Study to Evaluate the Effects of BPN14770 on Scopolamine-induced Cognitive Impairment in Healthy Volunteers
Condition: Alzheimer Disease
MeSH terms: Alzheimer Disease; Cognitive Dysfunction
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a Phase 1, randomized, double-blind, placebo-controlled, 6-period crossover study to
      evaluate the effects of BPN14770 10 mg and 50 mg in reversing scopolamine-induced cognitive
      impairment in healthy volunteers. A positive control, donepezil 10 mg, will be included, and
      additivity of BPN14770 50 mg to donepezil 10 mg in reversing scopolamine effects will also be
      evaluated.
    

Detailed description: 
      A total of 38 subjects will be enrolled into the study. The study duration will be up to 12
      weeks with 6 weeks of single-dose Treatment Visits. The study will consist of a Screening
      Visit (up to 28 days prior to first study drug administration), six inpatient Treatment
      Visits (Periods 1 through 6), and a Follow-Up/Early Termination Visit (7-10 days after the
      last dose of study medication). An additional study visit may be necessary to complete the
      required cognitive test familiarization if not completed during the Screening Visit. Each
      Treatment Visit will occur approximately one week apart, allowing a 6 to 8 day washout
      period.

      Subjects will be randomized to 1 of 6 treatment sequences based on a computer-generated
      randomization schedule. Subjects will receive all 6 treatments as specified by the treatment
      sequence according to a 6 × 6 Williams Latin square design. The following treatments will be
      administered:

      A. Scopolamine placebo + BPN14770 placebo + donepezil placebo

      B. Scopolamine 0.5 mg + BPN14770 placebo + donepezil placebo

      C. Scopolamine 0.5 mg + BPN14770 10 mg + donepezil placebo

      D. Scopolamine 0.5 mg + BPN14770 50 mg + donepezil placebo

      E. Scopolamine 0.5 mg + donepezil 10 mg +BPN14770 placebo

      F. Scopolamine 0.5 mg + BPN14770 50 mg + donepezil 10 mg

      During each of the Treatment Visits (Periods 1 through 6), subjects will be admitted to the
      Clinical Research Unit (CRU) the day prior to each study drug administration (Day -1) and
      discharged the day after study drug administration (Day 2). On the morning of study drug
      administration (Day 1), subjects will be given study drug (BPN14770, donepezil, or placebo)
      with 240mL of room temperature water 2 hours prior to the scopolamine or scopolamine placebo
      sc injection. The timing for study drug administration will be referred to as t-2 (Hour -2).
      Breakfast should be available approximately 30 minutes following the morning drug
      administration. Two hours after study drug administration, the scopolamine or scopolamine
      placebo sc injection will be administered. The time at which the scopolamine or scopolamine
      placebo sc injection is administered will be referred to as t0 (Hour 0).

      Cognitive testing will be performed 30 minutes prior to treatment with scopolamine injection
      and at hours 1, 2, 3, 4, and 6 post-scopolamine injection.

      PK samples will be collected during the treatment period to confirm study drug is present.

      Safety assessments throughout the study will include physical exams, ECGs, vital signs,
      chemistry, hematology, and urinalysis.
    

Intervention name(s): BPN14770; BPN14770 placebo; Donepezil; Donepezil placebo; Scopolamine 0.6 MG/ML; Scopolamine placebo
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): investigational drug; placebo; comparator; placebo; cognition impairment; placebo
Other intervention name(s): Aricept; Aricept placebo; Hyoscine s.c.; Hyoscine s.c. placebo
Intervention MeSH terms: Scopolamine; Donepezil; Butylscopolammonium Bromide; BPN14770
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Cognition; Dementia; Phosphodiesterase Type 4D; PDE4D; Scopolamine; Donepezil