HealthyPhase 1NCT02716987

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

A Phase 1 study testing TAK-831 and [18F]PGM299 in people with Healthy, run by Neurocrine Biosciences at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 25 to 55 years, men onlyHealthy volunteers can take part
Conditions the study is for: Healthy
What is being tested?: TAK-831 and [18F]PGM299
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 20 participants
Where: 1 siteUnited Kingdom
Study dates: 21 Mar 2016to 30 Aug 2016
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 25 to 55 years
Men only
Healthy volunteers accepted
Adult

Who may be able to join

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.

Who cannot join

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.

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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.
Has donated or lost 450 milliliter (mL) or more of his blood volume (including plasmapheresis), or had a transfusion of any blood product within 90 days prior to Confinement Period 1.
Has an abnormal CS ECG at Screening, Check-in for Confinement Period 1, or at Check-in for Confinement Period 2. Entry of any participant with an abnormal (not clinically significant [NCS]) ECG must be approved and documented by signature of the coordinating investigator or delegate.
Has a supine blood pressure outside the ranges of 100 to 140 millimeter of mercury (mm Hg) for systolic and 50 to 90 mm Hg for diastolic, confirmed with 1 repeat testing within a maximum of 30 minutes, at the Screening Visit, Check-in for Confinement Period 1, or Confinement Period 2.
Has a resting heart rate outside the range of 50 to 90 beats/minute, confirmed with 1 repeat testing within a maximum of 30 minutes, at the Screening Visit, Check-in for Confinement Period 1, or Confinement Period 2.
Has a Fridericia's Correction Formula (QTcF) - QTcF interval greater than (>) 450 millisecond (msec) or PR outside the range of 120 to 220 msec, confirmed with 1 repeat testing within a maximum of 30 minutes, at the Screening Visit, Check-in for Confinement Period 1, or Confinement Period 2.
Has abnormal Screening laboratory values that suggest a CS underlying disease or the following laboratory abnormalities: Alanine Aminotransferase (ALT) and/or Alanine serum transaminase AST >1.5*upper limit of normal (ULN).
Has a risk of suicide according to the investigator's clinical judgment (example, per Columbia-Suicide Severity Rating Scale [C-SSRS]) or has made an attempt in the previous 6 months.
Has had a seizure or convulsion (lifetime), including absence seizure and febrile convulsion.
In the opinion of the investigator, is unlikely to comply with the protocol or is unsuitable for any other reason.
Has had previous exposure to ionizing radiation such that, in combination with the exposure from this study, their exposure will be >10 millisievert (mSv) for the previous year.
Has a contraindication to medical resonance imaging (MRI) based on the standard MRI screening questionnaire. Contraindications include ferromagnetic foreign bodies (example, shrapnel, ferromagnetic fragments in the orbital area), certain implanted medical devices (example, aneurysm clips, cardiac pacemakers) or claustrophobia.
Has findings on screening brain MRI scan that will potentially compromise participant safety or the scientific integrity of the study data, if the participant were to participate in this study.
Has prolonged prothrombin time (PT) or activated partial thromboplastin time (PTT) or reduced platelet count (less than [<] 100*10^9/Liter [L]).

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

Study site
London

Other trials in United Kingdom

About this study

Official title: A Phase 1, Open-Label, Positron Emission Tomography Study in Healthy Subjects to Determine D-Amino Acid Oxidase Brain Enzyme Occupancy of TAK-831 After Single-Dose Oral Administration in Healthy Subjects

Read the 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.

Conditions: Healthy
Being tested: TAK-831, [18F]PGM299
Keywords: Drug therapy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

TAK-831Drug
TAK-831 oral suspension.
[18F]PGM299Drug
[18F]PGM299 injection

Study groups in NCT02716987
Study group	Role	What they receive
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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: [18F]PGM299

What is being measured

The primary outcome is the main question the study is designed to answer.

Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan
Measured: 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
Measured: 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.
Measured: 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
EC50 was obtained from global VT model. The affinity constant relating plasma concentration of TAK-831 to DAO occupancy (EC50) was estimated by fitting the PET and plasma concentration data (VT, Cp). It was calculated as VT= VsBase (EC50/EC50+Cp) + VND, where Vs Base was the group-level (global) volume of distribution of the specific binding in the target region (cerebellar GM) and VND was the volume of distribution of the non-displaceable component (non-specific bound and free radiotracer) of the target region.
Measured: 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
Dose of TAK-831 that corresponds to 50% DAO brain enzyme occupancy in cerebellum at the time of maximum observed plasma concentration (Tmax) of TAK-831 was estimated.
Measured: 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
CoV was calculated as COV (P)(%) = 100 * mean/ standard deviation, where P was different participant scanned under baseline condition.
Measured: Set B: Baseline up to Day 10
Set A: Plasma Concentrations of TAK-831 During Each Post-TAK-831 Dosing PET Scan Periods
Measured: 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)
Measured: Set A: Baseline, 24 hours post-TAK-831 dose
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 Ratio of D-serine to Total Serine
Measured: Set A: Baseline, 24 hours post-TAK-831 dose
Set A: Percent Change in Maximum Drug-induced Effect (Emax,Serine) on Change in Plasma Concentrations of D-serine and L-serine
Measured: Set A: Baseline, 24 hours post-TAK-831 dose
Set A: Percent Change in Maximum Drug-induced Effect (Emax, D: Total Serine Ratio) on the Ratio of D-serine to Total Serine
Measured: Set A: Baseline, 24 hours post-TAK-831 dose
Set A: Time to Reach the Maximum PD Effect (Time to Emax,Serine) for D-serine and L-serine
Measured: Set A: Day -1 At 1, 4 and 12 hours post check-in and Day 1 pre-dose and at multiple time points (up to 24 hours) post-TAK-831 dose
Set A: Time to Reach the Maximum PD Effect (Time to Emax,Serine) for Ratio of D-serine to Total Serine
Measured: Set A: Day -1 At 1, 4 and 12 hours post check-in and Day 1 pre-dose and at multiple time points (up to 24 hours) post-TAK-831 dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

21 Mar 201630 Aug 2016

First posted23 Mar 2016 (estimated)
Study start21 Mar 2016
Primary completion30 Aug 2016
Study completion30 Aug 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for HealthyStudies of the same condition, open and under way.
More trials run by Neurocrine BiosciencesThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Other
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 20 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02716987
Sponsor's protocol ID: TAK-831-1003
Other IDs: 2015-004509-17, U1111-1176-7493, 15/LO/1916, 2015
Status last verified: Jun 2021
First submitted: 17 Mar 2016
Last updated: 14 Jun 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 14 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1, Open-Label, Positron Emission Tomography Study in Healthy Subjects to Determine D-Amino Acid Oxidase Brain Enzyme Occupancy of TAK-831 After Single-Dose Oral Administration in Healthy Subjects
ClinicalTrials.gov ID: NCT02716987
Acronym / sponsor ID: TAK-831-1003
Conditions: Healthy
Keywords: Drug therapy
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 20 participants (actual)
Lead sponsor: Neurocrine BiosciencesIndustry (pharma, biotech, devices)
Collaborators: Takeda
Study start: 21 Mar 2016 (actual)
Primary completion: 30 Aug 2016 (actual)
Study completion: 30 Aug 2016 (actual)
First posted: 23 Mar 2016 (estimated)
Results: Posted 7 Aug 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Other
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 5

Arm	Type	Receives
Set A: TAK-831 100 mg	Experimental	Drug: TAK-831, Drug: [18F]PGM299TAK-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 mg	Experimental	Drug: TAK-831, Drug: [18F]PGM299TAK-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 mg	Experimental	Drug: TAK-831, Drug: [18F]PGM299TAK-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 mg	Experimental	Drug: TAK-831, Drug: [18F]PGM299TAK-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]PGM299	Experimental	Drug: [18F]PGM299[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.

Who may qualify

Ages: 25 to 55 years
Sex: Male only
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (6 listed)

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.

Key exclusion criteria (28 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
TAK-831TAK-831 oral suspension.	Drug	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[18F]PGM299 injection	Drug	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

Primary outcome

Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan
Time frame: 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
Time frame: 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
Time frame: 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.

10 secondary outcomes

Set A: EC50- Plasma Concentration of TAK-831 That Corresponds to 50 Percent (%) DAO Brain Enzyme Occupancy in Cerebellum
Time frame: 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
Time frame: 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
Time frame: Set B: Baseline up to Day 10
Set A: Plasma Concentrations of TAK-831 During Each Post-TAK-831 Dosing PET Scan Periods
Time frame: 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)
Time frame: Set A: Baseline, 24 hours post-TAK-831 dose
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 Ratio of D-serine to Total Serine
Time frame: Set A: Baseline, 24 hours post-TAK-831 dose
Set A: Percent Change in Maximum Drug-induced Effect (Emax,Serine) on Change in Plasma Concentrations of D-serine and L-serine
Time frame: Set A: Baseline, 24 hours post-TAK-831 dose
Set A: Percent Change in Maximum Drug-induced Effect (Emax, D: Total Serine Ratio) on the Ratio of D-serine to Total Serine
Time frame: Set A: Baseline, 24 hours post-TAK-831 dose
Set A: Time to Reach the Maximum PD Effect (Time to Emax,Serine) for D-serine and L-serine
Time frame: Set A: Day -1 At 1, 4 and 12 hours post check-in and Day 1 pre-dose and at multiple time points (up to 24 hours) post-TAK-831 dose
Set A: Time to Reach the Maximum PD Effect (Time to Emax,Serine) for Ratio of D-serine to Total Serine
Time frame: Set A: Day -1 At 1, 4 and 12 hours post check-in and Day 1 pre-dose and at multiple time points (up to 24 hours) post-TAK-831 dose

Results and safety

Results posted to the registry on 7 Aug 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Set A: TAK-831 100 mg	4	4
Set A: TAK-831 200 mg	2	2
Set A: TAK-831 250 mg	5	4
Set A: TAK-831 500 mg	2	2
Set B: [18F]PGM299	6	5
Set A: [18F]PGM299 Baseline	1	0

Primary outcome: Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan

Time frame: 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). Number. Unit: milliliter per cubic centimeter(mL/cm^3)

Measure	Set A: TAK-831 100 mg n = 4	Set A: TAK-831 200 mg n = 2	Set A: TAK-831 250 mg n = 5	Set A: TAK-831 500 mg n = 2	Set B: [18F]PGM299 n = 6	Set A: [18F]PGM299 Baseline n = 1
Participant 1- PET Scan 1	1.211	1.247	1.349	1.683	0.658	0.863
Participant 1- PET Scan 2	0.400	0.126	0.247	0.114	1.109	NA
Participant 1- PET Scan 3	1.467	0.543	0.58	1.182	NA	NA
Participant 2- PET Scan 1	0.663	1.585	0.743	2.095	0.884	NA
Participant 2- PET Scan 2	0.241	0.217	0.266	0.172	1.130	NA
Participant 2- PET Scan 3	0.809	0.77	0.425	0.553	NA	NA
Participant 3- PET Scan 1	1.397	NA	0.981	NA	1.504	NA
Participant 3- PET Scan 2	0.858	NA	0.189	NA	1.388	NA

Population analysed: The set included all participants who had at least 1 technically adequate PET scan.

Primary outcome: Non-displaceable Binding Potential (BPND) of [18F]PGM299 in the Cerebellar GM for Each PET Scan

Time frame: 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). Number. Unit: ratio

Measure	Set A: TAK-831 100 mg n = 4	Set A: TAK-831 200 mg n = 2	Set A: TAK-831 250 mg n = 5	Set A: TAK-831 500 mg n = 2	Set B: [18F]PGM299 n = 6	Set A: [18F]PGM299 Baseline n = 1
Participant 1- PET Scan 1	10.99	7.31	6.71	8.96	3.77	5.49
Participant 1- PET Scan 2	3.26	-0.28	0.47	-0.20	4.99	NA
Participant 1- PET Scan 3	7.89	4.22	4.32	11.19	NA	NA
Participant 2- PET Scan 1	3.88	8.38	3.53	13.35	13.49	NA
Participant 2- PET Scan 2	1.01	0.16	0.25	0.06	5.89	NA
Participant 2- PET Scan 3	4.39	6.06	2.17	4.59	NA	NA
Participant 3- PET Scan 1	7.22	NA	4.80	NA	7.13	NA
Participant 3- PET Scan 2	5.13	NA	0.01	NA	7.46	NA

Population analysed: The set included all participants who had at least 1 technically adequate PET scan.

Primary outcome: D-amino Acid Oxidase (DAO) Occupancy Estimation in the Cerebellar GM

Time frame: 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)

Population analysed: Due to variability in localization of \[18F\]PGM299 in both Cerebellar GM and Frontal Cortex GM, DAO occupancy estimation as a percent difference from baseline and post-TAK-831 dosing PET scans in Cerebellar GM based on VT values could not be made.

10 secondary outcomes are reported in the full results.

Adverse events

Time frame: Treatment-emergent adverse events are adverse events that started after the first dose of study drug up to Day 15 in set A and up to Day 12 in set B.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Set A: [18F]PGM299 Dose 1 to Prior TAK-831 100 mg Dose	0 of 4 (0%)	2 of 4 (50%)	Not reported
Set A: [18F]PGM299 Dose 1 to Prior TAK-831 200 mg Dose	0 of 2 (0%)	0 of 2 (0%)	Not reported
Set A: [18F]PGM299 Dose 1 to Prior TAK-831 250 mg Dose	0 of 5 (0%)	1 of 5 (20%)	Not reported
Set A: [18F]PGM299 Dose 1 to Prior TAK-831 500 mg Dose	0 of 2 (0%)	0 of 2 (0%)	Not reported
Set A: TAK-831 100 mg Dose to Prior [18F]PGM299 Dose 2	0 of 4 (0%)	0 of 4 (0%)	Not reported
Set A: TAK-831 200 mg Dose to Prior [18F]PGM299 Dose 2	0 of 2 (0%)	0 of 2 (0%)	Not reported
Set A: TAK-831 250 mg Dose to Prior [18F]PGM299 Dose 2	0 of 5 (0%)	2 of 5 (40%)	Not reported
Set A: TAK-831 500 mg Dose to Prior [18F]PGM299 Dose 2	0 of 2 (0%)	1 of 2 (50%)	Not reported
SetA:TAK-831 100mg:[18F]PGM299 Dose 3 up to Follow-up (Day 15)	0 of 4 (0%)	2 of 4 (50%)	Not reported
SetA:TAK-831 200mg:[18F]PGM299 Dose 3 up to Follow-up (Day 15)	0 of 2 (0%)	0 of 2 (0%)	Not reported
SetA:TAK-831 250mg:[18F]PGM299 Dose 3 up to Follow-up (Day 15)	0 of 5 (0%)	0 of 5 (0%)	Not reported
SetA:TAK-831 500mg:[18F]PGM299 Dose 3 up to Follow-up (Day 15)	0 of 2 (0%)	1 of 2 (50%)	Not reported
Set B: [18F]PGM299	0 of 6 (0%)	0 of 6 (0%)	Not reported
Set A: [18F]PGM299 Baseline	0 of 1 (0%)	0 of 1 (0%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 14 Jun 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing TAK-831 and [18F]PGM299 in people with Healthy, run by Neurocrine Biosciences at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Aug 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Total Volume of Distribution (VT) of [18F]PGM299 in the Cerebellar Grey Matter (GM) for Each PET Scan (time frame: 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)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02716987.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jun 2021.