Ketamine Challenge Study With JNJ-40411813
Condition: Perceptual Disorders; Confusion; Schizophrenia
MeSH terms: Confusion; Perceptual Disorders; Schizophrenia
Study type: Interventional
Phase: Phase 1

Summary: 
      The objective of this study is to investigate whether JNJ-40411813 versus placebo reduces
      psychosis-like symptoms, induced by infusion of a low dose of ketamine. Effects of
      JNJ-40411813 on ketamine-induced symptoms will be evaluated about 3 hours after a single oral
      dose when the concentration of JNJ-40411813 in the blood is at its maximum and up to 24 hours
      after dose administration to assess the duration of a potential JNJ-40411813 effect.
    

Detailed description: 
      This will be a double-blind (neither physician nor the volunteer knowns whether placebo or
      active drug is administered), placebo-controlled, randomized (study drug is assigned by
      chance), 2-way crossover (the same procedure is repeated twice so that the volunteer receives
      placebo as well as active drug) study in cohorts of a maximum of 16 healthy male volunteers
      each, to investigate the effect of JNJ 40411813 or placebo on ketamine-induced psychosis-like
      symptoms. In the first cohort (Cohort 1), JNJ 40411813 effects at a dose level of 500 mg will
      be evaluated at the time of maximal plasma concentrations. If JNJ 40411813 significantly
      reduces psychotic symptoms relative to placebo, a second cohort (Cohort 2) will be initiated
      to investigate the effects of JNJ 40411813 at 24 hours following dose administration. If
      Cohort 1 shows no relevant effects of JNJ 40411813 the study will be stopped. If there are no
      relevant effects of JNJ 40411813 on the psychotic symptoms at 24 hours after dosing, a third
      cohort (Cohort 3) will be initiated to investigate the effects at 12 hours after dosing. If
      there are relevant effects of JNJ 40411813 at 24 hours after dosing, a fourth cohort (Cohort
      4) following the same procedures as Cohort 1, will be initiated to investigate the effects at
      peak plasma concentration using a lower dose of JNJ 40411813. Volunteers will be randomly
      assigned in a crossover procedure to one of two sequences (JNJ 40411813/placebo or placebo/
      JNJ 40411813) on Day -1 of the first study period of each cohort. At peak plasma level
      (Cohorts 1 and 4), 24 hours (Cohort 2) or 12 hours (Cohort 3) after dosing volunteers will
      receive ketamine as an infusion (i.e. directly into the vein) over 60 minutes. The ketamine
      administration will be preceded by a saline infusion over 90 minutes. Tests on the
      psychological function of the volunteers will be performed during and after saline and
      ketamine infusion. Safety assessments include daily ECG and vital signs, clinical laboratory
      assessments at the start and end of each study period, pulse oximetry (measurement of the
      oxygen content of the blood ) during each ketamine infusion and continuous Adverse Event
      Reporting. The study will be double blind for oral JNJ-40411813 or placebo, but open label
      (everyone knows the identity) for the IV administration of saline and ketamine. JNJ-40411813:
      500 mg single oral dose or lower or matching placebo. Ketamine: continuous intravenous
      infusion of 0.005 mg/kg/min over 60 minutes.
    

Intervention name(s): JNJ-40411813; normal saline; ketamine; Placebo
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): 500 mg as 20 mL of oral suspension; single dose; 20 mL of oral suspension; single dose
Intervention MeSH terms: Ketamine
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double
Primary purpose: Basic Science
Keywords: Activity of JNJ-40411813; Challenge study