Multiple Ascending Dose Study of ALZ-801
Condition: Alzheimer Disease
MeSH terms: Alzheimer Disease
Study type: Interventional
Phase: Phase 1

Summary: 
      Phase I, single-center, double-blind, randomized, placebo-controlled, parallel-group study of
      the safety, tolerability, and pharmacokinetics (PK) in plasma and urine, of multiple
      ascending doses of ALZ-801 (capsule, Part 1; prototype tablet Part 2) and the primary
      metabolite in healthy male or female subjects.
    

Detailed description: 
      The study was conducted in two parts:

      Part 1 Primary objective: To evaluate the safety, tolerability, and pharmacokinetics, of
      multiple doses of ALZ-801 capsule formulation in healthy elderly subjects.

      Methodology: Phase I, single center, in-patient and out-patient, double-blind, randomized,
      placebo-controlled, parallel-group study of the safety, tolerability and pharmacokinetics
      (PK) in plasma and urine of multiple ascending doses of ALZ-801 in healthy male or female
      subjects aged 50 to 75 years, inclusive. A total of 36 subjects were enrolled into 3
      successive cohorts (A, B, C with 12 subjects per cohort) and randomized in a 3:1 ratio to
      receive treatment with ALZ-801 capsules (9 subjects) or placebo capsules (3 subjects) for 2
      weeks. Progression to the next cohort was permitted after review of safety and available PK
      data suggested that it was safe to do so. Subjects were confined to the clinical unit for the
      first day of dosing (Day 1 and for Days 7 through 14). Subjects took investigational drug at
      home for Days 2 through 6).

      Cohorts A was dosed in the fasted state and evaluated 171 mg ALZ-801 or placebo QD for 1 day,
      followed by 171 mg ALZ-801 or placebo BID for 6 days and 256.5 mg or placebo QD for 7 days.

      Cohort B was dosed in the fasted state and evaluated 256.5 mg ALZ-801 or placebo QD for 1
      day, followed by 256.5 mg ALZ-801 or placebo BID for 6 days and 340 mg or placebo QD for 7
      days.

      Cohort C was dosed in the fed state and evaluated 256.5 mg ALZ-801 or placebo QD for 1 day,
      followed by 256.5 mg ALZ-801 or placebo BID for 6 days, then 340 mg or placebo BID for 6 days
      and 340 mg or placebo QD for 1 day.

      Part 2 Primary objective: To evaluate the safety, tolerability, and pharmacokinetics, of
      multiple doses of prototype ALZ-801 tablet formulation in healthy elderly subjects.

      Methodology: Phase I, single center, in-patient and out-patient, double-blind, randomized,
      placebo-controlled, parallel-group study of the safety, tolerability and pharmacokinetics
      (PK) in plasma and urine of multiple ascending doses of ALZ-801 in healthy male or female
      subjects aged 60 to 75 years, inclusive. A total of 12 subjects were enrolled into one cohort
      (D) and randomized in a 3:1 ratio to receive treatment with ALZ-801 tablets (9 subjects) or
      placebo capsules (3 subjects) for 1 week.

      Cohort D was dosed in the fed state and evaluated 265 mg ALZ-801 or placebo QD for 1 day,
      followed by 265 mg ALZ-801 prototype tablet or placebo BID for 5 days, 265 mg or placebo QD
      for 1 day.

      For all subjects in the study blood and urine samples for the determination of concentrations
      of ALZ-801, and its metabolites, were collected for up to 24 h after the first dose of
      medication on Day1; and for up to 48 hours after the last dose of medication on Day 7 (Cohort
      D) or Day 14 (Cohorts A, B and C). All subjects had blood samples and safety assessment at 72
      and 96 hours after the final dose of medication. All subjects returned for a post treatment
      follow-up 7-10 days after the last dose of study medication.
    

Intervention name(s): ALZ-801 or matching placebo
Intervention type(s): Drug
Allocation: Randomized
Intervention model: Sequential Assignment
Intervention model description: double blind, placebo controlled, matching placebo
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment