Title: Evaluation of a Novel PET Radioligand for Phosphodiesterase-4D (PDE4D)

NCT03861000 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 19006419-M-0064
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

Background: The brain enzyme phosphodiesterase-4D (PDE4D) may affect thinking and depression. Drugs with some radioactivity can attach to enzymes and be seen on a scan. Researchers want to test a new radioactive drug, 11C-T-1650, to measure PDE4D in the brain and body. They also want to see if the new drug BPN14770 blocks 11C-T-1650 from the brain. They want to learn more about psychiatric disorders and possible treatments. Objectives: To study how well 11C-T-1650 helps show PDE4D on a scan and to see if BPN14770 blocks it. Eligibility: Healthy adults at least 18 years old Design: Participants will be screened in other protocols. Some participants will have 1 body PET scan. Some participants will have 2 brain PET scans and 1 brain MRI within 1 year. Some participants (ages 18 55) will: Have 3 brain PET scans and 1 MRI Take BPN14770 by mouth twice daily for 3 7 days Have blood and urine tests Have a follow-up physical exam and heart test PET (positron emission tomography) scans will take 2 3 hours. Participants will: Have a thin plastic tube (catheter) placed in an arm vein by needle. Get a small amount of 11C-T-1650 injected via catheter. Another catheter may be placed to draw blood. Lie quietly on a bed that slides into a donut-shaped scanner without sleeping. They may get a short break. Have heart and vital signs monitored. Have blood and urine tests. Learn about drinking fluids and urinating after the scan MRI (magnetic resonance imagining) scans will take 30 60 minutes: Participants will lie on a table that slides into a metal cylinder in a magnetic field. Sponsoring Institute: National Institute of Mental Health ...

Conditions

Depression

Keywords

Healthy Control Subjects; PET Imaging; Receptor Occupancy; Depression

Outcome Measures

Primary Outcomes (5)

• Whole Brain Total Distribution Volume (VT) - Baseline

  To determine whether the uptake of 11C-T-1650 in brain reflects the distribution of PDE4D

  120 minutes after the start of the first scan

• Whole Brain Total Distribution Volume (VT)-1st Blocked

  To determine whether the uptake of 11C-T-1650 in brain reflects the distribution of PDE4D

  120 minutes after the start of the second scan

• Standard UptakeValue (SUV) Area Under the Curve (AUC) (60-120min)-Baseline Whole Brain

  Measure binding site occupancy of BPN14770 administered at doses that may be used in clinical trials.

  120 minutes after the start of the scan

• Standard UptakeValue (SUV) Area Under the Curve (AUC) (60-120min)-1st Blocked Whole Brain

  Measure binding site occupancy of BPN14770 administered at doses that may be used in clinical trials.

  120 minutes after the start of the first scan

• Standard UptakeValue (SUV) Area Under the Curve (AUC) (60-120min)-2nd Blocked Whole Brain

  Measure binding site occupancy of BPN14770 administered at doses that may be used in clinical trials.

  120 minutes after the start of the first scan

Study Arms (2)

Whole body PET Scan with intravenous 11C-T-1650

EXPERIMENTAL

10 mCi of 11C-T-1650 given intravenously once followed by a Whole Body PET scan. This was done for whole body dosimetry calculations.

Drug: [C-11]T-1650

Brain PET scan with 11C-T-1650 and blocking with BPN14770

EXPERIMENTAL

Baseline brain PET scan (scan 1) with 20 mCi of 11C-T-1650 given intravenously, followed by a second Brain PET scan (scan 2) 90-180 minutes after first dose administration of BPN14770 50mg given orally. A third brain PET scan (scan 3) is performed after the last dose of BPN14770. 20 mCi of 11C-T-1650 is given intravenously with each PET scan. BPN14770 50mg given orally twice a day for a total of seven doses. BPN14770 is a PDE4D-inhibitor.

Drug: [C-11]T-1650; Drug: BPN14770

Interventions

[C-11]T-1650 DRUG

radio-labeled drug

Brain PET scan with 11C-T-1650 and blocking with BPN14770; Whole body PET Scan with intravenous 11C-T-1650

BPN14770 DRUG

selective compound

Brain PET scan with 11C-T-1650 and blocking with BPN14770

Eligibility Criteria

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

You may qualify if:

• All phases
• Age greater than equal 18.
• Able to give written informed consent.
• Medically and psychiatrically healthy.
• Enrolled in 01-M-0254 The Evaluation of Participants with Mood and Anxiety Disorders and Healthy Volunteers (PI: Dr. Carlos Zarate) or 17-M-0181 Recruitment and Characterization of Healthy Research Volunteers for NIMH Intramural Studies (PI: Dr. Joyce Chung).
• Age less than or equal to 55.
• Body mass index between 18 kg/m2 to 32 kg/m2, inclusive, and body weight of greater than equal 50 kg (110 pounds).
• 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 two barrier methods of contraception from initial screening until one month after taking the last dose of study drug.
• 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).

You may not qualify if:

• All phases
• Clinically significant laboratory abnormalities based on the following tests (performed under screening protocol 01-M-0254 or 17-M-0181): CBC; acute care panel; hepatic panel; mineral panel; urinalysis; urine drug screen; urine pregnancy test (females); and lipid panel; hepatitis panel (A, B, C); syphilis screening test; total protein; uric acid;creatine kinase; cholesterol; thyroid panel; prothrombin and partial prothrombin tests; and EKG.
• Have a brain disease (such as multiple sclerosis or stroke).
• Any current Axis I diagnosis, based on interview and self-reporting performed under screening protocol 01-M-0254 or 17-M-0181.
• Positive HIV test.
• Current or past history of significant cardiovascular, cerebrovascular, pulmonary, renal, or liver disease. Stable, well-controlled hypertension and hyperlipidemias are allowed.
• Taking psychotropic drugs (i.e. benzodiazepines or antidepressants) including sedative antihistamines; moderate to strong inhibitors or inducers (i.e. fluconazole or ciprofloxacin) of any CYP450 enzyme. A complete listing of such inhibitors or inducers may be found in Attachment 1, List of P450 inhibitors.
• Recent exposure to radiation related to research (e.g., PET from other research) that, when combined with this study, would be above the allowable limits.
• Inability to lie flat on camera bed for at least two hours.
• Pregnancy or breastfeeding.
• Positive screen for drugs of abuse or cotinine (at screen or upon admission), or a positive alcohol result (upon admission).
• Current use of psychiatric medications.
• NIMH employees and staff or immediate family members of NIMH employee/staff.
• coagulation disorder;
• thrombocytopenia;

Sponsors & Collaborators

• National Institute of Mental Health (NIMH): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Depression

Interventions

BPN14770

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Results Point of Contact

• Title: Dr Robert Innis
• Organization: National Institute of Mental Health

innisr@mail.nih.gov

+1 301 693 2979

Study Officials

• Robert B Innis, M.D.

  National Institute of Mental Health (NIMH)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: March 1, 2019
• First Posted: March 4, 2019
• Study Start: March 12, 2019
• Primary Completion: February 11, 2020
• Study Completion: February 11, 2020
• Last Updated: March 22, 2021
• Results First Posted: February 12, 2021

Record last verified: 2020-02

Locations

US (1)