Putative Cognitive Enhancer VU319
Condition: Cognitive Impairment
MeSH terms: Cognitive Dysfunction
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a safety study of the molecule VU319 to ascertain pharmacokinetic and pharmacodynamic
      data and test cognitive enhancement in healthy volunteers.
    

Detailed description: 
      Alzheimer's Disease (AD) is a chronic and irreversible neurodegenerative disease
      characterized by the deterioration of memory and other cognitive functions, progressive
      impairments in normal daily living, and severe neuropsychiatric symptoms and behavioral
      disturbances1,2. Currently, there is no available prevention or cure for AD. Therapeutic
      strategies for the cognitive impairments in AD involve only symptomatic treatments, primarily
      through enhancement of cholinergic neurotransmission using AChEIs1,2.

      This first trial will be First-in-Human single ascending dose (SAD) phase 1 trial in healthy
      volunteers. One dose will be selected for expansion and evaluation of the effect of food on
      bioavailability. This Phase I trial, if successful, would serve as the basis for the design
      of multiple ascending dose (MAD) Phase I trial.

      Primary objectives To establish the safety and tolerability of single dose (up to VU319
      steady state) VU319 administration in healthy volunteers To establish the maximum tolerated
      dose of single dose (up to VU319 steady state) VU319 administration in healthy volunteers To
      characterize the plasma pharmacokinetics and urinary excretion of VU319 and metabolite after
      single dose oral administration in healthy volunteers Secondary objectives To establish the
      effect of food on the bioavailability and pharmacokinetic parameters of VU319 in healthy
      volunteers Exploratory Objectives To gain preliminary evidence that tolerable doses of VU319
      engage central M1 receptors by 1) altering/enhancing cognitive performance, and 2) enhancing
      cortical event related potentials (ERP) as a measure of increased cognitive function in
      healthy volunteers This will be a double blind, randomized, placebo controlled, and
      sequential dose escalation in male or female healthy volunteers. Gender will be balanced to
      the extent possible. Volunteers will receive oral VU319 single dose administration in the
      fasted state. Subjects meeting entry criteria will be enrolled in successive dose escalating
      cohorts of 8 subjects each (2 placebo and 6 active drug per dose level). The dose levels will
      be tested sequentially until the Maximum Tolerated Dose (MTD) is reached, or saturation of
      exposure occurs, or sustained VU319 plasma level above the safe daily exposure determined
      from animal toxicokinetic studies is achieved.

      The food effect sequence will be double blind, placebo controlled, two sequences, balanced
      and sequential cross-over in 12 healthy male or female volunteers (2 placebo and 10 active
      drug). Volunteers will receive oral VU319 single dose administration repeated once under
      either the fed (i.e. high fatty meal per FDA recommendations) or fasted state. The order of
      the two periods will be randomized and balanced with 6 subjects receiving treatment in the
      fed/fast or fast/fed order, respectively.

      Clinical safety endpoints include adverse event and symptoms data, vital signs (HR, BP,
      Respiratory Rate, body weight), 12-lead ECG changes, and laboratory safety assessments
      (hematology, plasma biochemistry, coagulation, urinalysis).
    

Intervention name(s): Single Dose of VU319; Single Dose Placebo; Fed State; Fasted State; Dose Escalation of VU319; Placebo Dose Escalation
Intervention type(s): Drug; Drug; Other; Other; Drug; Drug
Intervention description(s): Single dose of VU319; Single dose of placebo; drug is given 30 minutes after a high fat breakfast; drug is given after an overnight fast; dose levels of the cohorts will be increased step wise; dose levels of the cohorts will be increased step wise
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment