A Phase 1 (First in Human) Randomized, Double-blind, Placebo-controlled SAD, MAD Study With Oral REM0046127
Condition: Alzheimer Disease
MeSH terms: Alzheimer Disease
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a phase 1 randomized double blind, first in human (FIH) study with the novel oral
      Alzheimer drug candidate REM0046127, which consists of two main parts, a single ascending
      dose (SAD) study with 7 cohorts followed by a multiple ascending dose (MAD) study with 2
      cohorts.
    

Detailed description: 
      SAD

      As a baseline, 5 cohorts of 8 young healthy males are foreseen, with a repeat to assess food
      impact and an additional elderly cohort. Depending on the early FIH findings, the number of
      cohorts could be more or less. FIH studies include initially only males due to the incomplete
      nature of preclinical reproductive toxicology studies

        -  Treatment duration: single day

        -  Each cohort:

             -  2 volunteers on placebos, of which 1 sentinel

             -  6 volunteers on study drug, of which 1 sentinel

        -  Timing for each cohort will be about 21 days

             -  Subjects will be screened for selection from day -21 to day -1 before starting the
                experimental phase of each cohort

             -  First the 2 sentinels will be dosed

             -  Following the review of sentinel safety and tolerability data through the Data
                Safety Monitoring Board (DSMB) after one day or 2 half-life times following the
                sentinel dosing, the remaining 1+5 subjects will be randomized and dosed
                approximately 7 days after the sentinels

      MAD

        -  First cohort of 10 healthy young male subjects. This cohort can be initiated after the
           food interaction has been assessed in the last safe SAD cohort, and does not need to
           wait for the elderly cohort.

        -  Second cohort of 12 healthy elderly subjects:

             -  The 1st cohort of healthy young male at about 75% of the Maximum Tolerated Dose
                (MTD) of the SAD

             -  The 2nd cohort of healthy older male and female (not of child-bearing potential) at
                about 50 or 100% of the highest tolerable dose of the SAD, depending on the
                observations in the 1st MAD cohort to assess potential impact of age on
                Pharmacokinetics (PK)

             -  Treatment duration: 7 days

             -  Timing for each cohort will be about 35 days

        -  Subjects will be screened for selection from day -21 to day -1 before starting the
           experimental phase each cohort

        -  First the sentinels will be dosed

        -  Following the review of sentinel safety and tolerability data through the DSMB, the
           remaining subjects will be randomized and dosed approximately 14 days later

        -  According to plan the sentinels of the 2nd cohort will be dosed about 35 days after the
           sentinels of the 1st cohort.
    

Intervention name(s): REM0046127; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Oral solution: 100 mg/mL REM0046127; Oral solution with 0 mg/mL REM0046127
Allocation: Randomized
Intervention model: Sequential Assignment
Intervention model description: A Single Ascending Dose study with 6 Cohorts with 8 young male subjects each and 1 cohort with 4 male and 4 female subjects A Multiple Ascending Dose MAD study with 2 Cohorts: (Cohort 1: 10 young male subjects, Cohort 2: 6 elderly male and 6 elderly female (not of CBP) subjects.
Masking: Double (Participant, Investigator)
Primary purpose: Treatment