This is a multicenter, randomized, double-blind, placebo-controlled, three period crossover study to evaluate the effects of RO5545965 on the functioning of key brain circuitry involved in negative symptoms using functional magnetic resonance imaging (fMRI) and reward-based learning in stable participants with mild to moderate negative symptoms of schizophrenia treated with antipsychotics. Participants will be randomized to one of six different sequences during which each participant will receive three 3-week treatment courses with RO5545965 5 milligrams (mg), RO5545965 15 mg and placebo. Each treatment period will be separated by a washout period of 14 days. Total duration of study will be approximately 17 weeks.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
33
Participants will receive placebo matched to RO5545965 capsules orally daily in any of the three intervention period.
Participants will receive RO5545965 5 mg capsules or RO5545965 15 mg capsules (5 mg for 3 days, 10 mg for 3 days and 15 mg for 15 days) orally daily in any of the three intervention period.
CNS Network
Garden Grove, California, United States
Parexel California Clinical Trials Medical Group
Glendale, California, United States
St Louis Clinical Trials
St Louis, Missouri, United States
Apparent volume of distribution (Vz/F)
Time frame: Pre-dose on Days 8, 15, 22, 43, 50, 57, 78, 85 and 96; additional 2 hour post-dose on Days 15, 50, and 85
Activity of the ventral striatum during reward expectation in a monetary incentive delay fMRI task as measured by blood oxygen level dependent (BOLD) activity
Time frame: Baseline (Day 1) up to end of study (up to 17 weeks)
Performance in reward based learning tasks as measured by the working memory reinforcement learning task
Time frame: Day 22 up to Day 92
Performance in reward based learning tasks as measured by the effort cost/benefit tradeoff task
Time frame: Day 22 up to Day 92
Apparent oral clearance (CL/F)
Time frame: Pre-dose on Days 8, 15, 22, 43, 50, 57, 78, 85 and 96; additional 2 hour post-dose on Days 15, 50, and 85
Activity in the dorsolateral prefrontal cortex in the N-back working memory task as measured by BOLD activity
Time frame: Baseline (Day 1) up to end of study (up to 17 weeks)
Cerebral blood flow in key brain areas (ventral striatum, orbitofrontal cortex) implicated in the etiology of negative symptoms as measured by arterial spin labeling (ASL)
Time frame: Baseline (Day 1) up to end of study (up to 17 weeks)
Overall symptoms score of schizophrenia based on total PANSS
Time frame: Baseline (Day 1), Days 22, 57, and 92
Symptom domains of schizophrenia based on PANSS factor subscales
Time frame: Baseline (Day 1), Days 22, 57, and 92
Negative symptoms score of schizophrenia based on brief negative symptom scale (BNSS)
Time frame: Baseline (Day 1), Days 22, 57, and 92
Overall clinical status based on CGI-S scores
Time frame: Baseline (Day 1), Days 22, 57, and 92
Overall clinical status based on CGI-Improvement (CGI-I) score
Time frame: Baseline (Day 1), Days 22, 57, and 92
Overall global impression of negative symptoms based on CGI-S negative symptoms
Time frame: Baseline (Day 1), Days 22, 57, and 92
Overall global impression of negative symptoms based on CGI-I negative symptoms
Time frame: Baseline (Day 1), Days 22, 57, and 92
Area under the concentration-time curve (AUC)
Time frame: Pre-dose on Days 8, 15, 22, 43, 50, 57, 78, 85 and 96; additional 2 hour post-dose on Days 15, 50, and 85
Maximum observed plasma concentration (Cmax)
Time frame: Pre-dose on Days 8, 15, 22, 43, 50, 57, 78, 85 and 96; additional 2 hour post-dose on Days 15, 50, and 85
Number of participants with adverse events (AEs) and serious adverse events (SAEs)
Time frame: Screening (Day -15 to Day -1) up to end of study (up to 17 weeks)
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