Schizophrenia - This study will be conducted to investigate whether or not administration of RO4917838 along with their current antipsychotic regimen to stable patients can lead to further improvement in symptoms including the potential for improving cognitive function and negative symptoms in addition to improvement in positive symptoms. MedDRA version: 9.1 Level: LLT Classification code 10039626 Term: Schizophrenia
Conditions
Interventions
Product Name: Glyt1(1) inhibitor
Product Code: RO4917838
Pharmaceutical Form: Capsule, hard
CAS Number: 845614-11-1
Current Sponsor code: RO4917838/F03
Concentration unit: mg milligram(s)
Concentratio
Sponsors
F.Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Capable of providing informed consent and informed consent form signed by the patient before any study assessments are done 2. Age 18-60 3. Males or females. If female and not infertile (defined below) must agree for the 16 weeks of the study to a) refrain from heterosexual intercourse or b) use one of the following forms of contraception 1) systemic hormonal treatment 2) an IUD which was implanted at least 2 months prior to screening or 3) "double-barrier" contraception (condom, diaphragm and spermicide are each considered a barrier). Females are considered to be infertile if they are either a) surgically sterile or b) have had spontaneous amenorrhea for at least the last two years and at least two years after the onset of amenorrhea while not receiving hormone replacement therapy had an FSH level greater than 40 mIU/mL and an estradiol level less than 30 pg/mL 4. Has a caregiver or some other identified responsible person (eg, family member, social worker, caseworker or nurse) considered reliable by the investigator in providing support to the patient to help ensure compliance with study treatment, study visits and protocol procedures who preferably is also able to provide input helpful for completing study rating scales. 5. Based on the screening SCID-CT a DSM-IV TR diagnosis of schizophrenia 6. Outpatient with no hospitalization for worsening of schizophrenia within 3 months (hospitalization for social management within this time is acceptable) 7. Medically stable over the prior 1 month and psychiatrically stable without symptom exacerbation within prior 3 months. 8. Except for risperidone long-acting, no depot or long-acting antipsychotics or clozapine within 3 months 9. If on risperidone long-acting, no dose change within 3 months 10. For oral antipsychotics, no dose change within 1 month 11. On no more than 2 antipsychotics where risperidone and risperidone long-acting are considered to be two different antipsychotics 12. Antipsychotic regimen: a) Patients must be on a "primary" antipsychotic. Patients may also be on a second antipsychotic. However, if a patient is on a second antipsychotic, by using approximate dose equivalents (explained below), the following will apply: i) The amount of the second antipsychotic must be less than the equivalent dose of the primary antipsychotic ii) The sum of the primary and secondary antipsychotics must be less than or equal to 6 mg of risperidone equivalents 12 b) The six allowed primary antipsychotics* are olanzapine, quetiapine, paliperidone, oral risperidone, risperidone long-acting by injection and aripiprazole. As a primary agent the allowed ranges are: i) Risperidone 2-6 mg/day or ii) Olanzapine 5-20 mg/day or iii) Quetiapine 150-750 mg/day or iv) Paliperidone 3-12 mg/day or v) Risperidone long-acting injection 25-50 mg every 2 weeks or vi) Aripiprazole 6-30 mg/day *Information on antipsychotic dosing included in this protocol provides usual minimum and maximum prescribed doses but should always be used in the dose range according to the approved local prescribing information c) For patients on a second antipsychotic, [Appendix 3] explains, for each primary antipsychotic regimen, what the allowed second antipsychotics are and the maximum dose of the second antipsychotic. The table considers 4 mg risperidone to be equipotent to 15 mg of olanzapine, 600 mg of quetiapine, 9 mg of paliperidone and 37.5 mg of risperidone long-acting (given every 2 weeks) and 15 mg of aripip
Exclusion criteria
Exclusion criteria: Treatment history 1. Previously received RO4917838 2. Previously entered screening for this study but did not meet inclusion/exclusion criteria based on a screening assessment (see [Table 2]) 3. Participation in a clinical trial within 3 months or more than 2 clinical trials within 12 months 4. ECT within 6 months 5. Began a new non-medication treatment for schizophrenia or other psychiatric condition within the last 3 months (e.g. individual psychotherapy, cognitive behavioral therapy, rehabilitative therapy) 6. Lithium, anticonvulsants, or any other agent used as a mood stabilizer within 4 months 7. On more than one antidepressant or if on one antidepressant, a change in dose within 3 months 8. Change in benzodiazepine or sleep medication regimen within 1 month (regimen may be PRN or continuous treatment) 9. Except for medications mentioned above, receiving any other psychotropic or medication used as a psychotropic within 1 month (defined in Concomitant Medications and Treatment section [9]). 10. Change in anti-EPS medication within 2 weeks (see Concomitant Medications and Treatment section [9]) 11. Taking any medication which is an inhibitor or inducer of CYP3A4 (see [Appendix 4] for a list of common medications to exclude) Diagnosis and psychiatric history 12. Based on the screening SCID-CT: a) other current DSM-IV TR Axis I diagnosis requiring exclusion b) alcohol or substance abuse or dependence within 3 months (excluding nicotine) 13. PANSS item G6, depression moderate or worse 14. Urine drug screen detects heroin, amphetamines (including MDMA/ecstasy), cocaine, hallucinogens or PCP 15. In the investigator’s judgment, a significant risk of suicide or violent behavior Past and current medical history 16. History of neuroleptic malignant syndrome 17. A prior or current general medical condition that may be impairing cognition or other psychiatric functioning (e.g. head trauma, dementia, seizure disorder, stroke, neurodegenerative, inflammatory, infectious, neoplastic, toxic, metabolic, endocrine etc.) 18. A movement disorder due to antipsychotic treatment not currently controlled with anti-EPS treatment or another movement disorder which may affect the ratings on the EPS scales (e.g. Parkinson's disease) 19. Pregnant or breastfeeding females 20. Hemoglobin less than 130 g/L (13 g/dL) in males or 120 g/L (12 g/dL) in females 21. History of hemoglobinopathy such as thalassemia major or sickle-cell anemia 22. History of G6PDH (glucose-6-phosphate dehydrogenase) deficiency 23. History of HIV infection, or history of HepB infection within the past year, or history of HepC infection which has not been adequately treated 24. QTcF interval greater than 450 msec or other clinically significant abnormality on screening ECG based on centralized reading (Note: retesting for screening ECG is not permitted.) 25. Clinically significant abnormality on screening blood or urine safety tests which does not improve on retesting (for ALT and AST clinically significant is above twice the upper limit of normal) 26. Gastrointestinal, hepatic or renal disease which may significantly alter the absorption, metabolism or elimination of RO4917838 27. Significant or unstable physical condition which in the investigator’s judgment may require a change in medication or hospitalization within the next 3 months 28. Does not make an effortful attempt to complete the cognition battery at screening as explained in section [11.3.3.5]
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of RO4917838 compared to placebo on negative symptoms based on the mean change from baseline in Positive and Negative Syndrome Scale (PANSS) negative factor score after 8 weeks of treatment;Secondary Objective: •Overall symptoms based on the mean change from baseline in total PANSS score •Mean change from baseline for the PANSS subscales and remaining PANSS factors •Neg. symptom clinical response based on proportion of patients having a 20% or greater improvement in PANSS neg. factor score •Clinical Global scores: CGI-Improvement, CGI-I Improvement in neg. Symptoms, CGI-Severity and CGI-Severity in neg. Symptoms •Cognition status changes based on the Cognitive Battery •Functional response based on the mean change in Personal and Social Performance Scale (PSP) total score •Quality of life based on change in the Schizophrenia Quality of Life Scale (SQLS) •Safety assessments as described in the statistical section •PK as described in the PK section •Biomarker assessments as described in the biomarker section (BSR) • Consistency in safety, efficacy, and PK results of the patients from Japanese sites as compared with patients in the rest of the world;Primary end point(s): The primary efficacy variable is change from baseline at week 8 in PANSS total score. | — |
Countries
Austria, France, Germany, Hungary
Outcome results
None listed