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TAK-831

Phase 2

Friedreich Ataxia | Small molecule | Rare Disease |Neurocrine Biosciences, Inc.|Last Updated: Jun 30, 2021

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Trial Design

RandomizedDouble-BlindPLACEBO_CONTROLLEDDMC
Total Trials1
Total Enrollment67

FDA Designations

No designations recorded

Clinical trial landscape

TAK-831 · 5 trials · 3 indications

Phase 2 1Phase 1 4
NCT03214588Efficacy, Tolerability, and Pharmacokinetics of Multiple Doses of Oral TAK-831 in Adults With Friedreich AtaxiaFriedreich Ataxia
COMPLETED67 Analytics
PHASE2COMPLETED
Efficacy, Tolerability, and Pharmacokinetics of Multiple Doses of Oral TAK-831 in Adults With Friedreich Ataxia
Friedreich AtaxiaUnlock trial analytics

Study Endpoints

Primary Endpoints

Change From Baseline in the Inverse Time to Complete the 9-Hole Peg Test (9-HPT-1)
Baseline and Week 12

The 9-HPT-1 is a measure of timed upper extremity (arm and hand) function and manual dexterity. The participant picks up pegs 1 at a time (9 in total), using 1 hand only, and places them into holes on the board as quickly as possible, in any order until all holes are filled. Then, without pausing, the participant removes the pegs 1 at a time and returns them as quickly as possible. Each participant performs this task twice with each hand separately. Results on both tests are then averaged for an overall task completion time and the inverse transform is performed. A positive change from Baseline indicates improvement. Change from Baseline in 9-HPT-1 was analyzed using mixed model for repeated measures (MMRM) analysis of covariance (ANCOVA) with Baseline 9-HPT-1 as a covariate; pooled site, visit, treatment, and ambulation status (randomization factor) as fixed factors; and treatment-by-visit and Baseline 9-HPT-1-by-visit interactions.

Period 1: Percent Absolute Bioavailability (%F) for TAK-831
Day 1 pre-dose and at multiple time points (up to 96.5 hours) post-dose in Treatment Period 1

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-831 as \[Actual Dose (IV) x AUCinf (oral)\] / \[Actual Dose (oral) x AUCinf (IV)\] x 100.

Period 2: Total Radioactivity Expressed as Cumulative Percentage of Dose of [14C]TAK-831 Eliminated in Urine and Feces Combined [Combined Cum%Dose]
Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
Period 2: Total Radioactivity Expressed as Cumulative Amount of [14C]TAK-831 Eliminated in Urine and Feces Combined (Combined CumAe)
Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
Period 2: Percentage of Administered Radioactive Dose of [14C]TAK-831 Excreted in Urine (Cum%Dose [UR])
Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
Period 2: Percentage of Administered Radioactive Dose of [14C]TAK-831 Excreted in Feces (Cum%Dose [Fe])
Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
Period 2: Cmax: Maximum Observed Plasma Concentration of TAK-831
Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose
Period 2: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of TAK-831
Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
Period 2: t(1/2)z: Terminal Disposition Phase Half-life of TAK-831 in Plasma
Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
Period 2: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity of TAK-831
Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
Period 2: AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration of TAK-831
Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
Period 2: Cmax: Maximum Observed Plasma Radioactivity Concentration
Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
Period 2: Tmax: Time to Reach the Maximum Plasma Radioactivity Concentration (Cmax)
Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
Period 2: t(1/2)z: Terminal Disposition Phase Half-life of Plasma Radioactivity Concentration
Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
Period 2: AUCinf: Area Under the Plasma Radioactivity Concentration-time Curve From Time 0 to Infinity
Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
Period 2: AUClast: Area Under the Plasma Radioactivity Concentration-time Curve From Time 0 to Last Quantifiable Concentration
Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
Period 2: Cmax: Maximum Observed Whole Blood Radioactivity Concentration
Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
Period 2: Tmax: Time to Reach the Maximum Whole Blood Radioactivity Concentration (Cmax)
Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
Period 2: t(1/2)z: Terminal Disposition Phase Half-life of Whole Blood Radioactivity Concentration
Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
Period 2: AUCinf: Area Under the Whole Blood Radioactivity Concentration-time Curve From Time 0 to Infinity
Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
Period 2: AUClast: Area Under the Whole Blood Radioactivity Concentration-time Curve From Time 0 to Last Quantifiable Concentration
Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose in Treatment Period 2
Period 2: CLR: Renal Clearance for TAK-831 in Urine
Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose
Number of Participants Reporting at Least One Treatment-emergent Adverse Event (TEAE)
Cohort 1: Baseline up to Day 23; Cohorts 2-5: Baseline up to Day 31
Number of Participants Reporting at Least One TEAE Related to Laboratory Test Results
Cohort 1: Baseline up to Day 23; Cohorts 2-5: Baseline up to Day 31
Number of Participants Reporting at Least One TEAE Related to Vital Sign
Cohort 1: Baseline up to Day 23; Cohorts 2-5: Baseline up to Day 31
Number of Participants Reporting at Least One TEAE Related to Body Weight
Cohort 1: Baseline up to Day 23; Cohorts 2-5: Baseline up to Day 31
Number of Participants Reporting at Least One TEAE Related to 12-lead Electrocardiogram (ECG) Parameters
Cohort 1: Baseline up to Day 23; Cohorts 2-5: Baseline up to Day 31
Cmax: Maximum Observed Plasma Concentration for TAK-831
Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-831
Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-831
Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan
Set A: Baseline (PET scan 1), 2 hours (PET scan 2) and 26 hours (PET scan 3) post-TAK-831 dose; Set B: Day 1 (PET scan 1) and Day 10 (PET scan 2)
Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan
Set A: Baseline (PET scan 1), 2 hours (PET scan 2) and 26 hours (PET scan 3) post-TAK-831 dose; Set B: Day 1 (PET scan 1) and Day 10 (PET scan 2)
D-amino Acid Oxidase (DAO) Occupancy Estimation in the Cerebellar GM
Set A: Baseline (PET scan 1), 2 hours (PET scan 2) and 26 hours (PET scan 3) post-TAK-831 dose; Set B: Day 1 (PET scan 1) and Day 10 (PET scan 2)

DAO occupancy is calculated as percent difference between baseline and postdose \[18F\]PGM299 BPND for each participant.

Secondary Endpoints

Change From Baseline in the Activities of Daily Living (ADL) Component Score of the Friedreich Ataxia Rating Scale (FARS)
Baseline and Weeks 2, 7 and 12
Change From Baseline in the Inverse Time to Complete the 9-HPT-1
Baseline and Weeks 2 and 7
Change From Baseline in the ADL Component Individual Item Scores
Baseline and Weeks 2, 7 and 12
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Study Design & Arms

AllocationRANDOMIZED
MaskingQUADRUPLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
PlaceboPLACEBO_COMPARATORTAK-831 placebo-matching tablets, orally, twice daily for up to 12 weeks.
TAK-831 75 mgEXPERIMENTALTAK-831 75 mg, tablets, orally, twice daily for up to 12 weeks.
TAK-831 300 mgEXPERIMENTALTAK-831 300 mg, tablets, orally, twice daily for up to 12 weeks.
TAK-831 500 mg + [14C]TAK-831 50 μg + [14C]TAK-831 500 mgEXPERIMENTALTAK-831 500 mg, tablet, orally, once on Day 1, followed by \[14C\]TAK-831 50 micrograms (μg) \[approximately 1 microcurie (μCi)\], infusion, intravenously (IV), once on Day 1 of Treatment Period 1, followed by a washout period of 8 days, further followed by \[14C\]TAK-831 500 mg (approximately 100 μCi), suspension, orally, once under fasted state on Day 1 of Treatment Period 2.
Japanese Cohort 1-A; TAK-831 100 mg + TAK-831 300 mgEXPERIMENTALTAK-831 100 milligrams (mg), tablets, orally, once daily on Day 1, followed by TAK-831 300 mg, tablets, orally, once daily on Day 9 in healthy Japanese participants.
Japanese Cohort 1-B; TAK-831 100 mg + PlaceboEXPERIMENTALTAK-831 100 mg, tablets, orally, once daily on Day 1 followed by TAK-831 matching placebo, tablets, orally, once daily on Day 9 in healthy Japanese participants.
Japanese Cohort 1-C; Placebo + TAK-831 300 mgEXPERIMENTALTAK-831 matching placebo, tablets, orally, once daily on Day 1 followed by TAK-831 300 mg, tablets, orally, once daily on Day 9 in healthy Japanese participants.
Japanese Cohort 2; TAK-831 300 mgEXPERIMENTALTAK-831 300 mg or TAK-831 matching placebo, tablets, orally, once daily on Day 1 followed by TAK-831 300 mg or TAK-831 matching placebo, tablets, orally, once daily from Day 4 to Day 17 in healthy Japanese participants.
Chinese Cohort 3; TAK-831 600 mgEXPERIMENTALTAK-831 600 mg or TAK-831 matching placebo, tablets, orally, once daily on Day 1 followed by TAK-831 600 mg or TAK-831 matching placebo, tablets, orally, once daily from Day 4 to Day 17 in healthy Chinese participants. This cohort is optional and will be decided to run based on the data of Cohorts 1 and 2. The dose will be defined based on the result of Cohort 1 or Cohort 2.
Japanese Cohort 4; TAK-831 600 mgEXPERIMENTALTAK-831 600 mg or TAK-831 matching placebo, tablets, orally, once daily on Day 1 followed by TAK-831 600 mg or TAK-831 matching placebo, tablets, orally, once daily from Day 4 to Day 17 in healthy Japanese participants. This cohort is optional and will be decided to run based on the data of Cohorts 1 and 2. The dose will be defined based on the result of Cohort 1 or Cohort 2.
Japanese Cohort 5; TAK-831EXPERIMENTALTAK-831 50 mg or TAK-831 matching placebo, tablets, orally, once daily on Day 1 followed by TAK-831 50 mg or TAK-831 matching placebo, tablets, orally, once daily from Day 4 to Day 17 in healthy Japanese participants.
TAK-831 400 mg Fasted + TAK-831 400 mg FedEXPERIMENTALTAK-831 400 mg, film-coated tablets, orally under fasted state, once on Day 1 of Intervention Period 1, followed by 7 days washout period, further followed by TAK-831 400 mg, film-coated tablets, orally under fed state, once on Day 1 of Intervention Period 2.
TAK-831 400 mg Fed + TAK-831 400 mg FastedEXPERIMENTALTAK-831 400 mg, film-coated tablets, orally under fed state, once on Day 1 of Intervention Period 1, followed by 7 days washout period, further followed by TAK-831 400 mg, film-coated tablets, orally under fasted state, once on Day 1 of Intervention Period 2.
Set A: TAK-831 100 mgEXPERIMENTALTAK-831 100 milligram (mg), suspension, orally, once on Day 1 and up to 100 megabecquerel (MBq) of Positron Emission Tomography (PET) ligand PGM028299 labeled with \[18F\] (\[18F\]PGM299) with a maximal mass up to 12.5 microgram (mcg), injection, intravenously, prior to PET imaging at Baseline, 2 hours and 26 hours post-TAK-831 dose.
Set A: TAK-831 200 mgEXPERIMENTALTAK-831 200 mg, suspension, orally, once on Day 1 and up to 100 MBq of \[18F\]PGM299 with a maximal mass up to 12.5 mcg, injection, intravenously, prior to PET imaging at Baseline, 2 hours and 26 hours post-TAK-831 dose.
Set A: TAK-831 250 mgEXPERIMENTALTAK-831 250 mg, suspension, orally, once on Day 1 and up to 100 MBq of \[18F\]PGM299 with a maximal mass up to 12.5 mcg, injection, intravenously, prior to PET imaging at Baseline, 2 hours and 26 hours post-TAK-831 dose.
Set A: TAK-831 500 mgEXPERIMENTALTAK-831 500 mg, suspension, orally, once on Day 1 and up to 100 MBq of \[18F\]PGM299 with a maximal mass up to 12.5 mcg, injection, intravenously, prior to PET imaging at Baseline, 2 hours and 26 hours post-TAK-831 dose.
Set B: [18F]PGM299EXPERIMENTAL\[18F\]PGM299 up to 100 MBq (with a maximal mass up to 12.5 mcg), injection, intravenously, prior to PET imaging on Days 1 and 10.

Interventions

NameTypeDescription
TAK-831DRUGTAK-831 tablets
TAK-831 PlaceboDRUGTAK-831 placebo matching tablets
TAK-831 Oral TabletDRUGTAK-831 tablet.
[14C]TAK-831 IV InfusionDRUG\[14C\]TAK-831 IV infusion.
[14C]TAK-831 Oral SuspensionDRUG\[14C\]TAK-831 oral suspension.
PlaceboDRUGTAK-831 Matching Placebo Tablets.
[18F]PGM299DRUG\[18F\]PGM299 injection
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Eligibility Criteria

Age Range18 Years to 55 Years
SexALL
Healthy VolunteersNo
Study Sites6

Key Inclusion Criteria: 1\. Has a genetically-confirmed diagnosis (homozygous for guanine-adenine-adenine \[GAA\] repeat expansions in the frataxin gene \[FXN\] in the affected range of Friedreich ataxia \[FRDA\] or a compound heterozygous expansion with a point mutation or deletion), with an estab...

Countries:United StatesJapanUnited Kingdom
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Frequently asked questions about TAK-831

What is TAK-831 used for?

TAK-831 is an investigational small molecule being studied for the treatment of Friedreich Ataxia, a rare inherited disease that affects the nervous system. It has also been evaluated in healthy volunteers in early-phase clinical trials to assess its safety, tolerability, and pharmacokinetics.

Who makes TAK-831?

TAK-831 is being developed by Neurocrine Biosciences, Inc., a biopharmaceutical company traded on NASDAQ under the ticker symbol NBIX. The company is conducting clinical trials of TAK-831 in the United States and Japan for Friedreich Ataxia and in healthy volunteer studies.

What phase is TAK-831 in?

TAK-831 is in Phase 2 clinical development for Friedreich Ataxia. A Phase 2 trial evaluating its efficacy, tolerability, and pharmacokinetics in adults with Friedreich Ataxia has been completed. The drug is investigational and has not been approved by regulatory authorities.

What clinical trials is TAK-831 in?

TAK-831 has been studied in several completed clinical trials. NCT03214588 is a Phase 2 trial in adults with Friedreich Ataxia. NCT03101293 and NCT03687684 are Phase 1 trials in healthy volunteers in the United States and Japan, respectively. NCT04234672 is a Phase 1 study in healthy male participants.

Is TAK-831 FDA approved?

TAK-831 is not FDA approved. It is an investigational drug that has completed Phase 1 and Phase 2 clinical trials, but it remains in clinical development and has not received marketing authorization from the U.S. Food and Drug Administration or any other regulatory agency.