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
Effects of BPN14770 in Patients with Early Alzheimer’s Disease
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
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
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
7. All subjects must have a caregiver who is willing and able to ensure compliance with
study medications, visits, and study procedures.
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
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
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
- CiTrials, Inc., Bellflower, California, United States, 90709
- ATP Clinical Research, Inc, Costa Mesa, California, United States, 92626
- Alliance for Research, Long Beach, California, United States, 90807
- Pacific Research Network Inc., San Diego, California, United States, 92103
- HB Clinical Trials, Inc., Santa Ana, California, United States, 92704