Schizophrenia or schizoaffective disorder MedDRA version: 21.1 Level: PT Classification code 10039621 Term: Schizoaffective disorder System Organ Class: 10037175 - Psychiatric disorders MedDRA version: 20.0 Level: PT Classification code 10039626 Term: Schizophrenia System Organ Class: 10037175 - Psychiatric disorders
Conditions
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Male or female participants aged 18-55 years (inclusive) • Patients with a diagnostic and statistical manual of mental disorders, fifth edition (DSM-5) diagnosis of schizophrenia or schizoaffective disorder as confirmed by the mini international neuropsychiatric interview (MINI) • Part B only: Stable treatment with a dopamine 2 receptor (D2)/serotonin 2A receptor (5HT2A) antagonists or pure D2 antagonist(s), or a D2 partial agonist for a minimum of six months and receiving no more than two antipsychotics. Antipsychotic regimen: participants must be on a "primary" antipsychotic and may be on a secondary antipsychotic. The secondary antipsychotic dose must be equal to or less than the equivalent dose of the primary antipsychotic. The sum of the primary and secondary antipsychotics must be =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Part A only: Confirmed suicidal behavior based on Investigator judgment or violent behavior resulting in injury or property damage in the prior five years. A history prior to the last five years requires approval by the patient review committee (PRC) on a case-by-case basis • Part A only: Lifetime history of homicidal behavior • Moderate to severe substance use disorder within six months (excluding nicotine) as defined by DSM-5 • Any Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A) CGI subscore greater or equal to 3 • Other current DSM-5 diagnosis (e.g., bipolar disorder, major depressive disorder) • PANSS item G6 (depression) greater than or equal to 5 • Significant risk of suicide or harming him- or herself or others according to the Investigator’s judgment • A prior or current general medical condition that might be impairing cognition or other psychiatric functioning (e.g., migraine headaches requiring prophylactic treatment, head trauma, dementia, seizure disorder, stroke; or neurodegenerative, inflammatory, infectious, neoplastic, toxic, metabolic, endocrine conditions) • Positive result at screening for hepatitis B surface antigen (HBsAg), hepatitis C (hepatitis C antibody), or human immunodeficiency virus (HIV)-1 and -2. hepatitis C (HCV) antibody positive patients are eligible if HCV ribonucleic acid (RNA) is negative • Tardive dyskinesia that is moderate to severe or requires treatment • History of neuroleptic malignant syndrome • Average triplicate QTcF interval greater than 450 millisecond (msec) for males and 470 msec for females or other clinically significant abnormality on screening electrocardiogram (ECG) based on centralized reading • Clinically significant abnormalities in laboratory safety test results (including hepatic and renal panels, complete blood count, chemistry panel, coagulation, and urinalysis) o Aspartate transaminase (AST), alanine transaminase (ALT) >2 X upper limit of normal (ULN) o Total bilirubin >1.5 ULN with the exception of Gilbert syndrome o Serum creatinine >1.5 ULN • Significant or unstable physical condition that in the Investigator’s judgment might require a change in medication or hospitalization during the study • On more than one antidepressant (trazodone used at a dose up to and including 50 mg at bedtime is considered a hypnotic agent), or if on one antidepressant, a change in dose within 28 days prior to screening • History of clozapine treatment: Clozapine treatment for schizophrenia within 5 years prior to screening is prohibited. Low dose (< 200 mg/day) usage is permitted for insomnia or dyskinesia only, but not within 12 months prior to screening • History of treatment with electroconvulsive therapy (ECT) • Concomitant use of prohibited medications • Positive urine drug screen for amphetamines, methamphetamines, opiates, buprenorphine, methadone, cannabinoids, cocaine and barbiturates. In case of uncertain or questionable results, the urine drug screen may be repeated once during the screening period to confirm eligibility • Receipt of an investigational drug within 28 days or five times the half-life of the investigational drug (whichever is longer) before the first study drug administration • Donation of blood over 400 milliliter (mL) within three months prior to screening • Diagnosis of corona virus (COVID-19) infection (confirmed or presumptive) 4 weeks prior to Screening or during Screening. Participants can be re-screened after 4 weeks of full recovery in addition
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • Part A: To compare the efficacy of 150 milligram (mg) once daily (QD) of RO6889450 as monotherapy with placebo on negative symptoms in patients with schizophrenia or schizoaffective disorder • Part B: To compare the efficacy of 150 mg or 300 mg QD of RO6889450 as add-on therapy with placebo on negative symptoms in patients with schizophrenia or schizoaffective disorder ;Secondary Objective: • To compare the effect of RO6889450 with placebo on clinical global impression severity (CGI-S) and clinical global impression change (CGI-I) (overall and negative symptoms) • To compare the effect of RO6889450 with placebo on symptoms of schizophrenia or schizoaffective disorder as assessed with the positive and negative syndrome scale (PANSS), brief negative symptom scale (BNSS) and defeatist performance attitude scale (DPAS) • To compare the safety and tolerability of 12 weeks of treatment with RO6889450 as monotherapy (Part A) or add-on therapy with placebo (Part B) • To evaluate the pharmacokinetics (PK) of RO6889450 and RO6889450-derived metabolite(s) ;Primary end point(s): 1. Change from baseline at Week 12 in the BNSS avolition/apathy sub-score (sum of items “behavior” and “internal experience”);Timepoint(s) of evaluation of this end point: 1. Baseline and Week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Change from baseline in CGI-S overall scores 2. Change from baseline in CGI-S negative symptoms scores 3. Change from baseline in CGI-I overall scores 4. Change from baseline in CGI-I negative symptoms scores 5. Change from baseline in PANSS total scores 6. Change from baseline in PANSS symptom factor scores 7. Change from baseline in BNSS total scores 8. Change from baseline in BNSS Symptom Factor scores 9. Change from baseline in DPAS scores 10. Incidence, nature, and severity of adverse events (AEs), serious AEs (SAEs), and of treatment discontinuations due to AEs 11. Change from baseline in vital signs 12. Change from baseline in ECG intervals 13. Incidence of laboratory abnormalities, based on hematology, clinical chemistry, coagulation and urinalysis test results 14. Change from baseline in Columbia-suicide severity rating scale (C-SSRS) 15. Change from baseline in extrapyramidal symptom rating scale, abbreviated (ESRS-A) 16. Steady state area under the curve (AUCss) and Maximum concentration (Cmax) of RO6889450, and, if feasible, of RO6889450-derived metabolite(s) at indicated time points 17. Concentration of RO6889450 and RO6889450-derived metabolite per time point;Timepoint(s) of evaluation of this end point: 1-15. Baseline to Week 12 16-17. Day 7, 14, 28, 42, 56, 84, and 112 | — |
Countries
Bulgaria, Croatia, Japan, Poland, Serbia, Spain, Ukraine, United States
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffmann-La Roche Ltd
Outcome results
None listed