Ketamine Challenge Study With JNJ-40411813

• ClinicalTrials.gov Identifier: NCT01101659
• Recruitment Status: Completed
• First Posted: April 12, 2010
• Last Update Posted: April 8, 2014
• Sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
• Information provided by (Responsible Party): Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Tracking Information

• First Submitted Date: April 8, 2010
• First Posted Date: April 12, 2010
• Last Update Posted Date: April 8, 2014
• Study Start Date: February 2010
• Primary Completion Date: Not Provided
• Current Primary Outcome Measures (submitted: April 12, 2010): 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 ]
• Original Primary Outcome Measures (submitted: April 8, 2010): To investigate the effect of JNJ- 40411813 on ketamine-induced positive psychotic symptoms based on 4 items of the brief psyciatric rating scale (BPRS) in healthy male volunteers [ Time Frame: 15 minutes after start of bolus injection of ketamine ]

Current Secondary Outcome Measures (submitted: April 12, 2010)

• 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 ]
• 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 ]
• 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 ]

Original Secondary Outcome Measures (submitted: April 8, 2010)

• 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 conciousness (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 ]
• 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 ]
• 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 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Ketamine Challenge Study With JNJ-40411813
• Official Title: A Double-Blind, 2-Way Crossover Study to Investigate the Effects of JNJ-40411813 on Ketamine-Induced Alterations in Neuropsychiatric Performance
• Brief 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.
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Double; Primary Purpose: Basic Science

Condition

• Perceptual Disorders
• Confusion
• Schizophrenia

Intervention

• Drug: JNJ-40411813
  500 mg as 20 mL of oral suspension
• Drug: normal saline
  single dose
• Drug: ketamine
  20 mL of oral suspension
• Drug: Placebo
  single dose

Study Arms

• Experimental: 001
  JNJ-40411813 500 mg as 20 mL of oral suspension single dose
  Intervention: Drug: JNJ-40411813
• Placebo Comparator: 002
  Placebo 20 mL of oral suspension single dose
  Intervention: Drug: Placebo
• 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
  Intervention: Drug: ketamine
• 004
  normal saline infusion 0.5 mL /min over 90 minutes
  Intervention: Drug: normal saline

Publications *

• Salih H, Anghelescu I, Kezic I, Sinha V, Hoeben E, Van Nueten L, De Smedt H, De Boer P. Pharmacokinetic and pharmacodynamic characterisation of JNJ-40411813, a positive allosteric modulator of mGluR2, in two randomised, double-blind phase-I studies. J Psychopharmacol. 2015 Apr;29(4):414-25. doi: 10.1177/0269881115573403. Epub 2015 Mar 3.
• Kleinloog D, Uit den Boogaard A, Dahan A, Mooren R, Klaassen E, Stevens J, Freijer J, van Gerven J. Optimizing the glutamatergic challenge model for psychosis, using S+ -ketamine to induce psychomimetic symptoms in healthy volunteers. J Psychopharmacol. 2015 Apr;29(4):401-13. doi: 10.1177/0269881115570082. Epub 2015 Feb 17.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 15, 2010): 40
• Original Estimated Enrollment (submitted: April 8, 2010): 48
• Actual Study Completion Date: July 2010
• Primary Completion Date: Not Provided

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years to 45 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Germany

Administrative Information

• NCT Number: NCT01101659
• Other Study ID Numbers: CR017161
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
• Study Sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
• Collaborators: Not Provided

Investigators

• Study Director: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial; Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

• PRS Account: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
• Verification Date: April 2014