Ketamine Challenge Study With JNJ-40411813

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier:
NCT01101659
First received: April 8, 2010
Last updated: April 7, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Perceptual Disorders
Confusion
Schizophrenia
Drug: JNJ-40411813
Drug: normal saline
Drug: ketamine
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Double-Blind
Primary Purpose: Basic Science
Official Title: A Double-Blind, 2-Way Crossover Study to Investigate the Effects of JNJ-40411813 on Ketamine-Induced Alterations in Neuropsychiatric Performance

Resource links provided by NLM:


Further study details as provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:

Primary Outcome Measures:
  • To investigate the effect of JNJ- 40411813 on ketamine-induced positive psychotic symptoms based on 4 items of the brief psychiatric rating scale (BPRS) in healthy male volunteers [ Time Frame: 15 minutes after start of bolus injection of ketamine ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Investigate the effects of JNJ 40411813 on ketamine-induced negative symptoms,based on 3 items of the BPRS, dissociative effects (based on the 5-dimensions altered state of consciousness (5D-ASC), and cognitive performance [ Time Frame: 15 min, 30 to 60 min after start of bolus injection of ketamine and at the end of ketamine infusion ] [ Designated as safety issue: No ]
  • Investigate the duration of action and the concentration-effect relationship of JNJ 40411813 [ Time Frame: 3, 12 and 24 hours after dosing of JNJ 40411813 ] [ Designated as safety issue: No ]
  • Investigate the safety, tolerability, and pharmacokinetics of JNJ 40411813 in healthy volunteers [ Time Frame: During each Period on Days 1, 2 and 3 (if applicable) and at follow up ] [ Designated as safety issue: No ]

Enrollment: 40
Study Start Date: February 2010
Study Completion Date: July 2010
Arms Assigned Interventions
Experimental: 001
JNJ-40411813 500 mg as 20 mL of oral suspension single dose
Drug: JNJ-40411813
500 mg as 20 mL of oral suspension
Placebo Comparator: 002
Placebo 20 mL of oral suspension single dose
Drug: Placebo
single dose
003
ketamine Ketanest S. vials of 20 ml with 5 mg/ml diluted with saline to 0.02 mg Ketamine per mL and per kg bodyweight of the volunteer
Drug: ketamine
20 mL of oral suspension
004
normal saline infusion 0.5 mL /min over 90 minutes
Drug: normal saline
single dose

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.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Body mass index (BMI) between 18 and 30 kg/m2
  • Nonsmokers
  • Healthy on the basis of a psychiatric examination according to the MINI screen
  • Healthy on the basis of clinical laboratory tests performed at screening
  • Healthy on the basis of physical examination, vital signs (including standing blood pressure and heart rate) or 12 lead ECG at Screening

Exclusion Criteria:

  • Having a contra-indication for the use of ketamine
  • Significant history of or current psychiatric or neurological illness
  • Positive urine screen for drugs of abuse at Screening or admission
  • Positive alcohol breath test at Screening or admission
  • History of alcohol or drug abuse
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01101659

Locations
Germany
Neuss, Germany
Sponsors and Collaborators
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Investigators
Study Director: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
  More Information

No publications provided

Responsible Party: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier: NCT01101659     History of Changes
Other Study ID Numbers: CR017161
Study First Received: April 8, 2010
Last Updated: April 7, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:
Activity of JNJ-40411813
Challenge study

Additional relevant MeSH terms:
Confusion
Perceptual Disorders
Schizophrenia
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Ketamine
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014