| Primary | Quantitative Estimates of Binding of [18F]MNI-1054 Based on PET Radiotracer Kinetic Models At Baseline Scan on Day -1 | Enzyme binding parameter [Ki] was obtained from irreversible 2-tissue compartment model (mL/cm^3/min). Data is reported for the following brain regions: cerebellum, frontal lobe, hippocampus, occipital Lobe, pons, and striatum. Here, mL/cm^3/min signifies 'milliliter per cubic centimeter per minute'. | The pharmacodynamics (PD) set included all participants who received TAK-418 and have at least 1 analyzable PET Scan following TAK-418. | Posted | | Mean | Standard Deviation | mL/cm^3/min | | Day -1 | | | | ID | Title | Description |
|---|
| OG000 | TAK-418 1.5 mg | TAK-418 1.5 mg, capsule, orally, once on Day 1 and up to 10 mCi of [18F]MNI-1054 PET radiotracer injection, intravenously, prior to each PET scans on Day 1, and either on Day 2 or 3 post-TAK-418 dose in the Treatment Period. All participants received [18F]MNI-1054 up to 10 mCi, injection, intravenously, prior to PET scan on Day -1 (Baseline scan). | | OG001 | TAK-418 10 mg | TAK-418 10 mg, capsule, orally, once on Day 1 and up to 10 mCi of [18F]MNI-1054 PET radiotracer injection, intravenously, prior to each PET scans on Day 1, and either on Day 2 or 3 post-TAK-418 dose in the Treatment Period. All participants received [18F]MNI-1054 up to 10 mCi, injection, intravenously, prior to PET scan on Day -1 (Baseline scan). | | OG002 | TAK-418 30 mg | TAK-418 30 mg, capsule, orally, once on Day 1 and up to 10 mCi of [18F]MNI-1054 PET radiotracer injection, intravenously, prior to each PET scans on Day 1, and either on Day 2 or 3 post-TAK-418 dose in the Treatment Period. All participants received [18F]MNI-1054 up to 10 mCi, injection, intravenously, prior to PET scan on Day -1 (Baseline scan). |
| | | Title | Denominators | Categories |
|---|
| Cerebellum | | | Title | Measurements |
|---|
| - OG0000.03405± 0.002192
- OG0010.03515± 0.005869
- OG0020.03560± 0.003394
|
| | Frontal Lobe |
| |
| Primary | Quantitative Estimates of Binding of [18F]MNI-1054 Based on PET Radiotracer Kinetic Models on Day 1 | Enzyme binding parameter [Ki] was obtained from irreversible 2-tissue compartment model (mL/cm^3/min). Data is reported for the following brain regions: cerebellum, frontal lobe, hippocampus, occipital Lobe, pons, and striatum. Here, mL/cm^3/min signifies 'milliliter per cubic centimeter per minute'. | The PD set included all participants who received TAK-418 and have at least 1 analyzable PET Scan following TAK-418. | Posted | | Mean | Standard Deviation | mL/cm^3/min | | Day 1 | | | | ID | Title | Description |
|---|
| OG000 | TAK-418 1.5 mg | TAK-418 1.5 mg, capsule, orally, once on Day 1 and up to 10 mCi of [18F]MNI-1054 PET radiotracer injection, intravenously, prior to each PET scans on Day 1, and either on Day 2 or 3 post-TAK-418 dose in the Treatment Period. All participants received [18F]MNI-1054 up to 10 mCi, injection, intravenously, prior to PET scan on Day -1 (Baseline scan). | | OG001 | TAK-418 10 mg | TAK-418 10 mg, capsule, orally, once on Day 1 and up to 10 mCi of [18F]MNI-1054 PET radiotracer injection, intravenously, prior to each PET scans on Day 1, and either on Day 2 or 3 post-TAK-418 dose in the Treatment Period. All participants received [18F]MNI-1054 up to 10 mCi, injection, intravenously, prior to PET scan on Day -1 (Baseline scan). | | OG002 |
|
| Primary | Quantitative Estimates of Binding of [18F]MNI-1054 Based on PET Radiotracer Kinetic Models on Day 2 | Enzyme binding parameter [Ki] was obtained from irreversible 2-tissue compartment model (mL/cm^3/min). Data is reported for the following brain regions: cerebellum, frontal lobe, hippocampus, occipital Lobe, pons, and striatum. Here, mL/cm^3/min signifies 'milliliter per cubic centimeter per minute'. | The PD set included all participants who received TAK-418 and have at least 1 analyzable PET Scan following TAK-418. | Posted | | Mean | Standard Deviation | mL/cm^3/min | | Day 2 | | | | ID | Title | Description |
|---|
| OG000 | TAK-418 1.5 mg | TAK-418 1.5 mg, capsule, orally, once on Day 1 and up to 10 mCi of [18F]MNI-1054 PET radiotracer injection, intravenously, prior to each PET scans on Day 1, and either on Day 2 or 3 post-TAK-418 dose in the Treatment Period. All participants received [18F]MNI-1054 up to 10 mCi, injection, intravenously, prior to PET scan on Day -1 (Baseline scan). | | OG001 | TAK-418 10 mg | TAK-418 10 mg, capsule, orally, once on Day 1 and up to 10 mCi of [18F]MNI-1054 PET radiotracer injection, intravenously, prior to each PET scans on Day 1, and either on Day 2 or 3 post-TAK-418 dose in the Treatment Period. All participants received [18F]MNI-1054 up to 10 mCi, injection, intravenously, prior to PET scan on Day -1 (Baseline scan). | | OG002 |
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| Primary | Percent Enzyme Occupancy Based on Quantitative Estimates of Binding for TAK-418 on Day 1 | Lysine-Specific Demethylase 1A (LSD1) enzyme occupancy (%) in region of interest (ROI) after a single dose of TAK-418 was obtained from the baseline and postdose Ki values as follows: occupancy (1st postdose) = 100*(Ki [baseline] - Ki [1st postdose]) / Ki (baseline). Data is reported for following brain regions: cerebellum, frontal lobe, hippocampus, occipital Lobe, pons, and striatum. | The PD set included all participants who received TAK-418 and have at least 1 analyzable PET Scan following TAK-418. | Posted | | Mean | Standard Deviation | percentage of occupancy | | Day 1 | | | | ID | Title | Description |
|---|
| OG000 | TAK-418 1.5 mg | TAK-418 1.5 mg, capsule, orally, once on Day 1 and up to 10 mCi of [18F]MNI-1054 PET radiotracer injection, intravenously, prior to each PET scans on Day 1, and either on Day 2 or 3 post-TAK-418 dose in the Treatment Period. All participants received [18F]MNI-1054 up to 10 mCi, injection, intravenously, prior to PET scan on Day -1 (Baseline scan). | | OG001 | TAK-418 10 mg | TAK-418 10 mg, capsule, orally, once on Day 1 and up to 10 mCi of [18F]MNI-1054 PET radiotracer injection, intravenously, prior to each PET scans on Day 1, and either on Day 2 or 3 post-TAK-418 dose in the Treatment Period. All participants received [18F]MNI-1054 up to 10 mCi, injection, intravenously, prior to PET scan on Day -1 (Baseline scan). |
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| Primary | Percent Enzyme Occupancy Based on Quantitative Estimates of Binding for TAK-418 on Day 2 | LSD1 enzyme occupancy (%) in ROI after a single dose of TAK-418 was obtained from the baseline and postdose Ki values as follows: occupancy (2nd postdose) = 100*(Ki [baseline] - Ki [2nd postdose]) / Ki (baseline). Data is reported for following brain regions: cerebellum, frontal lobe, hippocampus, occipital Lobe, pons, and striatum. | The PD set included all participants who received TAK-418 and have at least 1 analyzable PET Scan following TAK-418. | Posted | | Mean | Standard Deviation | percentage of occupancy | | Day 2 | | | | ID | Title | Description |
|---|
| OG000 | TAK-418 1.5 mg | TAK-418 1.5 mg, capsule, orally, once on Day 1 and up to 10 mCi of [18F]MNI-1054 PET radiotracer injection, intravenously, prior to each PET scans on Day 1, and either on Day 2 or 3 post-TAK-418 dose in the Treatment Period. All participants received [18F]MNI-1054 up to 10 mCi, injection, intravenously, prior to PET scan on Day -1 (Baseline scan). | | OG001 | TAK-418 10 mg | TAK-418 10 mg, capsule, orally, once on Day 1 and up to 10 mCi of [18F]MNI-1054 PET radiotracer injection, intravenously, prior to each PET scans on Day 1, and either on Day 2 or 3 post-TAK-418 dose in the Treatment Period. All participants received [18F]MNI-1054 up to 10 mCi, injection, intravenously, prior to PET scan on Day -1 (Baseline scan). | |
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| Primary | Cmax: Maximum Observed Plasma Concentration for TAK-418 | | The pharmacokinetic (PK) set included all participants from the safety set who received TAK-418 and had at least 1 measurable plasma concentration for TAK-418. | Posted | | Median | Full Range | nanogram per milliliter (ng/mL) | | Day 1: pre-dose and at multiple time points (up to 3 hours) post-dose, immediately before and after the Day 1 PET scan, and within 30 minutes before and 30 minutes after Day 2 or 3 PET scan | | | | ID | Title | Description |
|---|
| OG000 | TAK-418 1.5 mg | TAK-418 1.5 mg, capsule, orally, once on Day 1 and up to 10 mCi of [18F]MNI-1054 PET radiotracer injection, intravenously, prior to each PET scans on Day 1, and either on Day 2 or 3 post-TAK-418 dose in the Treatment Period. All participants received [18F]MNI-1054 up to 10 mCi, injection, intravenously, prior to PET scan on Day -1 (Baseline scan). | | OG001 | TAK-418 10 mg | TAK-418 10 mg, capsule, orally, once on Day 1 and up to 10 mCi of [18F]MNI-1054 PET radiotracer injection, intravenously, prior to each PET scans on Day 1, and either on Day 2 or 3 post-TAK-418 dose in the Treatment Period. All participants received [18F]MNI-1054 up to 10 mCi, injection, intravenously, prior to PET scan on Day -1 (Baseline scan). | | OG002 | TAK-418 30 mg | |
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| Primary | AUClast: Area Under the Plasma Concentration-time Curve (AUC) From Time 0 to Time of the Last Quantifiable Concentration for TAK-418 | | The PK set included all participants from the safety set who received TAK-418 and had at least 1 measurable plasma concentration for TAK-418. | Posted | | Median | Full Range | hour*nanogram per milliliter(h*ng/mL) | | Day 1: pre-dose and at multiple time points (up to 3 hours) post-dose, immediately before and after the Day 1 PET scan, and within 30 minutes before and 30 minutes after Day 2 or 3 PET scan | | | | ID | Title | Description |
|---|
| OG000 | TAK-418 1.5 mg | TAK-418 1.5 mg, capsule, orally, once on Day 1 and up to 10 mCi of [18F]MNI-1054 PET radiotracer injection, intravenously, prior to each PET scans on Day 1, and either on Day 2 or 3 post-TAK-418 dose in the Treatment Period. All participants received [18F]MNI-1054 up to 10 mCi, injection, intravenously, prior to PET scan on Day -1 (Baseline scan). | | OG001 | TAK-418 10 mg | TAK-418 10 mg, capsule, orally, once on Day 1 and up to 10 mCi of [18F]MNI-1054 PET radiotracer injection, intravenously, prior to each PET scans on Day 1, and either on Day 2 or 3 post-TAK-418 dose in the Treatment Period. All participants received [18F]MNI-1054 up to 10 mCi, injection, intravenously, prior to PET scan on Day -1 (Baseline scan). | | OG002 | TAK-418 30 mg |
|
| Primary | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-418 | | The PK set included all participants from the safety set who received TAK-418 and had at least 1 measurable plasma concentration for TAK-418. Here "overall number of participants" analyzed are those who were evaluable for this outcome measure. | Posted | | Median | Full Range | h*ng/mL | | Day 1: pre-dose and at multiple time points (up to 3 hours) post-dose, immediately before and after the Day 1 PET scan, and within 30 minutes before and 30 minutes after Day 2 or 3 PET scan | | | | ID | Title | Description |
|---|
| OG000 | TAK-418 1.5 mg | TAK-418 1.5 mg, capsule, orally, once on Day 1 and up to 10 mCi of [18F]MNI-1054 PET radiotracer injection, intravenously, prior to each PET scans on Day 1, and either on Day 2 or 3 post-TAK-418 dose in the Treatment Period. All participants received [18F]MNI-1054 up to 10 mCi, injection, intravenously, prior to PET scan on Day -1 (Baseline scan). | | OG001 | TAK-418 10 mg | TAK-418 10 mg, capsule, orally, once on Day 1 and up to 10 mCi of [18F]MNI-1054 PET radiotracer injection, intravenously, prior to each PET scans on Day 1, and either on Day 2 or 3 post-TAK-418 dose in the Treatment Period. All participants received [18F]MNI-1054 up to 10 mCi, injection, intravenously, prior to PET scan on Day -1 (Baseline scan). | | OG002 | TAK-418 30 mg |
|
| Secondary | ED50 PET Enzyme Occupancy | The relationship between PET enzyme occupancy and TAK-418 dose level was investigated using an Emax model containing the regression parameters maximal target occupancy (Emax) and dose that gives 50 percent (%) of Emax (ED50). ED50 values are reported for following brain regions: cerebellum, frontal lobe, hippocampus, occipital Lobe, pons, and striatum. The data tabulated are the estimated value and confidence intervals of the ED50 value derived from an Emax model fit across all data points from all arms. ED50 is the dose at which 50% enzyme occupancy is expected. | The PD set included all participants who received TAK-418 and have at least 1 analyzable PET Scan following TAK-418 | Posted | | Mean | 95% Confidence Interval | milligram (mg) | | Days 1 to 2 | | | | ID | Title | Description |
|---|
| OG000 | TAK-418 | TAK-418 1.5 mg, 10 mg, or 30 mg capsules, orally, once on Day 1 and up to 10 mCi of [18F]MNI-1054 PET radiotracer injection, intravenously, prior to each PET scans on Day 1, and either on Day 2 or 3 post-TAK-418 dose. All participants received [18F]MNI-1054 up to 10 mCi, injection, intravenously, prior to PET scan on Day -1 (Baseline scan). |
| |
| Secondary | Number of Participants Reporting One or More Adverse Events (AEs) and Serious Adverse Events (SAEs) | | The safety set included all enrolled participants who received at least 1 dose of [18F]MNI-1054 or TAK-418 | Posted | | Count of Participants | | Participants | | From first dose of [18F]MNI-1054 radiotracer injection up to Day 14 | | | | ID | Title | Description |
|---|
| OG000 | Baseline [18F]MNI-1054 | [18F]MNI-1054 up to 10 mCi, PET radiotracer injection, intravenously, prior to PET scan on Day -1 (Baseline scan). | | OG001 | TAK-418 1.5 mg | TAK-418 1.5 mg, capsule, orally, once on Day 1 and up to 10 mCi of [18F]MNI-1054 PET radiotracer injection, intravenously, prior to each PET scans on Day 1, and either on Day 2 or 3 post-TAK-418 dose in the Treatment Period. All participants received [18F]MNI-1054 up to 10 mCi, injection, intravenously, prior to PET scan on Day -1 (Baseline scan). | | OG002 | TAK-418 10 mg | TAK-418 10 mg, capsule, orally, once on Day 1 and up to 10 mCi of [18F]MNI-1054 PET radiotracer injection, intravenously, prior to each PET scans on Day 1, and either on Day 2 or 3 post-TAK-418 dose in the Treatment Period. All participants received [18F]MNI-1054 up to 10 mCi, injection, intravenously, prior to PET scan on Day -1 (Baseline scan). |
|
| Secondary | Number of Participants With Clinically Significant Abnormal Laboratory Values | | The safety set included all enrolled participants who received at least 1 dose of [18F]MNI-1054 or TAK-418 | Posted | | Count of Participants | | Participants | | From first dose of [18F]MNI-1054 radiotracer injection up to Day 14 | | | | ID | Title | Description |
|---|
| OG000 | Baseline [18F]MNI-1054 | [18F]MNI-1054 up to 10 mCi, PET radiotracer injection, intravenously, prior to PET scan on Day -1 (Baseline scan). | | OG001 | TAK-418 1.5 mg | TAK-418 1.5 mg, capsule, orally, once on Day 1 and up to 10 mCi of [18F]MNI-1054 PET radiotracer injection, intravenously, prior to each PET scans on Day 1, and either on Day 2 or 3 post-TAK-418 dose in the Treatment Period. All participants received [18F]MNI-1054 up to 10 mCi, injection, intravenously, prior to PET scan on Day -1 (Baseline scan). | | OG002 | TAK-418 10 mg | TAK-418 10 mg, capsule, orally, once on Day 1 and up to 10 mCi of [18F]MNI-1054 PET radiotracer injection, intravenously, prior to each PET scans on Day 1, and either on Day 2 or 3 post-TAK-418 dose in the Treatment Period. All participants received [18F]MNI-1054 up to 10 mCi, injection, intravenously, prior to PET scan on Day -1 (Baseline scan). |
|
| Secondary | Number of Participants With Clinically Significant Abnormal Vital Signs | | The safety set included all enrolled participants who received at least 1 dose of [18F]MNI-1054 or TAK-418. | Posted | | Count of Participants | | Participants | | From first dose of [18F]MNI-1054 radiotracer injection up to Day 14 | | | | ID | Title | Description |
|---|
| OG000 | Baseline [18F]MNI-1054 | [18F]MNI-1054 up to 10 mCi, PET radiotracer injection, intravenously, prior to PET scan on Day -1 (Baseline scan). | | OG001 | TAK-418 1.5 mg | TAK-418 1.5 mg, capsule, orally, once on Day 1 and up to 10 mCi of [18F]MNI-1054 PET radiotracer injection, intravenously, prior to each PET scans on Day 1, and either on Day 2 or 3 post-TAK-418 dose in the Treatment Period. All participants received [18F]MNI-1054 up to 10 mCi, injection, intravenously, prior to PET scan on Day -1 (Baseline scan). | | OG002 | TAK-418 10 mg | TAK-418 10 mg, capsule, orally, once on Day 1 and up to 10 mCi of [18F]MNI-1054 PET radiotracer injection, intravenously, prior to each PET scans on Day 1, and either on Day 2 or 3 post-TAK-418 dose in the Treatment Period. All participants received [18F]MNI-1054 up to 10 mCi, injection, intravenously, prior to PET scan on Day -1 (Baseline scan). |
|