Clinical trial NCT01101659: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Perceptual Disorders
Confusion
Schizophrenia
Keywords: Activity of JNJ-40411813
Challenge study
Lead sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Sponsor class: INDUSTRY
First posted: 2010-04-12
Enrollment: 40
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.

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

Primary outcomes:
measure: 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
timeFrame: 15 minutes after start of bolus injection of ketamine
Secondary outcomes:
measure: 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
timeFrame: 15 min, 30 to 60 min after start of bolus injection of ketamine and at the end of ketamine infusion
measure: Investigate the duration of action and the concentration-effect relationship of JNJ 40411813
timeFrame: 3, 12 and 24 hours after dosing of JNJ 40411813
measure: Investigate the safety, tolerability, and pharmacokinetics of JNJ 40411813 in healthy volunteers
timeFrame: During each Period on Days 1, 2 and 3 (if applicable) and at follow up
Other outcomes:
Locations:
city: Neuss
country: Germany
Study officials:
affiliation: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
name: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.