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

February 28, 2017 updated by: Takeda

An Open-Label, Positron Emission Tomography, Phase 1 Study With [18F]MNI-792 to Determine Cholesterol 24S-Hydroxylase Target Occupancy of TAK-935 After Single-Dose Oral Administration in Healthy Subjects.

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
11

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Connecticut
      • New Haven, Connecticut, United States

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

19 years to 55 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: OTHER
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 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.
Drug: TAK-935
TAK-935 oral solution.
Drug: [18F]MNI-792 (tracer)
[18F]MNI-792 injection.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Cholesterol 24S-Hydroxylase (CH24H) Brain Enzyme Occupancy as a Function of TAK-935 Plasma Concentration at 45 Minutes Post-TAK-935 Dose
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Plasma Concentration of TAK-935 During Post-TAK-935 Dosing PET Scan Periods
Time Frame: 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
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)
Time Frame: 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
Percent change was calculated as = [(Postdose AUEC24(2) - Baseline AUEC24(2))/Baseline AUEC24(2)]*100 percent.
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Takeda

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 1, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2015

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 9, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 9, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 14, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 11, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 28, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • TAK-935_1003
  • U1111-1170-0452 (Registry Identifier: WHO)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Epilepsy, Molecular Mechanisms of Pharmalogical Action, Protective Agents

Clinical Trials on TAK-935

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings