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

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

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

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: JNJ-40411813; Drug: JNJ-40411813; Drug: Antipsychotic medication; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Innsbruck, Austria
  • Salzburg, Austria
  • Wien, Austria
• Belgium
  • Dave, Belgium
  • Duffel, Belgium
  • Kortenberg, Belgium
  • Lede, Belgium
• Bulgaria
  • Plovdiv, Bulgaria
  • Radnevo N/A, Bulgaria
• Germany
  • Berlin, Germany
  • Hamburg, Germany
  • Mainz, Germany
  • Mannheim, Germany
  • München, Germany
• Romania
  • Arad, Romania
  • Brasov, Romania
  • Iasi, Romania
  • Sibiu, Romania
• Spain
  • Barcelona, Spain
  • Zamora, Spain

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: JNJ-40411813 (Part A); 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; 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; 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.
Experimental: JNJ-40411813 (Part B); 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; 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; 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.; Drug: Antipsychotic medication; 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.
Experimental: Placebo and JNJ-40411813 (Part B); 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; 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; 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.; Drug: Antipsychotic medication; 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.; Drug: Placebo; Placebo capsule (s) orally twice daily with a meal for 4 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Actual): November 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: March 24, 2011
• First Submitted That Met QC Criteria: March 24, 2011
• First Posted (Estimate): March 25, 2011

Study Record Updates

• Last Update Posted (Estimate): May 30, 2014
• Last Update Submitted That Met QC Criteria: May 22, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Keywords: JNJ-40411813
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Central Nervous System Depressants; Tranquilizing Agents; Psychotropic Drugs; Antipsychotic Agents
• Other Study ID Numbers: CR018340; 40411813SCH2001 (Other Identifier: Janssen Research & Development, LLC); 2010-023369-23 (EudraCT Number)