Status:
COMPLETED
Title: Evaluation of a Novel PET Radioligand for Phosphodiesterase-4D (PDE4D)
Lead Sponsor:
National Institute of Mental Health (NIMH)
Conditions:
Depression
Eligibility:
All Genders
18-55 years
Phase:
PHASE1
PHASE2
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...
Detailed Description
Objective Phosphodiesterase type 4 (PDE4) metabolizes 3 \<=,5 \<=-cyclic adenosine monophosphate (cAMP), thereby terminating this second messenger. PDE4 is selective to cAMP over cyclic guanosine mon...
Eligibility Criteria
Inclusion
- INCLUSION CRITERIA:
- 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).
- Additional inclusion criterial for Phase 2
- 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).
- EXCLUSION CRITERIA:
- 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.
- Additional exclusion criterial for Phase 2 and 4
- coagulation disorder;
- thrombocytopenia;
- Found to have inadequate collateral circulation of the radial artery
- Are unable to have an MRI scan (e.g., pacemakers or other implanted electrical devices, brain stimulators, dental implants, aneurysm clips (metal clips on the wall of a large artery), metallic prostheses (including metal pins and rods, heart valves, and cochlear implants), permanent eyeliner, implanted delivery pumps, or shrapnel fragments, metal fragments in the eye)
- Additional exclusion criterial for Phase 2
- Marked bradycardia (heart rate 45 beats per minute \[bpm\]) or tachycardia (heart rate 110 bpm) based on supine ECG values obtained at Screening, before the first dose of BPN14770 on the day of the study. Out-of-range vital signs may be repeated once at each eligibility assessment (prior to the start of dosing).
- History of hematological disorders (e.g., thrombocytopenia) in the immediate family (i.e., parents and siblings).
- Clinically important or significant conduction abnormalities on single ECG (including QTc interval 450 msec) or evidence or history of long QT syndrome. This exclusion applies to the ECGs obtained at Screening, before the first dose of BPN14770 on the day of the study.
- Current or past history of gastric or duodenal ulcers or other diseases of the gastrointestinal tract that could interfere with absorption of study drug. Note: Subjects with a history of appendectomy or cholecystectomy may be enrolled.
- Active acute or chronic infectious diseases.
- Any history of alcohol or drug abuse within the previous year prior to the Screening visit (per the current edition of the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition: DSM-5), or regular (daily) consumption of alcohol exceeding two bottles of beer, or the equivalent amount of other forms of alcohol (1 serving = 12 oz beer, 5.0 oz wine, or 1.5 oz distilled spirits).
- Unwilling to abstain from alcohol within 72 hours of before the first dose of BPN14770.
- Currently ingest nicotine in any way (including smoking cigarettes, vaping, and via patch), or have ingested any nicotine products within the past 3 months.
- Participation in other clinical studies involving investigational drug within the previous 30 days prior to the first day of the study.
- Unwilling to forgo donation of blood or blood products (including plasma) during the 8 weeks before the first day of the study.
- History of allergy to penicillin or sulfonamides, or any other clinically significant drug allergy that includes symptoms such as shortness of breath, rash, or edema.
- A suicidal ideation intensity score of 2 or higher per screening C-SSRS assessment and/or any suicidal behavior within the past 30 days.
Exclusion
Key Trial Info
Start Date :
March 12 2019
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
February 11 2020
Estimated Enrollment :
3 Patients enrolled
Trial Details
Trial ID
NCT03861000
Start Date
March 12 2019
End Date
February 11 2020
Last Update
March 22 2021
Active Locations (1)
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1
National Institutes of Health Clinical Center
Bethesda, Maryland, United States, 20892