Ketamine-Induced Brain Activity Changes, Psychotic-like Symptoms
Conditions
Keywords
Drug therapy
Brief summary
The purpose of this study is to determine whether ketamine-induced brain activity changes are modulated by TAK-063 administration using neuroimaging battery tests.
Detailed description
The drug being tested in this study is called TAK-063. This study will look at brain activity changes and treatment of psychotic-like symptoms induced by ketamine, in people who take TAK-063. The study will enroll approximately 27 participants. Participants will be randomly assigned to one of treatment sequences-which will remain undisclosed to the participants during the study (unless there is an urgent medical need). Participants will receive the following study medications by the end of the study: * Ketamine intravenous infusion (IV) AND * Placebo (dummy inactive pill) - this is a tablet that looks like the study drug but has no active ingredient AND * Two doses of TAK-063 at one of three dose levels All participants will be asked to take 3 tablets and will receive a ketamine IV on the first day of 3 separate study periods. Participants will then be assessed for brain activity changes and other symptoms. This single-center trial will be conducted in the United States. The overall time to participate in this study is up to 7 weeks. Participants will make 6 visits to the clinic.
Interventions
DRUGKetamine
Ketamine intravenous administration.
DRUGTAK-063
TAK-063 tablets
DRUGTAK-063 Placebo
TAK-063 placebo-matching tablets
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. In the opinion of the investigator, participant is capable of understanding and complying with protocol requirements. 2. The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures. 3. Is a healthy adult male. 4. Speaks English as their first language. 5. Is aged 18 to 45 years, inclusive, at the time of informed consent and first dose of study drug. 6. Weighs at least 50 kg and has a body mass index (BMI) between 18 and 32 kilogram per metre square (kg/m\^2), inclusive at Screening. 7. A male participant who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from signing of informed consent throughout the duration of the study and for 12 weeks after last dose. 8. Has a normal magnetic resonance imaging (MRI) scan and electroencephalogram (EEG) measurement at Screening.
Exclusion criteria
1. Has received any investigational compound or ketamine within 30 days prior to Day 1 of Period 1. 2. Has received TAK-063 in a previous clinical study or as a therapeutic agent. 3. Is an immediate family member, study site employee, or in a dependent relationship with a study site employee who is involved in the conduct of this study (e.g., spouse, parent, child, sibling) or may consent under duress. 4. Has uncontrolled, clinically significant neurologic, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, immunologic, endocrine disease, or psychiatric disorder, or other abnormality (including MRI or EEG), which may impact the ability of the participant to participate or potentially confound the study results. 5. Has a known hypersensitivity to any component of the formulation of TAK-063 or ketamine. 6. Has a contraindication for ketamine. 7. Has a positive result for drugs or alcohol at Screening or Check-in (Day -1 of Period 1). 8. Has a history of drug or alcohol abuse or dependence (as defined by Diagnostic \& Statistical Manual of Mental Disorders, fourth Edition \[DSM-IV\]) within 1 year prior to the screening visit or is unwilling to agree to abstain from alcohol and drugs throughout the study. 9. Has taken any excluded medication, supplements, or food products listed in the Excluded Medications and Dietary Products. 10. Has evidence of current cardiovascular, central nervous system (CNS), hepatic, hematopoietic disease, renal dysfunction, metabolic or endocrine dysfunction, serious allergy, asthma hypoxemia, hypertension, seizures, or allergic skin rash. There is any finding in the participant's medical history, physical examination, or safety laboratory tests giving reasonable suspicion of a disease that would contraindicate taking TAK-063 or ketamine or a similar drug in the same class, or that might interfere with the conduct of the study. This includes, but is not limited to, peptic ulcer disease, seizure disorders, and cardiac arrhythmias. 11. Has current or recent (within 6 months) gastrointestinal disease that would be expected to influence the absorption of drugs (ie, a history of malabsorption, esophageal reflux, peptic ulcer disease, erosive esophagitis frequent \[more than once per week\] occurrence of heartburn, or any surgical intervention \[e.g., cholecystectomy\]). 12. Has a history of cancer, except basal cell carcinoma which has been in remission for at least 5 years prior to Day 1 of Period 1. 13. Has a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV), or a known history of human immunodeficiency virus infection at Screening. 14. Has used nicotine-containing products (including but not limited to cigarettes, pipes, cigars, chewing tobacco, nicotine patch or nicotine gum) within 28 days prior to Check-in (Day -1 of Period 1) or cotinine test is positive at Screening or Check-in (Day -1 of Period 1). 15. Has poor peripheral arterial/venous access or recent wrist trauma. 16. Has donated or lost 450 mL or more of his or her blood volume (including plasmapheresis), or had a transfusion of any blood product within 3 months prior to Day 1 of Period 1. 17. Has a Screening and/or Check-in (Day -1 of Period 1) abnormal (clinically significant) electrocardiogram (ECG). Participant has a supine blood pressure outside the ranges of 90 to 140 mm Hg for systolic and 50 to 90 mm Hg for diastolic, if out of range may be repeated once for eligibility determination at the Screening Visit or Check-in (Day -1 of Period 1). 18. Has a resting heart rate outside the range 50 to 90 beats per minute (bpm), if out of range may be repeated once for eligibility determination at the Screening Visit and/or Check-in (Day -1 of Period 1). 19. Has a QT interval with Fridericia correction method (QTcF) greater than (\>) 430 milliseconds (ms) or PR outside the range 120 to 220 ms, if out of range may be repeated once for eligibility determination within a maximum of 5 minutes, at the Screening Visit and/or Check-in (Day -1 of Period 1). 20. Has abnormal Screening laboratory values that suggest a clinically significant underlying disease or participant with the following lab abnormalities: alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) \>1.5 upper limit of normal (ULN). 21. Has a history of Axis I/II mental disorders according to DSM-IV Axis I/II such as depression, anxiety disorders, bipolar disorder, attention deficit/hyperactivity disorder (ADHD), autism spectrum disorders, anorexia nervosa, bulimia nervosa, and schizophrenia. 22. Has a history of head injury or trauma. 23. Has any condition that would prevent an MRI from accurately or safely being performed (e.g., claustrophobia, cardiac pacemaker, metallic implants or clips), as verified per study site's standard MRI assessment questionnaire. 24. Has a risk of suicide according to the Investigator's clinical judgment (e.g., per Columbia-Suicide Severity Rating Scale \[C-SSRS\]) or has made a suicide attempt in the previous 6 months prior to Screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Day 1: 4 hours post TAK-063 dose or placebo | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax: Maximum Observed Plasma Concentration for TAK-063 and TAK-063 Metabolite (M-I) | Day 1: pre-dose and at multiple time points (up to 24 hours) postdose | — |
| Tmax: Time to Reach Cmax for TAK-063 and TAK-063 M-I | Day 1: pre-dose and at multiple time points (up to 24 hours) postdose | — |
| 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 | Day 1: Pre-dose and at multiple time points (up to 24 hours) post-dose | — |
| Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | Baseline up to 14 days after last dose of study drug (Day 32) | — |
| 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 | Baseline up to 14 days after last dose of study drug (Day 32) | The percentage of participants with any markedly abnormal standard safety laboratory values collected throughout study. |
| Percentage of Participants Who Meet the TGRD Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | Baseline up to 14 days after last dose of study drug (Day 32) | 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). |
| Percentage of Participants Who Meet the TGRD Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | Baseline up to 14 days after last dose of study drug (Day 32) | The percentage of participants who meet markedly abnormal criteria designated by TGRD measured throughout study. |
Countries
United States
Contacts
STUDY_DIRECTORMedical Director
Takeda Development Center Americas, Inc. (Note: This product was divested to Axsome in 2026)
Participant flow
Recruitment details
Participants took part in the study at 1 investigative site in the United States from 27 June 2013 to 28 August 2014.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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). | 3 |
| 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). | 3 |
| 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). | 3 |
| 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). | 3 |
| 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). | 3 |
| 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). | 3 |
| 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). | 3 |
| 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). | 3 |
| 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). | 3 |
| Total | 27 |
Baseline characteristics
| Characteristic | TAK-063 3 mg + TAK-063 30 mg + Placebo | TAK-063 30 mg + Placebo + TAK-063 3 mg | Placebo + TAK-063 3 mg + TAK-063 300 mg/10 mg | TAK-063 3 mg + TAK-063 300 mg/10 mg + Placebo | Placebo + TAK-063 3 mg + TAK-063 30 mg | TAK-063 300 mg/10 mg + Placebo + TAK-063 3 mg | Placebo + TAK-063 30 mg + TAK-063 300 mg/10 mg | TAK-063 30 mg + TAK-063 300 mg/10 mg + Placebo | TAK-063 300 mg/10 mg + Placebo + TAK-063 30 mg | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 28.7 years STANDARD_DEVIATION 7.64 | 23.7 years STANDARD_DEVIATION 6.66 | 32.3 years STANDARD_DEVIATION 5.13 | 23 years STANDARD_DEVIATION 5.2 | 27.7 years STANDARD_DEVIATION 3.21 | 22.3 years STANDARD_DEVIATION 3.51 | 27 years STANDARD_DEVIATION 7.94 | 24.7 years STANDARD_DEVIATION 2.08 | 23.7 years STANDARD_DEVIATION 5.69 | 25.9 years STANDARD_DEVIATION 5.6 |
| Body Mass Index | 28.38 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.557 | 25.30 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.19 | 23.39 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.844 | 26.99 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.108 | 26.06 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 4.43 | 23.28 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.611 | 24.20 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.417 | 25.71 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 1.011 | 23.69 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.269 | 25.22 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.997 |
| Caffeine Consumption Consumes Caffiene | 3 participants | 3 participants | 3 participants | 2 participants | 2 participants | 2 participants | 3 participants | 3 participants | 3 participants | 24 participants |
| Caffeine Consumption Not consumes Caffiene | 0 participants | 0 participants | 0 participants | 1 participants | 1 participants | 1 participants | 0 participants | 0 participants | 0 participants | 3 participants |
| Height | 182 centimeters (cm) STANDARD_DEVIATION 4.58 | 177 centimeters (cm) STANDARD_DEVIATION 8.19 | 187.7 centimeters (cm) STANDARD_DEVIATION 3.79 | 179.7 centimeters (cm) STANDARD_DEVIATION 10.79 | 179 centimeters (cm) STANDARD_DEVIATION 2.65 | 182.3 centimeters (cm) STANDARD_DEVIATION 3.06 | 183.3 centimeters (cm) STANDARD_DEVIATION 8.14 | 183.3 centimeters (cm) STANDARD_DEVIATION 6.51 | 182.7 centimeters (cm) STANDARD_DEVIATION 4.51 | 181.9 centimeters (cm) STANDARD_DEVIATION 6.06 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 participants | 0 participants | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Asian | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants | 0 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants | 0 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Multiracial | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Non Hispanic or Latino | 3 participants | 3 participants | 3 participants | 3 participants | 3 participants | 3 participants | 2 participants | 3 participants | 3 participants | 26 participants |
| Race/Ethnicity, Customized Pacific Islander-White | 3 participants | 3 participants | 3 participants | 2 participants | 3 participants | 3 participants | 2 participants | 2 participants | 3 participants | 24 participants |
| Region of Enrollment United States | 3 participants | 3 participants | 3 participants | 3 participants | 3 participants | 3 participants | 3 participants | 3 participants | 3 participants | 27 participants |
| Sex/Gender, Customized Female | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Sex/Gender, Customized Male | 3 participants | 3 participants | 3 participants | 3 participants | 3 participants | 3 participants | 3 participants | 3 participants | 3 participants | 27 participants |
| Smoking Classification Ex-smoker | 1 participants | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants | 1 participants | 0 participants | 1 participants | 4 participants |
| Smoking Classification Never smoked | 2 participants | 3 participants | 2 participants | 3 participants | 3 participants | 3 participants | 2 participants | 3 participants | 2 participants | 23 participants |
| Weight | 93.80 kilogram (kg) STANDARD_DEVIATION 4.784 | 79.87 kilogram (kg) STANDARD_DEVIATION 16.91 | 82.3 kilogram (kg) STANDARD_DEVIATION 12.643 | 87.47 kilogram (kg) STANDARD_DEVIATION 13.955 | 83.23 kilogram (kg) STANDARD_DEVIATION 11.981 | 77.33 kilogram (kg) STANDARD_DEVIATION 8.107 | 81.10 kilogram (kg) STANDARD_DEVIATION 5.821 | 86.40 kilogram (kg) STANDARD_DEVIATION 4.939 | 79.07 kilogram (kg) STANDARD_DEVIATION 11.716 | 83.40 kilogram (kg) STANDARD_DEVIATION 10.306 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| other Total, other adverse events | 15 / 22 | 7 / 14 | 8 / 14 | 13 / 15 | 2 / 2 |
| serious Total, serious adverse events | 0 / 22 | 0 / 14 | 0 / 14 | 0 / 15 | 0 / 2 |
Outcome results
Primary
Ketamine-Induced Brain Activity in Regions of Interest During Resting State
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 0.4487 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 1.5568 |
| Placebo | 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 |
| Placebo | 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 |
| TAK-063 3 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Left Amygdala | 0.4776 percent signal change in brain activity | Standard Deviation 0.72631 |
| TAK-063 3 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Left Posterior Cingulate Cortex | 0.4647 percent signal change in brain activity | Standard Deviation 0.52746 |
| TAK-063 3 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Right Posterior Cingulate Cortex | 0.4515 percent signal change in brain activity | Standard Deviation 0.57054 |
| TAK-063 3 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Right Striatum | 0.1154 percent signal change in brain activity | Standard Deviation 0.52174 |
| TAK-063 3 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Left Substantia Nigra | 0.2857 percent signal change in brain activity | Standard Deviation 0.61851 |
| TAK-063 3 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Left Subgenual Cingulate/BA25 | 0.2236 percent signal change in brain activity | Standard Deviation 1.2245 |
| TAK-063 3 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Right Anterior Cingulate Cortex | 0.2542 percent signal change in brain activity | Standard Deviation 0.55542 |
| TAK-063 3 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Left Striatum | 0.0644 percent signal change in brain activity | Standard Deviation 0.47601 |
| TAK-063 3 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Left Anterior Cingulate Cortex | 0.2943 percent signal change in brain activity | Standard Deviation 0.67925 |
| TAK-063 3 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Right Amygdala | 0.1180 percent signal change in brain activity | Standard Deviation 0.85125 |
| TAK-063 3 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Right Substantia Nigra | 0.2209 percent signal change in brain activity | Standard Deviation 0.69383 |
| TAK-063 3 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Left Thalamus | 0.3406 percent signal change in brain activity | Standard Deviation 0.58293 |
| TAK-063 3 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Right Thalamus | 0.3392 percent signal change in brain activity | Standard Deviation 0.59598 |
| TAK-063 3 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Left Ventrolateral Prefrontal Cortex | 0.5183 percent signal change in brain activity | Standard Deviation 0.66695 |
| TAK-063 3 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Right Ventrolateral Prefrontal Cortex | 0.5134 percent signal change in brain activity | Standard Deviation 0.69396 |
| TAK-063 3 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Left Dorsolateral Prefrontal Cortex | 0.2576 percent signal change in brain activity | Standard Deviation 0.56173 |
| TAK-063 3 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Right Dorsolateral Prefrontal Cortex | 0.2799 percent signal change in brain activity | Standard Deviation 0.53268 |
| TAK-063 3 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Left Hippocampus | 0.1790 percent signal change in brain activity | Standard Deviation 0.47311 |
| TAK-063 3 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Right Hippocampus | 0.1814 percent signal change in brain activity | Standard Deviation 0.51038 |
| TAK-063 3 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Right Subgenual Cingulate/BA25 | -0.3430 percent signal change in brain activity | Standard Deviation 1.15319 |
| TAK-063 3 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Left Paracingulate Gyrus/BA32 | 0.2799 percent signal change in brain activity | Standard Deviation 0.59577 |
| TAK-063 3 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Right Paracingulate Gyrus/BA32 | 0.3583 percent signal change in brain activity | Standard Deviation 0.58987 |
| TAK-063 10 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Left Ventrolateral Prefrontal Cortex | 0.6081 percent signal change in brain activity | Standard Deviation 0.73306 |
| TAK-063 10 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Right Anterior Cingulate Cortex | 0.4199 percent signal change in brain activity | Standard Deviation 0.70069 |
| TAK-063 10 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Left Paracingulate Gyrus/BA32 | 0.4069 percent signal change in brain activity | Standard Deviation 0.65537 |
| TAK-063 10 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Left Hippocampus | 0.3073 percent signal change in brain activity | Standard Deviation 0.41116 |
| TAK-063 10 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Left Amygdala | 0.4888 percent signal change in brain activity | Standard Deviation 0.60449 |
| TAK-063 10 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Left Posterior Cingulate Cortex | 0.5316 percent signal change in brain activity | Standard Deviation 0.77685 |
| TAK-063 10 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Left Anterior Cingulate Cortex | 0.4439 percent signal change in brain activity | Standard Deviation 0.72261 |
| TAK-063 10 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Right Posterior Cingulate Cortex | 0.6132 percent signal change in brain activity | Standard Deviation 0.79296 |
| TAK-063 10 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Right Hippocampus | 0.2141 percent signal change in brain activity | Standard Deviation 0.34537 |
| TAK-063 10 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Right Ventrolateral Prefrontal Cortex | 0.6661 percent signal change in brain activity | Standard Deviation 0.75274 |
| TAK-063 10 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Right Thalamus | 0.5159 percent signal change in brain activity | Standard Deviation 0.44482 |
| TAK-063 10 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Left Striatum | 0.3045 percent signal change in brain activity | Standard Deviation 0.51442 |
| TAK-063 10 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Left Thalamus | 0.5564 percent signal change in brain activity | Standard Deviation 0.52695 |
| TAK-063 10 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Left Subgenual Cingulate/BA25 | -0.2448 percent signal change in brain activity | Standard Deviation 1.46965 |
| TAK-063 10 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Right Amygdala | 0.0106 percent signal change in brain activity | Standard Deviation 0.76838 |
| TAK-063 10 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Left Dorsolateral Prefrontal Cortex | 0.4451 percent signal change in brain activity | Standard Deviation 0.62506 |
| TAK-063 10 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Right Dorsolateral Prefrontal Cortex | 0.5403 percent signal change in brain activity | Standard Deviation 0.78105 |
| TAK-063 10 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Right Striatum | 0.3124 percent signal change in brain activity | Standard Deviation 0.46817 |
| TAK-063 10 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Left Substantia Nigra | 0.5560 percent signal change in brain activity | Standard Deviation 0.67716 |
| TAK-063 10 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Right Subgenual Cingulate/BA25 | -0.6379 percent signal change in brain activity | Standard Deviation 2.30349 |
| TAK-063 10 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Right Substantia Nigra | 0.3398 percent signal change in brain activity | Standard Deviation 0.45331 |
| TAK-063 10 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Right Paracingulate Gyrus/BA32 | 0.4972 percent signal change in brain activity | Standard Deviation 0.82842 |
| TAK-063 30 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Right Substantia Nigra | 0.1148 percent signal change in brain activity | Standard Deviation 0.40258 |
| TAK-063 30 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Left Thalamus | 0.3589 percent signal change in brain activity | Standard Deviation 0.43768 |
| TAK-063 30 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Right Thalamus | 0.3734 percent signal change in brain activity | Standard Deviation 0.44173 |
| TAK-063 30 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Left Ventrolateral Prefrontal Cortex | 0.5900 percent signal change in brain activity | Standard Deviation 0.4792 |
| TAK-063 30 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Left Striatum | 0.2453 percent signal change in brain activity | Standard Deviation 0.40828 |
| TAK-063 30 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Right Subgenual Cingulate/BA25 | 0.0424 percent signal change in brain activity | Standard Deviation 1.71727 |
| TAK-063 30 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Right Ventrolateral Prefrontal Cortex | 0.6119 percent signal change in brain activity | Standard Deviation 0.44821 |
| TAK-063 30 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Left Anterior Cingulate Cortex | 0.3876 percent signal change in brain activity | Standard Deviation 0.47127 |
| TAK-063 30 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Left Dorsolateral Prefrontal Cortex | 0.3720 percent signal change in brain activity | Standard Deviation 0.30576 |
| TAK-063 30 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Right Posterior Cingulate Cortex | 0.3783 percent signal change in brain activity | Standard Deviation 0.55473 |
| TAK-063 30 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Right Dorsolateral Prefrontal Cortex | 0.4331 percent signal change in brain activity | Standard Deviation 0.3916 |
| TAK-063 30 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Left Posterior Cingulate Cortex | 0.3987 percent signal change in brain activity | Standard Deviation 0.49018 |
| TAK-063 30 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Left Hippocampus | 0.2123 percent signal change in brain activity | Standard Deviation 0.35146 |
| TAK-063 30 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Left Paracingulate Gyrus/BA32 | 0.3281 percent signal change in brain activity | Standard Deviation 0.3899 |
| TAK-063 30 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Right Striatum | 0.2617 percent signal change in brain activity | Standard Deviation 0.36033 |
| TAK-063 30 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Right Anterior Cingulate Cortex | 0.3251 percent signal change in brain activity | Standard Deviation 0.47592 |
| TAK-063 30 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Right Hippocampus | 0.0989 percent signal change in brain activity | Standard Deviation 0.35725 |
| TAK-063 30 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Right Paracingulate Gyrus/BA32 | 0.3969 percent signal change in brain activity | Standard Deviation 0.52267 |
| TAK-063 30 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Right Amygdala | 0.2686 percent signal change in brain activity | Standard Deviation 0.53395 |
| TAK-063 30 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Left Substantia Nigra | 0.2214 percent signal change in brain activity | Standard Deviation 0.36486 |
| TAK-063 30 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Left Subgenual Cingulate/BA25 | -0.0002 percent signal change in brain activity | Standard Deviation 2.18015 |
| TAK-063 30 mg | Ketamine-Induced Brain Activity in Regions of Interest During Resting State | Left Amygdala | 0.3435 percent signal change in brain activity | Standard Deviation 0.5756 |
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Left Anterior Cingulate Cortex: Values were obtained using analysis of variance (ANOVA) model with sequence, period, regimen and participant nested within sequence as factors by regions of interest.p-value: 0.25995% CI: [-0.6506, 0.1809]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Left Anterior Cingulate Cortex: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.86995% CI: [-0.4853, 0.4119]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Left Anterior Cingulate Cortex: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.30695% CI: [-0.6441, 0.2081]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Right Anterior Cingulate Cortex: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.16995% CI: [-0.6174, 0.1124]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Right Anterior Cingulate Cortex: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.83195% CI: [-0.4354, 0.3521]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Right Anterior Cingulate Cortex: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.19795% CI: [-0.6161, 0.1319]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Left Posterior Cingulate Cortex: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.4895% CI: [-0.4443, 0.2133]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Left Posterior Cingulate Cortex: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.34595% CI: [-0.1875, 0.5221]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Left Posterior Cingulate Cortex: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.37195% CI: [-0.4874, 0.1866]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Right Posterior Cingulate Cortex: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.36495% CI: [-0.5553, 0.2092]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Right Posterior Cingulate Cortex: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.50795% CI: [-0.2762, 0.5486]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Right Posterior Cingulate Cortex: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.2195% CI: [-0.6381, 0.1453]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Left Striatum: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.03995% CI: [-0.5955, -0.0162]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Left Striatum: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.93195% CI: [-0.2991, 0.326]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Left Striatum: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.43195% CI: [-0.4133, 0.1804]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Right Striatum: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.0295% CI: [-0.5985, -0.0554]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Right Striatum: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.56295% CI: [-0.3775, 0.2085]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Right Striatum: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.21695% CI: [-0.451, 0.1056]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Left Amygdala: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.96295% CI: [-0.3663, 0.3495]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Left Amygdala: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.85295% CI: [-0.4218, 0.3505]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Left Amygdala: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.24195% CI: [-0.5822, 0.1514]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Right Amygdala: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.44395% CI: [-0.4991, 0.223]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Right Amygdala: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.29595% CI: [-0.5933, 0.1859]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Right Amygdala: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.74395% CI: [-0.4303, 0.3098]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Left Substantia Nigra: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.27795% CI: [-0.504, 0.1491]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Left Substantia Nigra: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.75895% CI: [-0.4062, 0.2985]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Left Substantia Nigra: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.01295% CI: [-0.7724, -0.1031]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Right Substantia Nigra: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.4995% CI: [-0.4055, 0.1981]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Right Substantia Nigra: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.53495% CI: [-0.4263, 0.2249]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Right Substantia Nigra: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.16995% CI: [-0.5233, 0.0953]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Left Thalamus: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.0795% CI: [-0.551, 0.0228]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Left Thalamus: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.57995% CI: [-0.395, 0.2242]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Left Thalamus: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.195% CI: [-0.5387, 0.0494]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Right Thalamus: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.11395% CI: [-0.495, 0.055]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Right Thalamus: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.7295% CI: [-0.3495, 0.244]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Right Thalamus: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.19695% CI: [-0.4649, 0.0989]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Left Ventrolateral Prefrontal Cortex: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.31395% CI: [-0.6122, 0.202]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Left Ventrolateral Prefrontal Cortex: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.90895% CI: [-0.414, 0.4646]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Left Ventrolateral Prefrontal Cortex: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.14895% CI: [-0.7214, 0.1131]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Right Ventrolateral Prefrontal Cortex: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.06795% CI: [-0.7066, 0.0249]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Right Ventrolateral Prefrontal Cortex: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.73995% CI: [-0.4599, 0.3294]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Right Ventrolateral Prefrontal Cortex: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.03195% CI: [-0.7912, -0.0415]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Left Dorsolateral Prefrontal Cortex: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.16695% CI: [-0.4952, 0.0888]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Left Dorsolateral Prefrontal Cortex: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.55295% CI: [-0.2219, 0.4083]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Left Dorsolateral Prefrontal Cortex: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.27195% CI: [-0.4641, 0.1345]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Right Dorsolateral Prefrontal Cortex: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.12995% CI: [-0.5802, 0.077]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Right Dorsolateral Prefrontal Cortex: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.46895% CI: [-0.2266, 0.4825]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Right Dorsolateral Prefrontal Cortex: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.22895% CI: [-0.5401, 0.1334]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Left Hippocampus: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.14195% CI: [-0.4696, 0.0696]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Left Hippocampus: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.96495% CI: [-0.2975, 0.2844]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Left Hippocampus: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.16495% CI: [-0.4699, 0.0828]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Right Hippocampus: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.28595% CI: [-0.4152, 0.126]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Right Hippocampus: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.90395% CI: [-0.3096, 0.2744]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Right Hippocampus: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.24595% CI: [-0.4388, 0.1159]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Left Subgenual Cingulate/BA25: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.42995% CI: [-0.563, 1.2948]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Left Subgenual Cingulate/BA25: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.93795% CI: [-0.9628, 1.0419]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Left Subgenual Cingulate/BA25: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.10195% CI: [-0.1618, 1.7423]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Right Subgenual Cingulate/BA25: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.32195% CI: [-1.3296, 0.4488]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Right Subgenual Cingulate/BA25: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.32895% CI: [-1.428, 0.491]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Right Subgenual Cingulate/BA25: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.35695% CI: [-0.4914, 1.3314]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Left Paracingulte gyrus/BA32. Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.18895% CI: [-0.5666, 0.1158]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Left Paracingulte gyrus/BA32: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.89995% CI: [-0.3914, 0.3449]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Left Paracingulte gyrus/BA32: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.1595% CI: [-0.6032, 0.0963]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Right Paracingulte gyrus/BA3: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.14895% CI: [-0.669, 0.1048]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Right Paracingulte gyrus/BA32: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.81795% CI: [-0.4655, 0.3695]ANOVA
Comparison: Test the equality on the means between TAK-063 and Placebo for the region Right Paracingulte gyrus/BA32: Values were obtained using an ANOVA model with sequence, period, regimen, and participant nested within sequence as factors by regions of interest.p-value: 0.09195% CI: [-0.7361, 0.057]ANOVA
Secondary
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
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 38.46 |
| Placebo | 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 |
| TAK-063 3 mg | 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 | 548.58 nanogram hours per milliliter (ng*hr/mL) | Standard Deviation 122.686 |
| TAK-063 3 mg | 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 | 582.91 nanogram hours per milliliter (ng*hr/mL) | Standard Deviation 201.503 |
| TAK-063 10 mg | 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 | 1298.89 nanogram hours per milliliter (ng*hr/mL) | Standard Deviation 331.095 |
| TAK-063 10 mg | 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 | 1285.18 nanogram hours per milliliter (ng*hr/mL) | Standard Deviation 499.431 |
Secondary
Cmax: Maximum Observed Plasma Concentration for TAK-063 and TAK-063 Metabolite (M-I)
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 2.86 |
| Placebo | 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 |
| TAK-063 3 mg | Cmax: Maximum Observed Plasma Concentration for TAK-063 and TAK-063 Metabolite (M-I) | TAK-063 | 48.16 nanogram per milliliter (ng/mL) | Standard Deviation 8.769 |
| TAK-063 3 mg | Cmax: Maximum Observed Plasma Concentration for TAK-063 and TAK-063 Metabolite (M-I) | M-I | 48.94 nanogram per milliliter (ng/mL) | Standard Deviation 11.5 |
| TAK-063 10 mg | Cmax: Maximum Observed Plasma Concentration for TAK-063 and TAK-063 Metabolite (M-I) | TAK-063 | 109.9 nanogram per milliliter (ng/mL) | Standard Deviation 27.053 |
| TAK-063 10 mg | Cmax: Maximum Observed Plasma Concentration for TAK-063 and TAK-063 Metabolite (M-I) | M-I | 103.72 nanogram per milliliter (ng/mL) | Standard Deviation 32.635 |
Secondary
Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE)
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 68.2 percentage of participants |
| TAK-063 3 mg | Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 50 percentage of participants |
| TAK-063 10 mg | Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 57.1 percentage of participants |
| TAK-063 30 mg | Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 86.7 percentage of participants |
| TAK-063 300 mg | Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) | 100 percentage of participants |
Secondary
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
The percentage of participants with any markedly abnormal standard safety laboratory values collected throughout study.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | 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 |
| TAK-063 3 mg | 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 | 0 percentage of participants |
| TAK-063 10 mg | 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 | 14.3 percentage of participants |
| TAK-063 30 mg | 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 | 6.7 percentage of participants |
| TAK-063 300 mg | 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 | 0 percentage of participants |
Secondary
Percentage of Participants Who Meet the TGRD Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose
The percentage of participants who meet markedly abnormal criteria designated by TGRD measured throughout study.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | 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 |
| TAK-063 3 mg | Percentage of Participants Who Meet the TGRD Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | 14.3 percentage of participants |
| TAK-063 10 mg | Percentage of Participants Who Meet the TGRD Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | 35.7 percentage of participants |
| TAK-063 30 mg | Percentage of Participants Who Meet the TGRD Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | 53.3 percentage of participants |
| TAK-063 300 mg | Percentage of Participants Who Meet the TGRD Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose | 100 percentage of participants |
Secondary
Percentage of Participants Who Meet the TGRD Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose
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).
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Meet the TGRD Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | 50.0 percentage of participants |
| TAK-063 3 mg | Percentage of Participants Who Meet the TGRD Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | 64.3 percentage of participants |
| TAK-063 10 mg | Percentage of Participants Who Meet the TGRD Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | 57.1 percentage of participants |
| TAK-063 30 mg | Percentage of Participants Who Meet the TGRD Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | 53.3 percentage of participants |
| TAK-063 300 mg | Percentage of Participants Who Meet the TGRD Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | 100 percentage of participants |
Secondary
Tmax: Time to Reach Cmax for TAK-063 and TAK-063 M-I
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Tmax: Time to Reach Cmax for TAK-063 and TAK-063 M-I | TAK-063 | 3.02 hours | Full Range 2.86 |
| Placebo | Tmax: Time to Reach Cmax for TAK-063 and TAK-063 M-I | M-I | 2.96 hours | — |
| TAK-063 3 mg | Tmax: Time to Reach Cmax for TAK-063 and TAK-063 M-I | M-I | 3.03 hours | — |
| TAK-063 3 mg | Tmax: Time to Reach Cmax for TAK-063 and TAK-063 M-I | TAK-063 | 3.03 hours | — |
| TAK-063 10 mg | Tmax: Time to Reach Cmax for TAK-063 and TAK-063 M-I | M-I | 4.23 hours | — |
| TAK-063 10 mg | Tmax: Time to Reach Cmax for TAK-063 and TAK-063 M-I | TAK-063 | 3.02 hours | — |