Healthy
Conditions
Keywords
Drug therapy
Brief summary
The purpose of this study is to determine the relationship between TAK-831 dose, plasma exposure, extent and duration of brain D-amino acid oxidase (DAO) enzyme occupancy following single oral dosing of TAK-831 in healthy participants.
Detailed description
The drug being tested in this study is called TAK-831. TAK-831 is a highly selective and potent inhibitor of DAO, a peroxisomal enzyme active towards neutral D-amino acids which potentially effects cerebellar dysfunction. This study will look at the relationship between TAK-831 plasma exposure and the extent and duration of brain DAO enzyme occupancy after single oral dosing of TAK-831 in healthy male participants using \[18F\]PGM299 radioactive tracer injection and PET imaging. The study will enroll up to 22 participants in two different sets. Up to 16 participants will be enrolled in Set A. Within that total, up to 5 dose levels of TAK-831 may be evaluated, with up to 6 participants per dose level, although typically, there will be 2 to 3 participants per dose level. All participants in Set A will also receive up to 3 doses of \[18F\]PGM299. Up to 6 participants will be enrolled in Set B. All participants in Set B will be assigned to single treatment group to receive 2 doses of \[18F\]PGM299. All participants in Set A will be asked to take single oral dose of TAK-831 suspension on Day 1. In Set A, each of the participant will receive a maximum of 3 PET scans with \[18F\]PGM299; 1 at baseline 2 following a single oral dose of TAK-831 on Days 1 and 2. In Set B, each of the participant will receive 2 PET scans with \[18F\]PGM299 on Days 1 and 10. Set B will be conducted after the confirmation of blockade of \[18F\]PGM299 binding by TAK-831 in 2 to 4 participants of Set A. This multi-center trial will be conducted in the United Kingdom. The overall time to participate in this study is 62 days. Participants in Set A will make 4 visits to the clinic, and participants in Set B will make 3 visits to the clinic and all will be contacted by telephone on Day 15 (Set A) and Day 12 (Set B) of treatment period for a follow-up assessment.
Interventions
DRUGTAK-831
TAK-831 oral suspension.
DRUG[18F]PGM299
\[18F\]PGM299 injection
Sponsors
Takeda
Neurocrine Biosciences
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
25 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Is capable of understanding and complying with protocol requirements. 2. Signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures. 3. Is in good health as determined by physical examination, electrocardiogram (ECG), and laboratory evaluations. 4. Is a healthy male aged 25 to 55 years, inclusive, at the time of informed consent and first injection of the PET tracer. 5. Weighs at least 45 kilogram (kg) and has a body mass index (BMI) from 18.0 to 30.0 kilogram per square meter (kg/m\^2), inclusive, at Screening. 6. Agrees to use adequate contraception from signing of informed consent throughout the duration of the study and for 90 days after last dose.
Exclusion criteria
1. Has received any investigational compound or device within 3 months or 5 half-lives, whichever is longer, prior to Check-in for Screening. 2. Is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in the conduct of this study (example, spouse, parent, child, sibling) or may consent under duress. 3. Has uncontrolled, clinically significant (CS), neurologic (including seizure disorder), cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal (GI), urologic, immunologic, or endocrine disease or psychiatric disorder, or other abnormality, which may impact the ability of the participant to participate or potentially confound the study results. 4. Has a known hypersensitivity to any component of the formulation of TAK-831 or related compounds, or to \[18 F\]PGM299 or to any of its components. 5. Has a positive urine or breath test result for drugs of abuse (defined as any illicit drug use), ethanol (alcohol), or cotinine at Screening, Check-in for Baseline Imaging/Confinement Period 1, or Check-in for the Treatment/Confinement Period 2 (Day -1) for a participant participating in Set A or at Screening, Check-in for Tracer TEST PET Imaging/Confinement Period 1, or Check-in for RE-TEST PET Imaging/Confinement Period 2 for a participant participating in Set B. 6. Has a history of drug abuse (defined as any illicit drug use) or a history of ethanol (alcohol) abuse within 1 year prior to the screening visit or is unwilling to agree to abstain from ethanol (alcohol) and drugs throughout the study. 7. Has taken any medication, supplements, or food products during the time periods listed in the excluded medications and dietary products table. 8. Intends to donate sperm during the course of this study or for 90 days after the last dose of study medication. 9. Has evidence of current cardiovascular, central nervous system, hepatic, or hematopoietic disease; renal, metabolic or endocrine dysfunction; serious allergy, asthma, hypoxemia, hypertension, or allergic skin rash; or 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-831 or a similar drug in the same class, which might interfere with the conduct of the study. This includes, but is not limited to, peptic ulcer disease and cardiac arrhythmias. 10. Has current or recent (within 6 months) GI disease that would be expected to influence the absorption of drugs (that is, a history of malabsorption), any surgical intervention known to impact absorption (example, bariatric surgery or bowel resection), esophageal reflux, peptic ulcer disease, erosive esophagitis, or frequent (more than once per week) occurrence of heartburn. 11. Has a history of cancer, except basal cell carcinoma that has been in remission for at least 5 years prior to Day 1. 12. Has a positive test result for hepatitis B virus surface antigen (HBsAg), hepatitis C virus (HCV) antibody (HCAB), or human immunodeficiency virus (HIV) infection at Screening. 13. Has used nicotine-containing products (including but not limited to cigarettes, pipes, cigars, chewing tobacco, nicotine patch or nicotine gum) within 44 days prior to Check-in for Confinement Period 1. Cotinine test is positive at Screening, or Check-in for Confinement Period 1, or Confinement Period 2. 14. Has poor peripheral venous access. 15. Has an abnormal Allen's test in either upper extremity. 16. Has donated or lost 450 milliliter (mL) or more of his blood volume (including plasmapheresis), or had a transfusion of any blood product within 90 days prior to Confinement Period 1. 17. Has an abnormal CS ECG at Screening, Check-in for Confinement Period 1, or at Check-in for Confinement Period 2. Entry of any participant with an abnormal (not clinically significant \[NCS\]) ECG must be approved and documented by signature of the coordinating investigator or delegate. 18. Has a supine blood pressure outside the ranges of 100 to 140 millimeter of mercury (mm Hg) for systolic and 50 to 90 mm Hg for diastolic, confirmed with 1 repeat testing within a maximum of 30 minutes, at the Screening Visit, Check-in for Confinement Period 1, or Confinement Period 2. 19. Has a resting heart rate outside the range of 50 to 90 beats/minute, confirmed with 1 repeat testing within a maximum of 30 minutes, at the Screening Visit, Check-in for Confinement Period 1, or Confinement Period 2. 20. Has a Fridericia's Correction Formula (QTcF) - QTcF interval greater than (\>) 450 millisecond (msec) or PR outside the range of 120 to 220 msec, confirmed with 1 repeat testing within a maximum of 30 minutes, at the Screening Visit, Check-in for Confinement Period 1, or Confinement Period 2. 21. Has abnormal Screening laboratory values that suggest a CS underlying disease or the following laboratory abnormalities: Alanine Aminotransferase (ALT) and/or Alanine serum transaminase AST \>1.5\*upper limit of normal (ULN). 22. Has a risk of suicide according to the investigator's clinical judgment (example, per Columbia-Suicide Severity Rating Scale \[C-SSRS\]) or has made an attempt in the previous 6 months. 23. Has had a seizure or convulsion (lifetime), including absence seizure and febrile convulsion. 24. In the opinion of the investigator, is unlikely to comply with the protocol or is unsuitable for any other reason. 25. Has had previous exposure to ionizing radiation such that, in combination with the exposure from this study, their exposure will be \>10 millisievert (mSv) for the previous year. 26. Has a contraindication to medical resonance imaging (MRI) based on the standard MRI screening questionnaire. Contraindications include ferromagnetic foreign bodies (example, shrapnel, ferromagnetic fragments in the orbital area), certain implanted medical devices (example, aneurysm clips, cardiac pacemakers) or claustrophobia. 27. Has findings on screening brain MRI scan that will potentially compromise participant safety or the scientific integrity of the study data, if the participant were to participate in this study. 28. Has prolonged prothrombin time (PT) or activated partial thromboplastin time (PTT) or reduced platelet count (less than \[\<\] 100\*10\^9/Liter \[L\]).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Set A: Baseline (PET scan 1), 2 hours (PET scan 2) and 26 hours (PET scan 3) post-TAK-831 dose; Set B: Day 1 (PET scan 1) and Day 10 (PET scan 2) | — |
| Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Set A: Baseline (PET scan 1), 2 hours (PET scan 2) and 26 hours (PET scan 3) post-TAK-831 dose; Set B: Day 1 (PET scan 1) and Day 10 (PET scan 2) | — |
| D-amino Acid Oxidase (DAO) Occupancy Estimation in the Cerebellar GM | Set A: Baseline (PET scan 1), 2 hours (PET scan 2) and 26 hours (PET scan 3) post-TAK-831 dose; Set B: Day 1 (PET scan 1) and Day 10 (PET scan 2) | DAO occupancy is calculated as percent difference between baseline and postdose \[18F\]PGM299 BPND for each participant. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Set A: Plasma Concentrations of TAK-831 During Each Post-TAK-831 Dosing PET Scan Periods | Set A: Days 1 and 2 At time 0 (at tracer injection), 60 minutes after tracer injection and 120 minutes after tracer injection for each post TAK-831 dosing PET scan period | — |
| Set A: Percent Change From Baseline to Post-TAK-831 Dose in AUEC(0-24)Serine: Area Under the Effect-time Curve From Time 0 to 24 Hours Post-TAK-831 Dose for Dextro-serine (D-serine) and Levo-serine (L-serine) | Set A: Baseline, 24 hours post-TAK-831 dose | — |
| Set A: Percent Change From Baseline to Post-TAK-831 Dose in AUEC(0-24)Serine: Area Under the Effect-time Curve From Time 0 to 24 Hours Post-TAK-831 Dose for Ratio of D-serine to Total Serine | Set A: Baseline, 24 hours post-TAK-831 dose | — |
| Set A: EC50- Plasma Concentration of TAK-831 That Corresponds to 50 Percent (%) DAO Brain Enzyme Occupancy in Cerebellum | Set A: Baseline, 2 and 26 hours post-TAK-831 dose | EC50 was obtained from global VT model. The affinity constant relating plasma concentration of TAK-831 to DAO occupancy (EC50) was estimated by fitting the PET and plasma concentration data (VT, Cp). It was calculated as VT= VsBase (EC50/EC50+Cp) + VND, where Vs Base was the group-level (global) volume of distribution of the specific binding in the target region (cerebellar GM) and VND was the volume of distribution of the non-displaceable component (non-specific bound and free radiotracer) of the target region. |
| Set A: Percent Change in Maximum Drug-induced Effect (Emax, D: Total Serine Ratio) on the Ratio of D-serine to Total Serine | Set A: Baseline, 24 hours post-TAK-831 dose | — |
| Set A: Time to Reach the Maximum PD Effect (Time to Emax,Serine) for D-serine and L-serine | Set A: Day -1 At 1, 4 and 12 hours post check-in and Day 1 pre-dose and at multiple time points (up to 24 hours) post-TAK-831 dose | — |
| Set A: Time to Reach the Maximum PD Effect (Time to Emax,Serine) for Ratio of D-serine to Total Serine | Set A: Day -1 At 1, 4 and 12 hours post check-in and Day 1 pre-dose and at multiple time points (up to 24 hours) post-TAK-831 dose | — |
| Set A: Percent Change in Maximum Drug-induced Effect (Emax,Serine) on Change in Plasma Concentrations of D-serine and L-serine | Set A: Baseline, 24 hours post-TAK-831 dose | — |
| Set A: Dose of TAK-831 That Corresponds to 50% DAO Brain Enzyme Occupancy in Cerebellum | Set A: At 2 and 26 hours post-TAK-831 dose | Dose of TAK-831 that corresponds to 50% DAO brain enzyme occupancy in cerebellum at the time of maximum observed plasma concentration (Tmax) of TAK-831 was estimated. |
| Set B: Coefficient of Variation (CoV) of [18F]PGM299 Binding in Healthy Human Brain | Set B: Baseline up to Day 10 | CoV was calculated as COV (P)(%) = 100 \* mean/ standard deviation, where P was different participant scanned under baseline condition. |
Countries
United Kingdom
Participant flow
Recruitment details
Participants took part in the study at 2 investigative sites in the United Kingdom from 21-Mar-2016 to 30-Aug-2016.
Pre-assignment details
Healthy participants in Set A received up to 100 megabecquerel (MBq) of \[18F\]PGM299 for 3 PET scans at baseline, 2, and 26 hours post TAK-831. Set A participants also received a single dose of TAK-831 (100 milligram \[mg\], 200 mg, 250 mg, or 500 mg). Healthy participants in Set B received up 100 MBq of \[18F\]PGM299 for 2 PET scans on Day 1 and 10.
Participants by arm
| Arm | Count |
|---|---|
| Set A: TAK-831 100 mg TAK-831 100 mg, suspension, orally, once on Day 1 and up to 100 MBq of \[18F\]PGM299 with a maximal mass up to 12.5 mcg, injection, intravenously, prior to PET imaging at Baseline, 2 hours and 26 hours post-TAK-831 dose. | 4 |
| Set A: TAK-831 200 mg TAK-831 200 mg, suspension, orally, once on Day 1 and up to 100 MBq of \[18F\]PGM299 with a maximal mass up to 12.5 mcg, injection, intravenously, prior to PET imaging at Baseline, 2 hours and 26 hours post-TAK-831 dose. | 2 |
| Set A: TAK-831 250 mg TAK-831 250 mg, suspension, orally, once on Day 1 and up to 100 MBq of \[18F\]PGM299 with a maximal mass up to 12.5 mcg, injection, intravenously, prior to PET imaging at Baseline, 2 hours and 26 hours post-TAK-831 dose. | 5 |
| Set A: TAK-831 500 mg TAK-831 500 mg, suspension, orally, once on Day 1 and up to 100 MBq of \[18F\]PGM299 with a maximal mass up to 12.5 mcg, injection, intravenously, prior to PET imaging at Baseline, 2 hours and 26 hours post-TAK-831 dose. | 2 |
| Set B: [18F]PGM299 \[18F\]PGM299 up to 100 MBq (with a maximal mass up to 12.5 mcg), injection, intravenously, prior to PET imaging on Days 1 and 10. | 6 |
| Set A: [18F]PGM299 Baseline \[18F\]PGM299 up to 100 MBq with a maximal mass up to 12.5 mcg, injection, intravenously, prior to PET imaging at Baseline only. Participant in this reporting group discontinued from the study and did not receive any TAK-831 dose. | 1 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Ligand synthesis failure | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Set A: TAK-831 100 mg | Set A: TAK-831 200 mg | Set A: TAK-831 250 mg | Set A: TAK-831 500 mg | Set B: [18F]PGM299 | Set A: [18F]PGM299 Baseline | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 2 Participants | 5 Participants | 2 Participants | 6 Participants | 1 Participants | 20 Participants |
| Alcohol Classification Current drinker | 3 Participants | 2 Participants | 3 Participants | 1 Participants | 3 Participants | 0 Participants | 12 Participants |
| Alcohol Classification Ex-drinker | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 3 Participants |
| Alcohol Classification Never drunk | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 5 Participants |
| Caffeine Consumption Caffeine consumption | 4 Participants | 2 Participants | 5 Participants | 2 Participants | 3 Participants | 1 Participants | 17 Participants |
| Caffeine Consumption No caffeine consumption | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 4 Participants | 0 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 2 Participants | 3 Participants | 1 Participants | 2 Participants | 1 Participants | 12 Participants |
| Region of Enrollment United Kingdom | 4 Participants | 2 Participants | 5 Participants | 2 Participants | 6 Participants | 1 Participants | 20 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 4 Participants | 2 Participants | 5 Participants | 2 Participants | 6 Participants | 1 Participants | 20 Participants |
| Smoking Classification Ex-smoker | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants | 0 Participants | 4 Participants |
| Smoking Classification Never smoked | 4 Participants | 2 Participants | 3 Participants | 2 Participants | 4 Participants | 1 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 4 | 0 / 2 | 1 / 5 | 0 / 2 | 0 / 4 | 0 / 2 | 2 / 5 | 1 / 2 | 2 / 4 | 0 / 2 | 0 / 5 | 1 / 2 | 0 / 6 | 0 / 1 |
| serious Total, serious adverse events | 0 / 4 | 0 / 2 | 0 / 5 | 0 / 2 | 0 / 4 | 0 / 2 | 0 / 5 | 0 / 2 | 0 / 4 | 0 / 2 | 0 / 5 | 0 / 2 | 0 / 6 | 0 / 1 |
Outcome results
Primary
D-amino Acid Oxidase (DAO) Occupancy Estimation in the Cerebellar GM
DAO occupancy is calculated as percent difference between baseline and postdose \[18F\]PGM299 BPND for each participant.
Time frame: Set A: Baseline (PET scan 1), 2 hours (PET scan 2) and 26 hours (PET scan 3) post-TAK-831 dose; Set B: Day 1 (PET scan 1) and Day 10 (PET scan 2)
Population: Due to variability in localization of \[18F\]PGM299 in both Cerebellar GM and Frontal Cortex GM, DAO occupancy estimation as a percent difference from baseline and post-TAK-831 dosing PET scans in Cerebellar GM based on VT values could not be made.
Primary
Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan
Time frame: Set A: Baseline (PET scan 1), 2 hours (PET scan 2) and 26 hours (PET scan 3) post-TAK-831 dose; Set B: Day 1 (PET scan 1) and Day 10 (PET scan 2)
Population: The set included all participants who had at least 1 technically adequate PET scan.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Set A: TAK-831 100 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 1- PET Scan 1 | 10.99 ratio |
| Set A: TAK-831 100 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 5- PET Scan 1 | NA ratio |
| Set A: TAK-831 100 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 2- PET Scan 3 | 4.39 ratio |
| Set A: TAK-831 100 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 2- PET Scan 1 | 3.88 ratio |
| Set A: TAK-831 100 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 4- PET Scan 1 | 7.37 ratio |
| Set A: TAK-831 100 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 6- PET Scan 2 | NA ratio |
| Set A: TAK-831 100 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 1- PET Scan 3 | 7.89 ratio |
| Set A: TAK-831 100 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 5- PET Scan 3 | NA ratio |
| Set A: TAK-831 100 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 3- PET Scan 2 | 5.13 ratio |
| Set A: TAK-831 100 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 3- PET Scan 1 | 7.22 ratio |
| Set A: TAK-831 100 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 6- PET Scan 1 | NA ratio |
| Set A: TAK-831 100 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 5- PET Scan 2 | NA ratio |
| Set A: TAK-831 100 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 4- PET Scan 2 | 2.72 ratio |
| Set A: TAK-831 100 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 2- PET Scan 2 | 1.01 ratio |
| Set A: TAK-831 100 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 3-PET Scan 3 | 4.53 ratio |
| Set A: TAK-831 100 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 1- PET Scan 2 | 3.26 ratio |
| Set A: TAK-831 100 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 4-PET Scan 3 | 11.13 ratio |
| Set A: TAK-831 200 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 1- PET Scan 2 | -0.28 ratio |
| Set A: TAK-831 200 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 4-PET Scan 3 | NA ratio |
| Set A: TAK-831 200 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 5- PET Scan 1 | NA ratio |
| Set A: TAK-831 200 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 5- PET Scan 2 | NA ratio |
| Set A: TAK-831 200 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 3- PET Scan 2 | NA ratio |
| Set A: TAK-831 200 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 6- PET Scan 2 | NA ratio |
| Set A: TAK-831 200 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 1- PET Scan 1 | 7.31 ratio |
| Set A: TAK-831 200 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 1- PET Scan 3 | 4.22 ratio |
| Set A: TAK-831 200 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 2- PET Scan 1 | 8.38 ratio |
| Set A: TAK-831 200 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 2- PET Scan 2 | 0.16 ratio |
| Set A: TAK-831 200 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 4- PET Scan 1 | NA ratio |
| Set A: TAK-831 200 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 6- PET Scan 1 | NA ratio |
| Set A: TAK-831 200 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 2- PET Scan 3 | 6.06 ratio |
| Set A: TAK-831 200 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 3- PET Scan 1 | NA ratio |
| Set A: TAK-831 200 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 3-PET Scan 3 | NA ratio |
| Set A: TAK-831 200 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 5- PET Scan 3 | NA ratio |
| Set A: TAK-831 200 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 4- PET Scan 2 | NA ratio |
| Set A: TAK-831 250 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 1- PET Scan 1 | 6.71 ratio |
| Set A: TAK-831 250 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 2- PET Scan 1 | 3.53 ratio |
| Set A: TAK-831 250 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 2- PET Scan 3 | 2.17 ratio |
| Set A: TAK-831 250 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 5- PET Scan 1 | 3.69 ratio |
| Set A: TAK-831 250 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 6- PET Scan 2 | NA ratio |
| Set A: TAK-831 250 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 5- PET Scan 3 | NA ratio |
| Set A: TAK-831 250 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 4- PET Scan 1 | 4.84 ratio |
| Set A: TAK-831 250 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 5- PET Scan 2 | NA ratio |
| Set A: TAK-831 250 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 2- PET Scan 2 | 0.25 ratio |
| Set A: TAK-831 250 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 4-PET Scan 3 | 3.38 ratio |
| Set A: TAK-831 250 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 1- PET Scan 2 | 0.47 ratio |
| Set A: TAK-831 250 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 4- PET Scan 2 | 0.37 ratio |
| Set A: TAK-831 250 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 1- PET Scan 3 | 4.32 ratio |
| Set A: TAK-831 250 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 3- PET Scan 1 | 4.80 ratio |
| Set A: TAK-831 250 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 3- PET Scan 2 | 0.01 ratio |
| Set A: TAK-831 250 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 6- PET Scan 1 | NA ratio |
| Set A: TAK-831 250 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 3-PET Scan 3 | 3.53 ratio |
| Set A: TAK-831 500 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 1- PET Scan 1 | 8.96 ratio |
| Set A: TAK-831 500 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 2- PET Scan 1 | 13.35 ratio |
| Set A: TAK-831 500 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 3-PET Scan 3 | NA ratio |
| Set A: TAK-831 500 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 2- PET Scan 2 | 0.06 ratio |
| Set A: TAK-831 500 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 4- PET Scan 2 | NA ratio |
| Set A: TAK-831 500 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 4-PET Scan 3 | NA ratio |
| Set A: TAK-831 500 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 2- PET Scan 3 | 4.59 ratio |
| Set A: TAK-831 500 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 5- PET Scan 1 | NA ratio |
| Set A: TAK-831 500 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 3- PET Scan 1 | NA ratio |
| Set A: TAK-831 500 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 4- PET Scan 1 | NA ratio |
| Set A: TAK-831 500 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 5- PET Scan 3 | NA ratio |
| Set A: TAK-831 500 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 6- PET Scan 2 | NA ratio |
| Set A: TAK-831 500 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 5- PET Scan 2 | NA ratio |
| Set A: TAK-831 500 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 1- PET Scan 2 | -0.20 ratio |
| Set A: TAK-831 500 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 3- PET Scan 2 | NA ratio |
| Set A: TAK-831 500 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 6- PET Scan 1 | NA ratio |
| Set A: TAK-831 500 mg | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 1- PET Scan 3 | 11.19 ratio |
| Set B: [18F]PGM299 | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 6- PET Scan 2 | NA ratio |
| Set B: [18F]PGM299 | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 4- PET Scan 1 | 7.48 ratio |
| Set B: [18F]PGM299 | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 4- PET Scan 2 | 4.35 ratio |
| Set B: [18F]PGM299 | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 5- PET Scan 1 | 5.30 ratio |
| Set B: [18F]PGM299 | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 1- PET Scan 1 | 3.77 ratio |
| Set B: [18F]PGM299 | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 1- PET Scan 2 | 4.99 ratio |
| Set B: [18F]PGM299 | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 1- PET Scan 3 | NA ratio |
| Set B: [18F]PGM299 | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 2- PET Scan 2 | 5.89 ratio |
| Set B: [18F]PGM299 | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 2- PET Scan 3 | NA ratio |
| Set B: [18F]PGM299 | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 3- PET Scan 1 | 7.13 ratio |
| Set B: [18F]PGM299 | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 3- PET Scan 2 | 7.46 ratio |
| Set B: [18F]PGM299 | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 3-PET Scan 3 | NA ratio |
| Set B: [18F]PGM299 | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 4-PET Scan 3 | NA ratio |
| Set B: [18F]PGM299 | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 5- PET Scan 2 | 6.38 ratio |
| Set B: [18F]PGM299 | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 5- PET Scan 3 | NA ratio |
| Set B: [18F]PGM299 | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 6- PET Scan 1 | 8.29 ratio |
| Set B: [18F]PGM299 | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 2- PET Scan 1 | 13.49 ratio |
| Set A: [18F]PGM299 Baseline | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 4- PET Scan 2 | NA ratio |
| Set A: [18F]PGM299 Baseline | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 3-PET Scan 3 | NA ratio |
| Set A: [18F]PGM299 Baseline | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 3- PET Scan 2 | NA ratio |
| Set A: [18F]PGM299 Baseline | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 3- PET Scan 1 | NA ratio |
| Set A: [18F]PGM299 Baseline | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 4- PET Scan 1 | NA ratio |
| Set A: [18F]PGM299 Baseline | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 5- PET Scan 3 | NA ratio |
| Set A: [18F]PGM299 Baseline | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 2- PET Scan 3 | NA ratio |
| Set A: [18F]PGM299 Baseline | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 2- PET Scan 2 | NA ratio |
| Set A: [18F]PGM299 Baseline | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 1- PET Scan 3 | NA ratio |
| Set A: [18F]PGM299 Baseline | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 1- PET Scan 2 | NA ratio |
| Set A: [18F]PGM299 Baseline | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 2- PET Scan 1 | NA ratio |
| Set A: [18F]PGM299 Baseline | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 6- PET Scan 1 | NA ratio |
| Set A: [18F]PGM299 Baseline | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 1- PET Scan 1 | 5.49 ratio |
| Set A: [18F]PGM299 Baseline | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 5- PET Scan 1 | NA ratio |
| Set A: [18F]PGM299 Baseline | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 4-PET Scan 3 | NA ratio |
| Set A: [18F]PGM299 Baseline | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 6- PET Scan 2 | NA ratio |
| Set A: [18F]PGM299 Baseline | Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan | Participant 5- PET Scan 2 | NA ratio |
Primary
Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan
Time frame: Set A: Baseline (PET scan 1), 2 hours (PET scan 2) and 26 hours (PET scan 3) post-TAK-831 dose; Set B: Day 1 (PET scan 1) and Day 10 (PET scan 2)
Population: The set included all participants who had at least 1 technically adequate PET scan.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Set A: TAK-831 100 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 4- PET Scan 2 | 0.592 milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 100 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 5- PET Scan 3 | NA milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 100 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 1- PET Scan 1 | 1.211 milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 100 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 4-PET Scan 3 | 1.055 milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 100 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 5- PET Scan 2 | NA milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 100 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 5- PET Scan 1 | NA milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 100 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 4- PET Scan 1 | 1.297 milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 100 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 1- PET Scan 3 | 1.467 milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 100 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 6 -PET Scan 2 | NA milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 100 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 3-PET Scan 3 | 1.078 milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 100 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 3- PET Scan 1 | 1.397 milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 100 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 6- PET Scan 1 | NA milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 100 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 3- PET Scan 2 | 0.858 milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 100 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 2- PET Scan 3 | 0.809 milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 100 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 2- PET Scan 2 | 0.241 milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 100 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 2- PET Scan 1 | 0.663 milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 100 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 1- PET Scan 2 | 0.400 milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 200 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 4-PET Scan 3 | NA milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 200 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 1- PET Scan 3 | 0.543 milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 200 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 3- PET Scan 1 | NA milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 200 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 4- PET Scan 2 | NA milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 200 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 1- PET Scan 1 | 1.247 milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 200 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 1- PET Scan 2 | 0.126 milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 200 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 2- PET Scan 1 | 1.585 milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 200 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 2- PET Scan 2 | 0.217 milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 200 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 2- PET Scan 3 | 0.77 milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 200 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 3- PET Scan 2 | NA milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 200 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 3-PET Scan 3 | NA milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 200 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 4- PET Scan 1 | NA milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 200 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 5- PET Scan 1 | NA milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 200 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 5- PET Scan 2 | NA milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 200 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 5- PET Scan 3 | NA milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 200 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 6- PET Scan 1 | NA milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 200 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 6 -PET Scan 2 | NA milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 250 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 5- PET Scan 2 | NA milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 250 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 2- PET Scan 3 | 0.425 milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 250 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 5- PET Scan 1 | 0.976 milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 250 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 2- PET Scan 1 | 0.743 milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 250 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 2- PET Scan 2 | 0.266 milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 250 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 6- PET Scan 1 | NA milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 250 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 6 -PET Scan 2 | NA milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 250 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 4-PET Scan 3 | 0.67 milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 250 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 3- PET Scan 1 | 0.981 milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 250 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 1- PET Scan 2 | 0.247 milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 250 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 1- PET Scan 1 | 1.349 milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 250 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 5- PET Scan 3 | NA milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 250 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 4- PET Scan 2 | 0.254 milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 250 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 1- PET Scan 3 | 0.58 milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 250 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 4- PET Scan 1 | 0.853 milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 250 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 3-PET Scan 3 | 0.802 milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 250 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 3- PET Scan 2 | 0.189 milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 500 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 3-PET Scan 3 | NA milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 500 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 6 -PET Scan 2 | NA milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 500 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 1- PET Scan 1 | 1.683 milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 500 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 5- PET Scan 2 | NA milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 500 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 1- PET Scan 2 | 0.114 milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 500 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 5- PET Scan 1 | NA milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 500 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 2- PET Scan 2 | 0.172 milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 500 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 5- PET Scan 3 | NA milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 500 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 6- PET Scan 1 | NA milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 500 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 2- PET Scan 3 | 0.553 milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 500 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 4-PET Scan 3 | NA milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 500 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 3- PET Scan 1 | NA milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 500 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 2- PET Scan 1 | 2.095 milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 500 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 1- PET Scan 3 | 1.182 milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 500 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 3- PET Scan 2 | NA milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 500 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 4- PET Scan 2 | NA milliliter per cubic centimeter(mL/cm^3) |
| Set A: TAK-831 500 mg | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 4- PET Scan 1 | NA milliliter per cubic centimeter(mL/cm^3) |
| Set B: [18F]PGM299 | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 1- PET Scan 1 | 0.658 milliliter per cubic centimeter(mL/cm^3) |
| Set B: [18F]PGM299 | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 1- PET Scan 3 | NA milliliter per cubic centimeter(mL/cm^3) |
| Set B: [18F]PGM299 | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 4- PET Scan 1 | 1.459 milliliter per cubic centimeter(mL/cm^3) |
| Set B: [18F]PGM299 | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 6 -PET Scan 2 | NA milliliter per cubic centimeter(mL/cm^3) |
| Set B: [18F]PGM299 | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 2- PET Scan 1 | 0.884 milliliter per cubic centimeter(mL/cm^3) |
| Set B: [18F]PGM299 | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 2- PET Scan 2 | 1.130 milliliter per cubic centimeter(mL/cm^3) |
| Set B: [18F]PGM299 | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 2- PET Scan 3 | NA milliliter per cubic centimeter(mL/cm^3) |
| Set B: [18F]PGM299 | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 3- PET Scan 1 | 1.504 milliliter per cubic centimeter(mL/cm^3) |
| Set B: [18F]PGM299 | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 6- PET Scan 1 | 1.036 milliliter per cubic centimeter(mL/cm^3) |
| Set B: [18F]PGM299 | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 3- PET Scan 2 | 1.388 milliliter per cubic centimeter(mL/cm^3) |
| Set B: [18F]PGM299 | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 3-PET Scan 3 | NA milliliter per cubic centimeter(mL/cm^3) |
| Set B: [18F]PGM299 | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 1- PET Scan 2 | 1.109 milliliter per cubic centimeter(mL/cm^3) |
| Set B: [18F]PGM299 | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 4-PET Scan 3 | NA milliliter per cubic centimeter(mL/cm^3) |
| Set B: [18F]PGM299 | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 5- PET Scan 1 | 0.895 milliliter per cubic centimeter(mL/cm^3) |
| Set B: [18F]PGM299 | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 5- PET Scan 2 | 1.077 milliliter per cubic centimeter(mL/cm^3) |
| Set B: [18F]PGM299 | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 4- PET Scan 2 | 0.979 milliliter per cubic centimeter(mL/cm^3) |
| Set B: [18F]PGM299 | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 5- PET Scan 3 | NA milliliter per cubic centimeter(mL/cm^3) |
| Set A: [18F]PGM299 Baseline | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 1- PET Scan 3 | NA milliliter per cubic centimeter(mL/cm^3) |
| Set A: [18F]PGM299 Baseline | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 5- PET Scan 2 | NA milliliter per cubic centimeter(mL/cm^3) |
| Set A: [18F]PGM299 Baseline | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 1- PET Scan 1 | 0.863 milliliter per cubic centimeter(mL/cm^3) |
| Set A: [18F]PGM299 Baseline | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 3-PET Scan 3 | NA milliliter per cubic centimeter(mL/cm^3) |
| Set A: [18F]PGM299 Baseline | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 4- PET Scan 1 | NA milliliter per cubic centimeter(mL/cm^3) |
| Set A: [18F]PGM299 Baseline | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 4- PET Scan 2 | NA milliliter per cubic centimeter(mL/cm^3) |
| Set A: [18F]PGM299 Baseline | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 6- PET Scan 1 | NA milliliter per cubic centimeter(mL/cm^3) |
| Set A: [18F]PGM299 Baseline | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 3- PET Scan 2 | NA milliliter per cubic centimeter(mL/cm^3) |
| Set A: [18F]PGM299 Baseline | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 3- PET Scan 1 | NA milliliter per cubic centimeter(mL/cm^3) |
| Set A: [18F]PGM299 Baseline | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 2- PET Scan 3 | NA milliliter per cubic centimeter(mL/cm^3) |
| Set A: [18F]PGM299 Baseline | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 2- PET Scan 2 | NA milliliter per cubic centimeter(mL/cm^3) |
| Set A: [18F]PGM299 Baseline | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 1- PET Scan 2 | NA milliliter per cubic centimeter(mL/cm^3) |
| Set A: [18F]PGM299 Baseline | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 5- PET Scan 3 | NA milliliter per cubic centimeter(mL/cm^3) |
| Set A: [18F]PGM299 Baseline | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 2- PET Scan 1 | NA milliliter per cubic centimeter(mL/cm^3) |
| Set A: [18F]PGM299 Baseline | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 5- PET Scan 1 | NA milliliter per cubic centimeter(mL/cm^3) |
| Set A: [18F]PGM299 Baseline | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 6 -PET Scan 2 | NA milliliter per cubic centimeter(mL/cm^3) |
| Set A: [18F]PGM299 Baseline | Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan | Participant 4-PET Scan 3 | NA milliliter per cubic centimeter(mL/cm^3) |
Secondary
Set A: Dose of TAK-831 That Corresponds to 50% DAO Brain Enzyme Occupancy in Cerebellum
Dose of TAK-831 that corresponds to 50% DAO brain enzyme occupancy in cerebellum at the time of maximum observed plasma concentration (Tmax) of TAK-831 was estimated.
Time frame: Set A: At 2 and 26 hours post-TAK-831 dose
Population: The PET target occupancy set included all participants who received study drug (TAK-831) and had a technically adequate baseline PET scan and at least 1 technically adequate post-TAK-831 dose PET scan.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Set A: TAK-831 100 mg | Set A: Dose of TAK-831 That Corresponds to 50% DAO Brain Enzyme Occupancy in Cerebellum | 100 mg |
Secondary
Set A: EC50- Plasma Concentration of TAK-831 That Corresponds to 50 Percent (%) DAO Brain Enzyme Occupancy in Cerebellum
EC50 was obtained from global VT model. The affinity constant relating plasma concentration of TAK-831 to DAO occupancy (EC50) was estimated by fitting the PET and plasma concentration data (VT, Cp). It was calculated as VT= VsBase (EC50/EC50+Cp) + VND, where Vs Base was the group-level (global) volume of distribution of the specific binding in the target region (cerebellar GM) and VND was the volume of distribution of the non-displaceable component (non-specific bound and free radiotracer) of the target region.
Time frame: Set A: Baseline, 2 and 26 hours post-TAK-831 dose
Population: The PET target occupancy set included all participants who received study drug (TAK-831) and had a technically adequate baseline PET scan and at least 1 technically adequate post-TAK-831 dose PET scan.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Set A: TAK-831 100 mg | Set A: EC50- Plasma Concentration of TAK-831 That Corresponds to 50 Percent (%) DAO Brain Enzyme Occupancy in Cerebellum | 12.7 nanogram per milliliter (ng/mL) |
Secondary
Set A: Percent Change From Baseline to Post-TAK-831 Dose in AUEC(0-24)Serine: Area Under the Effect-time Curve From Time 0 to 24 Hours Post-TAK-831 Dose for Dextro-serine (D-serine) and Levo-serine (L-serine)
Time frame: Set A: Baseline, 24 hours post-TAK-831 dose
Population: The pharmacodynamic (PD) set for D- and L-serine included all participants in Set A who received study drug (TAK-831) and had at least 1 measurable D- and L-serine plasma measurement both at pre-dose and following TAK-831 dosing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Set A: TAK-831 100 mg | Set A: Percent Change From Baseline to Post-TAK-831 Dose in AUEC(0-24)Serine: Area Under the Effect-time Curve From Time 0 to 24 Hours Post-TAK-831 Dose for Dextro-serine (D-serine) and Levo-serine (L-serine) | D-serine | 8.65 percent change | Standard Deviation 7.209 |
| Set A: TAK-831 100 mg | Set A: Percent Change From Baseline to Post-TAK-831 Dose in AUEC(0-24)Serine: Area Under the Effect-time Curve From Time 0 to 24 Hours Post-TAK-831 Dose for Dextro-serine (D-serine) and Levo-serine (L-serine) | L-serine | 10.88 percent change | Standard Deviation 5.905 |
| Set A: TAK-831 200 mg | Set A: Percent Change From Baseline to Post-TAK-831 Dose in AUEC(0-24)Serine: Area Under the Effect-time Curve From Time 0 to 24 Hours Post-TAK-831 Dose for Dextro-serine (D-serine) and Levo-serine (L-serine) | D-serine | 21.90 percent change | — |
| Set A: TAK-831 200 mg | Set A: Percent Change From Baseline to Post-TAK-831 Dose in AUEC(0-24)Serine: Area Under the Effect-time Curve From Time 0 to 24 Hours Post-TAK-831 Dose for Dextro-serine (D-serine) and Levo-serine (L-serine) | L-serine | 2.00 percent change | — |
| Set A: TAK-831 250 mg | Set A: Percent Change From Baseline to Post-TAK-831 Dose in AUEC(0-24)Serine: Area Under the Effect-time Curve From Time 0 to 24 Hours Post-TAK-831 Dose for Dextro-serine (D-serine) and Levo-serine (L-serine) | D-serine | 18.08 percent change | Standard Deviation 8.309 |
| Set A: TAK-831 250 mg | Set A: Percent Change From Baseline to Post-TAK-831 Dose in AUEC(0-24)Serine: Area Under the Effect-time Curve From Time 0 to 24 Hours Post-TAK-831 Dose for Dextro-serine (D-serine) and Levo-serine (L-serine) | L-serine | -2.46 percent change | Standard Deviation 10.301 |
| Set A: TAK-831 500 mg | Set A: Percent Change From Baseline to Post-TAK-831 Dose in AUEC(0-24)Serine: Area Under the Effect-time Curve From Time 0 to 24 Hours Post-TAK-831 Dose for Dextro-serine (D-serine) and Levo-serine (L-serine) | L-serine | 5.10 percent change | — |
| Set A: TAK-831 500 mg | Set A: Percent Change From Baseline to Post-TAK-831 Dose in AUEC(0-24)Serine: Area Under the Effect-time Curve From Time 0 to 24 Hours Post-TAK-831 Dose for Dextro-serine (D-serine) and Levo-serine (L-serine) | D-serine | 8.70 percent change | — |
Secondary
Set A: Percent Change From Baseline to Post-TAK-831 Dose in AUEC(0-24)Serine: Area Under the Effect-time Curve From Time 0 to 24 Hours Post-TAK-831 Dose for Ratio of D-serine to Total Serine
Time frame: Set A: Baseline, 24 hours post-TAK-831 dose
Population: The PD set for D- and L-serine included all participants in Set A who received study drug (TAK-831) and had at least 1 measurable D- and L-serine plasma measurement both at pre-dose and following TAK-831 dosing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Set A: TAK-831 100 mg | Set A: Percent Change From Baseline to Post-TAK-831 Dose in AUEC(0-24)Serine: Area Under the Effect-time Curve From Time 0 to 24 Hours Post-TAK-831 Dose for Ratio of D-serine to Total Serine | -1.18 percent change | Standard Deviation 4.748 |
| Set A: TAK-831 200 mg | Set A: Percent Change From Baseline to Post-TAK-831 Dose in AUEC(0-24)Serine: Area Under the Effect-time Curve From Time 0 to 24 Hours Post-TAK-831 Dose for Ratio of D-serine to Total Serine | 19.75 percent change | — |
| Set A: TAK-831 250 mg | Set A: Percent Change From Baseline to Post-TAK-831 Dose in AUEC(0-24)Serine: Area Under the Effect-time Curve From Time 0 to 24 Hours Post-TAK-831 Dose for Ratio of D-serine to Total Serine | 21.30 percent change | Standard Deviation 6.958 |
| Set A: TAK-831 500 mg | Set A: Percent Change From Baseline to Post-TAK-831 Dose in AUEC(0-24)Serine: Area Under the Effect-time Curve From Time 0 to 24 Hours Post-TAK-831 Dose for Ratio of D-serine to Total Serine | 6.25 percent change | — |
Secondary
Set A: Percent Change in Maximum Drug-induced Effect (Emax, D: Total Serine Ratio) on the Ratio of D-serine to Total Serine
Time frame: Set A: Baseline, 24 hours post-TAK-831 dose
Population: The PD set for D- and L-serine included all participants in Set A who received study drug (TAK-831) and had at least 1 measurable D- and L-serine plasma measurement both at pre-dose and following TAK-831 dosing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Set A: TAK-831 100 mg | Set A: Percent Change in Maximum Drug-induced Effect (Emax, D: Total Serine Ratio) on the Ratio of D-serine to Total Serine | -1.40 percent change | Standard Deviation 9.515 |
| Set A: TAK-831 200 mg | Set A: Percent Change in Maximum Drug-induced Effect (Emax, D: Total Serine Ratio) on the Ratio of D-serine to Total Serine | 20.95 percent change | — |
| Set A: TAK-831 250 mg | Set A: Percent Change in Maximum Drug-induced Effect (Emax, D: Total Serine Ratio) on the Ratio of D-serine to Total Serine | 25.38 percent change | Standard Deviation 12.604 |
| Set A: TAK-831 500 mg | Set A: Percent Change in Maximum Drug-induced Effect (Emax, D: Total Serine Ratio) on the Ratio of D-serine to Total Serine | 20.45 percent change | — |
Secondary
Set A: Percent Change in Maximum Drug-induced Effect (Emax,Serine) on Change in Plasma Concentrations of D-serine and L-serine
Time frame: Set A: Baseline, 24 hours post-TAK-831 dose
Population: The PD set for D- and L-serine included all participants in Set A who received study drug (TAK-831) and had at least 1 measurable D- and L-serine plasma measurement both at pre-dose and following TAK-831 dosing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Set A: TAK-831 100 mg | Set A: Percent Change in Maximum Drug-induced Effect (Emax,Serine) on Change in Plasma Concentrations of D-serine and L-serine | D-serine | 9.58 percent change | Standard Deviation 9.769 |
| Set A: TAK-831 100 mg | Set A: Percent Change in Maximum Drug-induced Effect (Emax,Serine) on Change in Plasma Concentrations of D-serine and L-serine | L-serine | 17.40 percent change | Standard Deviation 7.318 |
| Set A: TAK-831 200 mg | Set A: Percent Change in Maximum Drug-induced Effect (Emax,Serine) on Change in Plasma Concentrations of D-serine and L-serine | L-serine | 11.50 percent change | — |
| Set A: TAK-831 200 mg | Set A: Percent Change in Maximum Drug-induced Effect (Emax,Serine) on Change in Plasma Concentrations of D-serine and L-serine | D-serine | 27.05 percent change | — |
| Set A: TAK-831 250 mg | Set A: Percent Change in Maximum Drug-induced Effect (Emax,Serine) on Change in Plasma Concentrations of D-serine and L-serine | D-serine | 17.46 percent change | Standard Deviation 9.122 |
| Set A: TAK-831 250 mg | Set A: Percent Change in Maximum Drug-induced Effect (Emax,Serine) on Change in Plasma Concentrations of D-serine and L-serine | L-serine | -2.02 percent change | Standard Deviation 12.917 |
| Set A: TAK-831 500 mg | Set A: Percent Change in Maximum Drug-induced Effect (Emax,Serine) on Change in Plasma Concentrations of D-serine and L-serine | D-serine | 40.30 percent change | — |
| Set A: TAK-831 500 mg | Set A: Percent Change in Maximum Drug-induced Effect (Emax,Serine) on Change in Plasma Concentrations of D-serine and L-serine | L-serine | 16.10 percent change | — |
Secondary
Set A: Plasma Concentrations of TAK-831 During Each Post-TAK-831 Dosing PET Scan Periods
Time frame: Set A: Days 1 and 2 At time 0 (at tracer injection), 60 minutes after tracer injection and 120 minutes after tracer injection for each post TAK-831 dosing PET scan period
Population: Pharmacokinetic(PK) set where data at specified time points post-tracer injection was available.PK set included all participants who received study drug(TAK-831)and had at least 1 measurable plasma concentration for TAK-831.Data was reported for Participant 1,2,3 and 4 of each of TAK-831 100,250mg and Participant 1 and 2 of TAK-831 200,500mg arms.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Set A: TAK-831 100 mg | Set A: Plasma Concentrations of TAK-831 During Each Post-TAK-831 Dosing PET Scan Periods | Day 1: 60 minutes post-tracer dose | 83.375 nanogram per milliliter (ng/mL) |
| Set A: TAK-831 100 mg | Set A: Plasma Concentrations of TAK-831 During Each Post-TAK-831 Dosing PET Scan Periods | Day 1: pre-tracer dose | 211.250 nanogram per milliliter (ng/mL) |
| Set A: TAK-831 100 mg | Set A: Plasma Concentrations of TAK-831 During Each Post-TAK-831 Dosing PET Scan Periods | Day 2: 60 minutes post-tracer dose | 3.140 nanogram per milliliter (ng/mL) |
| Set A: TAK-831 100 mg | Set A: Plasma Concentrations of TAK-831 During Each Post-TAK-831 Dosing PET Scan Periods | Day 1: 120 minutes post-tracer dose | 42.500 nanogram per milliliter (ng/mL) |
| Set A: TAK-831 100 mg | Set A: Plasma Concentrations of TAK-831 During Each Post-TAK-831 Dosing PET Scan Periods | Day 2: 120 minutes post-tracer dose | 3.123 nanogram per milliliter (ng/mL) |
| Set A: TAK-831 100 mg | Set A: Plasma Concentrations of TAK-831 During Each Post-TAK-831 Dosing PET Scan Periods | Day 2: pre-tracer dose | 4.028 nanogram per milliliter (ng/mL) |
| Set A: TAK-831 200 mg | Set A: Plasma Concentrations of TAK-831 During Each Post-TAK-831 Dosing PET Scan Periods | Day 2: 60 minutes post-tracer dose | 5.205 nanogram per milliliter (ng/mL) |
| Set A: TAK-831 200 mg | Set A: Plasma Concentrations of TAK-831 During Each Post-TAK-831 Dosing PET Scan Periods | Day 2: 120 minutes post-tracer dose | 5.380 nanogram per milliliter (ng/mL) |
| Set A: TAK-831 200 mg | Set A: Plasma Concentrations of TAK-831 During Each Post-TAK-831 Dosing PET Scan Periods | Day 2: pre-tracer dose | 7.360 nanogram per milliliter (ng/mL) |
| Set A: TAK-831 200 mg | Set A: Plasma Concentrations of TAK-831 During Each Post-TAK-831 Dosing PET Scan Periods | Day 1: 60 minutes post-tracer dose | 129.050 nanogram per milliliter (ng/mL) |
| Set A: TAK-831 200 mg | Set A: Plasma Concentrations of TAK-831 During Each Post-TAK-831 Dosing PET Scan Periods | Day 1: pre-tracer dose | 416.500 nanogram per milliliter (ng/mL) |
| Set A: TAK-831 200 mg | Set A: Plasma Concentrations of TAK-831 During Each Post-TAK-831 Dosing PET Scan Periods | Day 1: 120 minutes post-tracer dose | 82.000 nanogram per milliliter (ng/mL) |
| Set A: TAK-831 250 mg | Set A: Plasma Concentrations of TAK-831 During Each Post-TAK-831 Dosing PET Scan Periods | Day 1: pre-tracer dose | 273.750 nanogram per milliliter (ng/mL) |
| Set A: TAK-831 250 mg | Set A: Plasma Concentrations of TAK-831 During Each Post-TAK-831 Dosing PET Scan Periods | Day 1: 120 minutes post-tracer dose | 89.925 nanogram per milliliter (ng/mL) |
| Set A: TAK-831 250 mg | Set A: Plasma Concentrations of TAK-831 During Each Post-TAK-831 Dosing PET Scan Periods | Day 2: pre-tracer dose | 11.025 nanogram per milliliter (ng/mL) |
| Set A: TAK-831 250 mg | Set A: Plasma Concentrations of TAK-831 During Each Post-TAK-831 Dosing PET Scan Periods | Day 1: 60 minutes post-tracer dose | 122.725 nanogram per milliliter (ng/mL) |
| Set A: TAK-831 250 mg | Set A: Plasma Concentrations of TAK-831 During Each Post-TAK-831 Dosing PET Scan Periods | Day 2: 120 minutes post-tracer dose | 8.665 nanogram per milliliter (ng/mL) |
| Set A: TAK-831 250 mg | Set A: Plasma Concentrations of TAK-831 During Each Post-TAK-831 Dosing PET Scan Periods | Day 2: 60 minutes post-tracer dose | 9.658 nanogram per milliliter (ng/mL) |
| Set A: TAK-831 500 mg | Set A: Plasma Concentrations of TAK-831 During Each Post-TAK-831 Dosing PET Scan Periods | Day 2: 120 minutes post-tracer dose | 33.975 nanogram per milliliter (ng/mL) |
| Set A: TAK-831 500 mg | Set A: Plasma Concentrations of TAK-831 During Each Post-TAK-831 Dosing PET Scan Periods | Day 1: pre-tracer dose | 1404.500 nanogram per milliliter (ng/mL) |
| Set A: TAK-831 500 mg | Set A: Plasma Concentrations of TAK-831 During Each Post-TAK-831 Dosing PET Scan Periods | Day 1: 60 minutes post-tracer dose | 376.500 nanogram per milliliter (ng/mL) |
| Set A: TAK-831 500 mg | Set A: Plasma Concentrations of TAK-831 During Each Post-TAK-831 Dosing PET Scan Periods | Day 1: 120 minutes post-tracer dose | 176.000 nanogram per milliliter (ng/mL) |
| Set A: TAK-831 500 mg | Set A: Plasma Concentrations of TAK-831 During Each Post-TAK-831 Dosing PET Scan Periods | Day 2: pre-tracer dose | 23.400 nanogram per milliliter (ng/mL) |
| Set A: TAK-831 500 mg | Set A: Plasma Concentrations of TAK-831 During Each Post-TAK-831 Dosing PET Scan Periods | Day 2: 60 minutes post-tracer dose | 28.455 nanogram per milliliter (ng/mL) |
Secondary
Set A: Time to Reach the Maximum PD Effect (Time to Emax,Serine) for D-serine and L-serine
Time frame: Set A: Day -1 At 1, 4 and 12 hours post check-in and Day 1 pre-dose and at multiple time points (up to 24 hours) post-TAK-831 dose
Population: The PD set for D- and L-serine included all participants in Set A who received study drug (TAK-831) and had at least 1 measurable D- and L-serine plasma measurement both at pre-dose and following TAK-831 dosing. PD set where data at specified time points were available.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Set A: TAK-831 100 mg | Set A: Time to Reach the Maximum PD Effect (Time to Emax,Serine) for D-serine and L-serine | D-serine: Day -1 | 4.955 hours |
| Set A: TAK-831 100 mg | Set A: Time to Reach the Maximum PD Effect (Time to Emax,Serine) for D-serine and L-serine | D-serine: Day 1 | 18.000 hours |
| Set A: TAK-831 100 mg | Set A: Time to Reach the Maximum PD Effect (Time to Emax,Serine) for D-serine and L-serine | L-serine: Day -1 | 4.267 hours |
| Set A: TAK-831 100 mg | Set A: Time to Reach the Maximum PD Effect (Time to Emax,Serine) for D-serine and L-serine | L-serine: Day 1 | 13.993 hours |
| Set A: TAK-831 200 mg | Set A: Time to Reach the Maximum PD Effect (Time to Emax,Serine) for D-serine and L-serine | L-serine: Day 1 | 24.000 hours |
| Set A: TAK-831 200 mg | Set A: Time to Reach the Maximum PD Effect (Time to Emax,Serine) for D-serine and L-serine | L-serine: Day -1 | 5.750 hours |
| Set A: TAK-831 200 mg | Set A: Time to Reach the Maximum PD Effect (Time to Emax,Serine) for D-serine and L-serine | D-serine: Day 1 | 18.000 hours |
| Set A: TAK-831 200 mg | Set A: Time to Reach the Maximum PD Effect (Time to Emax,Serine) for D-serine and L-serine | D-serine: Day -1 | 1.000 hours |
| Set A: TAK-831 250 mg | Set A: Time to Reach the Maximum PD Effect (Time to Emax,Serine) for D-serine and L-serine | L-serine: Day -1 | 6.086 hours |
| Set A: TAK-831 250 mg | Set A: Time to Reach the Maximum PD Effect (Time to Emax,Serine) for D-serine and L-serine | L-serine: Day 1 | 12.026 hours |
| Set A: TAK-831 250 mg | Set A: Time to Reach the Maximum PD Effect (Time to Emax,Serine) for D-serine and L-serine | D-serine: Day 1 | 15.206 hours |
| Set A: TAK-831 250 mg | Set A: Time to Reach the Maximum PD Effect (Time to Emax,Serine) for D-serine and L-serine | D-serine: Day -1 | 3.320 hours |
| Set A: TAK-831 500 mg | Set A: Time to Reach the Maximum PD Effect (Time to Emax,Serine) for D-serine and L-serine | D-serine: Day 1 | 25.100 hours |
| Set A: TAK-831 500 mg | Set A: Time to Reach the Maximum PD Effect (Time to Emax,Serine) for D-serine and L-serine | D-serine: Day -1 | 11.900 hours |
| Set A: TAK-831 500 mg | Set A: Time to Reach the Maximum PD Effect (Time to Emax,Serine) for D-serine and L-serine | L-serine: Day 1 | 30.200 hours |
| Set A: TAK-831 500 mg | Set A: Time to Reach the Maximum PD Effect (Time to Emax,Serine) for D-serine and L-serine | L-serine: Day -1 | 2.350 hours |
Secondary
Set A: Time to Reach the Maximum PD Effect (Time to Emax,Serine) for Ratio of D-serine to Total Serine
Time frame: Set A: Day -1 At 1, 4 and 12 hours post check-in and Day 1 pre-dose and at multiple time points (up to 24 hours) post-TAK-831 dose
Population: The PD set for D- and L-serine included all participants in Set A who received study drug (TAK-831) and had at least 1 measurable D- and L-serine plasma measurement both at pre-dose and following TAK-831 dosing. PD set where data at specified time points were available.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Set A: TAK-831 100 mg | Set A: Time to Reach the Maximum PD Effect (Time to Emax,Serine) for Ratio of D-serine to Total Serine | Day -1 | 6.875 hours |
| Set A: TAK-831 100 mg | Set A: Time to Reach the Maximum PD Effect (Time to Emax,Serine) for Ratio of D-serine to Total Serine | Day 1 | 26.725 hours |
| Set A: TAK-831 200 mg | Set A: Time to Reach the Maximum PD Effect (Time to Emax,Serine) for Ratio of D-serine to Total Serine | Day 1 | 25.000 hours |
| Set A: TAK-831 200 mg | Set A: Time to Reach the Maximum PD Effect (Time to Emax,Serine) for Ratio of D-serine to Total Serine | Day -1 | 1.000 hours |
| Set A: TAK-831 250 mg | Set A: Time to Reach the Maximum PD Effect (Time to Emax,Serine) for Ratio of D-serine to Total Serine | Day -1 | 1.875 hours |
| Set A: TAK-831 250 mg | Set A: Time to Reach the Maximum PD Effect (Time to Emax,Serine) for Ratio of D-serine to Total Serine | Day 1 | 23.750 hours |
| Set A: TAK-831 500 mg | Set A: Time to Reach the Maximum PD Effect (Time to Emax,Serine) for Ratio of D-serine to Total Serine | Day -1 | 11.100 hours |
| Set A: TAK-831 500 mg | Set A: Time to Reach the Maximum PD Effect (Time to Emax,Serine) for Ratio of D-serine to Total Serine | Day 1 | 30.100 hours |
Secondary
Set B: Coefficient of Variation (CoV) of [18F]PGM299 Binding in Healthy Human Brain
CoV was calculated as COV (P)(%) = 100 \* mean/ standard deviation, where P was different participant scanned under baseline condition.
Time frame: Set B: Baseline up to Day 10
Population: The analysis set included all participants in Set B who had completed technically evaluable test and re-test PET scans.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Set A: TAK-831 100 mg | Set B: Coefficient of Variation (CoV) of [18F]PGM299 Binding in Healthy Human Brain | 30.13 percentage of CoV |