Clinical trial NCT04044781: A Phase 1, Open-Label, PET Study of T2310 & BPN14770
Official title: A Phase 1, Open-Label, Positron Emission Tomography Study in Healthy Subjects to Determine the Relationship Between Plasma Concentration and Brain Target Occupancy of BPN14770
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: To Determine Brain Target Occupancy of BPN14770
Lead sponsor: Tetra Discovery Partners
Sponsor class: INDUSTRY
First posted: 2019-08-05
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: This is a sponsor initiated, single site, first-in-human study of an investigational imaging agent for quantifying the topographically specific concentrations of the phosphodiesterase enzyme Type 4D (PDE4D) with positron emission tomography (PET) using a selective radioligand, \[11C\]T2310. T2310 will be measured with imaging techniques to characterize plasma exposure levels versus regionally specific target engagement fractions for oral doses of BPN14770, an investigational new drug (IND) for modulating PDE4D. BPN14770 is under evaluation for the treatment of Fragile X syndrome and Alzheimer's disease.


Eligibility criteria: Inclusion Criteria:

* 1. Willing and able to provide written informed consent.
* 2. Subjectively healthy
* 3. Between 18 and 75 years, inclusive, but preference will be given to subjects who are less than 55 years old.
* 4. The subject weighs at least 45 kg and has a body mass index between 18.0 and 32 kg/m2.
* 5. Subjects should be willing to observe the following contraception requirements from Screening until 90 days after the final follow-up visit: Male subjects must be willing to inform female partners of their participation in the study and must agree to use adequate contraceptive methods (vasectomy performed at least 6 months prior to dosing BPN14770 or use at least one barrier method of birth control). Female subjects: Female subjects must be surgically sterile (bilateral tubal ligation, hysterectomy, or bilateral oophorectomy at least 6 months prior to dosing of BPN14770), at least two years post-menopausal, or willing to use one barrier plus a hormonal contraceptive method of contraception from initial screening until one month after taking the last dose of study drug

Exclusion Criteria:

* 1. Known history or evidence of a clinically significant medical condition, disorder, or disease that, in the opinion of the investigator, would pose a risk to subject safety, proper completion of the procedures, or the integrity of the study.
* 2. Clinical laboratory studies suggestive of a medically meaningful disease or condition that, in the opinion of the investigator, could pose a risk to subject safety, proper completion of the procedures, or the integrity of the study.
* 3. Contraindication to MRI based on the standard MRI screening questionnaire at CBIC. Contraindications include ferromagnetic foreign bodies (e.g., shrapnel, ferromagnetic sheet metal fragments in the orbital area), certain implanted medical devices (e.g., older aneurysm clips, cardiac pacemakers), or claustrophobia.
* 4. Unexpected findings on screening MRI that are indicative of an occult brain disease, or will potentially compromise subject safety or the scientific integrity of the study data.
* 5. Previous exposure to ionizing radiation for research purposes, such that, in combination with the exposure from this study, their exposure to research associated radiation will be \>50 mSv/year for the previous year.
* 6. Subjects who are atopic, or have a known hypersensitivity to any component of the formulation of BPN14770 or to \[11C\]T2310 PET scan.
* 7. History of substance dependence, or current use of drugs of abuse.
* 8. History of regular weekly alcohol consumption \>21 units for male subjects or \>14units for female subjects or unable to abstain from alcohol from 24 hours prior to Screening visits and 24 hours prior to Period 2 Day (-1) until discharge at the end of Period 2.

  9. Female subjects who are pregnant or lactating. 10. Use of any prescription drugs within 14 days or 5 half-lives (whichever is longer) before the first dose of an investigational product, unless in the opinion of the investigator (or delegate) and the Sponsor's Medical Monitor the medication will not interfere with the study procedures, the pharmacokinetics of either the radiopharmaceutical or the investigational drug product, or compromise subject safety. An example of potentially acceptable drug use might be beta blockers in eye drops for glaucoma.
* 11. Use of any non-prescription drugs, including vitamins, herbal and dietary supplements within 14 days or 5 half-lives (whichever is longer) before the first dose of the study agents, unless in the opinion of the Investigator (or delegate) and the Sponsor's Medical Monitor the medication will not interfere with the study procedures, the pharmacokinetics of either the radiopharmaceutical or the investigational drug product, or compromise subject safety.
* 12. Subjects who have received an investigational drug as part in another study within the last 30 days or 5 half-lives of the investigational drug for the previous study (whichever is longer).
* 13. History of acquired immunodeficiency syndrome (AIDS).
* 14. Poor peripheral venous access.
* 15. Donation of ≥450 mL blood or loss of blood during surgery within 30 days prior to Day 1.
* 16. Plasma donation \>100 mL within 7 days prior to Day 1.
* 17. In the Investigator's judgement it is better for the subject not to be enrolled in the study.

Primary outcomes:
measure: Adverse Events
timeFrame: 1-8 Days
measure: Plasma Concentration
timeFrame: 24 Hours
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
Study officials:
affiliation: Weill Cornell College of Medicine
name: Paul D Mozley, MD
role: PRINCIPAL_INVESTIGATOR
References: