg n=14 Participants TAK-063 3 mg, tablets, orally along with ketamine, infusion, intravenously on Day 1 in either intervention period 1, 2 or 3.	TAK-063 10 mg n=14 Participants TAK-063 10 mg, tablets, orally along with ketamine, infusion, intravenously on Day 1 in intervention period 1, 2 or 3.	TAK-063 30 mg n=15 Participants TAK-063 30 mg, tablets, orally along with ketamine, infusion, intravenously on Day 1 in intervention period 1, 2 or 3.	TAK-063 300 mg TAK-063 300 mg, tablets, orally along with ketamine, infusion, intravenously on Day 1 in intervention period 1, 2 and 3.
Ketamine-Induced Brain Activity in Regions of Interest During Resting State Left Ventrolateral Prefrontal Cortex	0.6355 percent signal change in brain activity Standard Deviation 0.79768	0.5183 percent signal change in brain activity Standard Deviation 0.66695	0.6081 percent signal change in brain activity Standard Deviation 0.73306	0.5900 percent signal change in brain activity Standard Deviation 0.47920	—
Ketamine-Induced Brain Activity in Regions of Interest During Resting State Left Anterior Cingulate Cortex	0.4954 percent signal change in brain activity Standard Deviation 0.53382	0.2943 percent signal change in brain activity Standard Deviation 0.67925	0.4439 percent signal change in brain activity Standard Deviation 0.72261	0.3876 percent signal change in brain activity Standard Deviation 0.47127	—
Ketamine-Induced Brain Activity in Regions of Interest During Resting State Right Anterior Cingulate Cortex	0.4611 percent signal change in brain activity Standard Deviation 0.44870	0.2542 percent signal change in brain activity Standard Deviation 0.55542	0.4199 percent signal change in brain activity Standard Deviation 0.70069	0.3251 percent signal change in brain activity Standard Deviation 0.47592	—
Ketamine-Induced Brain Activity in Regions of Interest During Resting State Left Posterior Cingulate Cortex	0.4922 percent signal change in brain activity Standard Deviation 0.52563	0.4647 percent signal change in brain activity Standard Deviation 0.52746	0.5316 percent signal change in brain activity Standard Deviation 0.77685	0.3987 percent signal change in brain activity Standard Deviation 0.49018	—
Ketamine-Induced Brain Activity in Regions of Interest During Resting State Right Posterior Cingulate Cortex	0.5412 percent signal change in brain activity Standard Deviation 0.52336	0.4515 percent signal change in brain activity Standard Deviation 0.57054	0.6132 percent signal change in brain activity Standard Deviation 0.79296	0.3783 percent signal change in brain activity Standard Deviation 0.55473	—
Ketamine-Induced Brain Activity in Regions of Interest During Resting State Left Striatum	0.2914 percent signal change in brain activity Standard Deviation 0.40513	0.0644 percent signal change in brain activity Standard Deviation 0.47601	0.3045 percent signal change in brain activity Standard Deviation 0.51442	0.2453 percent signal change in brain activity Standard Deviation 0.40828	—
Ketamine-Induced Brain Activity in Regions of Interest During Resting State Right Striatum	0.3605 percent signal change in brain activity Standard Deviation 0.37202	0.1154 percent signal change in brain activity Standard Deviation 0.52174	0.3124 percent signal change in brain activity Standard Deviation 0.46817	0.2617 percent signal change in brain activity Standard Deviation 0.36033	—
Ketamine-Induced Brain Activity in Regions of Interest During Resting State Left Amygdala	0.3413 percent signal change in brain activity Standard Deviation 0.66866	0.4776 percent signal change in brain activity Standard Deviation 0.72631	0.4888 percent signal change in brain activity Standard Deviation 0.60449	0.3435 percent signal change in brain activity Standard Deviation 0.57560	—
Ketamine-Induced Brain Activity in Regions of Interest During Resting State Right Amygdala	0.2102 percent signal change in brain activity Standard Deviation 0.72431	0.1180 percent signal change in brain activity Standard Deviation 0.85125	0.0106 percent signal change in brain activity Standard Deviation 0.76838	0.2686 percent signal change in brain activity Standard Deviation 0.53395	—
Ketamine-Induced Brain Activity in Regions of Interest During Resting State Left Substantia Nigra	0.3989 percent signal change in brain activity Standard Deviation 0.49787	0.2857 percent signal change in brain activity Standard Deviation 0.61851	0.5560 percent signal change in brain activity Standard Deviation 0.67716	0.2214 percent signal change in brain activity Standard Deviation 0.36486	—
Ketamine-Induced Brain Activity in Regions of Interest During Resting State Right Substantia Nigra	0.2925 percent signal change in brain activity Standard Deviation 0.45514	0.2209 percent signal change in brain activity Standard Deviation 0.69383	0.3398 percent signal change in brain activity Standard Deviation 0.45331	0.1148 percent signal change in brain activity Standard Deviation 0.40258	—
Ketamine-Induced Brain Activity in Regions of Interest During Resting State Left Thalamus	0.5166 percent signal change in brain activity Standard Deviation 0.40051	0.3406 percent signal change in brain activity Standard Deviation 0.58293	0.5564 percent signal change in brain activity Standard Deviation 0.52695	0.3589 percent signal change in brain activity Standard Deviation 0.43768	—
Ketamine-Induced Brain Activity in Regions of Interest During Resting State Right Thalamus	0.4807 percent signal change in brain activity Standard Deviation 0.35272	0.3392 percent signal change in brain activity Standard Deviation 0.59598	0.5159 percent signal change in brain activity Standard Deviation 0.44482	0.3734 percent signal change in brain activity Standard Deviation 0.44173	—
Ketamine-Induced Brain Activity in Regions of Interest During Resting State Right Ventrolateral Prefrontal Cortex	0.7932 percent signal change in brain activity Standard Deviation 0.59179	0.5134 percent signal change in brain activity Standard Deviation 0.69396	0.6661 percent signal change in brain activity Standard Deviation 0.75274	0.6119 percent signal change in brain activity Standard Deviation 0.44821	—
Ketamine-Induced Brain Activity in Regions of Interest During Resting State Left Dorsolateral Prefrontal Cortex	0.3918 percent signal change in brain activity Standard Deviation 0.41983	0.2576 percent signal change in brain activity Standard Deviation 0.56173	0.4451 percent signal change in brain activity Standard Deviation 0.62506	0.3720 percent signal change in brain activity Standard Deviation 0.30576	—
Ketamine-Induced Brain Activity in Regions of Interest During Resting State Right Dorsolateral Prefrontal Cortex	0.4715 percent signal change in brain activity Standard Deviation 0.40803	0.2799 percent signal change in brain activity Standard Deviation 0.53268	0.5403 percent signal change in brain activity Standard Deviation 0.78105	0.4331 percent signal change in brain activity Standard Deviation 0.39160	—
Ketamine-Induced Brain Activity in Regions of Interest During Resting State Left Hippocampus	0.3150 percent signal change in brain activity Standard Deviation 0.37531	0.1790 percent signal change in brain activity Standard Deviation 0.47311	0.3073 percent signal change in brain activity Standard Deviation 0.41116	0.2123 percent signal change in brain activity Standard Deviation 0.35146	—
Ketamine-Induced Brain Activity in Regions of Interest During Resting State Right Hippocampus	0.2540 percent signal change in brain activity Standard Deviation 0.27489	0.1814 percent signal change in brain activity Standard Deviation 0.51038	0.2141 percent signal change in brain activity Standard Deviation 0.34537	0.0989 percent signal change in brain activity Standard Deviation 0.35725	—
Ketamine-Induced Brain Activity in Regions of Interest During Resting State Left Subgenual Cingulate/BA25	-0.3974 percent signal change in brain activity Standard Deviation 1.60367	0.2236 percent signal change in brain activity Standard Deviation 1.22450	-0.2448 percent signal change in brain activity Standard Deviation 1.46965	-0.0002 percent signal change in brain activity Standard Deviation 2.18015	—
Ketamine-Induced Brain Activity in Regions of Interest During Resting State Right Subgenual Cingulate/BA25	-0.1463 percent signal change in brain activity Standard Deviation 1.55680	-0.3430 percent signal change in brain activity Standard Deviation 1.15319	-0.6379 percent signal change in brain activity Standard Deviation 2.30349	0.0424 percent signal change in brain activity Standard Deviation 1.71727	—
Ketamine-Induced Brain Activity in Regions of Interest During Resting State Left Paracingulate Gyrus/BA32	0.4776 percent signal change in brain activity Standard Deviation 0.43067	0.2799 percent signal change in brain activity Standard Deviation 0.59577	0.4069 percent signal change in brain activity Standard Deviation 0.65537	0.3281 percent signal change in brain activity Standard Deviation 0.38990	—
Ketamine-Induced Brain Activity in Regions of Interest During Resting State Right Paracingulate Gyrus/BA32	0.5849 percent signal change in brain activity Standard Deviation 0.51897	0.3583 percent signal change in brain activity Standard Deviation 0.58987	0.4972 percent signal change in brain activity Standard Deviation 0.82842	0.3969 percent signal change in brain activity Standard Deviation 0.52267	—

SECONDARY outcome

Timeframe: Day 1: pre-dose and at multiple time points (up to 24 hours) postdose

Population: The pharmacokinetic (PK) analysis set included all participants in the safety set and with at least 1 measurable plasma concentration. PK analysis set did not include 2 participants treated with 300 mg.

Outcome measures

Measure	Placebo n=14 Participants TAK-063 placebo-matching tablets, orally and ketamine, infusion, intravenously on Day 1 in either intervention period 1, 2 or 3.	TAK-063 3 mg n=14 Participants TAK-063 3 mg, tablets, orally along with ketamine, infusion, intravenously on Day 1 in either intervention period 1, 2 or 3.	TAK-063 10 mg n=15 Participants TAK-063 10 mg, tablets, orally along with ketamine, infusion, intravenously on Day 1 in intervention period 1, 2 or 3.	TAK-063 30 mg TAK-063 30 mg, tablets, orally along with ketamine, infusion, intravenously on Day 1 in intervention period 1, 2 or 3.	TAK-063 300 mg TAK-063 300 mg, tablets, orally along with ketamine, infusion, intravenously on Day 1 in intervention period 1, 2 and 3.
Cmax: Maximum Observed Plasma Concentration for TAK-063 and TAK-063 Metabolite (M-I) TAK-063	10.35 nanogram per milliliter (ng/mL) Standard Deviation 2.860 • Interval 0.5 to 6.0	48.16 nanogram per milliliter (ng/mL) Standard Deviation 8.769	109.9 nanogram per milliliter (ng/mL) Standard Deviation 27.053	—	—
Cmax: Maximum Observed Plasma Concentration for TAK-063 and TAK-063 Metabolite (M-I) M-I	12.07 nanogram per milliliter (ng/mL) Standard Deviation 3.235	48.94 nanogram per milliliter (ng/mL) Standard Deviation 11.500	103.72 nanogram per milliliter (ng/mL) Standard Deviation 32.635	—	—

SECONDARY outcome

Timeframe: Day 1: pre-dose and at multiple time points (up to 24 hours) postdose

Population: The PK analysis set included all participants in the safety set and with at least 1 measurable plasma concentration. PK analysis set did not include 2 participants treated with 300 mg.

Outcome measures

Measure	Placebo n=14 Participants TAK-063 placebo-matching tablets, orally and ketamine, infusion, intravenously on Day 1 in either intervention period 1, 2 or 3.	TAK-063 3 mg n=14 Participants TAK-063 3 mg, tablets, orally along with ketamine, infusion, intravenously on Day 1 in either intervention period 1, 2 or 3.	TAK-063 10 mg n=15 Participants TAK-063 10 mg, tablets, orally along with ketamine, infusion, intravenously on Day 1 in intervention period 1, 2 or 3.	TAK-063 30 mg TAK-063 30 mg, tablets, orally along with ketamine, infusion, intravenously on Day 1 in intervention period 1, 2 or 3.	TAK-063 300 mg TAK-063 300 mg, tablets, orally along with ketamine, infusion, intravenously on Day 1 in intervention period 1, 2 and 3.
Tmax: Time to Reach Cmax for TAK-063 and TAK-063 M-I TAK-063	3.02 hours Full Range 2.860 • Interval 0.5 to 6.0	3.03 hours Interval 2.0 to 5.8	3.02 hours Interval 2.0 to 5.8	—	—
Tmax: Time to Reach Cmax for TAK-063 and TAK-063 M-I M-I	2.96 hours Interval 1.9 to 4.3	3.03 hours Interval 2.0 to 5.7	4.23 hours Interval 2.0 to 6.0	—	—

SECONDARY outcome

Timeframe: Day 1: Pre-dose and at multiple time points (up to 24 hours) post-dose

Population: The PK analysis set included all participants in the safety set and with at least 1 measurable plasma concentration. PK analysis set did not include 2 participants treated with 300 mg.

Outcome measures

Measure	Placebo n=14 Participants TAK-063 placebo-matching tablets, orally and ketamine, infusion, intravenously on Day 1 in either intervention period 1, 2 or 3.	TAK-063 3 mg n=14 Participants TAK-063 3 mg, tablets, orally along with ketamine, infusion, intravenously on Day 1 in either intervention period 1, 2 or 3.	TAK-063 10 mg n=15 Participants TAK-063 10 mg, tablets, orally along with ketamine, infusion, intravenously on Day 1 in intervention period 1, 2 or 3.	TAK-063 30 mg TAK-063 30 mg, tablets, orally along with ketamine, infusion, intravenously on Day 1 in intervention period 1, 2 or 3.	TAK-063 300 mg TAK-063 300 mg, tablets, orally along with ketamine, infusion, intravenously on Day 1 in intervention period 1, 2 and 3.
AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-063 and TAK-063 M-I TAK-063	111.36 nanogram hours per milliliter (ng*hr/mL) Standard Deviation 38.460	548.58 nanogram hours per milliliter (ng*hr/mL) Standard Deviation 122.686	1298.89 nanogram hours per milliliter (ng*hr/mL) Standard Deviation 331.095	—	—
AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-063 and TAK-063 M-I M-I	114.81 nanogram hours per milliliter (ng*hr/mL) Standard Deviation 48.453	582.91 nanogram hours per milliliter (ng*hr/mL) Standard Deviation 201.503	1285.18 nanogram hours per milliliter (ng*hr/mL) Standard Deviation 499.431	—	—

SECONDARY outcome

Timeframe: Baseline up to 14 days after last dose of study drug (Day 32)

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

Outcome measures

Measure	Placebo n=22 Participants TAK-063 placebo-matching tablets, orally and ketamine, infusion, intravenously on Day 1 in either intervention period 1, 2 or 3.	TAK-063 3 mg n=14 Participants TAK-063 3 mg, tablets, orally along with ketamine, infusion, intravenously on Day 1 in either intervention period 1, 2 or 3.	TAK-063 10 mg n=14 Participants TAK-063 10 mg, tablets, orally along with ketamine, infusion, intravenously on Day 1 in intervention period 1, 2 or 3.	TAK-063 30 mg n=15 Participants TAK-063 30 mg, tablets, orally along with ketamine, infusion, intravenously on Day 1 in intervention period 1, 2 or 3.	TAK-063 300 mg n=2 Participants TAK-063 300 mg, tablets, orally along with ketamine, infusion, intravenously on Day 1 in intervention period 1, 2 and 3.
Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE)	68.2 percentage of participants	50 percentage of participants	57.1 percentage of participants	86.7 percentage of participants	100 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to 14 days after last dose of study drug (Day 32)

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

The percentage of participants with any markedly abnormal standard safety laboratory values collected throughout study.

Outcome measures

Measure	Placebo n=22 Participants TAK-063 placebo-matching tablets, orally and ketamine, infusion, intravenously on Day 1 in either intervention period 1, 2 or 3.	TAK-063 3 mg n=14 Participants TAK-063 3 mg, tablets, orally along with ketamine, infusion, intravenously on Day 1 in either intervention period 1, 2 or 3.	TAK-063 10 mg n=14 Participants TAK-063 10 mg, tablets, orally along with ketamine, infusion, intravenously on Day 1 in intervention period 1, 2 or 3.	TAK-063 30 mg n=15 Participants TAK-063 30 mg, tablets, orally along with ketamine, infusion, intravenously on Day 1 in intervention period 1, 2 or 3.	TAK-063 300 mg n=2 Participants TAK-063 300 mg, tablets, orally along with ketamine, infusion, intravenously on Day 1 in intervention period 1, 2 and 3.
Percentage of Participants Who Meet the Takeda Global Research and Development Center, Inc. (TGRD) Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose	9.1 percentage of participants	0 percentage of participants	14.3 percentage of participants	6.7 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to 14 days after last dose of study drug (Day 32)

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

The percentage of participants who meet markedly abnormal criteria designated by TGRD. Vital signs included oral temperature, respiration, blood pressure and pulse (beats per minute).

Outcome measures

Measure	Placebo n=22 Participants TAK-063 placebo-matching tablets, orally and ketamine, infusion, intravenously on Day 1 in either intervention period 1, 2 or 3.	TAK-063 3 mg n=14 Participants TAK-063 3 mg, tablets, orally along with ketamine, infusion, intravenously on Day 1 in either intervention period 1, 2 or 3.	TAK-063 10 mg n=14 Participants TAK-063 10 mg, tablets, orally along with ketamine, infusion, intravenously on Day 1 in intervention period 1, 2 or 3.	TAK-063 30 mg n=15 Participants TAK-063 30 mg, tablets, orally along with ketamine, infusion, intravenously on Day 1 in intervention period 1, 2 or 3.	TAK-063 300 mg n=2 Participants TAK-063 300 mg, tablets, orally along with ketamine, infusion, intravenously on Day 1 in intervention period 1, 2 and 3.
Percentage of Participants Who Meet the TGRD Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose	50.0 percentage of participants	64.3 percentage of participants	57.1 percentage of participants	53.3 percentage of participants	100 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to 14 days after last dose of study drug (Day 32)

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

The percentage of participants who meet markedly abnormal criteria designated by TGRD measured throughout study.

Outcome measures

Measure	Placebo n=22 Participants TAK-063 placebo-matching tablets, orally and ketamine, infusion, intravenously on Day 1 in either intervention period 1, 2 or 3.	TAK-063 3 mg n=14 Participants TAK-063 3 mg, tablets, orally along with ketamine, infusion, intravenously on Day 1 in either intervention period 1, 2 or 3.	TAK-063 10 mg n=14 Participants TAK-063 10 mg, tablets, orally along with ketamine, infusion, intravenously on Day 1 in intervention period 1, 2 or 3.	TAK-063 30 mg n=15 Participants TAK-063 30 mg, tablets, orally along with ketamine, infusion, intravenously on Day 1 in intervention period 1, 2 or 3.	TAK-063 300 mg n=2 Participants TAK-063 300 mg, tablets, orally along with ketamine, infusion, intravenously on Day 1 in intervention period 1, 2 and 3.
Percentage of Participants Who Meet the TGRD Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose	27.3 percentage of participants	14.3 percentage of participants	35.7 percentage of participants	53.3 percentage of participants	100 percentage of participants

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 15 other events

Deaths: 0 deaths

TAK-063 3 mg

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

TAK-063 10 mg

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

TAK-063 30 mg

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

TAK-063 300 mg

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Placebo n=22 participants at risk TAK-063 placebo-matching tablets, orally and ketamine, infusion, intravenously on Day 1 in either intervention period 1, 2 or 3.	TAK-063 3 mg n=14 participants at risk TAK-063 3 mg, tablets, orally along with ketamine, infusion, intravenously on Day 1 in either intervention period 1, 2 or 3.	TAK-063 10 mg n=14 participants at risk TAK-063 10 mg, tablets, orally along with ketamine, infusion, intravenously on Day 1 in intervention period 1, 2 or 3.	TAK-063 30 mg n=15 participants at risk TAK-063 30 mg, tablets, orally along with ketamine, infusion, intravenously on Day 1 in intervention period 1, 2 or 3.	TAK-063 300 mg n=2 participants at risk TAK-063 300 mg, tablets, orally along with ketamine, infusion, intravenously on Day 1 in intervention period 1, 2 and 3.
Eye disorders Diplopia	0.00% 0/22 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/14 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/14 • Baseline up to 14 days after last dose of study drug (Day 32) 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.	6.7% 1/15 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/2 • Baseline up to 14 days after last dose of study drug (Day 32) 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 Vomiting	45.5% 10/22 • Baseline up to 14 days after last dose of study drug (Day 32) 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.	21.4% 3/14 • Baseline up to 14 days after last dose of study drug (Day 32) 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.	42.9% 6/14 • Baseline up to 14 days after last dose of study drug (Day 32) 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.	53.3% 8/15 • Baseline up to 14 days after last dose of study drug (Day 32) 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.	50.0% 1/2 • Baseline up to 14 days after last dose of study drug (Day 32) 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 Nausea	27.3% 6/22 • Baseline up to 14 days after last dose of study drug (Day 32) 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.	14.3% 2/14 • Baseline up to 14 days after last dose of study drug (Day 32) 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.	21.4% 3/14 • Baseline up to 14 days after last dose of study drug (Day 32) 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.	13.3% 2/15 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/2 • Baseline up to 14 days after last dose of study drug (Day 32) 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 Dry Mouth	0.00% 0/22 • Baseline up to 14 days after last dose of study drug (Day 32) 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.	7.1% 1/14 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/14 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/15 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/2 • Baseline up to 14 days after last dose of study drug (Day 32) 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 Retching	9.1% 2/22 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/14 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/14 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/15 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/2 • Baseline up to 14 days after last dose of study drug (Day 32) 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 Fatigue	13.6% 3/22 • Baseline up to 14 days after last dose of study drug (Day 32) 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.	7.1% 1/14 • Baseline up to 14 days after last dose of study drug (Day 32) 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.	28.6% 4/14 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/15 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/2 • Baseline up to 14 days after last dose of study drug (Day 32) 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.
Infections and infestations Upper Respiratory Tract Infection	0.00% 0/22 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/14 • Baseline up to 14 days after last dose of study drug (Day 32) 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.	7.1% 1/14 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/15 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/2 • Baseline up to 14 days after last dose of study drug (Day 32) 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.
Infections and infestations Pharyngitis	4.5% 1/22 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/14 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/14 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/15 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/2 • Baseline up to 14 days after last dose of study drug (Day 32) 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.
Musculoskeletal and connective tissue disorders Back Pain	0.00% 0/22 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/14 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/14 • Baseline up to 14 days after last dose of study drug (Day 32) 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.	6.7% 1/15 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/2 • Baseline up to 14 days after last dose of study drug (Day 32) 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.
Musculoskeletal and connective tissue disorders Muscle Tightness	0.00% 0/22 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/14 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/14 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/15 • Baseline up to 14 days after last dose of study drug (Day 32) 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.	50.0% 1/2 • Baseline up to 14 days after last dose of study drug (Day 32) 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 Somnolence	9.1% 2/22 • Baseline up to 14 days after last dose of study drug (Day 32) 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.	7.1% 1/14 • Baseline up to 14 days after last dose of study drug (Day 32) 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.	28.6% 4/14 • Baseline up to 14 days after last dose of study drug (Day 32) 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.	46.7% 7/15 • Baseline up to 14 days after last dose of study drug (Day 32) 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.	50.0% 1/2 • Baseline up to 14 days after last dose of study drug (Day 32) 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 Headache	4.5% 1/22 • Baseline up to 14 days after last dose of study drug (Day 32) 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.	14.3% 2/14 • Baseline up to 14 days after last dose of study drug (Day 32) 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.	7.1% 1/14 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/15 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/2 • Baseline up to 14 days after last dose of study drug (Day 32) 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	4.5% 1/22 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/14 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/14 • Baseline up to 14 days after last dose of study drug (Day 32) 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.	13.3% 2/15 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/2 • Baseline up to 14 days after last dose of study drug (Day 32) 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 Dysarthria	0.00% 0/22 • Baseline up to 14 days after last dose of study drug (Day 32) 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.	7.1% 1/14 • Baseline up to 14 days after last dose of study drug (Day 32) 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.	7.1% 1/14 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/15 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/2 • Baseline up to 14 days after last dose of study drug (Day 32) 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 Lethargy	0.00% 0/22 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/14 • Baseline up to 14 days after last dose of study drug (Day 32) 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.	7.1% 1/14 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/15 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/2 • Baseline up to 14 days after last dose of study drug (Day 32) 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 Paraesthesia	0.00% 0/22 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/14 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/14 • Baseline up to 14 days after last dose of study drug (Day 32) 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.	6.7% 1/15 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/2 • Baseline up to 14 days after last dose of study drug (Day 32) 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 Coordination Abnormal	4.5% 1/22 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/14 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/14 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/15 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/2 • Baseline up to 14 days after last dose of study drug (Day 32) 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 Hypoaesthesia	4.5% 1/22 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/14 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/14 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/15 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/2 • Baseline up to 14 days after last dose of study drug (Day 32) 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 Syncope	4.5% 1/22 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/14 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/14 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/15 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/2 • Baseline up to 14 days after last dose of study drug (Day 32) 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 Disorientation	4.5% 1/22 • Baseline up to 14 days after last dose of study drug (Day 32) 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.	14.3% 2/14 • Baseline up to 14 days after last dose of study drug (Day 32) 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.	7.1% 1/14 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/15 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/2 • Baseline up to 14 days after last dose of study drug (Day 32) 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 Restlessness	0.00% 0/22 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/14 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/14 • Baseline up to 14 days after last dose of study drug (Day 32) 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.	6.7% 1/15 • Baseline up to 14 days after last dose of study drug (Day 32) 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.	50.0% 1/2 • Baseline up to 14 days after last dose of study drug (Day 32) 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 Communication Disorder	0.00% 0/22 • Baseline up to 14 days after last dose of study drug (Day 32) 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.	7.1% 1/14 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/14 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/15 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/2 • Baseline up to 14 days after last dose of study drug (Day 32) 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 Confusional State	0.00% 0/22 • Baseline up to 14 days after last dose of study drug (Day 32) 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.	7.1% 1/14 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/14 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/15 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/2 • Baseline up to 14 days after last dose of study drug (Day 32) 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 Insomnia	0.00% 0/22 • Baseline up to 14 days after last dose of study drug (Day 32) 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.	7.1% 1/14 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/14 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/15 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/2 • Baseline up to 14 days after last dose of study drug (Day 32) 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.
Vascular disorders Pallor	0.00% 0/22 • Baseline up to 14 days after last dose of study drug (Day 32) 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.	7.1% 1/14 • Baseline up to 14 days after last dose of study drug (Day 32) 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.	21.4% 3/14 • Baseline up to 14 days after last dose of study drug (Day 32) 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.	13.3% 2/15 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/2 • Baseline up to 14 days after last dose of study drug (Day 32) 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.
Vascular disorders Hot Flush	4.5% 1/22 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/14 • Baseline up to 14 days after last dose of study drug (Day 32) 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.	7.1% 1/14 • Baseline up to 14 days after last dose of study drug (Day 32) 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.	6.7% 1/15 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/2 • Baseline up to 14 days after last dose of study drug (Day 32) 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.
Vascular disorders Hypotension	0.00% 0/22 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/14 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/14 • Baseline up to 14 days after last dose of study drug (Day 32) 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.	6.7% 1/15 • Baseline up to 14 days after last dose of study drug (Day 32) 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% 0/2 • Baseline up to 14 days after last dose of study drug (Day 32) 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 No publication related to study results will be made without Sponsor's prior written approval. Any proposed publication or presentation will be submitted to Sponsor for review 60 days in advance of publication. Institution will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for an additional 60 days to preserve intellectual property
• Publication restrictions are in place

Restriction type: OTHER