A Study With [18F]MNI-1054 to Determine Lysine -Specific Demethylase 1A (LSD1) Brain Enzyme Occupancy of TAK-418 After Single-Dose Oral Administration in Healthy Participants

NCT04202497 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: TAK-418-0004U1111-1242-8485
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine brain LSD1 enzyme occupancy and the relationship of occupancy to TAK-418 dose and plasma exposure after single oral dosing of TAK-418 in healthy participants using \[18F\]MNI-1054 positron emission tomography (PET) imaging.

Conditions

Healthy Volunteers

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (8)

• Quantitative Estimates of Binding of [18F]MNI-1054 Based on PET Radiotracer Kinetic Models At Baseline Scan on Day -1

  Enzyme binding parameter \[Ki\] was obtained from irreversible 2-tissue compartment model (mL/cm\^3/min). Data is reported for the following brain regions: cerebellum, frontal lobe, hippocampus, occipital Lobe, pons, and striatum. Here, mL/cm\^3/min signifies 'milliliter per cubic centimeter per minute'.

  Day -1

• Quantitative Estimates of Binding of [18F]MNI-1054 Based on PET Radiotracer Kinetic Models on Day 1

  Enzyme binding parameter \[Ki\] was obtained from irreversible 2-tissue compartment model (mL/cm\^3/min). Data is reported for the following brain regions: cerebellum, frontal lobe, hippocampus, occipital Lobe, pons, and striatum. Here, mL/cm\^3/min signifies 'milliliter per cubic centimeter per minute'.

  Day 1

• Quantitative Estimates of Binding of [18F]MNI-1054 Based on PET Radiotracer Kinetic Models on Day 2

  Enzyme binding parameter \[Ki\] was obtained from irreversible 2-tissue compartment model (mL/cm\^3/min). Data is reported for the following brain regions: cerebellum, frontal lobe, hippocampus, occipital Lobe, pons, and striatum. Here, mL/cm\^3/min signifies 'milliliter per cubic centimeter per minute'.

  Day 2

• Percent Enzyme Occupancy Based on Quantitative Estimates of Binding for TAK-418 on Day 1

  Lysine-Specific Demethylase 1A (LSD1) enzyme occupancy (%) in region of interest (ROI) after a single dose of TAK-418 was obtained from the baseline and postdose Ki values as follows: occupancy (1st postdose) = 100\*(Ki \[baseline\] - Ki \[1st postdose\]) / Ki (baseline). Data is reported for following brain regions: cerebellum, frontal lobe, hippocampus, occipital Lobe, pons, and striatum.

  Day 1

• Percent Enzyme Occupancy Based on Quantitative Estimates of Binding for TAK-418 on Day 2

  LSD1 enzyme occupancy (%) in ROI after a single dose of TAK-418 was obtained from the baseline and postdose Ki values as follows: occupancy (2nd postdose) = 100\*(Ki \[baseline\] - Ki \[2nd postdose\]) / Ki (baseline). Data is reported for following brain regions: cerebellum, frontal lobe, hippocampus, occipital Lobe, pons, and striatum.

  Day 2

• Cmax: Maximum Observed Plasma Concentration for TAK-418

  Day 1: pre-dose and at multiple time points (up to 3 hours) post-dose, immediately before and after the Day 1 PET scan, and within 30 minutes before and 30 minutes after Day 2 or 3 PET scan

• AUClast: Area Under the Plasma Concentration-time Curve (AUC) From Time 0 to Time of the Last Quantifiable Concentration for TAK-418

  Day 1: pre-dose and at multiple time points (up to 3 hours) post-dose, immediately before and after the Day 1 PET scan, and within 30 minutes before and 30 minutes after Day 2 or 3 PET scan

• AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-418

  Day 1: pre-dose and at multiple time points (up to 3 hours) post-dose, immediately before and after the Day 1 PET scan, and within 30 minutes before and 30 minutes after Day 2 or 3 PET scan

Secondary Outcomes (4)

• ED50 PET Enzyme Occupancy

  Days 1 to 2

• Number of Participants Reporting One or More Adverse Events (AEs) and Serious Adverse Events (SAEs)

  From first dose of [18F]MNI-1054 radiotracer injection up to Day 14

• Number of Participants With Clinically Significant Abnormal Laboratory Values

  From first dose of [18F]MNI-1054 radiotracer injection up to Day 14

• Number of Participants With Clinically Significant Abnormal Vital Signs

  From first dose of [18F]MNI-1054 radiotracer injection up to Day 14

Study Arms (1)

TAK-418 1.5 mg

EXPERIMENTAL

TAK-418 1.5 milligram (mg), orally, once on Day 1. Participants will also receive 10 millicurie (mCi) of \[18F\]MNI-1054 injection intravenously, prior to each PET scans on Day -1, Day 1, and either on Day 2 or 3. Dose levels for subsequent participants may vary based on available review of imaging and pharmacokinetics (PK) data.

Drug: TAK-418; Drug: [18F]MNI-1054 (radiotracer)

Interventions

TAK-418 DRUG

TAK-418 orally.

TAK-418 1.5 mg

[18F]MNI-1054 (radiotracer) DRUG

\[18F\]MNI-1054 injection.

TAK-418 1.5 mg

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The participant must have a body mass index (BMI) greater than or equal to (\>=) 18.5 and less than or equal to (\<=) 30.0 kilogram per square meter (kg/m\^2) at the screening visit.
• The participant must be a current nonsmoker at screening as demonstrated by negative cotinine test.
• The participant has adequate circulation to both hands for safe placement of arterial lines (as determined by Allen's test).

You may not qualify if:

• Has a known hypersensitivity to any component of the formulation of TAK-418 or related compounds, including \[18F\]MNI-1054.
• The participant has a positive alcohol or drug screen.
• The participant has a history of alcohol consumption exceeding 2 standard drinks per day on average (1 glass is approximately equivalent to the following: beer \[354 milliliter (mL)/12 ounce (oz)\], wine \[118 mL/4 oz\], or distilled spirits \[29.5 mL/1 oz\] per day).
• The participant consumes excessive amounts, defined as greater than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, energy drinks, or other caffeinated beverages per day.
• The participant has a substance abuse disorder.
• The participant cannot tolerate venipuncture or has poor venous access that would cause difficulty in collecting blood samples.
• The participant has contraindications to undergoing magnetic resonance imaging (MRI) examination including but not limited to implants, such as implanted cardiac pacemakers or defibrillators, insulin pumps, cochlear implants, metallic ocular foreign body, implanted neural stimulators, central nervous system aneurysm clips, and other medical implants that have not been certified for MRI, or history of claustrophobia in MRI.
• The participant has clinically significant abnormal findings on brain MRI scan that in the opinion of the investigator may interfere with the interpretation of the PET imaging.
• The participant has experienced an acute illness within 10 days before the screening visit.
• The participant has a risk of suicide according to the investigator's clinical judgement per the Columbia-Suicide Severity Rating Scale at screening or has made a suicide attempt in the 12 months before screening.
• The participant has luteinizing hormone, follicle stimulating hormone (FSH), or estradiol levels that are clinically abnormal.
• The participant has existing skin rashes that can be diagnosed as dermatitis.

Sponsors & Collaborators

• Takeda: lead

Study Sites (1)

Invicro, A Konica Minolta Company

New Haven, Connecticut, 06510, United States

Location

MeSH Terms

Interventions

TAK-418

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2019
• First Posted: December 17, 2019
• Study Start: December 18, 2019
• Primary Completion: March 5, 2020
• Study Completion: March 19, 2020
• Last Updated: July 30, 2021
• Results First Posted: July 30, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

Locations

US (1)