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

Epilepsy Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02497235
• Other study ID #: TAK-935_1003
• Secondary ID: U1111-1170-0452
• Status: Completed
• Phase: Phase 1
• First received: July 9, 2015
• Last updated: February 15, 2016
• Start date: July 2015
• Est. completion date: December 2015

Study information

• Verified date: February 2016
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 microgram (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 22 for follow-up safety assessments.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 11
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 19 Years to 55 Years

Eligibility

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 Design

Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Epilepsy

Intervention

Drug:
• TAK-935
TAK-935 oral solution.
• [18F]MNI-792 (tracer)
[18F]MNI-792 injection.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cholesterol 24S-Hydroxylase (CH24H) Brain Enzyme Occupancy as a Function of TAK-935 Plasma Concentration	CH24H target occupancy after a single dose of TAK-935 obtained by graphical analysis according to the global occupancy plot will be 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 non-displaceable volume of distribution VND as the x-intercept.	Baseline (Day -1), after first and second [18F]MNI-792 PET tracer injection on Days 1 and 2	No
Secondary	Plasma Concentration of TAK-935 during Postdose PET Scan Period	The concentrations of TAK-935 in plasma will be summarized by dose level over each scheduled sampling time point.	Days 1 and 2: at the time of tracer injection, 1 and 2 hours post-tracer injection	No
Secondary	Percent Change from Baseline in Maximum Observed Effect (Emax)	Emax is defined as the maximum observed effect post-TAK-935 dose. Emax is the measure of change in plasma concentration of 24S hydroxycholesterol (24HC). Percent change from Baseline Emax will be determined, as appropriate, depending on the Baseline profile of plasma 24HC.	Baseline (Day -1): 1, 4, and 12 hours post check-in; Day 1: pre-dose (within 30 minutes prior to dosing), 1, 4, 8, 12, 20, 24 and 30 hours post-TAK-935 dose	No
Secondary	Percent Change from Baseline in the Area under the Effect-Time Curve from Time 0 to Last 24HC Sampling Time Point (t) (AUECt)	AUECt is the area under the effect-time curve from time 0 to last sampling time point (t). TAK-935 effect was measured from the change in the plasma concentration of 24HC. Percent change from Baseline AUECt will be determined, as appropriate, depending on the Baseline profile of plasma 24HC.	Baseline (Day -1): 1, 4, and 12 hours post check-in; Day 1: pre-dose (within 30 minutes prior to dosing), 1, 4, 8, 12, 20, 24 and 30 hours post-TAK-935 dose.	No