Investigation of the Safety, Tolerability and Potential Therapeutic Effects of JNJ-40411813 in Patients With Schizophrenia

Study Overview
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Brief Summary
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The purpose of this study is to explore the safety, tolerability, and potential clinical efficacy of JNJ 40411813 in schizophrenic patients.

Detailed Description
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This is a first-in-human study of JNJ-40411813 in schizophrenic patients who are not currently receiving antipsychotic drug treatment (referred to as (sub) acute patients) and in patients who are currently taking antipsychotic drug treatment (referred to as stable patients). The study will consist of 2 parts: Part A and Part B. Part A will be open-label (patients will know the identity of study treatment), and (sub)acute schizophrenic patients will receive monotherapy (treatment with one drug) with JNJ-40411813. Part B will be double-blind (patient and study staff will not know the identity of study treatment) and will randomize (assign by chance) patients with stable but symptomatic schizophrenia to receive treatment with JNJ-40411813 or a placebo (treatment identical in appearance to JNJ-40411813 but does not contain active drug) as add-on therapy to their currently prescribed antipsychotic medication. Parts A (JNJ-40411813 monotherapy) and B (JNJ-40411813 add-on therapy) will run simultaneously. Patients will take JNJ-40411813 and placebo capsules orally (by mouth) twice daily (bid) with a meal. Part A: Patients will take JNJ-40411813 50 mg (1 capsule) bid up to 150 mg (3 capsules) bid for up to 12 weeks. Part B: Patients will take JNJ-40411813 50 mg bid or placebo bid for 4 weeks. After 4 weeks, the dose of JNJ-40411813 may be increased up to 150 mg bid for 6 weeks, and patients assigned to placebo may take JNJ-40411813 50 mg bid to 150 mg bid for up to 10 weeks.

Official Title
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First-in-Patient Study to Assess the Safety and Tolerability and to Explore the Potential Therapeutic Efficacy of a Novel Glutamate Modulator as Monotherapy and as Add-On Therapy in Patients With Schizophrenia

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: JNJ-40411813
* Drug: JNJ-40411813
* Drug: Placebo
* Drug: Antipsychotic medication


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body Mass Index (BMI) between 18 and 35 kg/m2 inclusive Medically stable on the basis of physical examination, medical history, vital signs, 12-lead ECG and clinical laboratory tests In- or outpatients who have been diagnosed with schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) at least 1 year prior to screening. Exclusion Criteria: A current DSM-IV axis I diagnosis other than schizophrenia Any medical condition that could potentially alter the absorption, metabolism, or excretion of the study medication, such as Crohn's disease, liver disease, or renal disease Relevant history of any significant and/or unstable cardiovascular, respiratory, neurologic (including seizures or significant cerebrovascular disorders), renal, hepatic, endocrine, or immunologic diseases PANSS score <50 or >120 Other significant and/or unstable systemic illnesses

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: JNJ-40411813 (Part A)<br>JNJ-40411813 starting dose from 50 to 150 mg according to tolerability dose range increased stepwise from 50 mg to 150 mg capsule by mouth orally. Capsule (s) taken twice daily with a meal for 12 weeks. | Drug: JNJ-40411813<br>* JNJ-40411813 starting dose from 50 to 150 mg according to tolerability dose range increased stepwise from 50 mg to 150 mg capsule by mouth orally. Capsule (s) taken twice daily with a meal for 12 weeks.<br>|
| Experimental: JNJ-40411813 (Part B)<br>JNJ-40411813 starting dose from 50 to 150 mg according to tolerability dose range increased stepwise from 50 mg to 150 mg capsule by mouth orally. Capsule (s) taken twice daily with a meal for 10 weeks. | Drug: JNJ-40411813<br>* JNJ-40411813 starting dose from 50 to 150 mg as an add-on therapy. Dose is increased step-wise from 50 mg to 150 mg. Capsule(s) taken by mouth twice daily with a meal for 10 weeks.<br>Drug: Antipsychotic medication<br>* Regular antipsychotic medications (Risperidone, Olanzapine, Clozapine, Amisulpride, Quetiapine, Paliperidone, Aripiprazole, Haloperidol, Levomepromazine, Zuclopenthixol Hydrochloride, Clotiapine, Pipamperone Hydrochloride, Benperidol, Flupentixol, Fluphenazine Decanoate, Melperone Hydrochloride, or Chlorpromazine Hydrochloride) will be continued in Part B.<br>|
| Experimental: Placebo and JNJ-40411813 (Part B)<br>Placebo capsule (s) orally twice daily with a meal for 4 weeks followed by JNJ-40411813 according to tolerability dose range increased from 50 mg to 150 mg twice daily with a meal to 6 weeks. | Drug: JNJ-40411813<br>* JNJ-40411813 starting dose from 50 to 150 mg as an add-on therapy. Dose is increased step-wise from 50 mg to 150 mg. Capsule(s) taken by mouth twice daily with a meal for 10 weeks.<br>Drug: Placebo<br>* Placebo capsule (s) orally twice daily with a meal for 4 weeks.<br>Drug: Antipsychotic medication<br>* Regular antipsychotic medications (Risperidone, Olanzapine, Clozapine, Amisulpride, Quetiapine, Paliperidone, Aripiprazole, Haloperidol, Levomepromazine, Zuclopenthixol Hydrochloride, Clotiapine, Pipamperone Hydrochloride, Benperidol, Flupentixol, Fluphenazine Decanoate, Melperone Hydrochloride, or Chlorpromazine Hydrochloride) will be continued in Part B.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Udvalg for Klinische Undersogelser (UKU) ratings for side effects reported by patients |  | Up to 12 weeks | 
| The number of patients with abnormal results from clinical laboratory tests performed as a measure of safety and tolerability |  | Up to 12 weeks | 
| The number of patients with abnormal results from electrocardiograms (ECGs) performed as a measure of safety and tolerability |  | Up to 12 weeks | 
| The number of patients with abnormal results from physical examinations (including vital signs measurements) performed as a measure of safety and tolerability |  | Up to 12 weeks | 
| Number of patients with adverse events reported as a measure of safety and tolerability |  | Up to 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Positive and Negative Syndrome Scale (PANSS) scores to explore potential therapeutic effect of study drug |  | Up to 12 weeks | 
| Clinical Global Impression - Schizophrenia (CGI-SCH) ratings to explore potential therapeutic effect of study drug |  | Up to 12 weeks | 
| Subjective Well-being under Neuroleptics Scale (SWN) scores to explore potential therapeutic effect of study drug |  | Up to 12 weeks | 
| Plasma (blood) concentration of JNJ-40411813 |  | Up to 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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JNJ-40411813