Clinical trial NCT04202497: 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
Official title: A Phase 1, Open-label, Positron Emission Tomography Study With [18F]MNI-1054 to Determine Lysine-Specific Demethylase 1A Brain Enzyme Occupancy of TAK-418 After Single-Dose Oral Administration in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2019-12-17
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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.

Detailed description: The drug being tested in this study is called TAK-418. TAK-418 is being tested to determine the relationship between brain LSD1 enzyme occupancy and TAK-418 plasma concentration. This study will utilize the PET radiotracer \[18F\]MNI-1054 to evaluate the brain LSD1 enzyme occupancy of TAK-418 after single dose oral administration in healthy adult participants.

The study will enroll approximately 16 participants. The TAK-418 starting dose is 1.5 mg, given on Day 1. Each participant will receive one dose of TAK-418 and up to 3 dynamic \[18F\]MNI-1054 PET scans to assess enzyme occupancy on baseline, Day 1 and Day 2 or 3 post-TAK-418 dosing.

This single center trial will be conducted in the United States. The overall time to participate in this study is 62 days. Participants will be followed up on Day 14 for follow-up safety assessments.

Eligibility criteria: Inclusion Criteria:

1. 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.
2. The participant must be a current nonsmoker at screening as demonstrated by negative cotinine test.
3. The participant has adequate circulation to both hands for safe placement of arterial lines (as determined by Allen's test).

Exclusion Criteria:

1. Has a known hypersensitivity to any component of the formulation of TAK-418 or related compounds, including \[18F\]MNI-1054.
2. The participant has a positive alcohol or drug screen.
3. 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).
4. 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.
5. The participant has a substance abuse disorder.
6. The participant cannot tolerate venipuncture or has poor venous access that would cause difficulty in collecting blood samples.
7. 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.
8. 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.
9. The participant has experienced an acute illness within 10 days before the screening visit.
10. 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.
11. The participant has luteinizing hormone, follicle stimulating hormone (FSH), or estradiol levels that are clinically abnormal.
12. The participant has existing skin rashes that can be diagnosed as dermatitis.

Primary outcomes:
measure: Quantitative Estimates of Binding of [18F]MNI-1054 Based on PET Radiotracer Kinetic Models At Baseline Scan on Day -1
timeFrame: Day -1
measure: Quantitative Estimates of Binding of [18F]MNI-1054 Based on PET Radiotracer Kinetic Models on Day 1
timeFrame: Day 1
measure: Quantitative Estimates of Binding of [18F]MNI-1054 Based on PET Radiotracer Kinetic Models on Day 2
timeFrame: Day 2
measure: Percent Enzyme Occupancy Based on Quantitative Estimates of Binding for TAK-418 on Day 1
timeFrame: Day 1
measure: Percent Enzyme Occupancy Based on Quantitative Estimates of Binding for TAK-418 on Day 2
timeFrame: Day 2
measure: Cmax: Maximum Observed Plasma Concentration for TAK-418
timeFrame: 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
measure: AUClast: Area Under the Plasma Concentration-time Curve (AUC) From Time 0 to Time of the Last Quantifiable Concentration for TAK-418
timeFrame: 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
measure: AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-418
timeFrame: 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:
measure: ED50 PET Enzyme Occupancy
timeFrame: Days 1 to 2
measure: Number of Participants Reporting One or More Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: From first dose of [18F]MNI-1054 radiotracer injection up to Day 14
measure: Number of Participants With Clinically Significant Abnormal Laboratory Values
timeFrame: From first dose of [18F]MNI-1054 radiotracer injection up to Day 14
measure: Number of Participants With Clinically Significant Abnormal Vital Signs
timeFrame: From first dose of [18F]MNI-1054 radiotracer injection up to Day 14
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Invicro, A Konica Minolta Company
state: Connecticut
Study officials:
affiliation: Takeda
name: Medical Director
role: STUDY_DIRECTOR
References: