A Positron Emission Tomography Occupancy Study Using Ligand [11C]AS2471907 and Following Oral Dosing of ASP3662

NCT02194491 | Completed Phase 1

• 1 other identifier: 3662-CL-0011
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate a novel PET tracer (\[11C\]AS2471907), and to use \[11C\]AS2471907 to assess the level and time-course of enzyme occupancy in the human brain prior to and following single oral dose administration of ASP3662.

Conditions

Pharmacokinetics of ASP3662; Displacement of Radiotracer; Healthy Volunteers

Keywords

[11C]AS2471907; ASP3662; Positron Emission Tomography (PET); Brain enzyme occupancy

Outcome Measures

Primary Outcomes (8)

• Positron Emission Tomography measure: volume of distribution

  Day 1 and 2 (Part 1 and Part 2)

• Positron Emission Tomography measure: brain time-activity curves

  Day 1 and 2 (Part 1 and Part 2)

• Positron Emission Tomography measure: enzyme occupancy

  Day 1 and 2 (Part 1 and Part 2)

• Positron Emission Tomography measure: binding potentials

  Day 1 and 2 (Part 1 and Part 2)

• Pharmacokinetic parameter of ASP3662 and its metabolite (AS2570469): AUClast (Part 2 only)

  Area under the plasma concentration - time curve from time zero to time of last measurable concentration (AUClast)

  Day 1 and 2

• Pharmacokinetic parameter of ASP3662 and its metabolite (AS2570469): Cmax (Part 2 only)

  Maximum concentration (Cmax)

  Day 1 and 2

• Pharmacokinetic parameter of ASP3662 and its metabolite (AS2570469): tmax (Part 2 only)

  Time to attain Cmax (tmax)

  Day 1 and 2

• Safety as assessed by laboratory tests, 12-lead electrocardiograms, vital signs, adverse events, physical exams, neurological exams and Columbia Suicide Severity Rating Scale

  up to 9 days (Part 1 and Part 2)

Study Arms (2)

[11C]AS2471907 administration (Part 1)

EXPERIMENTAL

Up to 4 single dose IV administrations (≤ 10 mL infused over approximately 1 minute) are planned, totaling less than 100 μg.

Other: [11C]AS2471907; Radiation: Positron Emission Tomography (PET)

ASP3662 administration (Part 2)

EXPERIMENTAL

The dose levels used in part 2 will depend on the ongoing analysis of EO (enzyme occupancy) from previously dosed subjects.

Radiation: Positron Emission Tomography (PET); Drug: ASP3662

Interventions

[11C]AS2471907 OTHER

intravenous radiotracer

Also known as: Up to 4 single dose IV administrations (≤ 10 mL infused over approximately 1 minute) are planned, totaling less than 100 μg.

[11C]AS2471907 administration (Part 1)

Positron Emission Tomography (PET) RADIATION

Imaging scanning procedure

ASP3662 administration (Part 2); [11C]AS2471907 administration (Part 1)

ASP3662 DRUG

oral

ASP3662 administration (Part 2)

Eligibility Criteria

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

You may qualify if:

• Subject is of non-Asian descent.
• Subject has a body mass index (BMI) range of 18.5 to 32 kg/m2, inclusive and weighs at least 50 kg at screening.
• Subject and his female spouse/partner who is of childbearing potential must be using highly effective contraception1 consisting of 2 forms of birth control (at least one of which must be a barrier method) starting at screening and continuing throughout the study period and for 90 days after final study drug administration.
• Subject must not donate sperm starting at screening, throughout the study period and for at least 90 days after final study drug administration.
• Subject agrees not to participate in another investigational study while on study treatment.

You may not qualify if:

• Subject has a known or suspected hypersensitivity to ASP3662, \[11C\]AS2471907 or intolerance of drugs with the same mechanism of action as ASP3662.
• Subject has an allergy to topical anesthetics, such as, lidocaine (if used for catheter placement).
• Subject has previously participated in a clinical study with ASP3662 or part 1 of the current study.
• Subject has any clinically significant history of allergic conditions.
• Subject with a history of a suicide attempt or suicidal behavior.
• Subject has a history of smoking within the past 6 months.
• Subject has any history or evidence of any clinically significant cardiovascular, gastrointestinal (GI), endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal and/or other major disease or malignancy, as judged by the investigator or designee.
• Subject has/had febrile illness or symptomatic viral, bacterial (including upper respiratory infection) or fungal (non-cutaneous) infection within 1 week before clinic check-in.
• Subject has any clinically significant abnormality following the investigator's review of the physical examination, electrocardiogram (ECG) and protocol-defined clinical laboratory tests at screening or clinic check-in.
• Subject has a mean pulse \< 40 or \> 90 beats per minute; mean systolic blood pressure \> 140 mmHg or mean diastolic blood pressure \> 90 mmHg (measurements taken in triplicate after subject has been resting in supine position for 10 minutes) at screening. If the mean pulse or mean systolic blood pressure (SBP) or mean diastolic blood pressure (DBP) is out of the range specified above, 1 additional triplicate measurement may be taken at screening.
• Subject has a mean QTcF interval of \> 430 msec at screening or check-in. If the mean QTcF exceeds the limits above, 1 additional triplicate ECG can be taken at screening. If this triplicate also gives an abnormal result, the subject should be excluded.
• Subject has a history of unexplained syncope, cardiac arrest, unexplained cardiac arrhythmias or torsade de pointes, structural heart disease or a family history of Long QT Syndrome.
• Subject has use of any prescribed or non-prescribed drugs (including vitamins, natural and herbal remedies, e.g., St. John's wort) in the 2 weeks before study drug administration, except for occasional use of acetaminophen (up to 2 g/day).
• Subject has history of consuming more than 14 units of alcoholic beverages per week within 6 months prior to screening or has a history of alcoholism or drug/chemical or substance abuse within the past 2 years prior to screening (Note: 1 unit = 12 ounces of beer, 4 ounces of wine or 1 ounce of spirits/hard liquor) or the subject tests positive at screening or clinic admission for alcohol or drugs of abuse (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine and opiates).
• Subject has any use of drugs of abuse within 3 months before screening or check-in.

Sponsors & Collaborators

• Astellas Pharma Global Development, Inc.: lead
• Yale University: collaborator

Study Sites (1)

Site US10001

New Haven, Connecticut, 06520-8-48, United States

Location

MeSH Terms

Interventions

AS2471907; Magnetic Resonance Spectroscopy; ASP3662

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Senior Medical Director

  Astellas Pharma Global Development, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2014
• First Posted: July 18, 2014
• Study Start: April 1, 2014
• Primary Completion: May 1, 2016
• Study Completion: May 1, 2016
• Last Updated: June 28, 2016

Record last verified: 2016-06

Locations

US (1)