A Study of the Safety, Tolerability and Pharmacokientics of RO5545965 in Patients With Schizophrenia on Risperidone

Study Overview
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Brief Summary
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This randomized, double-blinded, placebo-controlled study will investigate the safety, tolerability, and pharmacokinetics of multiple doses of RO5545965 administered orally to psychiatrically stable patients with schizophrenia receiving risperidone.

Official Title
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A SINGLE-CENTER, RANDOMIZED, INVESTIGATOR/SUBJECT-BLIND, MULTIPLE-DOSE, PLACEBO-CONTROLLED, PARALLEL STUDY TO INVESTIGATE THE SAFETY, TOLERABILITY AND PHARMACOKINETICS OF RO5545965 IN PATIENTS WITH SCHIZOPHRENIA ON RISPERIDONE.

Conditions
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Schizophrenia

Intervention / Treatment
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* Other: Placebo
* Drug: RO5545965
* Drug: risperidone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females aged >/= 18 years and </= 60 years Clinically stable, mild or moderate schizophrenia On stable antipsychotic treatment for the last 6 months Generally healthy in the investigator's opinion, based on assessment of medical history, physical examination, vital signs, electrocardiogram (ECG), and the results of the hematology, clinical chemistry, urinalysis, serology, and other laboratory tests Willingness to be hospitalized for approximately 3 weeks BMI > 18.5 kg/m2 and < 38 kg/m2 Use of highly effective contraception as defined by the study protocol. Men must also not donate sperm until at least 30 days after the last dose, and women cannot be pregnant or breastfeeding Exclusion Criteria: Treatment with antiparkinson medication including anticholinergic drugs Treatment with depot antipsychotic medication within the last three months prior to screening Participation in a clinical trial with an investigational drug or device < 3 months prior to screening Smokes more than 20 cigarettes per day Current drug abuse (excluding nicotine) or drug abuse within 3 months prior to the screening visit Any donation of blood or significant blood loss within three months prior to first administration of the study drug Use of prohibited medications (including vitamins or herbal remedies) taken within 14 days or within 5 times the elimination half-life of the medication (whichever is longer) before the first study drug administration

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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 |
| --- | --- |
| Placebo Comparator: Placebo + risperidone<br> | Other: Placebo<br>* Oral daily administration from Days 1-12<br>Drug: risperidone<br>* 13 day run-in phase until 4 mg daily dose level is reached. 4 mg daily oral dose until Day 17 of study, for a total of 30 days. Dose may be increased up to 6 mg at the investigator's discretion. After study treatment, risperidone dosage may be decreased, increased or omitted at the investigator's discretion during a wash-out phase while patients return to their chronic antipsychotic treatment. Patient response during wash-out will be monitored in-house for 48 hours after the last dose of RO5545965 or placebo is administered. This in-house observation may be extended as needed by the investigator.<br>|
| Experimental: RO5545965 + risperidone<br> | Drug: RO5545965<br>* Oral daily administration from Days 1-12<br>Drug: risperidone<br>* 13 day run-in phase until 4 mg daily dose level is reached. 4 mg daily oral dose until Day 17 of study, for a total of 30 days. Dose may be increased up to 6 mg at the investigator's discretion. After study treatment, risperidone dosage may be decreased, increased or omitted at the investigator's discretion during a wash-out phase while patients return to their chronic antipsychotic treatment. Patient response during wash-out will be monitored in-house for 48 hours after the last dose of RO5545965 or placebo is administered. This in-house observation may be extended as needed by the investigator.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events |  | Up to 10 weeks | 
| Health of the patients, assessed through a complete medical examination including physical examination, electrocardiogram (ECG) and vital signs. |  | Up to 10 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics: Plasma area under the concentration-time curve (AUC) of RO5545965 |  | 17 days | 
| Pharmacokinetics: Plasma area under the concentration-time curve (AUC) of risperidone |  | 15 days |