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Tetra PICASSO AD Trial: Study to Evaluate Effects of BPN14770 in Early Alzheimer's Subjects

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ClinicalTrials.gov Identifier: NCT03817684
Recruitment Status : Active, not recruiting
First Posted : January 25, 2019
Last Update Posted : October 31, 2019
Sponsor:
Information provided by (Responsible Party):
Tetra Discovery Partners

Tracking Information
First Submitted Date  ICMJE January 18, 2019
First Posted Date  ICMJE January 25, 2019
Last Update Posted Date October 31, 2019
Actual Study Start Date  ICMJE April 30, 2019
Estimated Primary Completion Date February 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 23, 2019)
Repeatable Battery for the Assessment of Neurological Status- Delayed Memory Index (RBANS- DMI) [ Time Frame: Week 13 ]
Change from baseline of RBANS-DMI score. Power based on true difference of 7.15 units on normalized mean of score of 100 between 25mg dose Arm vs Placebo
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 23, 2019)
  • Repeatable Battery for the Assessment of Neurological Status (RBANS) total score [ Time Frame: Weeks 1,2,4,8,13 ]
    Comparison of RBANs Total scores to baseline at each timepoint
  • Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) [ Time Frame: Week 8, 13 ]
    ADCS-ADL total score compared to baseline at each time point
  • Mini-Mental State Exam (MMSE) Score [ Time Frame: Weeks 1,2,4,8,13 ]
    MMSE total score versus baseline at each timepoint
  • Clinical Dementia Rating Sum of Boxes Score (CDR-SB) [ Time Frame: Week 13 ]
    CDR-SB versus Baseline at each timepoint
  • Clinical Global Impression - Improvement (CGI-I) Score [ Time Frame: Week 1,2,4,8,13 ]
    CGI-I Score versus Baseline at each timepoint
  • Pharmacokinetics: Maximum Drug Plasma Levels [ Time Frame: Weeks 1,4,8,13 ]
    Maximum Drug plasma concentration levels by study arm
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Tetra PICASSO AD Trial: Study to Evaluate Effects of BPN14770 in Early Alzheimer's Subjects
Official Title  ICMJE 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
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
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Alzheimer's Disease
Intervention  ICMJE
  • Drug: BPN14770
    Drug BPN14770
  • Drug: Placebo
    Placebo
Study Arms  ICMJE
  • Experimental: BPN14770 10mg bid
    10 mg bid dose of the Drug BPN14770
    Intervention: Drug: BPN14770
  • Experimental: BPN 14770 25mg bid
    25mg bid dose of the Drug BPN14770
    Intervention: Drug: BPN14770
  • Placebo Comparator: Placebo
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: January 23, 2019)
255
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 2020
Estimated Primary Completion Date February 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 55 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03817684
Other Study ID Numbers  ICMJE BPN14770-CNS-201
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Tetra Discovery Partners
Study Sponsor  ICMJE Tetra Discovery Partners
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Scott Reines, MD Tetra Discovery Partners
PRS Account Tetra Discovery Partners
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP