Clinical trial NCT02716987
Conditions: Healthy
Keywords: Drug therapy
Sponsor: Neurocrine Biosciences
Start date: 2016-03-21; Completion date: 2016-08-30
Enrollment: 20 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to determine the relationship between TAK-831 dose, plasma exposure, extent and duration of brain D-amino acid oxidase (DAO) enzyme occupancy following single oral dosing of TAK-831 in healthy participants.

Detailed description:
The drug being tested in this study is called TAK-831. TAK-831 is a highly selective and potent inhibitor of DAO, a peroxisomal enzyme active towards neutral D-amino acids which potentially effects cerebellar dysfunction. This study will look at the relationship between TAK-831 plasma exposure and the extent and duration of brain DAO enzyme occupancy after single oral dosing of TAK-831 in healthy male participants using \[18F\]PGM299 radioactive tracer injection and PET imaging.

The study will enroll up to 22 participants in two different sets. Up to 16 participants will be enrolled in Set A. Within that total, up to 5 dose levels of TAK-831 may be evaluated, with up to 6 participants per dose level, although typically, there will be 2 to 3 participants per dose level. All participants in Set A will also receive up to 3 doses of \[18F\]PGM299. Up to 6 participants will be enrolled in Set B. All participants in Set B will be assigned to single treatment group to receive 2 doses of \[18F\]PGM299.

All participants in Set A will be asked to take single oral dose of TAK-831 suspension on Day 1. In Set A, each of the participant will receive a maximum of 3 PET scans with \[18F\]PGM299; 1 at baseline 2 following a single oral dose of TAK-831 on Days 1 and 2. In Set B, each of the participant will receive 2 PET scans with \[18F\]PGM299 on Days 1 and 10. Set B will be conducted after the confirmation of blockade of \[18F\]PGM299 binding by TAK-831 in 2 to 4 participants of Set A.

This multi-center trial will be conducted in the United Kingdom. The overall time to participate in this study is 62 days. Participants in Set A will make 4 visits to the clinic, and participants in Set B will make 3 visits to the clinic and all will be contacted by telephone on Day 15 (Set A) and Day 12 (Set B) of treatment period for a follow-up assessment.

Arms: arm 1: TAK-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. arm 2: TAK-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. arm 3: TAK-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. arm 4: TAK-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. arm 5: \[18F\]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: intervention 1: TAK-831 intervention 2: [18F]PGM299
Intervention descriptions: intervention 1: TAK-831 oral suspension. intervention 2: \[18F\]PGM299 injection

Protocol documents: