A Study to Investigate the Safety, Tolerability and Pharmacokinetics of JNJ-54861911 in Healthy Volunteers Compared With Placebo
Condition: Healthy
Study type: Interventional
Phase: Phase 1

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

Detailed description: 
      This study is a first-in-human, 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),
      single-ascending dose study. The study is designed to evaluate the safety (side effects),
      tolerability and 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 which is currently
      being developed for the treatment of Alzheimer's Disease.

      The study population will consist of approximately 64 healthy participants divided among
      approximately 8 cohorts (small groups). Each cohort will have 8 participants.

      For all participants the study will consist of 3 phases: a screening phase (between 28 and 2
      days prior to the first dose administration), a double-blind treatment phase, and a follow-up
      examination (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 and
      will remain in the unit until the evening of Day 3.

      The double-blind treatment phase will consist of three parts: Part 1 (Cohorts 1 to 3) is a
      single ascending dose part in young healthy male participants, between 18 and 54 years of
      age. Part 2 (Cohorts 4 to 7) is a single-ascending dose part in elderly male and female
      participants between 55 and 75 years of age including continuous cerebrospinal fluid (CSF)
      sampling. Within Parts 1 and 2 of the study, participants will be randomized (assigned by
      chance) to treatment with JNJ-54861911 (n=6/cohort) or matching placebo (n=2/cohort).
      Following each dose level, the observed safety and tolerability profile will be evaluated. If
      no side effects are observed and the pharmacokinetic data are roughly in line with predicted
      safe values, the dose will be escalated. Each participant of the next cohort will be given a
      higher dose of JNJ-54861911. As a general safety precaution for a first-in-human study, all
      dose administrations in Part 1, Cohort 1 and all further cohorts will be staggered.

      Part 1 of the study will primarily focus on determining safety and tolerability of
      JNJ-54861911 after single ascending dose administrations and understanding the primary
      pharmacokinetic characteristics of JNJ-54861911. In addition possible pharmacodynamic effects
      of JNJ-54861911 on plasma amyloid beta (Aβ) levels will be explored. The primary focus of
      Part 2 will be determining the maximal tolerated dose level of JNJ-54861911 or determine the
      safety and tolerability at the maximum feasible exposure level, whichever is reached first in
      healthy elderly participants. In addition the reduction in CSF Aβ over 36 hours post single
      dose administration of JNJ-54861911 will be explored. Planned doses will be 1 mg, 3 mg, 9 mg,
      27 mg, 81 mg, and 160 mg of JNJ- 54861911 or matching placebo, administered as a single oral
      dose. The starting dose of JNJ-54861911 in Part 2 will be the dose level tested in Part 1
      found to be safe and well tolerated, and that is expected to reduce CSF Aβ by 20 percent or
      more. The initial dose tested in Part 2 will not be higher than the doses tested in Part 1.

      Part 3 (Cohort 8) of the study will evaluate the effect of food on how JNJ-54861911 is
      absorbed, distributed within the body, and removed from the body. One single dose of
      JNJ-54861911 or matching placebo will be tested after consumption of a high fat breakfast.
      The dose of JNJ-54861911 tested in this part will be derived from the results obtained in
      Parts 1 and 2. Part 3 may be performed in parallel with Part 1 or 2 of the study. Depending
      on the pharmacokinetic properties and safety and tolerability profile of JNJ-54861911, young
      or elderly healthy participants may be recruited for this part. In addition male participants
      enrolled in Part 1 or Part 2 may also be enrolled for Part 3.

      Participants will be discharged from the clinical unit after the last study assessment on Day
      3 has been obtained. Participants will only be discharged if in the opinion of the
      investigator it is safe for the participants to be discharged. The participant will return to
      the clinical unit on Day 4 (72 h post dose) and Day 5 (96 h post dose) for plasma PK
      sampling. Safety assessments will be performed throughout the study. The maximal study
      duration for a participant will not exceed 6 weeks.
    

Intervention name(s): JNJ-54861911 1mg; JNJ-54861911 3 mg; JNJ-54861911 9 mg; JNJ-54861911 27 mg; JNJ-54861911 81 mg; JNJ-54861911 160 mg; JNJ-54861911 tbd; JNJ-54861911 9 mg; Placebo
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): JNJ-54861911 1 mg will be administered as a single oral dose after an overnight fast of at least 10 hours.; JNJ-54861911 3 mg will be administered as a single oral dose.; JNJ-54861911 9 mg will be administered as a single oral dose.; JNJ-54861911 27 mg will be administered as a single oral dose.; JNJ-54861911 81 mg will be administered as a single oral dose.; JNJ-54861911 160 mg will be administered as a single oral dose.; The dose of JNJ-54861911 will be derived from the results obtained in Parts 1 and 2.; Study drug will be administered after an overnight fast of at least 10 hours and within 120 minutes after placement of the spinal catheter.; Matching placebo will be given as a single oral dose.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Healthy; Safety; Tolerability; Pharmacokinetic; Alzheimer's Disease; JNJ-54861911