A Phase 1 Positron Emission Tomography Study to Measure Cholesterol 24S-Hydroxylase Target Occupancy of TAK-935

NCT ID: NCT02497235

Last Updated: 2017-04-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 11 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-07-31
• Study Completion Date: 2016-01-31

Brief Summary

The purpose of this study is to determine the brain cholesterol 24S-hydroxylase (CH24H) enzyme occupancy of TAK-935 after single oral dose in healthy participants using the positron emission tomography (PET) ligand [18F]MNI-792 and PET imaging and to determine the relationship of occupancy to TAK-935 exposure.

Detailed Description

The drug being tested in this study is called TAK-935. TAK-935 is being tested to examine the degree and duration of brain CH24H enzyme occupancy/target engagement as a function of TAK-935 plasma concentration in order to guide dosing and schedule for future clinical trials with TAK-935. This study will utilize the PET ligand [18F]MNI-792 to evaluate the brain CH24H occupancy of TAK-935 after single dose oral administration in healthy adult participants. The study will evaluate up to 16 participants. The first 2 participants will take TAK-935 600 mg oral solution and undergo PET imaging using tracer [18F]MNI-792 up to 5 mcg (up to 370 MBq), injection, intravenously prior to each PET scan at Baseline, 45 minutes and 10 hours post-TAK-935 dose. TAK-935 dose and timing of post-dose scans for subsequent participants will be based on the data from the previous participants. This single-center trial will be conducted in the United States. The overall time to participate in this study is up to 55 days. Participants will make 4 visits to the clinic, including 2 confinement periods to the clinic for PET imaging. Participants will be contacted by phone on Day 28 for follow-up safety assessments.

Conditions

Epilepsy, Molecular Mechanisms of Pharmalogical Action, Protective Agents

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

TAK-935

A single dose of TAK-935 600 milligram (mg), oral solution on Day 1 as a starting dose and up to 370 megabecquerel (MBq) (10 millicurie \[mCi\]) of \[18F\]MNI-792 with a mass of up to 5 microgram (mcg), injection intravenously (IV), prior to each PET imaging at Baseline, 45 minutes and 10 hours post-TAK-935 dose. Subsequent dose of TAK-935 oral solution and timing of PET imaging will be based on safety, tolerability and occupancy data from previous level participants.

Group Type: EXPERIMENTAL

TAK-935

Intervention Type: DRUG

TAK-935 oral solution.

[18F]MNI-792 (tracer)

Intervention Type: DRUG

\[18F\]MNI-792 injection.

Interventions

TAK-935

TAK-935 oral solution.

Intervention Type: DRUG

[18F]MNI-792 (tracer)

\[18F\]MNI-792 injection.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. In the opinion of the investigator, is capable of understanding and complying with protocol requirements.

2. Signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures including requesting that a participant fast for any laboratory evaluations.

3. Is a healthy male or female and aged 19 to 55 years, inclusive, at the time of informed consent and first study medication dose.

4. 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.

5. A female of non-bearing potential (example post-menopausal by history; or history of hysterectomy, bilateral salpingectomy, or oophorectomy).

Exclusion Criteria

1. Have a known history or evidence of a clinically significant disorder (including neurologic and psychiatric), or disease that in the opinion of the study investigator would pose a risk to the participant safety or interfere with the study evaluation, procedures or completion.

2. Contraindication to magnetic resonance imaging (MRI) based on the standard MRI radiography screening questionnaire.

3. Had exposure to any radiation greater than (>) 15 millisievert (mSv)/year (example, occupational or radiation therapy) within the previous year prior to Baseline imaging.

4. Has a known hypersensitivity to any component of the formulation of TAK-935 or related compounds, or to [18F]MNI-792 or to any of its components.

5. Clinically significant abnormal findings on brain MRI scan or findings on brain MRI that may interfere with the interpretation of the PET imaging.

6. Use of any over-the-counter, herbal, or prescription medications or supplements within 30 days prior to baseline imaging.

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Takeda

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Takeda

Locations

New Haven, Connecticut, United States

Countries

United States

References

Constantinescu CC, Brown T, Wang S, Yin W, Barret O, Jennings D, Tauscher J. Clinical Characterization of [18F]T-008, a Cholesterol 24-Hydroxylase PET Ligand: Dosimetry, Kinetic Modeling, Variability, and Soticlestat Occupancy. J Nucl Med. 2023 Dec 1;64(12):1972-1979. doi: 10.2967/jnumed.123.265912.

Reference Type: DERIVED

PMID: 37770111 (View on PubMed)

Other Identifiers

U1111-1170-0452

Identifier Type: REGISTRY

Identifier Source: secondary_id

TAK-935_1003

Identifier Type: -

Identifier Source: org_study_id