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

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

Tracking Information

• First Submitted Date: January 18, 2019
• First Posted Date: January 25, 2019
• Last Update Posted Date: October 31, 2019
• Actual Study Start Date: April 30, 2019
• Estimated Primary Completion Date: February 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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: Same as current

Current Secondary Outcome Measures (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: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Alzheimer's Disease

Intervention

• Drug: BPN14770
  Drug BPN14770
• Drug: Placebo
  Placebo

Study Arms

• 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

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: January 23, 2019): 255
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: February 2020
• Estimated Primary Completion Date: February 2020 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 55 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03817684
• Other Study ID Numbers: 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

• Plan to Share IPD: No

• Responsible Party: Tetra Discovery Partners
• Study Sponsor: Tetra Discovery Partners
• Collaborators: Not Provided

Investigators

• Study Director: Scott Reines, MD; Tetra Discovery Partners

• PRS Account: Tetra Discovery Partners
• Verification Date: October 2019