Clinical trial NCT02566759
Conditions: Schizophrenia, Cerebellar Ataxia
Keywords: Drug therapy
Sponsor: Neurocrine Biosciences
Start date: 2015-09-23; Completion date: 2016-07-12
Enrollment: 110 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to determine the safety, tolerability and pharmacokinetics (PK) of single and multiple rising doses of TAK-831 in healthy participants.

Detailed description:
The drug being tested in this study is called TAK-831. TAK-831 is being tested to treat participant who have schizophrenia and cerebellar ataxia. This study will look at the PK, safety and tolerability of TAK-831 in healthy participants. The study will enroll approximately 120 participants. The study will include 4 parts: Part 1 (single-rising dose \[SRD\]), Part 2 (SRD/multiple-rising dose \[MRD\]), Part 3 (MRD) and Part 4 (relative bioavailability study). Participants will be randomly assigned (by chance, like flipping a coin) to receive either active drug TAK-831 or placebo which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need):

* Part 1, Cohort 1: single dose of TAK-831 100 mg
* Part 1, Cohort 2: single dose of TAK-831 250 mg
* Part 1, Cohort 3: single dose of TAK-831 500 mg
* Part 1, Cohort 4: single dose of TAK-831 30 mg
* Part 1, Cohort 5: single dose of TAK-831 750 mg
* Part 1, Cohort 6: single dose of TAK-831 10 mg
* Part 2, Cohort 1: single dose of TAK-831 30 mg
* Part 2, Cohort 2: single dose of TAK-831 100 mg
* Part 2, Cohort 3: single dose of TAK-831 200 mg
* Part 2, Cohort 4: single dose of TAK-831 400 mg
* Part 3, Cohort 1: TAK-831 400 mg
* Part 4: TAK-831 100 mg (Tablet Fasted + Tablet Fed + Suspension Fasted)
* Part 4: TAK-831 100 mg (Tablet Fed + Tablet Fasted + Suspension Fasted)
* Part 4: TAK-831 100 mg (Suspension Fasted+ Tablet Fed + Tablet Fasted)

Dosing with TAK-831 will progress into study Part 2, 3 and 4, only after review of all available safety, tolerability, and PK data collected in Cohorts 1 to 6 of the Study Part 1. This single center trial will be conducted in the United Kingdom. The overall time to participate in this study is approximately up to 58 days. Participants will be admitted in the clinic for the up to 20 days, and will be contacted by telephone 14 days after last dose of study drug for a follow-up assessment.

The study was terminated by Takeda due to the discomfort observed in the study participants from the CSF collection procedure in Part 3 of the study, hence it is was not feasible to collect further CSF samples that were required to meet the exploratory objectives of the study. Part 1, 2 and 4 of the study were completed as planned.

Arms: arm 1: TAK-831 100 milligram (mg), suspension, orally or TAK-831 placebo-matching suspension, orally, once on Day 1. arm 2: TAK-831 250 mg, suspension, orally or TAK-831 placebo-matching suspension, orally, once on Day 1. arm 3: TAK-831 500 mg, suspension, orally or TAK-831 placebo-matching suspension, orally, once on Day 1. arm 4: TAK-831 30 mg, suspension, orally or TAK-831 placebo-matching suspension, orally, once on Day 1. arm 5: TAK-831 750 mg, suspension, orally or TAK-831 placebo-matching suspension, orally, once on Day 1. arm 6: TAK-831 10 mg, suspension, orally or TAK-831 placebo-matching suspension, orally, once on Day 1. arm 7: TAK-831 30 mg, suspension, orally or TAK-831 placebo-matching suspension, orally, once on Day 1 and once daily from Days 4 to 16. arm 8: TAK-831 100 mg, suspension, orally or TAK-831 placebo-matching suspension, orally, once on Day 1 and once daily from Days 4 to 16. arm 9: TAK-831 200 mg, suspension, orally or TAK-831 placebo-matching suspension, orally, once on Day 1 and once daily from Days 4 to 16. arm 10: TAK-831 400 mg, suspension, orally or TAK-831 placebo-matching suspension, orally, once on Day 1 and once daily from Days 4 to 16. arm 11: TAK-831 400 mg, suspension, orally or TAK-831 placebo-matching suspension, orally, once daily from Days 1 to 14. arm 12: TAK-831 100 mg, tablet, orally, once after an overnight fast of at least 10 hours on Day 1 of Period 1, followed by a washout interval of 5 days, further followed by TAK-831 100 mg, tablet, orally, once 30 minutes after starting a high fat meal on Day 1 of Period 2, followed by a washout interval of 5 days, further followed by TAK-831 100 mg, suspension, orally, once after an overnight fast of at least 10 hours on Day 1 of Period 3. arm 13: TAK-831 100 mg, tablet, orally, once 30 minutes after starting a high fat meal on Day 1 of Period 1, followed by a washout interval of 5 days, further followed by TAK-831 100 mg, tablet, orally, once after an overnight fast of at least 10 hours on Day 1 of Period 2, followed by a washout interval of 5 days, further followed by TAK-831 100 mg, suspension, orally, once after an overnight fast of at least 10 hours on Day 1 of Period 3. arm 14: TAK-831 100 mg, suspension, orally, once after an overnight fast of at least 10 hours on Day 1 of Period 1, followed by a washout interval of 5 days, further followed by TAK-831 100 mg, tablet, orally, once 30 minutes after starting a high fat meal on Day 1 of Period 2, followed by a washout interval of 5 days, further followed by TAK-831 100 mg, tablet, orally, once after an overnight fast of at least 10 hours on Day 1 of Period 3.
Interventions: intervention 1: TAK-831 Oral Suspension intervention 2: TAK-831 Placebo intervention 3: TAK-831 Tablet
Intervention descriptions: intervention 1: TAK-831 oral suspension. intervention 2: TAK-831 placebo-matching oral suspension. intervention 3: TAK-831 tablet.

Protocol documents: