Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
TAK-935 · 8 trials · 7 indications
Seizure frequency per 28 days is defined as total number of seizures (convulsive seizures for DS, drop seizures for LGS) reported during the period divided by number of days during the period seizures were assessed multiplied by 28. Percent change from Baseline is defined as (frequency of seizures per 28 days during maintenance period - frequency of seizures per 28 days at baseline) divided by frequency of seizures per 28 days at baseline multiplied by 100. Negative percent change from Baseline indicates improvement.
Bioavailability is defined as the proportion of a drug which enters the circulation when introduced into the body and so is able to have an active effect. Percent absolute bioavailability, calculated for plasma TAK-935 as \[Actual Dose (IV) x Area Under the Concentration-time Curve from Time 0 to Infinity {AUCinf} (oral)\] / \[Actual Dose (oral) x AUCinf (IV)\] x 100.
Renal clearance (CLr) is the volume of plasma entering the kidney that is completely cleared of drug per unit of time.
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
CH24H brain enzyme occupancy was obtained by graphical analysis of global occupancy plot. Global occupancy plot was calculated as: total volume of distribution \[VT\] (Baseline) - VT (Day 1) = Occupancy (Day 1) \* (VT \[Baseline\] - non-displaceable volume of distribution \[VND\]), where VT (Baseline) and VT (Day 1) are the total distribution volumes obtained at Baseline and after TAK-935 administration, respectively and VND is the non-displaceable volume of distribution. The occupancy is determined as the slope of the linear regression of the plot, and the VND as the x-intercept. Data was reported only for TAK-935 600 mg because only first two participants were analyzed at 45 minutes post-TAK-935 dose.
CH24H brain enzyme occupancy was obtained by graphical analysis of global occupancy plot. Global occupancy plot was calculated as: VT (Baseline) - VT (Day 1) = Occupancy (Day 1) \* (VT \[Baseline\] - VND), where VT (Baseline) and VT (Day 1) are the total distribution volumes obtained at Baseline and after TAK-935 administration, respectively and VND is the non-displaceable volume of distribution. The occupancy is determined as the slope of the linear regression of the plot, and the VND as the x-intercept.
CH24H brain enzyme occupancy was obtained by graphical analysis of global occupancy plot. Global occupancy plot was calculated as: VT (Baseline) - VT (Day 1) = Occupancy (Day 1) \* (VT \[Baseline\] - VND), where VT (Baseline) and VT (Day 1) are the total distribution volumes obtained at Baseline and after TAK-935 administration, respectively and VND is the non-displaceable volume of distribution. The occupancy is determined as the slope of the linear regression of the plot, and the VND as the x-intercept. Data was reported only for TAK-935 600 mg because only first two participants were analyzed at 10 hour post-TAK-935 dose.
CH24H brain enzyme occupancy was obtained by graphical analysis of global occupancy plot. Global occupancy plot was calculated as: VT (Baseline) - VT (Day 1) = Occupancy (Day 1) \* (VT \[Baseline\] - VND), where VT (Baseline) and VT (Day 1) are the total distribution volumes obtained at Baseline and after TAK-935 administration, respectively and VND is the non-displaceable volume of distribution. The occupancy is determined as the slope of the linear regression of the plot, and the VND as the x-intercept.
The percentage of participants with any markedly abnormal standard safety laboratory values (hematology, serum chemistries, and urinalysis) collected during the treatment period.
The percentage of participants with any markedly abnormal vital signs (oral temperature, respiration rate, pulse, and blood pressure) collected during the treatment period.
The percentage of participants with any markedly abnormal criteria for standard 12-lead ECG measured collected during the treatment period.
| Arm | Type | Description |
|---|---|---|
| Placebo | PLACEBO_COMPARATOR | TAK-935 placebo-matching tablets, orally or via gastrostomy tube (G-tube)/percutaneous endoscopic gastrostomy (PEG), twice a day (BID) up to Week 20. |
| TAK-935 | EXPERIMENTAL | TAK-935 tablets orally or via G-tube/PEG tube, BID. Participants weighing \<60 kg received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20. |
| Part 1, Cohort 1; TAK-935 200 mg | EXPERIMENTAL | Part 1, Cohort 1; TAK-935 200 mg, tablets, orally once on Days 1 in fasted state. |
| Part 1, Cohort 2; TAK-935 600 mg | EXPERIMENTAL | Part 1, Cohort 2; TAK-935 600 mg, tablets, orally once on Days 1 in fasted state. |
| Part 1, Cohort 3; TAK-935 1200 mg | EXPERIMENTAL | Part 1, Cohort 3; TAK-935 1200 mg, tablets, orally once on Days 1 in fasted state. |
| Part 1, Cohort 1-3; Placebo | PLACEBO_COMPARATOR | Part 1, Cohort 1-3; TAK-935 placebo-matching tablets, orally once on Days 1 in fasted state. |
| Part 2, Cohort 4: TAK-935 100 mg | EXPERIMENTAL | Part 2, Cohort 4: TAK-935 100 mg, tablets, orally twice on Days 1-7 in fasted state with multiple doses with titration. |
| Part 2, Cohort 4: TAK-935 200 mg | EXPERIMENTAL | Part 2, Cohort 4: TAK-935 200 mg, tablets, orally twice on Days 8-14 in fasted state with multiple doses with titration. |
| Part 2, Cohort 4: TAK-935 300 mg | EXPERIMENTAL | Part 2, Cohort 4: TAK-935 300 mg, tablets, orally twice on Days 15-21 in fasted state with multiple doses with titration. |
| Part 2, Cohort 4: Placebo | PLACEBO_COMPARATOR | Part 2, Cohort 4: TAK-935 placebo-matching tablets, orally twice on Days 1-21 in fasted state. |
| TAK-935 300 mg + [14C]TAK-935 50 μg + [14C]TAK-935 300 mg | EXPERIMENTAL | TAK-935 3×100 mg, tablets, orally, once on Day 1, followed by \[14C\]TAK-935 50 micrograms (μg) \[approximately 1 μCi\], IV infusion, once on Day 1 of Treatment Period 1, followed by a Washout Period of 7 days, further followed by \[14C\]TAK-935 300 mg (approximately 100 μCi) solution, orally, once on Day 1 of Treatment Period 2. |
| Part 1: Placebo | PLACEBO_COMPARATOR | TAK-935 matching-placebo tablets, orally or through gastrostomy tube (G-tube)/ percutaneous endoscopic gastrostomy (PEG) tube, twice daily (BID) from Days 1 to 30 in dose titration period. |
| Part 1: TAK-935 | EXPERIMENTAL | TAK-935 100 mg, tablet, orally or through G-tube/PEG tube, BID from Days 1 to 10 followed by TAK-935 100 mg tablets x2, orally or through G-tube/PEG tube, BID from Days 11 to 20 followed by TAK-935 100 mg tablets x3, orally or through G-tube/PEG tube, BID from Days 21 to 30 in dose titration period. The dose of TAK-935 was escalated or de-escalated during Part 1 as per investigator's discretion. |
| Part 2: TAK-935 | EXPERIMENTAL | TAK-935 100 mg tablets x2, orally or through G-tube/PEG tube, BID from Days 31 to 40 followed by TAK-935 100 mg tablets x1, x2 or x3, orally or through G-tube/PEG tube, BID from Days 31 to Day 85 as per investigator's discretion in the maintenance period. At the end of Part 2, the dose of TAK-935 was de-escalated until discontinuation. |
| TAK-935 300 mg (Tablets Fed+Tablets Fasted+Solution Fasted) | EXPERIMENTAL | TAK-935 300 mg, tablets, orally, 30 minutes after a high-fat meal on Day 1 of Intervention Period 1, followed by a washout period of at least 3 days, further followed by TAK-935 300 mg, tablets, orally, under fasted state on Day 1 of Intervention Period 2, followed by a washout period of at least 3 days, further followed by TAK-935 300 mg, solution, orally, in fasted state on Day 1 of Intervention Period 3. |
| TAK-935 300 mg (Tablets Fasted+Solution Fasted+Tablets Fed | EXPERIMENTAL | TAK-935 300 mg, tablets, orally under fasted state on Day 1 of Intervention Period 1, followed by a washout period of at least 3 days, further followed by TAK-935 300 mg, solution, orally, in fasted state on Day 1 of Intervention Period 2, followed by a washout period of at least 3 days, further followed by TAK-935 300 mg tablets, orally, 30 minutes after high-fat meal on Day 1 of Intervention Period 3. |
| TAK-935 300 mg (Solution Fasted+Tablets Fed+Tablets Fasted) | EXPERIMENTAL | TAK-935 300 mg, solution, orally, in fasted state on Day 1 of Intervention Period 1, followed by washout period of at least 3 days, further followed by TAK-935 300 mg, tablets, orally, 30 minutes after a high-fat meal on Day 1 of Intervention Period 2, followed by washout period of at least 3 days, further followed by TAK-935 300 mg, tablets, orally, under fasted state on Day 1 of Intervention Period 3. |
| Part 1, Cohort 1: TAK-935 100 mg QD | EXPERIMENTAL | TAK-935 100 milligram (mg), solution, orally, once daily (QD) or TAK-935 placebo-matching solution, orally, QD for up to 14 days. |
| Part 1, Cohort 2: TAK-935 300 mg QD | EXPERIMENTAL | TAK-935 300 mg, solution, orally, QD or TAK-935 placebo-matching solution, orally, QD for up to 14 days. |
| Part 1, Cohort 3: TAK-935 300 mg BID | EXPERIMENTAL | TAK-935 300 mg, solution, orally, twice daily (BID) or TAK-935 placebo-matching solution, orally, BID for up to 10 days. |
| Part 1, Cohort 4: TAK-935 600 mg QD | EXPERIMENTAL | TAK-935 600 mg, solution, orally, QD or TAK-935 placebo-matching solution, orally, QD for up to 10 days. |
| Part 1, Cohort 5: TAK-935 400 mg QD | EXPERIMENTAL | TAK-935 400 mg, solution, orally, QD or TAK-935 placebo-matching solution, orally, QD for up to 14 days. |
| Part 2, Cohort 6: TAK-935 Dose 1 | EXPERIMENTAL | TAK-935 first decided dose as determined from other TAK-935 trials and Cohorts 1 to 4 of Part 1, solution, orally, QD or TAK-935 placebo-matching solution, orally, QD for up to 14 days. |
| Part 2, Cohort 7: TAK-935 Dose 2 | EXPERIMENTAL | TAK-935 second decided dose as determined from other TAK-935 trials and Cohorts 1 to 4 of Part 1, solution, orally, QD or TAK-935 placebo-matching solution, orally, QD for up to 14 days. |
| Cohort 1: TAK-935 15 mg | EXPERIMENTAL | TAK-935 15 mg solution, orally, once, on Day 1. |
| Cohort 2: TAK-935 50 mg | EXPERIMENTAL | TAK-935 50 mg solution, orally, once, on Day 1. |
| Cohort 3: TAK-935 200 mg | EXPERIMENTAL | TAK-935 200 mg solution, orally, once, on Day 1. |
| Cohort 4: TAK-935 600 mg | EXPERIMENTAL | TAK-935 600 mg solution, orally, once, on Day 1. |
| Cohort 5: TAK-935 900 mg | EXPERIMENTAL | TAK-935 900 mg solution, orally, once, on Day 1. |
| Cohort 6: TAK-935 1350 mg | EXPERIMENTAL | TAK-935 1350 mg solution, orally, once, on Day 1. |
| Cohorts 1-6: Placebo | PLACEBO_COMPARATOR | TAK-935 placebo-matching solution, orally, once, on Day 1. |
| Name | Type | Description |
|---|---|---|
| TAK-935 | DRUG | TAK-935 tablets or mini-tablets. |
| Placebo | DRUG | TAK-935 placebo-matching tablets or mini-tablets. |
| TAK-935 Oral Tablet | DRUG | TAK-935 tablet |
| [14C]TAK-935 IV Infusion | DRUG | \[14C\]TAK-935 IV infusion |
| [14C]TAK-935 Oral Solution | DRUG | \[14C\]TAK-935 oral solution |
| TAK-935 Tablets | DRUG | Tablets |
| TAK-935 Oral Solution | DRUG | Oral solution |
| [18F]MNI-792 (tracer) | DRUG | \[18F\]MNI-792 injection. |
Inclusion Criteria: 1. Male and female participants aged greater than or equal to (\>=) 2 and less than or equal to (\<=) 17 years 2. Clinical diagnosis of DS or LGS 3. Weight of \>=10 kilogram (kg) at the Screening visit 4. Currently taking 1 to 4 anti-epileptic drugs (AEDs) at a stable dose 5. Fa...
TAK-935 is an investigational small molecule being studied for use in developmental and/or epileptic encephalopathies and epilepsy. It has been evaluated in Phase 1 clinical trials, including as an adjunctive therapy in participants with developmental and/or epileptic encephalopathies. TAK-935 is not approved and remains in clinical development.
TAK-935 is being developed by Takeda Pharmaceutical Company Limited, which trades under the ticker TAK. The company has sponsored multiple Phase 1 clinical trials of the drug in the United States and Japan.
TAK-935 is in Phase 1 clinical development. All completed trials of TAK-935 are Phase 1 studies, including trials in healthy volunteers and in patients with developmental and/or epileptic encephalopathies. The drug is investigational and has not been approved by regulatory authorities.
TAK-935 has been studied in several completed Phase 1 trials, including NCT02497235, a positron emission tomography study measuring target occupancy; NCT02906813, a bioavailability and food effect study; NCT03166215, a study as adjunctive therapy in developmental and/or epileptic encephalopathies; and NCT04461483, a study in healthy Japanese participants.
TAK-935 is also known as soticlestat. The drug has been investigated under both names in clinical trials for epilepsy and developmental and/or epileptic encephalopathies. It is an investigational small molecule being developed by Takeda Pharmaceutical Company Limited.