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| ID | Type | Description | Link |
|---|---|---|---|
| U1111-1224-5430 | Other Identifier | WHO | |
| 2018-004206-26 | EudraCT Number | ||
| NL68394.056.18 | Registry Identifier | CCMO |
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| Name | Class |
|---|---|
| Takeda | INDUSTRY |
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The primary purpose of this study is to determine whether TAK-653, in comparison to placebo, increases CNS excitability, assessed with TMS-evoked motor-evoked potential (MEP) in healthy participants.
The drug being tested in this study is called TAK-653. This study is designed to evaluate the central pharmacodynamic activity of TAK-653 using TMS. The study will enroll approximately 24 participants to yield 22 participants that complete treatment periods 1, 2, and 3. Participants will be randomly assigned to 1 of the 6 sequences to receive TAK-653 0.5 mg low dose or TAK-653 6 mg high dose or Placebo in double-blind treatment periods 1, 2, and 3, followed by Ketamine 0.5 mg/kg in open-label Treatment period 4.
All participants will receive one dose of TAK-653 (0.5 or 6 mg), or Placebo or Ketamine on Day 1 of each treatment period.
This single center trial will be conducted in the Netherlands. The overall time to participate in this study is 15 weeks. Participants will make 5 visits to the clinic. A washout period of minimum 10 days will be maintained between the doses in treatment periods 1 to 3. Follow-up phone call will be made on Day 14.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| TAK-653 6 mg + TAK-653 0.5 mg + Placebo + Ketamine 0.5 mg/kg | Experimental | TAK-653 6 milligram (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 milligram per kilogram (mg/kg), intravenous infusion, once on Day 1 of Treatment Period 4. A washout of 10 to 15 days will be maintained between each treatment period. |
|
| TAK-653 6 mg + Placebo + TAK-653 0.5 mg + Ketamine 0.5 mg/kg | Experimental | 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, intravenous infusion, once on Day 1 of Treatment Period 4. A washout of 10 to 15 days will be maintained between each treatment period. |
|
| TAK-653 0.5 mg + TAK-653 6 mg + Placebo + Ketamine 0.5 mg/kg | Experimental | 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, intravenous infusion, once on Day 1 of Treatment Period 4. A washout of 10 to 15 days will be maintained between each treatment period. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TAK-653 | Drug | TAK-653 tablets. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 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. | Baseline, 2.5 hours post TAK-653 dose |
| Change From Baseline in Resting Motor Threshold (rMT) Obtained With Single-pulse TMS for TAK-653 at 2.5 Hours Post TAK-653 Dose | 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. | Baseline, 2.5 hours post TAK-653 dose |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Millennium Pharmaceuticals, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CHDR | Leiden | Netherlands |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36153330 | Derived | Dijkstra F, O'Donnell P, Klaassen E, Buhl D, Asgharnejad M, Rosen L, Zuiker R, van Gerven J, Jacobs G. Central nervous system effects of TAK-653, an investigational alpha-amino-3-hydroxy-5-methyl-4-isoxazole receptor (AMPAR) positive allosteric modulator in healthy volunteers. Transl Psychiatry. 2022 Sep 24;12(1):408. doi: 10.1038/s41398-022-02148-w. |
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Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.
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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.
Participants took part in the study at 1 investigative site in Netherlands from 11 February 2019 to 18 June 2019.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Treatment Period 1 (1 Day) |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Apr 4, 2019 | Jun 12, 2020 |
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The study is a randomized, crossover 6 sequence study in Treatment Periods 1, 2, and 3.
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The study is double blind in Treatment Periods 1, 2, and 3 and open-label in Treatment Period 4.
| TAK-653 0.5 mg + Placebo + TAK-653 6 mg + Ketamine 0.5 mg/kg | Experimental | 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, intravenous infusion, once on Day 1 of Treatment Period 4. A washout of 10 to 15 days will be maintained between each treatment period. |
|
| Placebo + TAK-653 0.5 mg + TAK-653 6 mg + Ketamine 0.5 mg/kg | Experimental | 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, intravenous infusion, once on Day 1 of Treatment Period 4. A washout of 10 to 15 days will be maintained between each treatment period. |
|
| Placebo + TAK-653 6 mg + TAK-653 0.5 mg + Ketamine 0.5 mg/kg | Experimental | 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, intravenous infusion, once on Day 1 of Treatment Period 4. A washout of 10 to 15 days will be maintained between each treatment period. |
|
| Placebo | Drug | TAK-653 placebo-matching tablets. |
|
| Ketamine | Drug | Ketamine intravenous infusion. |
|
| Baseline, 2.5 hours post TAK-653 dose |
| 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 | 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. | Baseline, 2.5 hours post TAK-653 dose |
| 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 | 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. | Baseline, 2.5 hours post ketamine dose, and 24 hours post ketamine dose |
| 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 | 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. | Baseline, 2.5 hours post ketamine dose, and 24 hours post ketamine dose |
| FG001 | 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. |
| FG002 | 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. |
| FG003 | 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. |
| FG004 | 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. |
| FG005 | 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. |
| COMPLETED |
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| NOT COMPLETED |
|
| Washout Period 1 (10 Days) |
|
| Treatment Period 2 (1 Day) |
|
| Washout Period 2 (10 Days) |
|
| Treatment Period 3 (1 Day) |
|
| Washout Period 3 (10 Days) |
|
|
| Treatment Period 4 (2 Days) |
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The safety analysis set included all participants who were randomized and received at least 1 dose of study drug. Baseline characteristics data has been presented for overall participants analyzed.
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| ID | Title | Description |
|---|---|---|
| BG000 | All 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Region of Enrollment | Count of Participants | Participants |
| ||||||||||||||||||
| Weight | Mean | Standard Deviation | kilogram (Kg) |
| |||||||||||||||||
| Height | Mean | Standard Deviation | centimeter (cm) |
| |||||||||||||||||
| Body Mass Index (BMI) | Mean | Standard Deviation | kilogram per square meter (kg/m^2) |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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 | 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. | 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. | Posted | Mean | Standard Deviation | microvolt (mcV) | Baseline, 2.5 hours post TAK-653 dose |
|
|
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| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary | Change From Baseline in Resting Motor Threshold (rMT) Obtained With Single-pulse TMS for TAK-653 at 2.5 Hours Post TAK-653 Dose | 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. | 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. | Posted | Mean | Standard Deviation | percentage of maximum stimulator output | Baseline, 2.5 hours post TAK-653 dose |
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| Secondary | 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 | 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. | 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. | Posted | Mean | Standard Deviation | percent inhibition | Baseline, 2.5 hours post TAK-653 dose |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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 | 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. | 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. | Posted | Mean | Standard Deviation | percent inhibition | Baseline, 2.5 hours post TAK-653 dose |
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| Secondary | 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 | 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. | 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. | Posted | Mean | Standard Deviation | percentage of maximum stimulator output | Baseline, 2.5 hours post ketamine dose, and 24 hours post ketamine dose |
|
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| Secondary | 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 | 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. | 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. | Posted | Mean | Standard Deviation | mcV | Baseline, 2.5 hours post ketamine dose, and 24 hours post ketamine dose |
|
|
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.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | TAK-653 placebo-matching tablets, orally, once on Day 1 of Treatment Period 1, 2 or 3 as per assigned treatment sequence. | 0 | 24 | 0 | 24 | 7 | 24 |
| EG001 | 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. | 0 | 24 | 0 | 24 | 9 | 24 |
| EG002 | 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. | 0 | 24 | 0 | 24 | 12 | 24 |
| EG003 | Ketamine 0.5 mg/kg | Ketamine 0.5 mg/kg, infusion, intravenously, once on Day 1 of Treatment Period 4 in all 6 treatment sequences. | 0 | 20 | 0 | 20 | 20 | 20 |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dizziness | Nervous system disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Somnolence | Nervous system disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Oropharyngeal Pain | Respiratory, thoracic and mediastinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Dry Mouth | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Feeling Cold | General disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Feeling Drunk | General disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Seasonal Allergy | Immune system disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Vision Blurred | Eye disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Dissociation | Psychiatric disorders | MedDRA (22.0) | Systematic Assessment |
|
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director | Takeda | 1-877-825-3327 | medicalinformation@tpna.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 29, 2019 | Jun 12, 2020 | SAP_001.pdf |
| ID | Term |
|---|---|
| D007649 | Ketamine |
| ID | Term |
|---|---|
| D003510 | Cyclohexanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
Not provided
Not provided
| Physician Decision |
|
| Unknown or Not Reported |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Change at 2.5 Hours Post TAK-653 Dose |
|
|
| Mixed Models Analysis |
| 0.0269 |
Based on mixed model analysis, with treatment, period, sequence, treatment-by-period interaction as fixed factors, participant within sequence as a random factor, baseline as a covariate. |
| LSM difference |
| 338 |
| Standard Error of the Mean |
| 147 |
| 2-Sided |
| 90 |
| 90.5 |
| 585 |
| Superiority |
| OG002 |
| 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. |
|
|
|
| OG002 | 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. |
|
|
|
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.
| OG002 | 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. |
|
|
|
|
|
| Participants |
|
|