Clinical trial NCT03817684: Tetra PICASSO AD Trial: Study to Evaluate Effects of BPN14770 in Early Alzheimer's Subjects
Official title: A Randomized , Double Blind, Placebo Controlled, 3-Arm Parallel Design Study to Evaluate the Effects of BPN14770 in Patients With Early Stage Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Alzheimer's Disease
Lead sponsor: Tetra Discovery Partners
Sponsor class: INDUSTRY
First posted: 2019-01-25
Enrollment: 255
Sex: ALL
Minimum age (years): 55
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A Randomized, Double-blind, Placebo Controlled, 3-Arm Parallel Design Study to Evaluate the Effects of BPN14770 in Patients with Early Alzheimer's Disease


Eligibility criteria: Inclusion Criteria:

1. Males or females between the ages of 55 and 85 years with a clinical diagnosis of early stage AD, defined according to the following criteria assessed during Screening and at Baseline :

   1. Clinical Dementia Rating (CDR) score of 0.5 or 1, with Memory Box score of 0.5 or greater
   2. MMSE score of 20 or greater
   3. RBANS DMI score ≤ 85 Note: PET imaging for amyloid is not required for diagnosis, which will be made on clinical grounds.
2. Currently receiving a stable (at least 2 months) dose regimen of donepezil or another cholinesterase inhibitor for treatment of Alzheimer's disease. Doses of these drugs may not be changed during the trial.

   Note: Memantine is not permitted during the trial and must be discontinued at least 3 weeks prior to Baseline.
3. Modified Hachinski Ischemia score \< 4.
4. Body mass index (BMI) \< 38 kg/m2, inclusive, and body weight of \>48 kg (105 pounds) at screening.
5. Female subjects must be at least two years post-menopausal (subjected reported menopausal status), surgically sterile (bilateral tubal ligation, hysterectomy, or bilateral oophorectomy at least 6 months prior to first study drug administration), or willing to either (1) utilize hormonal contraception plus one barrier method or (2) use two barrier methods of contraception (e.g. diaphragm and spermicide) from initial screening until one month after taking the final dose. An intrauterine device (IUD) is considered a barrier method of contraception in this study. 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 first study drug administration, or use at least one barrier method of birth control).
6. Able to understand and comply with the study procedures, voluntarily agree to participate in this study, and provide written informed consent prior to start of any study-specific procedures.
7. All subjects must have a caregiver who is willing and able to ensure compliance with study medications, visits, and study procedures.

Exclusion Criteria:

1. Any medical or neurological condition (other than early stage AD) that might be a contributing cause to the subject's cognitive impairment.
2. History of stroke or multiple (\>3 discreet episodes) Transient Ischemic Attacks (TIAs), severe head trauma with cognitive sequelae, uncontrolled seizures, or unexplained prolonged loss of consciousness (\> 1 minute) during the past year.
3. Clinically significant major psychiatric illness during the past 6 months.
4. History of unstable angina, myocardial infarction, chronic heart failure, or clinically significant conduction abnormalities during the past year.
5. Clinically significant liver or renal disease.
6. Clinically significant abnormality, in the Investigator's judgment, in hematology, chemistry, or urinalysis.
7. Positive serology results for hepatitis B surface antigen (HbsAg) or hepatitis C virus (HCV).
8. Abnormal liver function test at the Screening Visit (aspartate aminotransferase or alanine aminotransferase \>2

   × the upper limit of normal \[ULN\], or total bilirubin \>1.7 × ULN, based on appropriate age and gender normal values). Subjects may be re-screened once.
9. Marked hypotension (systolic blood pressure \[BP\] ˂90 mmHg or diastolic BP ˂50 mmHg) or hypertension (systolic BP ˃160 mmHg or diastolic BP ˃100 mmHg) based on sitting values. O ut-of-range results may be repeated once at Screening, and eligibility must be confirmed at Baseline.
10. Marked bradycardia (heart rate ˂45 beats per minute \[bpm\]) or tachycardia (heart rate ˃115 bpm) based on supine ECG values. Out-of-range results may be repeated once at Screening, and eligibility must be confirmed at Baseline.
11. Clinically important conduction abnormalities on ECG, or evidence or history of long QT syndrome based on supine ECG values obtained at Screening. Out-of-range results may be repeated once and eligibility confirmed at Baseline.
12. Active 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.
13. Active acute or chronic infectious diseases that would interfere with subject's participation in the study.
14. Unable to discontinue centrally active medications (other than cholinesterase inhibitors), including memantine, psychotropic drugs other than SSRIs (which must have been stable for 2 months and remain stable throughout the study), sedative antihistamines or other centrally active medications with potential cognitive effects (e.g., CNS-penetrant beta blockers).
15. Unable to discontinue moderate to strong inhibitors or inducers of CYP3A4, CYP2D6, or other cytochromes at least 14 days prior to the first dose of study drug. A complete listing of such inhibitors or inducers may be found in http://medicine.iupui.edu/clinpharm/ddis/main-table (Other prescription or non-prescription drugs such as antihypertensive or cholesterol lowering agents are allowed, if, in the Investigator's judgement, they would not interfere with the study medication or the cognitive testing.)
16. A suicidal ideation intensity score of 3 or higher per screening Columbia Suicide Severity Rating Scale (CSSRS) assessment on Day 1 (Baseline) and/or any suicidal behavior within the past 28 days.
17. History of chronic alcohol or other substance abuse, including marijuana, 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).
18. Inability or unwillingness to comply with the protocol, including performing the cognitive function tests, or likely inability to complete the study.
19. Participation in other clinical studies involving investigational drug within the previous 30 days prior to the Screening Visit.
20. Donation of blood within 4 weeks, or blood products within 2 weeks, prior to first study drug administration.
21. History of clinically significant drug allergy that includes symptoms such as shortness of breath, rash, or edema.
22. Clinically significant B12 deficiency within 12 months prior to Visit 1 (Screening). Participants on stable replacement therapy for a minimum of 3 consecutive months immediately prior to Visit 1 (Screening) may be included

Primary outcomes:
measure: Change From Baseline in Repeatable Battery for the Assessment of Neurological Status- Delayed Memory Index (RBANS- DMI) at Week 13
timeFrame: Baseline, Week 13
Secondary outcomes:
measure: Change From Baseline in Repeatable Battery for the Assessment of Neurological Status (RBANS) Total Score at Week 13
timeFrame: Baseline, Week 13
measure: Change From Baseline in Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) Total Score at Week 13
timeFrame: Baseline, Week 13
measure: Change From Baseline in Mini-Mental State Exam (MMSE) Total Score at Week 13
timeFrame: Baseline, Week 13
measure: Change From Baseline in Clinical Dementia Rating Sum of Boxes Score (CDR-SB) at Week 13
timeFrame: Baseline, Week 13
measure: Clinical Global Impression - Improvement (CGI-I) Score
timeFrame: Week 13
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Generations at Agritopia/CCT Research
state: Arizona
city: Bellflower
country: United States
facility: CiTrials, Inc.
state: California
city: Costa Mesa
country: United States
facility: ATP Clinical Research, Inc
state: California
city: Long Beach
country: United States
facility: Alliance for Research
state: California
city: San Diego
country: United States
facility: Pacific Research Network Inc.
state: California
city: Santa Ana
country: United States
facility: HB Clinical Trials, Inc.
state: California
city: Denver
country: United States
facility: Mile High Research Center
state: Colorado
city: Atlantis
country: United States
facility: JEM Research Insitute
state: Florida
city: Coral Gables
country: United States
facility: Linfritz Research Group
state: Florida
city: Delray Beach
country: United States
facility: Brain Matters Research
state: Florida
city: Hallandale Beach
country: United States
facility: MD Clinical
state: Florida
city: Hialeah
country: United States
facility: Galiz Research
state: Florida
city: Lake Worth
country: United States
facility: Alzheimer's Research and Treatement Center
state: Florida
city: Miami
country: United States
facility: Optimus Clinical Research
state: Florida
city: Miami
country: United States
facility: BioMed Research Institute
state: Florida
city: Miami
country: United States
facility: Finlay Medical Research
state: Florida
city: Miami
country: United States
facility: Pharmax Research Clinic
state: Florida
city: Miami
country: United States
facility: Vitae Research Center, LLC
state: Florida
city: Miami
country: United States
facility: Arocha Research Center
state: Florida
city: Miami
country: United States
facility: Allied Biomedical Research Institute Inc.
state: Florida
city: Miami
country: United States
facility: Advanced Clinical Research Network
state: Florida
city: Orlando
country: United States
facility: Gutierrez Medical Center LLD
state: Florida
city: Ormond Beach
country: United States
facility: Neurology Associates of Ormond Beach
state: Florida
city: Palm Beach
country: United States
facility: Palm Beach Neurological Center
state: Florida
city: Palmetto Bay
country: United States
facility: IMIC Inc
state: Florida
city: Pensacola
country: United States
facility: Synergy Clinical Research
state: Florida
city: Pompano Beach
country: United States
facility: Quantum Laboratories
state: Florida
city: Elk Grove Village
country: United States
facility: Neurosciences Research
state: Illinois
city: Berlin
country: United States
facility: Hassman Research Institute
state: New Jersey
city: Toms River
country: United States
facility: Advanced Memory Research Institute of NJ PC
state: New Jersey
city: Brooklyn
country: United States
facility: Integrative Clinical Trials
state: New York
city: Lake Success
country: United States
facility: Neurological Associates of Long Island
state: New York
city: New York
country: United States
facility: Manhattan Behavioral Medicine PLLC
state: New York
city: Charlotte
country: United States
facility: Alzheimers Memory Center
state: North Carolina
city: Dayton
country: United States
facility: Neurology Diagnostics, Inc.
state: Ohio
city: Westerville
country: United States
facility: MDH Research
state: Ohio
city: Portland
country: United States
facility: Summit Research Network
state: Oregon
city: Allentown
country: United States
facility: Lehigh Center for Clinical Research
state: Pennsylvania
city: Cordova
country: United States
facility: Neurology Clinic, P.C.
state: Tennessee
city: Orem
country: United States
facility: Aspen Clinical Research
state: Utah
city: Salt Lake City
country: United States
facility: Wasatch Clinical Research, LLC
state: Utah
Study officials:
affiliation: Tetra Discovery Partners
name: Scott Reines, MD
role: STUDY_DIRECTOR
References: