A Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of JNJ-54861911 in Healthy Elderly Participants
Condition: Healthy
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and
      pharmacodynamics of multiple-ascending dose JNJ-54861911 which is currently being developed
      for the treatment of Alzheimer's disease.
    

Detailed description: 
      This multiple ascending dose study is anticipated to enroll 5 cohorts (small groups). Cohorts
      1 to 4 will be conducted as a double-blind (neither investigator nor participant knows which
      treatment the participant receives), randomized (participants are assigned different
      treatments based on chance), placebo-controlled (placebo is an inactive substance that is
      compared with a drug to test whether the drug has a real effect in a clinical trial) study.
      Cohort 5 will be performed as an open-label study (all people know the identity of the
      intervention), using a recently made available solid dose formulation of JNJ-54861911.

      The study is designed to evaluate the safety (side effects), tolerability, pharmacokinetics
      (how the drug is absorbed in the body, distributed within the body, and how it is removed
      from the body over time, ie, what the body does to the drug), and pharmacodynamics (what the
      drug does to the body) of JNJ-54861911. The study population will consist of approximately 38
      healthy elderly participants divided among approximately 5 cohorts. For all participants the
      study will consist of 3 phases: eligibility screening examination phase (between 28 and 2
      days prior to the first dose administration), a 14-day double-blind (Cohorts 1 to 4) or
      open-label (Cohort 5) treatment phase, and a follow-up examination phase (within 7 to 14 days
      after last dose administration). Participants who successfully complete the screening
      examination and are considered eligible to participate will be admitted to the clinical unit
      on Day -1 before administration of the study drug.

      Cohorts 1 to 4 will consist of 8 participants. Within these cohorts, participants will be
      randomly assigned to double-blind treatment with an oral suspension of JNJ-54861911 3 mg, 10
      mg, 30 mg, or 80 mg (n=6/cohort) or matching placebo (n=2/cohort). Cohorts 1 to 4 will be
      used for dose escalations and assessing the maximal tolerated dose using an oral suspension
      of JNJ-54861911. Cohort 5 will consist of 6 participants who will all receive open-label
      treatment with a single solid dose formulation of JNJ 54861911 25 mg. Cohort 5 will assess if
      the recently made available solid dose formulation (strength 25 mg) has similar
      pharmacokinetic properties and pharmacodynamic effects as the oral suspension at a dose level
      in the range that has been assessed earlier (Cohorts 1 to 4) and was found to be safe and
      well tolerated. All cohorts (Cohorts 1 to 5) will follow the same study assessments.

      Participants will be administered single doses of study medication on Days 1 to 14. Following
      and/or during each dose level of the study (cohort), the observed safety and tolerability
      profile of the ongoing cohort and previous cohort will be evaluated and doses will only be
      increased if the observed safety and tolerability profile is acceptable. Plasma
      pharmacokinetic profiles of the ongoing cohort (up to and including Day 7) and plasma and
      cerebrospinal fluid (CSF) pharmacokinetic profiles as well as CSF plasma amyloid beta (Aβ)
      profiles of the previous cohort (up to and including Day 14) if applicable, will support dose
      increase decisions. Actual dose levels as well as the magnitude of dose escalation will
      depend on the results of the ongoing single-ascending dose study (54861911ALZ1001), the
      observed safety and tolerability profile, as well as the observed exposures. Participants
      will be discharged from the clinical unit after the last study assessment on Day 16 or
      approximately 24 hours after the indwelling catheter has been removed, whatever occurs later.
      If discharged on Day 16, participants will return to the clinical unit on Day 17 (72 hours
      post-dose Day 14) for plasma pharmacokinetic sampling. Safety assessments will be performed
      throughout the study. The maximal study duration for a participant will not exceed 8 weeks.
    

Intervention name(s): JNJ-54861911 3 mg; JNJ-54861911 10 mg; JNJ-54861911 30 mg; JNJ-54861911 80 mg; JNJ-54861911 25 mg; Placebo
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): JNJ-54861911 3 mg will be administered as an oral suspension formulation.; JNJ-54861911 10 mg will be administered as an oral suspension formulation.; JNJ-54861911 30 mg will be administered as an oral suspension formulation.; JNJ-54861911 80 mg will be administered as an oral suspension formulation.; JNJ-54861911 25 mg will be administered as a solid dose formulation.; Matching placebo will be administered as an oral suspension formulation.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Healthy; Elderly; Safety; Tolerability; Pharmacokinetic; Alzheimer's Disease; JNJ-54861911