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

NCT02497235 | Completed Phase 1 Results

• 2 other identifiers: TAK-935_1003U1111-1170-0452
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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.

Conditions

Epilepsy, Molecular Mechanisms of Pharmalogical Action, Protective Agents

Keywords

Drug therapy, Positron Emission Tomography, Brain enzyme occupancy, Cholesterol 24S-hydroxylase, CH24H

Outcome Measures

Primary Outcomes (4)

• Cholesterol 24S-Hydroxylase (CH24H) Brain Enzyme Occupancy as a Function of TAK-935 Plasma Concentration at 45 Minutes Post-TAK-935 Dose

  CH24H brain enzyme occupancy was obtained by graphical analysis of global occupancy plot. Global occupancy plot was calculated as: total volume of distribution \[VT\] (Baseline) - VT (Day 1) = Occupancy (Day 1) \* (VT \[Baseline\] - non-displaceable volume of distribution \[VND\]), where VT (Baseline) and VT (Day 1) are the total distribution volumes obtained at Baseline and after TAK-935 administration, respectively and VND is the non-displaceable volume of distribution. The occupancy is determined as the slope of the linear regression of the plot, and the VND as the x-intercept. Data was reported only for TAK-935 600 mg because only first two participants were analyzed at 45 minutes post-TAK-935 dose.

  45 minutes post-TAK-935 dose

• CH24H Brain Enzyme Occupancy as a Function of TAK-935 Plasma Concentration at 2 Hours Post-TAK-935 Dose

  CH24H brain enzyme occupancy was obtained by graphical analysis of global occupancy plot. Global occupancy plot was calculated as: VT (Baseline) - VT (Day 1) = Occupancy (Day 1) \* (VT \[Baseline\] - VND), where VT (Baseline) and VT (Day 1) are the total distribution volumes obtained at Baseline and after TAK-935 administration, respectively and VND is the non-displaceable volume of distribution. The occupancy is determined as the slope of the linear regression of the plot, and the VND as the x-intercept.

  2 hours post-TAK-935 dose

• CH24H Brain Enzyme Occupancy as a Function of TAK-935 Plasma Concentration at 10 Hours Post-TAK-935 Dose

  CH24H brain enzyme occupancy was obtained by graphical analysis of global occupancy plot. Global occupancy plot was calculated as: VT (Baseline) - VT (Day 1) = Occupancy (Day 1) \* (VT \[Baseline\] - VND), where VT (Baseline) and VT (Day 1) are the total distribution volumes obtained at Baseline and after TAK-935 administration, respectively and VND is the non-displaceable volume of distribution. The occupancy is determined as the slope of the linear regression of the plot, and the VND as the x-intercept. Data was reported only for TAK-935 600 mg because only first two participants were analyzed at 10 hour post-TAK-935 dose.

  10 hours post-TAK-935 dose

• CH24H Brain Enzyme Occupancy as a Function of TAK-935 Plasma Concentration at 24 Hours Post-TAK-935 Dose

  CH24H brain enzyme occupancy was obtained by graphical analysis of global occupancy plot. Global occupancy plot was calculated as: VT (Baseline) - VT (Day 1) = Occupancy (Day 1) \* (VT \[Baseline\] - VND), where VT (Baseline) and VT (Day 1) are the total distribution volumes obtained at Baseline and after TAK-935 administration, respectively and VND is the non-displaceable volume of distribution. The occupancy is determined as the slope of the linear regression of the plot, and the VND as the x-intercept.

  24 hours post-TAK-935 dose

Secondary Outcomes (2)

• Plasma Concentration of TAK-935 During Post-TAK-935 Dosing PET Scan Periods

  At time 0 (just after tracer injection), 1 hour after tracer injection and 2 hours after tracer injection for each post-TAK-935 dosing PET scan period

• Percent Change From Baseline in the AUEC24 for Plasma 24S Hydroxycholesterol (24HC)

  Baseline (Day -1): 1 hour and at multiple timepoints (up to 12 hours) post check in and Day 1: pre-dose and at multiple timepoints (up to 24 hours) post-TAK-935 dose

Study Arms (1)

TAK-935

EXPERIMENTAL

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.

Drug: TAK-935; Drug: [18F]MNI-792 (tracer)

Interventions

TAK-935 DRUG

TAK-935 oral solution.

TAK-935

[18F]MNI-792 (tracer) DRUG

\[18F\]MNI-792 injection.

TAK-935

Eligibility Criteria

• Age: 19 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• In the opinion of the investigator, 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 including requesting that a participant fast for any laboratory evaluations.
• Is a healthy male or female and aged 19 to 55 years, inclusive, at the time of informed consent and first study medication dose.
• 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.
• A female of non-bearing potential (example post-menopausal by history; or history of hysterectomy, bilateral salpingectomy, or oophorectomy).

You may not qualify if:

• 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.
• Contraindication to magnetic resonance imaging (MRI) based on the standard MRI radiography screening questionnaire.
• Had exposure to any radiation greater than (\>) 15 millisievert (mSv)/year (example, occupational or radiation therapy) within the previous year prior to Baseline imaging.
• 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.
• Clinically significant abnormal findings on brain MRI scan or findings on brain MRI that may interfere with the interpretation of the PET imaging.
• Use of any over-the-counter, herbal, or prescription medications or supplements within 30 days prior to baseline imaging.

Sponsors & Collaborators

• Takeda: lead

Study Sites (1)

Unknown Facility

New Haven, Connecticut, United States

Location

Related Publications (1)

• 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.

  PMID: 37770111 DERIVED

MeSH Terms

Conditions

Epilepsy

Interventions

Product Labeling

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Product Packaging; Industry; Technology, Industry, and Agriculture

Results Point of Contact

• Title: Takeda
• Organization: Medical Director

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: July 9, 2015
• First Posted: July 14, 2015
• Study Start: July 1, 2015
• Primary Completion: December 1, 2015
• Study Completion: January 1, 2016
• Last Updated: April 11, 2017
• Results First Posted: April 11, 2017

Record last verified: 2017-02

Locations

US (1)