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

Sponsors

Lead Sponsor: Janssen Research & Development, LLC

Source Janssen Research & Development, LLC
Brief Summary

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

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.

Overall Status Completed
Start Date May 2011
Completion Date December 2012
Primary Completion Date November 2012
Phase Phase 2
Study Type Interventional
Primary 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
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
Enrollment 100
Condition
Intervention

Intervention Type: Drug

Intervention Name: JNJ-40411813

Description: 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.

Arm Group Label: JNJ-40411813 (Part A)

Intervention Type: Drug

Intervention Name: JNJ-40411813

Description: 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.

Intervention Type: Drug

Intervention Name: Placebo

Description: Placebo capsule (s) orally twice daily with a meal for 4 weeks.

Arm Group Label: Placebo and JNJ-40411813 (Part B)

Intervention Type: Drug

Intervention Name: Antipsychotic medication

Description: 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.

Eligibility

Criteria:

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

Gender: All

Minimum Age: 18 Years

Maximum Age: 65 Years

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Janssen Research & Development, LLC C. Clinical Trial Study Director Janssen Research & Development, LLC
Location
Facility:
| Innsbruck, Austria
| Salzburg, Austria
| Wien, Austria
| Dave, Belgium
| Duffel, Belgium
| Kortenberg, Belgium
| Lede, Belgium
| Plovdiv, Bulgaria
| Radnevo N/A, Bulgaria
| Berlin, Germany
| Hamburg, Germany
| Mainz, Germany
| Mannheim, Germany
| München, Germany
| Arad, Romania
| Brasov, Romania
| Iasi, Romania
| Sibiu, Romania
| Barcelona, Spain
| Zamora, Spain
Location Countries

Austria

Belgium

Bulgaria

Germany

Romania

Spain

Verification Date

May 2014

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 3
Arm Group

Label: JNJ-40411813 (Part A)

Type: Experimental

Description: 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.

Label: JNJ-40411813 (Part B)

Type: Experimental

Description: 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.

Label: Placebo and JNJ-40411813 (Part B)

Type: Experimental

Description: 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.

Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: Double (Participant, Investigator)

Source: ClinicalTrials.gov