Study to Determine D-amino Acid Oxidase Brain Enzyme Occupancy of TAK-831 After Single-dose Oral Administration

NCT02716987 | Completed Phase 1 Results

• 4 other identifiers: TAK-831-10032015-004509-17U1111-1176-749315/LO/1916
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (3)

• 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

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

  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)

Secondary Outcomes (10)

• Set A: EC50- Plasma Concentration of TAK-831 That Corresponds to 50 Percent (%) DAO Brain Enzyme Occupancy in Cerebellum

  Set A: Baseline, 2 and 26 hours post-TAK-831 dose

• Set A: Dose of TAK-831 That Corresponds to 50% DAO Brain Enzyme Occupancy in Cerebellum

  Set A: At 2 and 26 hours post-TAK-831 dose

• Set B: Coefficient of Variation (CoV) of [18F]PGM299 Binding in Healthy Human Brain

  Set B: Baseline up to Day 10

• Set A: Plasma Concentrations of TAK-831 During Each Post-TAK-831 Dosing PET Scan Periods

  Set A: Days 1 and 2 At time 0 (at tracer injection), 60 minutes after tracer injection and 120 minutes after tracer injection for each post TAK-831 dosing PET scan period

• Set A: Percent Change From Baseline to Post-TAK-831 Dose in AUEC(0-24)Serine: Area Under the Effect-time Curve From Time 0 to 24 Hours Post-TAK-831 Dose for Dextro-serine (D-serine) and Levo-serine (L-serine)

  Set A: Baseline, 24 hours post-TAK-831 dose

Study Arms (5)

Set A: TAK-831 100 mg

EXPERIMENTAL

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.

Drug: TAK-831; Drug: [18F]PGM299

Set A: TAK-831 200 mg

EXPERIMENTAL

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.

Drug: TAK-831; Drug: [18F]PGM299

Set A: TAK-831 250 mg

EXPERIMENTAL

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.

Drug: TAK-831; Drug: [18F]PGM299

Set A: TAK-831 500 mg

EXPERIMENTAL

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.

Drug: TAK-831; Drug: [18F]PGM299

Set B: [18F]PGM299

EXPERIMENTAL

\[18F\]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.

Drug: [18F]PGM299

Interventions

TAK-831 DRUG

TAK-831 oral suspension.

Set A: TAK-831 100 mg; Set A: TAK-831 200 mg; Set A: TAK-831 250 mg; Set A: TAK-831 500 mg

[18F]PGM299 DRUG

\[18F\]PGM299 injection

Set A: TAK-831 100 mg; Set A: TAK-831 200 mg; Set A: TAK-831 250 mg; Set A: TAK-831 500 mg; Set B: [18F]PGM299

Eligibility Criteria

• Age: 25 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Is capable of understanding and complying with protocol requirements.
• Signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
• Is in good health as determined by physical examination, electrocardiogram (ECG), and laboratory evaluations.
• Is a healthy male aged 25 to 55 years, inclusive, at the time of informed consent and first injection of the PET tracer.
• Weighs at least 45 kilogram (kg) and has a body mass index (BMI) from 18.0 to 30.0 kilogram per square meter (kg/m\^2), inclusive, at Screening.
• Agrees to use adequate contraception from signing of informed consent throughout the duration of the study and for 90 days after last dose.

You may not qualify if:

• Has received any investigational compound or device within 3 months or 5 half-lives, whichever is longer, prior to Check-in for Screening.
• Is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in the conduct of this study (example, spouse, parent, child, sibling) or may consent under duress.
• Has uncontrolled, clinically significant (CS), neurologic (including seizure disorder), cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal (GI), urologic, immunologic, or endocrine disease or psychiatric disorder, or other abnormality, which may impact the ability of the participant to participate or potentially confound the study results.
• Has a known hypersensitivity to any component of the formulation of TAK-831 or related compounds, or to \[18 F\]PGM299 or to any of its components.
• Has a positive urine or breath test result for drugs of abuse (defined as any illicit drug use), ethanol (alcohol), or cotinine at Screening, Check-in for Baseline Imaging/Confinement Period 1, or Check-in for the Treatment/Confinement Period 2 (Day -1) for a participant participating in Set A or at Screening, Check-in for Tracer TEST PET Imaging/Confinement Period 1, or Check-in for RE-TEST PET Imaging/Confinement Period 2 for a participant participating in Set B.
• Has a history of drug abuse (defined as any illicit drug use) or a history of ethanol (alcohol) abuse within 1 year prior to the screening visit or is unwilling to agree to abstain from ethanol (alcohol) and drugs throughout the study.
• Has taken any medication, supplements, or food products during the time periods listed in the excluded medications and dietary products table.
• Intends to donate sperm during the course of this study or for 90 days after the last dose of study medication.
• Has evidence of current cardiovascular, central nervous system, hepatic, or hematopoietic disease; renal, metabolic or endocrine dysfunction; serious allergy, asthma, hypoxemia, hypertension, or allergic skin rash; or there is any finding in the participant's medical history, physical examination, or safety laboratory tests giving reasonable suspicion of a disease that would contraindicate taking TAK-831 or a similar drug in the same class, which might interfere with the conduct of the study. This includes, but is not limited to, peptic ulcer disease and cardiac arrhythmias.
• Has current or recent (within 6 months) GI disease that would be expected to influence the absorption of drugs (that is, a history of malabsorption), any surgical intervention known to impact absorption (example, bariatric surgery or bowel resection), esophageal reflux, peptic ulcer disease, erosive esophagitis, or frequent (more than once per week) occurrence of heartburn.
• Has a history of cancer, except basal cell carcinoma that has been in remission for at least 5 years prior to Day 1.
• Has a positive test result for hepatitis B virus surface antigen (HBsAg), hepatitis C virus (HCV) antibody (HCAB), or human immunodeficiency virus (HIV) infection at Screening.
• Has used nicotine-containing products (including but not limited to cigarettes, pipes, cigars, chewing tobacco, nicotine patch or nicotine gum) within 44 days prior to Check-in for Confinement Period 1. Cotinine test is positive at Screening, or Check-in for Confinement Period 1, or Confinement Period 2.
• Has poor peripheral venous access.
• Has an abnormal Allen's test in either upper extremity.

Sponsors & Collaborators

• Neurocrine Biosciences: lead
• Takeda: collaborator

Study Sites (1)

Unknown Facility

London, United Kingdom

Location

Results Point of Contact

• Title: Neurocrine Medical Information
• Organization: Neurocrine Biosciences

medinfo@neurocrine.com

877-641-3461

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2016
• First Posted: March 23, 2016
• Study Start: March 21, 2016
• Primary Completion: August 30, 2016
• Study Completion: August 30, 2016
• Last Updated: June 14, 2021
• Results First Posted: August 7, 2020

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)