Trial Outcomes & Findings for A Study to Evaluate Central Nervous System (CNS) Pharmacodynamic Activity of TAK-653 in Healthy Participants Using Transcranial Magnetic Stimulation (TMS) (NCT NCT03792672)
NCT ID: NCT03792672
Last Updated: 2021-03-19
Results Overview
TMS was a neurophysiologic test for assessing upper motor neuron function. TMS was a noninvasive neuro stimulation method involving the application of brief magnetic pulses to the skull, based on the principles of electromagnetic induction, create an orthogonal electric current that can be sufficient to depolarize neurons and activate neuronal circuits. Single-pulse TMS was used to determine peak-to-peak amplitude of MEP at a stimulation intensity of 120 percent (%) of baseline resting motor threshold (rMT). rMT was defined as the minimum stimulus intensity to evoke an MEP. Change in peak-to peak amplitude of MEP was be assessed by TMS after treatment with 0.5 mg or 6 mg of TAK-653 versus (vs.) matched oral placebo.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
24 participants
Primary outcome timeframe
Baseline, 2.5 hours post TAK-653 dose
Results posted on
2021-03-19
Participant Flow
Participants took part in the study at 1 investigative site in Netherlands from 11 February 2019 to 18 June 2019.
Healthy participants were enrolled in 1 of the 6 treatment sequences of this 3-period crossover study to receive TAK 653 0.5 milligram (mg) (Low dose), TAK-653 6 mg (high dose), placebo in Treatment Periods 1 to 3, and ketamine 0.5 milligram per kilogram (mg/kg) in an open label treatment Period 4.
Participant milestones
| Measure |
Placebo + TAK-653 0.5 mg + TAK-653 6 mg + Ketamine 0.5 mg/kg
TAK-653 placebo-matching tablets, orally, once on Day 1 of Treatment Period 1, followed by TAK-653 0.5 mg low dose tablets, orally, once on Day 1 of Treatment Period 2, further followed by TAK-653 6 mg high dose tablets, orally, once on Day 1 of Treatment Period 3, followed by Ketamine 0.5 mg/kg, infusion, intravenously, once on Day 1 of Treatment Period 4. A Washout Period of at least 10 days was maintained between each treatment period.
|
Placebo + TAK-653 6 mg + TAK-653 0.5 mg + Ketamine 0.5 mg/kg
TAK-653 placebo-matching tablets, orally, once on Day 1 of Treatment Period 1, followed by TAK-653 6 mg high dose tablets, orally, once on Day 1 of Treatment Period 2, further followed by TAK-653 0.5 mg low dose tablets, orally, once on Day 1 of Treatment Period 3, followed by Ketamine 0.5 mg/kg, infusion, intravenously, once on Day 1 of Treatment Period 4. A Washout Period of at least 10 days was maintained between each treatment period.
|
TAK-653 0.5 mg + Placebo + TAK-653 6 mg + Ketamine 0.5 mg/kg
TAK-653 0.5 mg low dose tablets, orally, once on Day 1 of Treatment Period 1, followed by TAK-653 placebo-matching tablets, orally, once on Day 1 of Treatment Period 2, further followed by TAK-653 6 mg high dose tablets, orally, once on Day 1 of Treatment Period 3, followed by Ketamine 0.5 mg/kg, infusion, intravenously, once on Day 1 of Treatment Period 4. A Washout Period of at least 10 days was maintained between each treatment period.
|
TAK-653 0.5 mg + TAK-653 6 mg + Placebo + Ketamine 0.5 mg/kg
TAK-653 0.5 mg low dose tablets, orally, once on Day 1 of Treatment Period 1, followed by TAK-653 6 mg high dose tablets, orally, once on Day 1 of Treatment Period 2, further followed by TAK-653 placebo-matching tablets, orally, once on Day 1 of Treatment Period 3, followed by Ketamine 0.5 mg/kg, infusion, intravenously, once on Day 1 of Treatment Period 4. A Washout Period of at least 10 days was maintained between each treatment period.
|
TAK-653 6 mg + Placebo + TAK-653 0.5 mg + Ketamine 0.5 mg/kg
TAK-653 6 mg high dose tablets, orally, once on Day 1 of Treatment Period 1, followed by TAK-653 placebo-matching tablets, orally, once on Day 1 of Treatment Period 2, further followed by TAK-653 0.5 mg low dose tablets, orally, once on Day 1 of Treatment Period 3, followed by Ketamine 0.5 mg/kg, infusion, intravenously, once on Day 1 of Treatment Period 4. A Washout Period of at least 10 days was maintained between each treatment period.
|
TAK-653 6 mg + TAK-653 0.5 mg + Placebo + Ketamine 0.5 mg/kg
TAK-653 6 mg high dose tablets, orally, once on Day 1 of Treatment Period 1, followed by TAK-653 0.5 mg low dose tablets, orally, once on Day 1 of Treatment Period 2, further followed by TAK-653 placebo-matching tablets, orally, once on Day 1 of Treatment Period 3, followed by Ketamine 0.5 mg/kg, infusion, intravenously, once on Day 1 of Treatment Period 4. A Washout Period of at least 10 days was maintained between each treatment period.
|
|---|---|---|---|---|---|---|
|
Treatment Period 1 (1 Day)
STARTED
|
4
|
4
|
4
|
4
|
4
|
4
|
|
Treatment Period 1 (1 Day)
COMPLETED
|
4
|
4
|
4
|
4
|
4
|
4
|
|
Treatment Period 1 (1 Day)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Washout Period 1 (10 Days)
STARTED
|
4
|
4
|
4
|
4
|
4
|
4
|
|
Washout Period 1 (10 Days)
COMPLETED
|
4
|
4
|
4
|
4
|
4
|
4
|
|
Washout Period 1 (10 Days)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Treatment Period 2 (1 Day)
STARTED
|
4
|
4
|
4
|
4
|
4
|
4
|
|
Treatment Period 2 (1 Day)
COMPLETED
|
4
|
4
|
4
|
4
|
4
|
4
|
|
Treatment Period 2 (1 Day)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Washout Period 2 (10 Days)
STARTED
|
4
|
4
|
4
|
4
|
4
|
4
|
|
Washout Period 2 (10 Days)
COMPLETED
|
4
|
4
|
4
|
4
|
4
|
4
|
|
Washout Period 2 (10 Days)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Treatment Period 3 (1 Day)
STARTED
|
4
|
4
|
4
|
4
|
4
|
4
|
|
Treatment Period 3 (1 Day)
COMPLETED
|
4
|
4
|
4
|
4
|
4
|
4
|
|
Treatment Period 3 (1 Day)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Washout Period 3 (10 Days)
STARTED
|
4
|
4
|
4
|
4
|
4
|
4
|
|
Washout Period 3 (10 Days)
COMPLETED
|
3
|
4
|
3
|
2
|
4
|
4
|
|
Washout Period 3 (10 Days)
NOT COMPLETED
|
1
|
0
|
1
|
2
|
0
|
0
|
|
Treatment Period 4 (2 Days)
STARTED
|
3
|
4
|
3
|
2
|
4
|
4
|
|
Treatment Period 4 (2 Days)
COMPLETED
|
2
|
4
|
3
|
2
|
4
|
4
|
|
Treatment Period 4 (2 Days)
NOT COMPLETED
|
1
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Placebo + TAK-653 0.5 mg + TAK-653 6 mg + Ketamine 0.5 mg/kg
TAK-653 placebo-matching tablets, orally, once on Day 1 of Treatment Period 1, followed by TAK-653 0.5 mg low dose tablets, orally, once on Day 1 of Treatment Period 2, further followed by TAK-653 6 mg high dose tablets, orally, once on Day 1 of Treatment Period 3, followed by Ketamine 0.5 mg/kg, infusion, intravenously, once on Day 1 of Treatment Period 4. A Washout Period of at least 10 days was maintained between each treatment period.
|
Placebo + TAK-653 6 mg + TAK-653 0.5 mg + Ketamine 0.5 mg/kg
TAK-653 placebo-matching tablets, orally, once on Day 1 of Treatment Period 1, followed by TAK-653 6 mg high dose tablets, orally, once on Day 1 of Treatment Period 2, further followed by TAK-653 0.5 mg low dose tablets, orally, once on Day 1 of Treatment Period 3, followed by Ketamine 0.5 mg/kg, infusion, intravenously, once on Day 1 of Treatment Period 4. A Washout Period of at least 10 days was maintained between each treatment period.
|
TAK-653 0.5 mg + Placebo + TAK-653 6 mg + Ketamine 0.5 mg/kg
TAK-653 0.5 mg low dose tablets, orally, once on Day 1 of Treatment Period 1, followed by TAK-653 placebo-matching tablets, orally, once on Day 1 of Treatment Period 2, further followed by TAK-653 6 mg high dose tablets, orally, once on Day 1 of Treatment Period 3, followed by Ketamine 0.5 mg/kg, infusion, intravenously, once on Day 1 of Treatment Period 4. A Washout Period of at least 10 days was maintained between each treatment period.
|
TAK-653 0.5 mg + TAK-653 6 mg + Placebo + Ketamine 0.5 mg/kg
TAK-653 0.5 mg low dose tablets, orally, once on Day 1 of Treatment Period 1, followed by TAK-653 6 mg high dose tablets, orally, once on Day 1 of Treatment Period 2, further followed by TAK-653 placebo-matching tablets, orally, once on Day 1 of Treatment Period 3, followed by Ketamine 0.5 mg/kg, infusion, intravenously, once on Day 1 of Treatment Period 4. A Washout Period of at least 10 days was maintained between each treatment period.
|
TAK-653 6 mg + Placebo + TAK-653 0.5 mg + Ketamine 0.5 mg/kg
TAK-653 6 mg high dose tablets, orally, once on Day 1 of Treatment Period 1, followed by TAK-653 placebo-matching tablets, orally, once on Day 1 of Treatment Period 2, further followed by TAK-653 0.5 mg low dose tablets, orally, once on Day 1 of Treatment Period 3, followed by Ketamine 0.5 mg/kg, infusion, intravenously, once on Day 1 of Treatment Period 4. A Washout Period of at least 10 days was maintained between each treatment period.
|
TAK-653 6 mg + TAK-653 0.5 mg + Placebo + Ketamine 0.5 mg/kg
TAK-653 6 mg high dose tablets, orally, once on Day 1 of Treatment Period 1, followed by TAK-653 0.5 mg low dose tablets, orally, once on Day 1 of Treatment Period 2, further followed by TAK-653 placebo-matching tablets, orally, once on Day 1 of Treatment Period 3, followed by Ketamine 0.5 mg/kg, infusion, intravenously, once on Day 1 of Treatment Period 4. A Washout Period of at least 10 days was maintained between each treatment period.
|
|---|---|---|---|---|---|---|
|
Washout Period 3 (10 Days)
Withdrawal by Subject
|
1
|
0
|
0
|
2
|
0
|
0
|
|
Washout Period 3 (10 Days)
Physician Decision
|
0
|
0
|
1
|
0
|
0
|
0
|
|
Treatment Period 4 (2 Days)
Other
|
1
|
0
|
0
|
0
|
0
|
0
|
Baseline Characteristics
A Study to Evaluate Central Nervous System (CNS) Pharmacodynamic Activity of TAK-653 in Healthy Participants Using Transcranial Magnetic Stimulation (TMS)
Baseline characteristics by cohort
| Measure |
All Participants
n=24 Participants
TAK-653 placebo-matching tablets or TAK-653 0.5 mg low dose tablets or TAK-653 6 mg high dose tablets, orally, once, on Day 1 of respective Treatment Period 1, 2 or 3 and Ketamine 0.5 mg/kg, infusion, intravenously, once on Day 1 of Treatment Period 4. A Washout Period of at least 10 days was maintained between each treatment period.
|
|---|---|
|
Age, Continuous
|
27.9 years
STANDARD_DEVIATION 9.0 • n=5 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
23 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
24 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
22 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
Netherlands
|
24 Participants
n=5 Participants
|
|
Weight
|
79.12 kilogram (Kg)
STANDARD_DEVIATION 10.81 • n=5 Participants
|
|
Height
|
181.98 centimeter (cm)
STANDARD_DEVIATION 9.88 • n=5 Participants
|
|
Body Mass Index (BMI)
|
23.93 kilogram per square meter (kg/m^2)
STANDARD_DEVIATION 2.85 • n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, 2.5 hours post TAK-653 dosePopulation: The pharmacodynamics (PD) set included of all participants who received study drug and had at least one postdose PD measurement. The PD analysis set included all participants who had completed first 3 treatment periods. Participants who were evaluable for this measure at given time point were included for the assessment.
TMS was a neurophysiologic test for assessing upper motor neuron function. TMS was a noninvasive neuro stimulation method involving the application of brief magnetic pulses to the skull, based on the principles of electromagnetic induction, create an orthogonal electric current that can be sufficient to depolarize neurons and activate neuronal circuits. Single-pulse TMS was used to determine peak-to-peak amplitude of MEP at a stimulation intensity of 120 percent (%) of baseline resting motor threshold (rMT). rMT was defined as the minimum stimulus intensity to evoke an MEP. Change in peak-to peak amplitude of MEP was be assessed by TMS after treatment with 0.5 mg or 6 mg of TAK-653 versus (vs.) matched oral placebo.
Outcome measures
| Measure |
Placebo
n=24 Participants
TAK-653 placebo-matching tablets, orally, once on Day 1 of Treatment Period 1, 2 or 3 as per assigned treatment sequence.
|
TAK-653 0.5 mg
n=24 Participants
TAK-653 0.5 mg low dose tablets, orally, once on Day 1 of Treatment Period 1, 2 or 3 as per assigned treatment sequence.
|
TAK-653 6 mg
n=24 Participants
TAK-653 6 mg high dose tablets, orally, once on Day 1 of Treatment Period 1, 2 or 3 as per assigned treatment sequence.
|
|---|---|---|---|
|
Change From Baseline in Peak-to-Peak Amplitude of Motor-evoked Potential (MEP) Obtained With Single-pulse Transcranial Magnetic Stimulation (TMS) for TAK-653 at 2.5 Hours Post TAK-653 Dose
Baseline
|
898.828 microvolt (mcV)
Standard Deviation 693.1535
|
841.068 microvolt (mcV)
Standard Deviation 591.1367
|
1004.127 microvolt (mcV)
Standard Deviation 574.5982
|
|
Change From Baseline in Peak-to-Peak Amplitude of Motor-evoked Potential (MEP) Obtained With Single-pulse Transcranial Magnetic Stimulation (TMS) for TAK-653 at 2.5 Hours Post TAK-653 Dose
Change at 2.5 Hours Post TAK-653 Dose
|
-139.117 microvolt (mcV)
Standard Deviation 829.5901
|
17.265 microvolt (mcV)
Standard Deviation 466.2556
|
139.932 microvolt (mcV)
Standard Deviation 813.9705
|
PRIMARY outcome
Timeframe: Baseline, 2.5 hours post TAK-653 dosePopulation: The PD set included of all participants who received study drug and had at least one postdose PD measurement. The PD analysis set included all participants who had completed first 3 treatment periods.
The rMT was defined as the minimum stimulus intensity to evoke an MEP. Single-pulse TMS was used to determine rMT. A lower rMT value indicated greater neuronal excitability. TMS was a neurophysiologic test for assessing upper motor neuron function. TMS was a noninvasive neuro stimulation method involving the application of brief magnetic pulses to the skull, based on the principles of electromagnetic induction, create an orthogonal electric current that can be sufficient to depolarize neurons and activate neuronal circuits. Change in rMT was be assessed by TMS after treatment with 0.5 mg or 6 mg of TAK-653 vs. matched oral placebo.
Outcome measures
| Measure |
Placebo
n=24 Participants
TAK-653 placebo-matching tablets, orally, once on Day 1 of Treatment Period 1, 2 or 3 as per assigned treatment sequence.
|
TAK-653 0.5 mg
n=24 Participants
TAK-653 0.5 mg low dose tablets, orally, once on Day 1 of Treatment Period 1, 2 or 3 as per assigned treatment sequence.
|
TAK-653 6 mg
n=24 Participants
TAK-653 6 mg high dose tablets, orally, once on Day 1 of Treatment Period 1, 2 or 3 as per assigned treatment sequence.
|
|---|---|---|---|
|
Change From Baseline in Resting Motor Threshold (rMT) Obtained With Single-pulse TMS for TAK-653 at 2.5 Hours Post TAK-653 Dose
Baseline
|
55.3 percentage of maximum stimulator output
Standard Deviation 7.46
|
55.9 percentage of maximum stimulator output
Standard Deviation 8.99
|
55.3 percentage of maximum stimulator output
Standard Deviation 8.93
|
|
Change From Baseline in Resting Motor Threshold (rMT) Obtained With Single-pulse TMS for TAK-653 at 2.5 Hours Post TAK-653 Dose
Change at 2.5 hours post TAK-653 Dose
|
-0.1 percentage of maximum stimulator output
Standard Deviation 2.74
|
-0.5 percentage of maximum stimulator output
Standard Deviation 1.74
|
-0.3 percentage of maximum stimulator output
Standard Deviation 1.95
|
SECONDARY outcome
Timeframe: Baseline, 2.5 hours post TAK-653 dosePopulation: The PD set included of all participants who received study drug and had at least one postdose PD measurement. The PD analysis set included all participants who had completed first 3 treatment periods.
LICI was TMS stimulation paradigm that capture modulation of cortical excitation-inhibition balance with pairs of TMS pulses at stimulation intensity conditioning pulse and test pulse of 120% of baseline rMT. rMT was defined as the minimum stimulus intensity to evoke an MEP. TMS was a neurophysiologic test for assessing upper motor neuron function. TMS was a noninvasive neuro stimulation method involving the application of brief magnetic pulses to the skull, based on the principles of electromagnetic induction, create an orthogonal electric current that can be sufficient to depolarize neurons and activate neuronal circuits. Change in LICI was be assessed by TMS after treatment with 0.5 mg or 6 mg of TAK-653 vs. matched oral placebo.
Outcome measures
| Measure |
Placebo
n=24 Participants
TAK-653 placebo-matching tablets, orally, once on Day 1 of Treatment Period 1, 2 or 3 as per assigned treatment sequence.
|
TAK-653 0.5 mg
n=24 Participants
TAK-653 0.5 mg low dose tablets, orally, once on Day 1 of Treatment Period 1, 2 or 3 as per assigned treatment sequence.
|
TAK-653 6 mg
n=24 Participants
TAK-653 6 mg high dose tablets, orally, once on Day 1 of Treatment Period 1, 2 or 3 as per assigned treatment sequence.
|
|---|---|---|---|
|
Change From Baseline in Magnitude of Long Intracortical Inhibition (LICI) Obtained With Paired-pulse TMS for TAK-653 at 2.5 Hours Post TAK-653 Dose
Baseline: LICI 100 ms
|
16.167 percent inhibition
Standard Deviation 27.0976
|
10.430 percent inhibition
Standard Deviation 14.1289
|
46.808 percent inhibition
Standard Deviation 149.9806
|
|
Change From Baseline in Magnitude of Long Intracortical Inhibition (LICI) Obtained With Paired-pulse TMS for TAK-653 at 2.5 Hours Post TAK-653 Dose
Baseline: LICI 50 ms
|
75.113 percent inhibition
Standard Deviation 97.2865
|
96.515 percent inhibition
Standard Deviation 113.2728
|
96.568 percent inhibition
Standard Deviation 111.1657
|
|
Change From Baseline in Magnitude of Long Intracortical Inhibition (LICI) Obtained With Paired-pulse TMS for TAK-653 at 2.5 Hours Post TAK-653 Dose
Change at 2.5 Hours Post TAK-653 Dose: LICI 50 ms
|
0.675 percent inhibition
Standard Deviation 54.5725
|
18.319 percent inhibition
Standard Deviation 81.4378
|
19.395 percent inhibition
Standard Deviation 110.0870
|
|
Change From Baseline in Magnitude of Long Intracortical Inhibition (LICI) Obtained With Paired-pulse TMS for TAK-653 at 2.5 Hours Post TAK-653 Dose
Change at 2.5 Hours Post TAK-653 Dose: LICI 100 ms
|
0.147 percent inhibition
Standard Deviation 29.1567
|
5.905 percent inhibition
Standard Deviation 18.8939
|
-28.644 percent inhibition
Standard Deviation 142.5618
|
|
Change From Baseline in Magnitude of Long Intracortical Inhibition (LICI) Obtained With Paired-pulse TMS for TAK-653 at 2.5 Hours Post TAK-653 Dose
Baseline: LICI 200 ms
|
48.149 percent inhibition
Standard Deviation 33.1815
|
48.934 percent inhibition
Standard Deviation 48.6073
|
49.773 percent inhibition
Standard Deviation 37.7173
|
|
Change From Baseline in Magnitude of Long Intracortical Inhibition (LICI) Obtained With Paired-pulse TMS for TAK-653 at 2.5 Hours Post TAK-653 Dose
Change at 2.5 Hours Post TAK-653 Dose: LICI 200 ms
|
2.882 percent inhibition
Standard Deviation 21.2459
|
9.902 percent inhibition
Standard Deviation 42.5761
|
11.540 percent inhibition
Standard Deviation 30.1594
|
|
Change From Baseline in Magnitude of Long Intracortical Inhibition (LICI) Obtained With Paired-pulse TMS for TAK-653 at 2.5 Hours Post TAK-653 Dose
Baseline: LICI 300 ms
|
59.463 percent inhibition
Standard Deviation 31.1596
|
56.115 percent inhibition
Standard Deviation 36.8452
|
54.572 percent inhibition
Standard Deviation 30.5543
|
|
Change From Baseline in Magnitude of Long Intracortical Inhibition (LICI) Obtained With Paired-pulse TMS for TAK-653 at 2.5 Hours Post TAK-653 Dose
Change at 2.5 Hours Post TAK-653 Dose: LICI 300 ms
|
-9.996 percent inhibition
Standard Deviation 27.7151
|
8.618 percent inhibition
Standard Deviation 36.0453
|
1.638 percent inhibition
Standard Deviation 32.6843
|
SECONDARY outcome
Timeframe: Baseline, 2.5 hours post TAK-653 dosePopulation: The PD set included of all participants who received study drug and had at least one postdose PD measurement. The PD analysis set included all participants who had completed first 3 treatment periods. Participants who were evaluable for this measure at given time point were included for the assessment.
SICI was TMS stimulation paradigm that capture modulation of cortical excitation-inhibition balance with pairs of TMS pulses at stimulation intensity conditioning pulse 80% of baseline rMT and test pulse of 120% of baseline rMT. rMT was defined as the minimum stimulus intensity to evoke an MEP. TMS was a neurophysiologic test for assessing upper motor neuron function. TMS was a noninvasive neuro stimulation method involving the application of brief magnetic pulses to the skull, based on the principles of electromagnetic induction, create an orthogonal electric current that can be sufficient to depolarize neurons and activate neuronal circuits. Change in SICI was be assessed by TMS after treatment with 0.5 mg or 6 mg of TAK-653 vs. matched oral placebo.
Outcome measures
| Measure |
Placebo
n=24 Participants
TAK-653 placebo-matching tablets, orally, once on Day 1 of Treatment Period 1, 2 or 3 as per assigned treatment sequence.
|
TAK-653 0.5 mg
n=24 Participants
TAK-653 0.5 mg low dose tablets, orally, once on Day 1 of Treatment Period 1, 2 or 3 as per assigned treatment sequence.
|
TAK-653 6 mg
n=24 Participants
TAK-653 6 mg high dose tablets, orally, once on Day 1 of Treatment Period 1, 2 or 3 as per assigned treatment sequence.
|
|---|---|---|---|
|
Change From Baseline in Magnitude of Short Intracortical Inhibition (SICI) Obtained With Paired-pulse TMS for TAK-653 at 2.5 Hours Post TAK-653 Dose
Baseline: SICI 2 ms
|
43.095 percent inhibition
Standard Deviation 30.7011
|
39.159 percent inhibition
Standard Deviation 39.2536
|
47.951 percent inhibition
Standard Deviation 42.1139
|
|
Change From Baseline in Magnitude of Short Intracortical Inhibition (SICI) Obtained With Paired-pulse TMS for TAK-653 at 2.5 Hours Post TAK-653 Dose
Change at 2.5 Hours Post TAK-653 Dose: SICI 2 ms
|
5.052 percent inhibition
Standard Deviation 47.5676
|
1.772 percent inhibition
Standard Deviation 35.9158
|
-14.580 percent inhibition
Standard Deviation 37.7311
|
|
Change From Baseline in Magnitude of Short Intracortical Inhibition (SICI) Obtained With Paired-pulse TMS for TAK-653 at 2.5 Hours Post TAK-653 Dose
Baseline: SICI 5 ms
|
70.640 percent inhibition
Standard Deviation 49.8699
|
59.672 percent inhibition
Standard Deviation 37.7419
|
72.722 percent inhibition
Standard Deviation 62.0484
|
|
Change From Baseline in Magnitude of Short Intracortical Inhibition (SICI) Obtained With Paired-pulse TMS for TAK-653 at 2.5 Hours Post TAK-653 Dose
Change at 2.5 Hours Post TAK-653 Dose: SICI 5 ms
|
14.303 percent inhibition
Standard Deviation 81.6111
|
4.274 percent inhibition
Standard Deviation 30.8966
|
-7.247 percent inhibition
Standard Deviation 52.9205
|
SECONDARY outcome
Timeframe: Baseline, 2.5 hours post ketamine dose, and 24 hours post ketamine dosePopulation: The PD set included of all participants who received study drug and had at least one postdose PD measurement. The PD analysis set included all participants who had completed Treatment Period 4. Participants who were evaluable for this measure at given time point were included for the assessment.
The rMT was defined as the minimum stimulus intensity to evoke an MEP. Single-pulse TMS was used to determine rMT. A lower rMT value indicated greater neuronal excitability. TMS was a neurophysiologic test for assessing upper motor neuron function. TMS was a noninvasive neuro stimulation method involving the application of brief magnetic pulses to the skull, based on the principles of electromagnetic induction, create an orthogonal electric current that can be sufficient to depolarize neurons and activate neuronal circuits. Change in rMT was be assessed by TMS after treatment with 0.5 mg/kg Ketamine.
Outcome measures
| Measure |
Placebo
n=20 Participants
TAK-653 placebo-matching tablets, orally, once on Day 1 of Treatment Period 1, 2 or 3 as per assigned treatment sequence.
|
TAK-653 0.5 mg
TAK-653 0.5 mg low dose tablets, orally, once on Day 1 of Treatment Period 1, 2 or 3 as per assigned treatment sequence.
|
TAK-653 6 mg
TAK-653 6 mg high dose tablets, orally, once on Day 1 of Treatment Period 1, 2 or 3 as per assigned treatment sequence.
|
|---|---|---|---|
|
Change From Baseline in rMT Obtained With Single-pulse TMS to Assess the Effect of Ketamine at 2.5 Hours and 24 Hours Post-dose of Ketamine
Baseline
|
54.4 percentage of maximum stimulator output
Standard Deviation 9.28
|
—
|
—
|
|
Change From Baseline in rMT Obtained With Single-pulse TMS to Assess the Effect of Ketamine at 2.5 Hours and 24 Hours Post-dose of Ketamine
Change at 2.5 hours Ketamine Post Dose
|
0.7 percentage of maximum stimulator output
Standard Deviation 4.18
|
—
|
—
|
|
Change From Baseline in rMT Obtained With Single-pulse TMS to Assess the Effect of Ketamine at 2.5 Hours and 24 Hours Post-dose of Ketamine
Change at 24 hours Ketamine Post Dose
|
0.8 percentage of maximum stimulator output
Standard Deviation 3.10
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, 2.5 hours post ketamine dose, and 24 hours post ketamine dosePopulation: The PD set included of all participants who received study drug and had at least one postdose PD measurement. The PD analysis set included all participants who had completed Treatment Period 4. Participants who were evaluable for this measure at given time point were included for the assessment.
TMS was a neurophysiologic test for assessing upper motor neuron function. TMS was a noninvasive neuro stimulation method involving the application of brief magnetic pulses to the skull, based on the principles of electromagnetic induction, create an orthogonal electric current that can be sufficient to depolarize neurons and activate neuronal circuits. Single-pulse TMS was used to determine peak-to-peak amplitude of MEP at a stimulation intensity of 120% of baseline rMT. rMT was defined as the minimum stimulus intensity to evoke an MEP. Change in peak-to peak amplitude of MEP was be assessed by TMS after treatment 0.5 mg/kg Ketamine.
Outcome measures
| Measure |
Placebo
n=20 Participants
TAK-653 placebo-matching tablets, orally, once on Day 1 of Treatment Period 1, 2 or 3 as per assigned treatment sequence.
|
TAK-653 0.5 mg
TAK-653 0.5 mg low dose tablets, orally, once on Day 1 of Treatment Period 1, 2 or 3 as per assigned treatment sequence.
|
TAK-653 6 mg
TAK-653 6 mg high dose tablets, orally, once on Day 1 of Treatment Period 1, 2 or 3 as per assigned treatment sequence.
|
|---|---|---|---|
|
Change From Baseline in in Peak-to-Peak Amplitude of MEP Obtained With Single-pulse TMS to Assess the Effect of Ketamine at 2.5 Hours and 24 Hours Post Dose of Ketamine
Baseline
|
1150.618 mcV
Standard Deviation 1047.3920
|
—
|
—
|
|
Change From Baseline in in Peak-to-Peak Amplitude of MEP Obtained With Single-pulse TMS to Assess the Effect of Ketamine at 2.5 Hours and 24 Hours Post Dose of Ketamine
Change at 2.5 hours Ketamine Post Dose
|
-193.897 mcV
Standard Deviation 897.0245
|
—
|
—
|
|
Change From Baseline in in Peak-to-Peak Amplitude of MEP Obtained With Single-pulse TMS to Assess the Effect of Ketamine at 2.5 Hours and 24 Hours Post Dose of Ketamine
Change at 24 hours Ketamine Post Dose
|
-295.041 mcV
Standard Deviation 944.4889
|
—
|
—
|
Adverse Events
Placebo
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
TAK-653 0.5 mg
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
TAK-653 6 mg
Serious events: 0 serious events
Other events: 12 other events
Deaths: 0 deaths
Ketamine 0.5 mg/kg
Serious events: 0 serious events
Other events: 20 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Placebo
n=24 participants at risk
TAK-653 placebo-matching tablets, orally, once on Day 1 of Treatment Period 1, 2 or 3 as per assigned treatment sequence.
|
TAK-653 0.5 mg
n=24 participants at risk
TAK-653 0.5 mg low dose tablets, orally, once on Day 1 of Treatment Period 1, 2 or 3 as per assigned treatment sequence.
|
TAK-653 6 mg
n=24 participants at risk
TAK-653 6 mg high dose tablets, orally, once on Day 1 of Treatment Period 1, 2 or 3 as per assigned treatment sequence.
|
Ketamine 0.5 mg/kg
n=20 participants at risk
Ketamine 0.5 mg/kg, infusion, intravenously, once on Day 1 of Treatment Period 4 in all 6 treatment sequences.
|
|---|---|---|---|---|
|
Nervous system disorders
Dizziness
|
4.2%
1/24 • Number of events 1 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
0.00%
0/24 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
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.
|
4.2%
1/24 • Number of events 1 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
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.
|
40.0%
8/20 • Number of events 8 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
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
|
8.3%
2/24 • Number of events 3 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
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.
|
4.2%
1/24 • Number of events 1 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
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%
4/24 • Number of events 4 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
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.
|
15.0%
3/20 • Number of events 3 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Nervous system disorders
Somnolence
|
8.3%
2/24 • Number of events 2 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
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.
|
12.5%
3/24 • Number of events 3 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
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.
|
12.5%
3/24 • Number of events 3 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
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.
|
15.0%
3/20 • Number of events 4 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
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
|
4.2%
1/24 • Number of events 1 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
0.00%
0/24 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
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.
|
4.2%
1/24 • Number of events 1 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
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.
|
25.0%
5/20 • Number of events 5 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
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%
0/24 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
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.
|
12.5%
3/24 • Number of events 3 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
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.
|
4.2%
1/24 • Number of events 1 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
0.00%
0/20 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
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
|
8.3%
2/24 • Number of events 2 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
0.00%
0/24 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
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.
|
4.2%
1/24 • Number of events 1 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
0.00%
0/20 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
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.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal Pain
|
4.2%
1/24 • Number of events 1 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
0.00%
0/24 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
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%
2/24 • Number of events 2 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
0.00%
0/20 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
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.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
4.2%
1/24 • Number of events 1 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
0.00%
0/24 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
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.
|
4.2%
1/24 • Number of events 1 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
0.00%
0/20 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
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
Diarrhoea
|
0.00%
0/24 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
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.
|
4.2%
1/24 • Number of events 1 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
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.
|
4.2%
1/24 • Number of events 1 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
0.00%
0/20 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Gastrointestinal disorders
Dry Mouth
|
0.00%
0/24 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
0.00%
0/24 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
0.00%
0/24 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
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.
|
10.0%
2/20 • Number of events 2 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
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
Feeling Cold
|
0.00%
0/24 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
0.00%
0/24 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
0.00%
0/24 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
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.
|
10.0%
2/20 • Number of events 2 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
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
Feeling Drunk
|
0.00%
0/24 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
0.00%
0/24 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
0.00%
0/24 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
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.
|
10.0%
2/20 • Number of events 2 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
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.
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.00%
0/24 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
0.00%
0/24 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
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.
|
4.2%
1/24 • Number of events 1 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
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.
|
5.0%
1/20 • Number of events 1 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/24 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
0.00%
0/24 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
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.
|
4.2%
1/24 • Number of events 1 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
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.
|
5.0%
1/20 • Number of events 1 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
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.
|
|
Immune system disorders
Seasonal Allergy
|
0.00%
0/24 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
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.
|
4.2%
1/24 • Number of events 1 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
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.
|
4.2%
1/24 • Number of events 1 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
0.00%
0/20 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
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.
|
|
Eye disorders
Vision Blurred
|
0.00%
0/24 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
0.00%
0/24 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
0.00%
0/24 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
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.
|
10.0%
2/20 • Number of events 2 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/24 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
0.00%
0/24 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
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.
|
4.2%
1/24 • Number of events 1 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
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.
|
5.0%
1/20 • Number of events 1 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
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
Dissociation
|
0.00%
0/24 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
0.00%
0/24 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
0.00%
0/24 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
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.
|
75.0%
15/20 • Number of events 15 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 14 days after last dose in Treatment Period 4 (up to Day 48)
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