Trial Outcomes & Findings for An [^11C]T-773 Positron Emission Tomography (PET) Study to Determine Phosphodiesterase10A Occupancy by TAK-063 (NCT NCT02370602)
NCT ID: NCT02370602
Last Updated: 2015-03-20
Results Overview
Volume of tissue distribution (Vt) values will be estimated by several quantitative methods for each positron emission tomography (PET) scan. Based on the change in Vt before and after TAK-063 administration, PDE10A occupancy will be calculated. PET scan #2 in the Pilot Cohort and PET scan #1 in the Main Cohort will be used as a baseline for the occupancy calculation. Occupancy is reported for putamen only.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
13 participants
Primary outcome timeframe
3 hours post-dose
Results posted on
2015-03-20
Participant Flow
Participants took part in the study at 1 investigative site in Sweden from 13 August 2013 to 12 March 2014.
Healthy Volunteers received 1 of 5 treatments: 11C T-773,Tak-063 3 mg, Tak-063 10 mg, Tak-063 30 mg, Tak-063 100 mg or Tak-063 1000 mg.
Participant milestones
| Measure |
[^11C]T-773 Only
\[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenous (IV), once on Days 1 and 2 only.
|
TAK-063 3 mg + [^11C]T-773
TAK-063 3 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 10 mg + [^11C]T-773
TAK-063 10 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 30 mg + [^11C]T-773
For main cohort, TAK-063 30 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2. For pilot cohort, TAK-063 30 mg, tablets, orally, once on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 (before and after administration of TAK-063) and twice on Day 2.
|
TAK-063 100 mg + [^11C]T-773
TAK-063 100 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 1000 mg + [^11C]T-773
TAK-063 1000 mg, tablets, orally, once, on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 and twice on Day 2 (before and after administration of TAK-063).
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
1
|
2
|
2
|
3
|
3
|
2
|
|
Overall Study
COMPLETED
|
0
|
2
|
2
|
3
|
3
|
2
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
[^11C]T-773 Only
\[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenous (IV), once on Days 1 and 2 only.
|
TAK-063 3 mg + [^11C]T-773
TAK-063 3 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 10 mg + [^11C]T-773
TAK-063 10 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 30 mg + [^11C]T-773
For main cohort, TAK-063 30 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2. For pilot cohort, TAK-063 30 mg, tablets, orally, once on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 (before and after administration of TAK-063) and twice on Day 2.
|
TAK-063 100 mg + [^11C]T-773
TAK-063 100 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 1000 mg + [^11C]T-773
TAK-063 1000 mg, tablets, orally, once, on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 and twice on Day 2 (before and after administration of TAK-063).
|
|---|---|---|---|---|---|---|
|
Overall Study
Pretreatment Event/Adverse Event
|
1
|
0
|
0
|
0
|
0
|
0
|
Baseline Characteristics
An [^11C]T-773 Positron Emission Tomography (PET) Study to Determine Phosphodiesterase10A Occupancy by TAK-063
Baseline characteristics by cohort
| Measure |
[^11C]T-773
n=1 Participants
\[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenous (IV), once on Days 1 and 2 only.
|
TAK-063 3 mg + [^11C]T-773
n=2 Participants
TAK-063 3 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 10 mg + [^11C]T-773
n=2 Participants
TAK-063 10 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 30 mg + [^11C]T-773
n=3 Participants
For main cohort, TAK-063 30 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2. For pilot cohort, TAK-063 30 mg, tablets, orally, once on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 (before and after administration of TAK-063) and twice on Day 2.
|
TAK-063 100 mg + [^11C]T-773
n=3 Participants
TAK-063 100 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 1000 mg + [^11C]T-773
n=2 Participants
TAK-063 1000 mg, tablets, orally, once, on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 and twice on Day 2 (before and after administration of TAK-063).
|
Total
n=13 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|
|
Age, Continuous
|
24.0 years
STANDARD_DEVIATION NA • n=5 Participants
|
27.5 years
STANDARD_DEVIATION 4.95 • n=7 Participants
|
26.5 years
STANDARD_DEVIATION 0.71 • n=5 Participants
|
37.7 years
STANDARD_DEVIATION 7.09 • n=4 Participants
|
26.7 years
STANDARD_DEVIATION 3.51 • n=21 Participants
|
27.0 years
STANDARD_DEVIATION 1.41 • n=8 Participants
|
29.2 years
STANDARD_DEVIATION 6.08 • n=8 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
2 Participants
n=8 Participants
|
13 Participants
n=8 Participants
|
|
Race/Ethnicity, Customized
White
|
1 participants
n=5 Participants
|
2 participants
n=7 Participants
|
2 participants
n=5 Participants
|
3 participants
n=4 Participants
|
3 participants
n=21 Participants
|
2 participants
n=8 Participants
|
13 participants
n=8 Participants
|
|
Region of Enrollment
Sweden
|
1 participants
n=5 Participants
|
2 participants
n=7 Participants
|
2 participants
n=5 Participants
|
3 participants
n=4 Participants
|
3 participants
n=21 Participants
|
2 participants
n=8 Participants
|
13 participants
n=8 Participants
|
|
Height
|
183.0 cm
STANDARD_DEVIATION NA • n=5 Participants
|
180.5 cm
STANDARD_DEVIATION 4.95 • n=7 Participants
|
180.0 cm
STANDARD_DEVIATION 1.41 • n=5 Participants
|
178.0 cm
STANDARD_DEVIATION 8.19 • n=4 Participants
|
179.3 cm
STANDARD_DEVIATION 7.51 • n=21 Participants
|
177.0 cm
STANDARD_DEVIATION 4.24 • n=8 Participants
|
179.2 cm
STANDARD_DEVIATION 5.20 • n=8 Participants
|
|
Weight
|
83.00 kg
STANDARD_DEVIATION NA • n=5 Participants
|
76.40 kg
STANDARD_DEVIATION 0.566 • n=7 Participants
|
90.50 kg
STANDARD_DEVIATION 4.950 • n=5 Participants
|
85.90 kg
STANDARD_DEVIATION 3.651 • n=4 Participants
|
83.27 kg
STANDARD_DEVIATION 15.938 • n=21 Participants
|
80.65 kg
STANDARD_DEVIATION 4.596 • n=8 Participants
|
83.51 kg
STANDARD_DEVIATION 8.233 • n=8 Participants
|
|
Body Mass Index (BMI)
|
24.78 kg/m^2
STANDARD_DEVIATION NA • n=5 Participants
|
23.47 kg/m^2
STANDARD_DEVIATION 1.117 • n=7 Participants
|
27.92 kg/m^2
STANDARD_DEVIATION 1.089 • n=5 Participants
|
27.27 kg/m^2
STANDARD_DEVIATION 3.267 • n=4 Participants
|
25.86 kg/m^2
STANDARD_DEVIATION 4.584 • n=21 Participants
|
25.80 kg/m^2
STANDARD_DEVIATION 2.701 • n=8 Participants
|
26.04 kg/m^2
STANDARD_DEVIATION 2.883 • n=8 Participants
|
|
Smoking Classification
Never smoked
|
1 participants
n=5 Participants
|
2 participants
n=7 Participants
|
2 participants
n=5 Participants
|
1 participants
n=4 Participants
|
3 participants
n=21 Participants
|
2 participants
n=8 Participants
|
11 participants
n=8 Participants
|
|
Smoking Classification
Current smoker
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
0 participants
n=4 Participants
|
0 participants
n=21 Participants
|
0 participants
n=8 Participants
|
0 participants
n=8 Participants
|
|
Smoking Classification
Ex-smoker
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
2 participants
n=4 Participants
|
0 participants
n=21 Participants
|
0 participants
n=8 Participants
|
2 participants
n=8 Participants
|
PRIMARY outcome
Timeframe: 3 hours post-dosePopulation: Pharmacodynamic Analysis Set includes all participants with data available for pharmacodynamic analysis..
Volume of tissue distribution (Vt) values will be estimated by several quantitative methods for each positron emission tomography (PET) scan. Based on the change in Vt before and after TAK-063 administration, PDE10A occupancy will be calculated. PET scan #2 in the Pilot Cohort and PET scan #1 in the Main Cohort will be used as a baseline for the occupancy calculation. Occupancy is reported for putamen only.
Outcome measures
| Measure |
TAK-063 3 mg + [^11C]T-773
n=2 Participants
TAK-063 3 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 10 mg
n=2 Participants
TAK-063 10 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 30 mg + [^11C]T-773
n=3 Participants
For main cohort, TAK-063 30 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2. For pilot cohort, TAK-063 30 mg, tablets, orally, once on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 (before and after administration of TAK-063) and twice on Day 2.
|
TAK-063 100 mg + [^11C]T-773
n=3 Participants
TAK-063 100 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 1000 mg + [^11C]T-773
n=2 Participants
TAK-063 1000 mg, tablets, orally, once, on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 and twice on Day 2 (before and after administration of TAK-063).
|
TAK-063 1000 mg + [^11C]T-773
TAK-063 1000 mg, tablets, orally, once, on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 and twice on Day 2 (before and after administration of TAK-063).
|
|---|---|---|---|---|---|---|
|
Phosphodiesterase 10A (PDE10A) Occupancy of Brain Regions With [^11C]T-773 at 3 Hours Following a Single Dose of TAK-063
|
14.400 Percent
Standard Deviation 16.4049
|
26.650 Percent
Standard Deviation 2.4749
|
39.333 Percent
Standard Deviation 11.1096
|
53.633 Percent
Standard Deviation 0.9074
|
69.350 Percent
Standard Deviation 3.8891
|
—
|
SECONDARY outcome
Timeframe: 23 hours post-dosePopulation: Pharmacodynamic Analysis Set includes all participants with data available for pharmacodynamic analysis.
Volume of tissue distribution (Vt) values will be estimated by several quantitative methods for each positron emission tomography (PET) scan. Based on the change in Vt before and after TAK-063 administration, PDE10A occupancy will be calculated. PET scan #2 in the Pilot Cohort and PET scan #1 in the Main Cohort will be used as a baseline for the occupancy calculation. Data was not available for participants in the pilot cohort. Occupancy is reported for putamen only.
Outcome measures
| Measure |
TAK-063 3 mg + [^11C]T-773
n=2 Participants
TAK-063 3 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 10 mg
n=2 Participants
TAK-063 10 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 30 mg + [^11C]T-773
n=1 Participants
For main cohort, TAK-063 30 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2. For pilot cohort, TAK-063 30 mg, tablets, orally, once on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 (before and after administration of TAK-063) and twice on Day 2.
|
TAK-063 100 mg + [^11C]T-773
n=3 Participants
TAK-063 100 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 1000 mg + [^11C]T-773
TAK-063 1000 mg, tablets, orally, once, on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 and twice on Day 2 (before and after administration of TAK-063).
|
TAK-063 1000 mg + [^11C]T-773
TAK-063 1000 mg, tablets, orally, once, on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 and twice on Day 2 (before and after administration of TAK-063).
|
|---|---|---|---|---|---|---|
|
Phosphodiesterase 10A (PDE10A) Occupancy of Brain Regions With [^11C]T-773 at 23 Hours Following a Single Dose of TAK-063
|
-2.250 Percent
Standard Deviation 0.7778
|
14.750 Percent
Standard Deviation 1.7678
|
18.800 Percent
Standard Deviation NA
Standard deviation can not be calculated for 1 participant.
|
24.167 Percent
Standard Deviation 18.6001
|
—
|
—
|
SECONDARY outcome
Timeframe: First dose of study drug to 30 days after last dose of study drug (up to 46 days)Population: Safety analysis set included all participants who received at least one dose of study drug.
An adverse event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event is defined as an adverse event with an onset that occurs after receiving study drug.
Outcome measures
| Measure |
TAK-063 3 mg + [^11C]T-773
n=13 Participants
TAK-063 3 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 10 mg
n=12 Participants
TAK-063 10 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 30 mg + [^11C]T-773
For main cohort, TAK-063 30 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2. For pilot cohort, TAK-063 30 mg, tablets, orally, once on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 (before and after administration of TAK-063) and twice on Day 2.
|
TAK-063 100 mg + [^11C]T-773
TAK-063 100 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 1000 mg + [^11C]T-773
TAK-063 1000 mg, tablets, orally, once, on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 and twice on Day 2 (before and after administration of TAK-063).
|
TAK-063 1000 mg + [^11C]T-773
TAK-063 1000 mg, tablets, orally, once, on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 and twice on Day 2 (before and after administration of TAK-063).
|
|---|---|---|---|---|---|---|
|
Percentage of Participants Who Experienced at Least 1 Treatment-Emergent Adverse Event
|
38.5 percentage of participants
|
75.0 percentage of participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From Day 1 to Day 16Population: Safety analysis set included all participants who received at least one dose of study drug.
The percentage of participants with any markedly abnormal standard safety laboratory values was collected throughout study.
Outcome measures
| Measure |
TAK-063 3 mg + [^11C]T-773
n=13 Participants
TAK-063 3 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 10 mg
n=2 Participants
TAK-063 10 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 30 mg + [^11C]T-773
n=2 Participants
For main cohort, TAK-063 30 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2. For pilot cohort, TAK-063 30 mg, tablets, orally, once on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 (before and after administration of TAK-063) and twice on Day 2.
|
TAK-063 100 mg + [^11C]T-773
n=3 Participants
TAK-063 100 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 1000 mg + [^11C]T-773
n=3 Participants
TAK-063 1000 mg, tablets, orally, once, on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 and twice on Day 2 (before and after administration of TAK-063).
|
TAK-063 1000 mg + [^11C]T-773
n=2 Participants
TAK-063 1000 mg, tablets, orally, once, on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 and twice on Day 2 (before and after administration of TAK-063).
|
|---|---|---|---|---|---|---|
|
Percentage of Participants With Markedly Abnormal Safety Laboratory Findings
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: From Day 1 to Day 16Population: Safety analysis set included all participants who received at least one dose of study drug.
The percentage of participants with any markedly abnormal standard vital sign measurements was collected throughout study. BL=baseline. bpm=beats per minute.
Outcome measures
| Measure |
TAK-063 3 mg + [^11C]T-773
n=13 Participants
TAK-063 3 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 10 mg
n=2 Participants
TAK-063 10 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 30 mg + [^11C]T-773
n=2 Participants
For main cohort, TAK-063 30 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2. For pilot cohort, TAK-063 30 mg, tablets, orally, once on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 (before and after administration of TAK-063) and twice on Day 2.
|
TAK-063 100 mg + [^11C]T-773
n=3 Participants
TAK-063 100 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 1000 mg + [^11C]T-773
n=3 Participants
TAK-063 1000 mg, tablets, orally, once, on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 and twice on Day 2 (before and after administration of TAK-063).
|
TAK-063 1000 mg + [^11C]T-773
n=2 Participants
TAK-063 1000 mg, tablets, orally, once, on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 and twice on Day 2 (before and after administration of TAK-063).
|
|---|---|---|---|---|---|---|
|
Percentage of Participants With Markedly Abnormal Vital Sign Measurements
Temperature (Degree C) - <35.6 C
|
7.7 percentage of participants
|
50.0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Vital Sign Measurements
During Treatment (tx) - >Upper Cut-off
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Vital Sign Measurements
During tx - <Lower Cut-off
|
38.5 percentage of participants
|
50.0 percentage of participants
|
50.0 percentage of participants
|
33.3 percentage of participants
|
66.7 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Vital Sign Measurements
During tx - Change Relative to BL Upper Criteria
|
7.7 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
50.0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Vital Sign Measurements
During tx - Change Relative to BL Lower Criteria
|
0 percentage of participants
|
0 percentage of participants
|
50.0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Vital Sign Measurements
During tx - Overall
|
46.2 percentage of participants
|
50.0 percentage of participants
|
100.0 percentage of participants
|
33.3 percentage of participants
|
66.7 percentage of participants
|
50.0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Vital Sign Measurements
Pulse (bpm) - >120 bpm
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Vital Sign Measurements
Pulse (bpm) - <50 bpm
|
30.8 percentage of participants
|
50.0 percentage of participants
|
50.0 percentage of participants
|
33.3 percentage of participants
|
66.7 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Vital Sign Measurements
Pulse (bpm) - Increase of >30 bpm
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Vital Sign Measurements
Pulse (bpm) - Decrease of >30 bpm
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Vital Sign Measurements
Pulse (bpm) - Overall
|
30.8 percentage of participants
|
50.0 percentage of participants
|
50.0 percentage of participants
|
33.3 percentage of participants
|
66.7 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Vital Sign Measurements
Systolic Blood Pressure (mmHg) - >180 mmHg
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Vital Sign Measurements
Systolic Blood Pressure (mmHg) - <85 mmHg
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Vital Sign Measurements
Systolic Blood Pressure - Increase of >40 mmHg
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Vital Sign Measurements
Systolic Blood Pressure - Decrease of >40 mmHg
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Vital Sign Measurements
Systolic Blood Pressure (mmHg) - Overall
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Vital Sign Measurements
Diastolic Blood Pressure (mmHg) - >110 mmHg
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Vital Sign Measurements
Diastolic Blood Pressure (mmHg) - <50 mmHg
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Vital Sign Measurements
Diastolic BP (mmHg) - Increase of >20 mmHg
|
7.7 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
50.0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Vital Sign Measurements
Diastolic BP (mmHg) - Decrease of >20 mmHg
|
0 percentage of participants
|
0 percentage of participants
|
50.0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Vital Sign Measurements
Diastolic Blood Pressure (mmHg) - Overall
|
7.7 percentage of participants
|
0 percentage of participants
|
50.0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
50.0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Vital Sign Measurements
Temperature (Degree C) - >37.7 C
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Vital Sign Measurements
Temperature (Degree C) - Overall
|
7.7 percentage of participants
|
50.0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: From Day 1 to Day 16Population: Safety analysis set included all participants who received at least one dose of study drug.
The percentage of participants with any markedly abnormal standard 12-lead ECG measurements. QTc - Bazett's Interval (msec) is ≥500 msec OR ≥30 msec change from Baseline and ≥450 msec
Outcome measures
| Measure |
TAK-063 3 mg + [^11C]T-773
n=13 Participants
TAK-063 3 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 10 mg
n=2 Participants
TAK-063 10 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 30 mg + [^11C]T-773
n=2 Participants
For main cohort, TAK-063 30 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2. For pilot cohort, TAK-063 30 mg, tablets, orally, once on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 (before and after administration of TAK-063) and twice on Day 2.
|
TAK-063 100 mg + [^11C]T-773
n=3 Participants
TAK-063 100 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 1000 mg + [^11C]T-773
n=3 Participants
TAK-063 1000 mg, tablets, orally, once, on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 and twice on Day 2 (before and after administration of TAK-063).
|
TAK-063 1000 mg + [^11C]T-773
n=2 Participants
TAK-063 1000 mg, tablets, orally, once, on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 and twice on Day 2 (before and after administration of TAK-063).
|
|---|---|---|---|---|---|---|
|
Percentage of Participants With Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters
Heart Rate (bpm) - <50 bpm
|
7.7 percentage of participants
|
50.0 percentage of participants
|
50.0 percentage of participants
|
33.3 percentage of participants
|
66.7 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters
Heart Rate (bpm) - Overall
|
7.7 percentage of participants
|
50.0 percentage of participants
|
50.0 percentage of participants
|
33.3 percentage of participants
|
66.7 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters
RR Interval (msec) - ≥1440 msec
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
33.3 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters
RR Interval (msec) - ≤600 msec
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters
RR Interval (msec) - Overall
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
33.3 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters
PR Interval (msec) - ≥200 msec
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
33.3 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters
PR Interval (msec) - ≤80 msec
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters
PR Interval (msec) - Overall
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
33.3 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters
QRS Interval (msec) - ≥180 msec
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters
QRS Interval (msec) - ≤80 msec
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters
QRS Interval (msec) - Overall
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters
QT Interval (msec) - ≥460 msec
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
33.3 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters
QT Interval (msec) - <280 msec
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters
QT Interval (msec) - Overall
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
33.3 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters
QTc - Bazett's Interval (msec) - Overall
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters
QTc - Fredericia's Interval (msec) - Overall
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: Pilot Cohort: Day 2 predose and at multiple time points (up to 24 hours) post-dose. Main Cohort: Day 1 predose and at multiple time points (up to 24 hours) post-dose.Population: Pharmacokinetic Analysis Set
Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.
Outcome measures
| Measure |
TAK-063 3 mg + [^11C]T-773
n=2 Participants
TAK-063 3 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 10 mg
n=2 Participants
TAK-063 10 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 30 mg + [^11C]T-773
n=3 Participants
For main cohort, TAK-063 30 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2. For pilot cohort, TAK-063 30 mg, tablets, orally, once on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 (before and after administration of TAK-063) and twice on Day 2.
|
TAK-063 100 mg + [^11C]T-773
n=3 Participants
TAK-063 100 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 1000 mg + [^11C]T-773
n=2 Participants
TAK-063 1000 mg, tablets, orally, once, on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 and twice on Day 2 (before and after administration of TAK-063).
|
TAK-063 1000 mg + [^11C]T-773
TAK-063 1000 mg, tablets, orally, once, on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 and twice on Day 2 (before and after administration of TAK-063).
|
|---|---|---|---|---|---|---|
|
Cmax: Maximum Observed Plasma Concentration for TAK-063 and TAK-063 Metabolite M-I
TAK-063
|
11.25 ng/mL
Standard Deviation 3.323
|
22.78 ng/mL
Standard Deviation 0.035
|
80.67 ng/mL
Standard Deviation 35.147
|
77.05 ng/mL
Standard Deviation 16.898
|
258.75 ng/mL
Standard Deviation 18.031
|
—
|
|
Cmax: Maximum Observed Plasma Concentration for TAK-063 and TAK-063 Metabolite M-I
TAK-063 Metabolite M-I
|
15.60 ng/mL
Standard Deviation 7.637
|
19.65 ng/mL
Standard Deviation 0.283
|
49.63 ng/mL
Standard Deviation 18.393
|
80.43 ng/mL
Standard Deviation 26.831
|
146.50 ng/mL
Standard Deviation 10.607
|
—
|
SECONDARY outcome
Timeframe: Pilot Cohort: Day 2 predose and at multiple time points (up to 24 hours) post-dose. Main Cohort: Day 1 predose and at multiple time points (up to 24 hours) post-dose.Population: Pharmacokinetic Analysis Set
Time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax.
Outcome measures
| Measure |
TAK-063 3 mg + [^11C]T-773
n=2 Participants
TAK-063 3 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 10 mg
n=2 Participants
TAK-063 10 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 30 mg + [^11C]T-773
n=3 Participants
For main cohort, TAK-063 30 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2. For pilot cohort, TAK-063 30 mg, tablets, orally, once on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 (before and after administration of TAK-063) and twice on Day 2.
|
TAK-063 100 mg + [^11C]T-773
n=3 Participants
TAK-063 100 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 1000 mg + [^11C]T-773
n=2 Participants
TAK-063 1000 mg, tablets, orally, once, on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 and twice on Day 2 (before and after administration of TAK-063).
|
TAK-063 1000 mg + [^11C]T-773
TAK-063 1000 mg, tablets, orally, once, on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 and twice on Day 2 (before and after administration of TAK-063).
|
|---|---|---|---|---|---|---|
|
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-063 and TAK-063 Metabolite M-I
TAK-063
|
1.25 hour
Standard Deviation 0.354
|
2.99 hour
Standard Deviation 0.018
|
1.33 hour
Standard Deviation 0.289
|
2.33 hour
Standard Deviation 0.563
|
2.25 hour
Standard Deviation 1.137
|
—
|
|
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-063 and TAK-063 Metabolite M-I
TAK-063 Metabolite M-I
|
1.50 hour
Standard Deviation 0.000
|
2.99 hour
Standard Deviation 0.018
|
1.64 hour
Standard Deviation 1.116
|
2.00 hour
Standard Deviation 0.000
|
2.79 hour
Standard Deviation 1.120
|
—
|
SECONDARY outcome
Timeframe: Pilot Cohort: Day 2 predose and at multiple time points (up to 24 hours) post-dose. Main Cohort: Day 1 predose and at multiple time points (up to 24 hours) post-dose.Population: Pharmacokinetic Analysis Set
(AUC(0-tlqc) is a measure of total plasma exposure to the drug from Time 0 to Time of the Last Quantifiable Concentration (AUC\[0-tlqc\]).
Outcome measures
| Measure |
TAK-063 3 mg + [^11C]T-773
n=2 Participants
TAK-063 3 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 10 mg
n=2 Participants
TAK-063 10 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 30 mg + [^11C]T-773
n=3 Participants
For main cohort, TAK-063 30 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2. For pilot cohort, TAK-063 30 mg, tablets, orally, once on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 (before and after administration of TAK-063) and twice on Day 2.
|
TAK-063 100 mg + [^11C]T-773
n=3 Participants
TAK-063 100 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 1000 mg + [^11C]T-773
n=2 Participants
TAK-063 1000 mg, tablets, orally, once, on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 and twice on Day 2 (before and after administration of TAK-063).
|
TAK-063 1000 mg + [^11C]T-773
TAK-063 1000 mg, tablets, orally, once, on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 and twice on Day 2 (before and after administration of TAK-063).
|
|---|---|---|---|---|---|---|
|
AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-063 and TAK-063 Metabolite M-I
TAK-063
|
91.42 ng*hr/mL
Standard Deviation 5.795
|
318.56 ng*hr/mL
Standard Deviation 66.183
|
774.76 ng*hr/mL
Standard Deviation 127.644
|
897.17 ng*hr/mL
Standard Deviation 181.699
|
3288.62 ng*hr/mL
Standard Deviation 109.282
|
—
|
|
AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-063 and TAK-063 Metabolite M-I
TAK-063 Metabolite M-I
|
88.74 ng*hr/mL
Standard Deviation 23.833
|
245.24 ng*hr/mL
Standard Deviation 30.128
|
519.92 ng*hr/mL
Standard Deviation 233.914
|
850.26 ng*hr/mL
Standard Deviation 325.161
|
1859.28 ng*hr/mL
Standard Deviation 308.436
|
—
|
SECONDARY outcome
Timeframe: Pilot Cohort: Day 2 predose and at multiple time points (up to 24 hours) post-dose. Main Cohort: Day 1 predose and at multiple time points (up to 24 hours) post-dose.Population: Pharmacokinetic Analysis Set
AUC(0-24) is a measure of total plasma exposure to the drug from Time 0 to 24 hours post-dose.
Outcome measures
| Measure |
TAK-063 3 mg + [^11C]T-773
n=2 Participants
TAK-063 3 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 10 mg
n=2 Participants
TAK-063 10 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 30 mg + [^11C]T-773
n=3 Participants
For main cohort, TAK-063 30 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2. For pilot cohort, TAK-063 30 mg, tablets, orally, once on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 (before and after administration of TAK-063) and twice on Day 2.
|
TAK-063 100 mg + [^11C]T-773
n=3 Participants
TAK-063 100 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 1000 mg + [^11C]T-773
n=2 Participants
TAK-063 1000 mg, tablets, orally, once, on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 and twice on Day 2 (before and after administration of TAK-063).
|
TAK-063 1000 mg + [^11C]T-773
TAK-063 1000 mg, tablets, orally, once, on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 and twice on Day 2 (before and after administration of TAK-063).
|
|---|---|---|---|---|---|---|
|
AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-063 and TAK-063 Metabolite M-I
TAK-063
|
92.55 ng*hr/mL
Standard Deviation 5.348
|
324.98 ng*hr/mL
Standard Deviation 68.303
|
774.44 ng*hr/mL
Standard Deviation 129.997
|
910.12 ng*hr/mL
Standard Deviation 184.418
|
3289.62 ng*hr/mL
Standard Deviation 110.695
|
—
|
|
AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-063 and TAK-063 Metabolite M-I
TAK-063 Metabolite M-I
|
89.64 ng*hr/mL
Standard Deviation 23.672
|
249.82 ng*hr/mL
Standard Deviation 31.357
|
519.82 ng*hr/mL
Standard Deviation 233.869
|
864.14 ng*hr/mL
Standard Deviation 332.414
|
1859.97 ng*hr/mL
Standard Deviation 309.411
|
—
|
SECONDARY outcome
Timeframe: Pilot Cohort: Day 2 predose and at multiple time points (up to 24 hours) post-dose. Main Cohort: Day 1 predose and at multiple time points (up to 24 hours) post-dose.Population: Pharmacokinetic Analysis Set
Cavg is the average plasma concentration on Day 1, calculated as AUC(0-24)/24.
Outcome measures
| Measure |
TAK-063 3 mg + [^11C]T-773
n=2 Participants
TAK-063 3 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 10 mg
n=2 Participants
TAK-063 10 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 30 mg + [^11C]T-773
n=3 Participants
For main cohort, TAK-063 30 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2. For pilot cohort, TAK-063 30 mg, tablets, orally, once on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 (before and after administration of TAK-063) and twice on Day 2.
|
TAK-063 100 mg + [^11C]T-773
n=3 Participants
TAK-063 100 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 1000 mg + [^11C]T-773
n=2 Participants
TAK-063 1000 mg, tablets, orally, once, on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 and twice on Day 2 (before and after administration of TAK-063).
|
TAK-063 1000 mg + [^11C]T-773
TAK-063 1000 mg, tablets, orally, once, on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 and twice on Day 2 (before and after administration of TAK-063).
|
|---|---|---|---|---|---|---|
|
Average Plasma Concentration on Day 1 (Cavg) for TAK-063 and TAK-063 Metabolite M-I
TAK-063
|
3.86 ng/mL
Standard Deviation 0.223
|
13.54 ng/mL
Standard Deviation 2.846
|
32.27 ng/mL
Standard Deviation 5.417
|
37.92 ng/mL
Standard Deviation 7.684
|
137.07 ng/mL
Standard Deviation 4.612
|
—
|
|
Average Plasma Concentration on Day 1 (Cavg) for TAK-063 and TAK-063 Metabolite M-I
TAK-063 Metabolite M-I
|
3.74 ng/mL
Standard Deviation 0.986
|
10.41 ng/mL
Standard Deviation 1.307
|
21.66 ng/mL
Standard Deviation 9.745
|
36.01 ng/mL
Standard Deviation 13.851
|
77.50 ng/mL
Standard Deviation 12.892
|
—
|
SECONDARY outcome
Timeframe: Pilot Cohort: Day 2 predose and at multiple time points (up to 24 hours) post-dose. Main Cohort: Day 1 predose and at multiple time points (up to 24 hours) post-dose.Population: Pharmacokinetic Analysis Set
CL/F is apparent clearance of the drug from the plasma, calculated as the drug dose divided by area under the curve from time 0 to 24 hours post-dose, after multiple dosing (at steady state).
Outcome measures
| Measure |
TAK-063 3 mg + [^11C]T-773
n=2 Participants
TAK-063 3 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 10 mg
n=2 Participants
TAK-063 10 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 30 mg + [^11C]T-773
n=3 Participants
For main cohort, TAK-063 30 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2. For pilot cohort, TAK-063 30 mg, tablets, orally, once on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 (before and after administration of TAK-063) and twice on Day 2.
|
TAK-063 100 mg + [^11C]T-773
n=3 Participants
TAK-063 100 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 1000 mg + [^11C]T-773
n=2 Participants
TAK-063 1000 mg, tablets, orally, once, on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 and twice on Day 2 (before and after administration of TAK-063).
|
TAK-063 1000 mg + [^11C]T-773
TAK-063 1000 mg, tablets, orally, once, on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 and twice on Day 2 (before and after administration of TAK-063).
|
|---|---|---|---|---|---|---|
|
CL/F: Oral Clearance of TAK-063
|
26.19 liter/hour
Standard Deviation 1.099
|
18.31 liter/hour
Standard Deviation 7.477
|
24.90 liter/hour
Standard Deviation 2.209
|
88.86 liter/hour
Standard Deviation 25.806
|
252.33 liter/hour
Standard Deviation 21.971
|
—
|
SECONDARY outcome
Timeframe: Pilot Cohort: Day 2 predose and at multiple time points (up to 24 hours) post-dose. Main Cohort: Day 1 predose and at multiple time points (up to 24 hours) post-dose.Population: Pharmacokinetic Analysis Set
Cmax Ratio is the ratio of Cmax values of the metabolite compared to the parent calculated by dividing Cmax values of metabolite M-I with those of the parent drug TAK-063.
Outcome measures
| Measure |
TAK-063 3 mg + [^11C]T-773
n=2 Participants
TAK-063 3 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 10 mg
n=2 Participants
TAK-063 10 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 30 mg + [^11C]T-773
n=3 Participants
For main cohort, TAK-063 30 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2. For pilot cohort, TAK-063 30 mg, tablets, orally, once on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 (before and after administration of TAK-063) and twice on Day 2.
|
TAK-063 100 mg + [^11C]T-773
n=3 Participants
TAK-063 100 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 1000 mg + [^11C]T-773
n=2 Participants
TAK-063 1000 mg, tablets, orally, once, on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 and twice on Day 2 (before and after administration of TAK-063).
|
TAK-063 1000 mg + [^11C]T-773
TAK-063 1000 mg, tablets, orally, once, on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 and twice on Day 2 (before and after administration of TAK-063).
|
|---|---|---|---|---|---|---|
|
Ratio of TAK-063 Metabolite Cmax to TAK-063 Cmax
|
1.30 ratio
Standard Deviation 0.271
|
0.83 ratio
Standard Deviation 0.013
|
0.65 ratio
Standard Deviation 0.361
|
0.99 ratio
Standard Deviation 0.145
|
0.55 ratio
Standard Deviation 0.001
|
—
|
SECONDARY outcome
Timeframe: Pilot Cohort: Day 2 predose and at multiple time points (up to 24 hours) post-dose. Main Cohort: Day 1 predose and at multiple time points (up to 24 hours) post-dose.Population: Pharmacokinetic Analysis Set
AUC Ratio is the ratio of AUC values of the metabolite compared to the parent calculated by dividing AUC values of metabolite M-I with those of the parent drug TAK-063.
Outcome measures
| Measure |
TAK-063 3 mg + [^11C]T-773
n=2 Participants
TAK-063 3 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 10 mg
n=2 Participants
TAK-063 10 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 30 mg + [^11C]T-773
n=3 Participants
For main cohort, TAK-063 30 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2. For pilot cohort, TAK-063 30 mg, tablets, orally, once on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 (before and after administration of TAK-063) and twice on Day 2.
|
TAK-063 100 mg + [^11C]T-773
n=3 Participants
TAK-063 100 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 1000 mg + [^11C]T-773
n=2 Participants
TAK-063 1000 mg, tablets, orally, once, on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 and twice on Day 2 (before and after administration of TAK-063).
|
TAK-063 1000 mg + [^11C]T-773
TAK-063 1000 mg, tablets, orally, once, on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 and twice on Day 2 (before and after administration of TAK-063).
|
|---|---|---|---|---|---|---|
|
Ratio of TAK-063 Metabolite M-I AUC( 0-24) to TAK-063 AUC (0-24)
|
0.93 ratio
Standard Deviation 0.193
|
0.75 ratio
Standard Deviation 0.064
|
0.66 ratio
Standard Deviation 0.357
|
0.89 ratio
Standard Deviation 0.199
|
0.54 ratio
Standard Deviation 0.072
|
—
|
SECONDARY outcome
Timeframe: 3 hours post-dosePopulation: Pharmacokinetic Analysis Set
AUC values of TAK-063 and TAK-063 metabolite M-I during the PET scan at approximately 3 hours post TAK-063 administration.
Outcome measures
| Measure |
TAK-063 3 mg + [^11C]T-773
n=2 Participants
TAK-063 3 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 10 mg
n=2 Participants
TAK-063 10 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 30 mg + [^11C]T-773
n=3 Participants
For main cohort, TAK-063 30 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2. For pilot cohort, TAK-063 30 mg, tablets, orally, once on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 (before and after administration of TAK-063) and twice on Day 2.
|
TAK-063 100 mg + [^11C]T-773
n=3 Participants
TAK-063 100 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 1000 mg + [^11C]T-773
n=2 Participants
TAK-063 1000 mg, tablets, orally, once, on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 and twice on Day 2 (before and after administration of TAK-063).
|
TAK-063 1000 mg + [^11C]T-773
TAK-063 1000 mg, tablets, orally, once, on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 and twice on Day 2 (before and after administration of TAK-063).
|
|---|---|---|---|---|---|---|
|
AUC During the Positron Emission Tomography (PET) Scan Period (AUC(Scan)) at 3 Hours Post-dose for TAK-063 and TAK-063 Metabolite M-I
TAK-063
|
9.51 ng*hr/mL
Standard Deviation 1.217
|
25.68 ng*hr/mL
Standard Deviation 0.970
|
63.18 ng*hr/mL
Standard Deviation 13.667
|
82.25 ng*hr/mL
Standard Deviation 16.404
|
269.32 ng*hr/mL
Standard Deviation 23.429
|
—
|
|
AUC During the Positron Emission Tomography (PET) Scan Period (AUC(Scan)) at 3 Hours Post-dose for TAK-063 and TAK-063 Metabolite M-I
TAK-063 Metabolite M-I
|
10.23 ng*hr/mL
Standard Deviation 3.850
|
22.56 ng*hr/mL
Standard Deviation 1.272
|
49.09 ng*hr/mL
Standard Deviation 21.273
|
85.13 ng*hr/mL
Standard Deviation 29.151
|
162.23 ng*hr/mL
Standard Deviation 6.527
|
—
|
SECONDARY outcome
Timeframe: 3 hours post-dosePopulation: Pharmacokinetic Analysis Set
Cavg values of TAK-063 and TAK-063 metabolite M-I during the PET scan at approximately 3 hours post TAK-063 administration.
Outcome measures
| Measure |
TAK-063 3 mg + [^11C]T-773
n=2 Participants
TAK-063 3 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 10 mg
n=2 Participants
TAK-063 10 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 30 mg + [^11C]T-773
n=3 Participants
For main cohort, TAK-063 30 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2. For pilot cohort, TAK-063 30 mg, tablets, orally, once on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 (before and after administration of TAK-063) and twice on Day 2.
|
TAK-063 100 mg + [^11C]T-773
n=3 Participants
TAK-063 100 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 1000 mg + [^11C]T-773
n=2 Participants
TAK-063 1000 mg, tablets, orally, once, on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 and twice on Day 2 (before and after administration of TAK-063).
|
TAK-063 1000 mg + [^11C]T-773
TAK-063 1000 mg, tablets, orally, once, on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 and twice on Day 2 (before and after administration of TAK-063).
|
|---|---|---|---|---|---|---|
|
Cavg During the Positron Emission Tomography (PET) Scan Period (AUC(Scan)) at 3 Hours Post-dose for TAK-063 and TAK-063 Metabolite M-I
TAK-063
|
7.61 ng/mL
Standard Deviation 0.974
|
20.54 ng/mL
Standard Deviation 0.776
|
50.54 ng/mL
Standard Deviation 10.934
|
65.80 ng/mL
Standard Deviation 13.123
|
215.46 ng/mL
Standard Deviation 18.743
|
—
|
|
Cavg During the Positron Emission Tomography (PET) Scan Period (AUC(Scan)) at 3 Hours Post-dose for TAK-063 and TAK-063 Metabolite M-I
TAK-063 Metabolite M-I
|
8.18 ng/mL
Standard Deviation 3.080
|
18.05 ng/mL
Standard Deviation 1.018
|
39.27 ng/mL
Standard Deviation 17.018
|
68.10 ng/mL
Standard Deviation 23.321
|
129.78 ng/mL
Standard Deviation 5.222
|
—
|
SECONDARY outcome
Timeframe: 23 hours post-dosePopulation: Pharmacokinetic Analysis Set
AUC values of TAK-063 and TAK-063 metabolite M-I during the PET scan at approximately 23 hours post TAK-063 administration. Data was not available for participants in the pilot cohort.
Outcome measures
| Measure |
TAK-063 3 mg + [^11C]T-773
n=2 Participants
TAK-063 3 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 10 mg
n=2 Participants
TAK-063 10 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 30 mg + [^11C]T-773
n=1 Participants
For main cohort, TAK-063 30 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2. For pilot cohort, TAK-063 30 mg, tablets, orally, once on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 (before and after administration of TAK-063) and twice on Day 2.
|
TAK-063 100 mg + [^11C]T-773
n=3 Participants
TAK-063 100 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 1000 mg + [^11C]T-773
TAK-063 1000 mg, tablets, orally, once, on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 and twice on Day 2 (before and after administration of TAK-063).
|
TAK-063 1000 mg + [^11C]T-773
TAK-063 1000 mg, tablets, orally, once, on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 and twice on Day 2 (before and after administration of TAK-063).
|
|---|---|---|---|---|---|---|
|
AUC During the Positron Emission Tomography (PET) Scan Period (AUC(Scan)) at 23 Hours Post-dose for TAK-063 and TAK-063 Metabolite M-I
TAK-063
|
1.75 ng*hr/mL
Standard Deviation 0.496
|
11.44 ng*hr/mL
Standard Deviation 4.243
|
21.22 ng*hr/mL
Standard Deviation NA
Standard deviation can not be calculated for 1 participant.
|
21.15 ng*hr/mL
Standard Deviation 7.913
|
—
|
—
|
|
AUC During the Positron Emission Tomography (PET) Scan Period (AUC(Scan)) at 23 Hours Post-dose for TAK-063 and TAK-063 Metabolite M-I
TAK-063 Metabolite M-I
|
1.43 ng*hr/mL
Standard Deviation 0.071
|
8.20 ng*hr/mL
Standard Deviation 2.631
|
19.96 ng*hr/mL
Standard Deviation NA
Standard deviation can not be calculated for 1 participant.
|
22.97 ng*hr/mL
Standard Deviation 15.919
|
—
|
—
|
SECONDARY outcome
Timeframe: 23 hours post-dosePopulation: Pharmacokinetic Analysis Set
Cavg values of TAK-063 and TAK-063 metabolite M-I during the PET scan at approximately 23 hours post TAK-063 administration. Data is not available for the pilot cohort.
Outcome measures
| Measure |
TAK-063 3 mg + [^11C]T-773
n=2 Participants
TAK-063 3 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 10 mg
n=2 Participants
TAK-063 10 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 30 mg + [^11C]T-773
n=1 Participants
For main cohort, TAK-063 30 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2. For pilot cohort, TAK-063 30 mg, tablets, orally, once on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 (before and after administration of TAK-063) and twice on Day 2.
|
TAK-063 100 mg + [^11C]T-773
n=3 Participants
TAK-063 100 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2.
|
TAK-063 1000 mg + [^11C]T-773
TAK-063 1000 mg, tablets, orally, once, on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 and twice on Day 2 (before and after administration of TAK-063).
|
TAK-063 1000 mg + [^11C]T-773
TAK-063 1000 mg, tablets, orally, once, on Day 2, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, once on Day 1 and twice on Day 2 (before and after administration of TAK-063).
|
|---|---|---|---|---|---|---|
|
Cavg During the Positron Emission Tomography (PET) Scan Period (AUC(Scan)) at 23 Hours Post-dose for TAK-063 and TAK-063 Metabolite M-I
TAK-063
|
1.40 ng/mL
Standard Deviation 0.397
|
9.15 ng/mL
Standard Deviation 3.394
|
16.97 ng/mL
Standard Deviation NA
Standard deviation can not be calculated for 1 participant.
|
16.92 ng/mL
Standard Deviation 6.331
|
—
|
—
|
|
Cavg During the Positron Emission Tomography (PET) Scan Period (AUC(Scan)) at 23 Hours Post-dose for TAK-063 and TAK-063 Metabolite M-I
TAK-063 Metabolite M-
|
1.15 ng/mL
Standard Deviation 0.056
|
6.56 ng/mL
Standard Deviation 2.105
|
15.97 ng/mL
Standard Deviation NA
Standard deviation can not be calculated for 1 participant.
|
18.37 ng/mL
Standard Deviation 12.735
|
—
|
—
|
Adverse Events
[^11C]T-773
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
TAK-063
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
[^11C]T-773
n=13 participants at risk
\[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenous (IV), once on Days 1 and 2 only.
|
TAK-063
n=12 participants at risk
TAK-063 3 to 1000 mg, tablets, orally, once, on Day 1.
|
|---|---|---|
|
Vascular disorders
Haematoma
|
0.00%
0/13 • First dose of study drug to 30 days after last dose of study drug (up to 46 days)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
33.3%
4/12 • First dose of study drug to 30 days after last dose of study drug (up to 46 days)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Psychiatric disorders
Anxiety
|
7.7%
1/13 • First dose of study drug to 30 days after last dose of study drug (up to 46 days)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
16.7%
2/12 • First dose of study drug to 30 days after last dose of study drug (up to 46 days)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Nervous system disorders
Headache
|
7.7%
1/13 • First dose of study drug to 30 days after last dose of study drug (up to 46 days)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
16.7%
2/12 • First dose of study drug to 30 days after last dose of study drug (up to 46 days)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
General disorders
Infusion site pain
|
15.4%
2/13 • First dose of study drug to 30 days after last dose of study drug (up to 46 days)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
16.7%
2/12 • First dose of study drug to 30 days after last dose of study drug (up to 46 days)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/13 • First dose of study drug to 30 days after last dose of study drug (up to 46 days)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
16.7%
2/12 • First dose of study drug to 30 days after last dose of study drug (up to 46 days)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Nervous system disorders
Tremor
|
0.00%
0/13 • First dose of study drug to 30 days after last dose of study drug (up to 46 days)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
16.7%
2/12 • First dose of study drug to 30 days after last dose of study drug (up to 46 days)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
General disorders
Catheter site pain
|
7.7%
1/13 • First dose of study drug to 30 days after last dose of study drug (up to 46 days)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
8.3%
1/12 • First dose of study drug to 30 days after last dose of study drug (up to 46 days)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
General disorders
Chest pain
|
0.00%
0/13 • First dose of study drug to 30 days after last dose of study drug (up to 46 days)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
8.3%
1/12 • First dose of study drug to 30 days after last dose of study drug (up to 46 days)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Psychiatric disorders
Claustrophobia
|
0.00%
0/13 • First dose of study drug to 30 days after last dose of study drug (up to 46 days)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
8.3%
1/12 • First dose of study drug to 30 days after last dose of study drug (up to 46 days)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Nervous system disorders
Dizziness
|
0.00%
0/13 • First dose of study drug to 30 days after last dose of study drug (up to 46 days)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
8.3%
1/12 • First dose of study drug to 30 days after last dose of study drug (up to 46 days)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
General disorders
Fatigue
|
0.00%
0/13 • First dose of study drug to 30 days after last dose of study drug (up to 46 days)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
8.3%
1/12 • First dose of study drug to 30 days after last dose of study drug (up to 46 days)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
General disorders
Infusion site erythema
|
0.00%
0/13 • First dose of study drug to 30 days after last dose of study drug (up to 46 days)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
8.3%
1/12 • First dose of study drug to 30 days after last dose of study drug (up to 46 days)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/13 • First dose of study drug to 30 days after last dose of study drug (up to 46 days)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
8.3%
1/12 • First dose of study drug to 30 days after last dose of study drug (up to 46 days)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Research Organization shall not publish any articles or papers nor make any presentations, nor assist any other person in publishing any articles or papers or in making any presentations relating or referring to the Study or any results, data or insights from or any data, information or materials obtained or generated in the performance of its obligations without the prior written consent of Takeda, which consent may be granted or withheld in Takeda's sole discretion.
- Publication restrictions are in place
Restriction type: OTHER