Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
TAK-063 · 4 trials · 4 indications
PANSS assesses the positive symptoms, negative symptoms, and general psychopathology specifically associated with schizophrenia. The scale consists of 30 items. Each item is rated on a scale from 1 (symptom not present) to 7 (symptoms extremely severe). The sum of the 30 items is defined as the PANSS total score and ranges from 30 to 210; higher score indicates greater severity. Least square mean and standard error values were determined using a mixed model for repeated measures (MMRM). A negative change from Baseline indicates improvement.
Volume of tissue distribution (Vt) values will be estimated by several quantitative methods for each positron emission tomography (PET) scan. Based on the change in Vt before and after TAK-063 administration, PDE10A occupancy will be calculated. PET scan #2 in the Pilot Cohort and PET scan #1 in the Main Cohort will be used as a baseline for the occupancy calculation. Occupancy is reported for putamen only.
Ketamine model was used to enhance the sensitivity to detect an effect of phosphodiesterase 10a (PDE10a) inhibition by TAK-063 by ketamine using neuroimaging battery tests. Ketamine induced robust blood oxygen level-dependent(BOLD) functional magnetic resonance imaging(fMRI) response while maintaining minimal accompanying psychotomimetic symptoms. The regions of interest include:left anterior cingulate cortex,right anterior cingulate cortex,left posterior cingulate cortex,right posterior cingulate cortex,left striatum,right striatum,left amygdala,right amygdala,left substantia nigra,right substantia nigra,left thalamus,right thalamus,left ventrolateral prefrontal cortex,right ventrolateral prefrontal cortex,left dorsolateral prefrontal cortex,right dorsolateral prefrontal cortex,left hippocampus,right hippocampus,left subgenual cingulate/Ba25,right subgenual cingulate/Ba25,left paracingulate gyrus/Ba32, and right paracingulate gyrus/Ba32.
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
The percentage of participants with any markedly abnormal standard safety laboratory values, including hematology, serum chemistries, and urinalysis, during the treatment period.
The percentage of participants who meet markedly abnormal criteria for vital signs, including oral body temperature, respiration rate, pulse, and resting blood pressure and after standing
The percentage of participants who meet markedly abnormal criteria specified by the protocol and statistical analysis plan during the treatment period.
| Arm | Type | Description |
|---|---|---|
| TAK-063 20 mg | EXPERIMENTAL | TAK-063 20 mg, tablets, orally, once daily for up to 6 weeks. Dose may be titrated down to 10 mg/day, if intolerable. |
| Placebo | PLACEBO_COMPARATOR | TAK-063 matching-placebo tablets, orally, once daily for up to 6 weeks. |
| Pilot Cohort: [^11C]T-773 + TAK-063 | EXPERIMENTAL | \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenous (IV), once on Days 1 and 2 prior to PET scans and TAK-063 30 mg or 1000 mg, tablets, orally, once on Day 2 and after PET scan #2 and prior to PET scan #3 and \[\^11C\]T-773 IV after TAK-063 and prior to PET scan #3 on Day 2. |
| Main Cohort: TAK-063 + [^11C]T-773 | EXPERIMENTAL | TAK-063 3 to 100 mg, tablets, orally, once, on Day 1, and \[\^11C\]T-773 \<8 μg; 400MBq ± 10%, intravenously (IV), prior to PET scans, twice on Day 1 (before and after administration of TAK-063) and once on Day 2 . |
| Sequence 1: Placebo + TAK-063 3 mg + TAK-063 30 mg | EXPERIMENTAL | Period 1, Day 1: TAK-063 placebo-matching tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 2, Day 1: TAK-063 3 milligram (mg), orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 3, Day 1: TAK-063 30 mg tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight. Period 1 \& 2 are followed by 7 day washout period. |
| Sequence 2: TAK-063 3 mg + TAK-063 30 mg + Placebo | EXPERIMENTAL | Period 1, Day 1: TAK-063 3 mg tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 2, Day 1: TAK-063 30 mg tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 3, Day 1: TAK-063 placebo-matching tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight. Period 1 \& 2 are followed by 7 day washout period. |
| Sequence 3: TAK-063 30 mg + Placebo + TAK-063 3 mg | EXPERIMENTAL | Period 1, Day 1: TAK-063 30 mg tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 2, Day 1: TAK-063 placebo-matching tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 3, Day 1: TAK-063 3 mg tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight. Period 1 \& 2 are followed by 7 day washout period. |
| Sequence 4: Placebo + TAK-063 3 mg + TAK-063 300 mg | EXPERIMENTAL | Period 1, Day 1: TAK-063 placebo-matching tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 2, Day 1: TAK-063 3 mg tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 3, Day 1: TAK-063 300 mg (participants enrolled before protocol amendment 3) or 10 mg (participants enrolled after protocol amendment 3), tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight. Period 1 \& 2 are followed by 7 day washout period. |
| Sequence 5: TAK-063 3 mg + TAK-063 300 mg+ Placebo | EXPERIMENTAL | Period 1, Day 1: TAK-063 3 mg tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 2, Day 1: TAK-063 300 mg (participants enrolled before protocol amendment 3) or 10 mg (participants enrolled after protocol amendment 3), tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 3, Day 1: TAK-063 placebo-matching tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight. Period 1 \& 2 are followed by 7 day washout period |
| Sequence 6: TAK-063 300 mg + Placebo + TAK-063 3 mg | EXPERIMENTAL | Period 1, Day 1: TAK-063 300 mg (participants enrolled before protocol amendment 3) or 10 mg (participants enrolled after protocol amendment 3), tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 2, Day 1: TAK-063 placebo-matching tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 3, Day 1: TAK-063 3 mg tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight. Period 1 \& 2 are followed by 7 day washout period. |
| Sequence 7: Placebo + TAK-063 30 mg + TAK-063 300 mg | EXPERIMENTAL | Period 1, Day 1: TAK-063 placebo-matching tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight: Period 2, Day 1: TAK-063 30 mg tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 3, Day 1: TAK-063 300 mg (participants enrolled before protocol amendment 3) or 10 mg (participants enrolled after protocol amendment 3), tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight. Period 1 \& 2 are followed by 7 day washout period |
| Sequence 8: TAK-063 30 mg + TAK-063 300 mg + Placebo | EXPERIMENTAL | Period 1, Day 1: TAK-063 30 mg tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 2, Day 1: TAK-063 300 mg (participants enrolled before protocol amendment 3) or 10 mg (participants enrolled after protocol amendment 3), tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 3, Day 1: TAK-063 placebo-matching tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight. Period 1 \& 2 are followed by 7 day washout period. |
| Sequence 9: TAK-063 300 mg + Placebo + TAK-063 30 mg | EXPERIMENTAL | Period 1, Day 1: TAK-063 300 mg (participants enrolled before protocol amendment 3) or 10 mg (participants enrolled after protocol amendment 3), tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 2, Day 1: TAK-063 placebo-matching tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight; Period 3, Day 1: TAK-063 30 mg tablets, orally, single dose and ketamine, intravenous administration according to a bolus infusion adjusted to the participant's weight. Period 1 \& 2 are followed by 7 day washout period |
| TAK-063 3 mg | EXPERIMENTAL | TAK-063 3 mg, tablets, orally, once daily for 7 days. |
| TAK-063 10 mg | EXPERIMENTAL | TAK-063 10 mg, tablets, orally, once daily for 7 days. |
| TAK-063 30 mg | EXPERIMENTAL | TAK-063 30 mg, tablets, orally, once daily for 7 days. |
| TAK-063 100 mg | EXPERIMENTAL | TAK-063 100 mg, tablets, orally, once daily for 7 days. |
| Name | Type | Description |
|---|---|---|
| TAK-063 20 mg | DRUG | TAK-063 tablet. |
| Placebo | DRUG | TAK-063 matching-placebo tablet. |
| TAK-063 | DRUG | TAK-063 tablets |
| [^11C]T-773 | DRUG | \[\^11C\]T-773 IV solution |
| Ketamine | DRUG | Ketamine intravenous administration. |
| TAK-063 Placebo | DRUG | TAK-063 placebo-matching tablets |
Inclusion Criteria: 1. Is capable of understanding and complying with protocol requirements. 2. The participants or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation o...
TAK-063 is an investigational small molecule being studied for schizophrenia, ketamine-induced brain activity changes, and psychotic-like symptoms. It has been evaluated in healthy volunteers and in participants with stable schizophrenia or an acute exacerbation of schizophrenia. TAK-063 is not approved and remains in clinical development.
TAK-063 is being developed by Takeda Pharmaceutical Company Limited, which trades under the ticker TAK. The company has sponsored clinical trials of TAK-063 in the United States.
TAK-063 is in Phase 2 clinical development. It has completed Phase 1 trials and one Phase 2 trial. TAK-063 is investigational and has not been approved by regulatory authorities.
TAK-063 has completed four clinical trials: NCT01879722, NCT01892189, NCT02370602, and NCT02477020. These include Phase 1 studies in healthy volunteers and schizophrenia patients, a PET study measuring phosphodiesterase10A occupancy, and a Phase 2 efficacy and safety study in schizophrenia.
TAK-063 is not the same as T-773. T-773 is a separate compound used in a positron emission tomography (PET) study to determine phosphodiesterase10A occupancy by TAK-063. The study used [^11C]T-773 as a radiotracer to measure how TAK-063 binds to its target.