Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo first; then RO5545965 15 mg; then RO5545965 5mg | Placebo Comparator | Participants will receive placebo matched to RO5545965 capsules orally daily from Weeks 1 to 3 in first intervention period; then RO5545965 15 mg capsules (5 mg for 3 days, 10 mg for 3 days and 15 mg for 15 days) orally daily from Weeks 6 to 8 in second intervention period; followed by RO5545965 5 mg capsules orally daily from Weeks 11 to 13 in third intervention period. A washout period of minimum 14 days will be maintained between each period. |
|
| Placebo first; then RO5545965 5 mg; then RO5545965 15 mg | Placebo Comparator | Participants will receive placebo matched to RO5545965 capsules orally daily from Weeks 1 to 3 in first intervention period; then RO5545965 5 mg capsules orally daily from Weeks 6 to 8 in second intervention period; followed by RO5545965 15 mg capsules (5 mg for 3 days, 10 mg for 3 days and 15 mg for 15 days) orally daily from Weeks 11 to 13 in third intervention period. A washout period of minimum 14 days will be maintained between each period. |
|
| RO5545965 15 mg first; then Placebo; then RO5545965 5 mg | Experimental | Participants will receive RO5545965 15 mg capsules (5 mg for 3 days, 10 mg for 3 days and 15 mg for 15 days) orally daily from Weeks 1 to 3 in first intervention period; then placebo matched to RO5545965 capsules orally daily from Weeks 6 to 8 in second intervention period; followed by RO5545965 5 mg capsules orally daily from Weeks 11 to 13 in third intervention period. A washout period of minimum 14 days will be maintained between each period. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Drug | Participants will receive placebo matched to RO5545965 capsules orally daily in any of the three intervention period. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Apparent volume of distribution (Vz/F) | 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 | 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 | Day 22 up to Day 92 | |
| Performance in reward based learning tasks as measured by the effort cost/benefit tradeoff task | Day 22 up to Day 92 | |
| Apparent oral clearance (CL/F) | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Activity in the dorsolateral prefrontal cortex in the N-back working memory task as measured by BOLD activity | 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) |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CNS Network | Garden Grove | California | 92845 | United States | ||
| Parexel California Clinical Trials Medical Group |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40155941 | Derived | Omlor W, Cecere G, Huang GY, Spiller T, Misra AR, Rabe F, Kallen N, Kirschner M, Surbeck W, Burrer A, Garibaldi G, Holiga S, Dukart J, Umbricht D, Homan P. Exploratory analysis of the relationship between striatal connectivity and apathy during phosphodiesterase 10 inhibition in schizophrenia: findings from a randomized crossover trial. BMC Med. 2025 Mar 28;23(1):187. doi: 10.1186/s12916-025-04004-2. | |
| 33192706 |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D012559 | Schizophrenia |
| ID | Term |
|---|---|
| D019967 | Schizophrenia Spectrum and Other Psychotic Disorders |
| D001523 | Mental Disorders |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| RO5545965 15 mg first; then RO5545965 5 mg; then Placebo |
| Experimental |
Participants will receive RO5545965 15 mg capsules (5 mg for 3 days, 10 mg for 3 days and 15 mg for 15 days) orally daily from Weeks 1 to 3 in first intervention period; then RO5545965 5 mg capsules orally daily from Weeks 6 to 8 in second intervention period; followed by placebo matched to RO5545965 capsules orally daily from Weeks 11 to 13 in third intervention period. A washout period of minimum 14 days will be maintained between each period. |
|
| RO5545965 5 mg first; then Placebo; then RO5545965 15 mg | Experimental | Participants will receive RO5545965 5 mg capsules orally daily from Weeks 1 to 3 in first intervention period; then placebo matched to RO5545965 capsules orally daily from Weeks 6 to 8 in second intervention period; followed by RO5545965 15 mg capsules (5 mg for 3 days, 10 mg for 3 days and 15 mg for 15 days) orally daily from Weeks 11 to 13 in third intervention period. A washout period of minimum 14 days will be maintained between each period. |
|
| RO5545965 5 mg first; then RO5545965 15 mg; then Placebo | Experimental | Participants will receive RO5545965 5 mg capsules orally daily from Weeks 1 to 3 in first intervention period; then RO5545965 15 mg capsules (5 mg for 3 days, 10 mg for 3 days and 15 mg for 15 days) orally daily from Weeks 6 to 8 in second intervention period; followed by placebo matched to RO5545965 capsules orally daily from Weeks 11 to 13 in third intervention period. A washout period of minimum 14 days will be maintained between each period. |
|
| RO5545965 | Drug | 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. |
|
| Baseline (Day 1) up to end of study (up to 17 weeks) |
| Overall symptoms score of schizophrenia based on total PANSS | Baseline (Day 1), Days 22, 57, and 92 |
| Symptom domains of schizophrenia based on PANSS factor subscales | Baseline (Day 1), Days 22, 57, and 92 |
| Negative symptoms score of schizophrenia based on brief negative symptom scale (BNSS) | Baseline (Day 1), Days 22, 57, and 92 |
| Overall clinical status based on CGI-S scores | Baseline (Day 1), Days 22, 57, and 92 |
| Overall clinical status based on CGI-Improvement (CGI-I) score | Baseline (Day 1), Days 22, 57, and 92 |
| Overall global impression of negative symptoms based on CGI-S negative symptoms | Baseline (Day 1), Days 22, 57, and 92 |
| Overall global impression of negative symptoms based on CGI-I negative symptoms | Baseline (Day 1), Days 22, 57, and 92 |
| Area under the concentration-time curve (AUC) | 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) | 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) | Screening (Day -15 to Day -1) up to end of study (up to 17 weeks) |
| Glendale |
| California |
| 91206 |
| United States |
| St Louis Clinical Trials | St Louis | Missouri | 63141 | United States |
| Derived |
| Umbricht D, Cheng WY, Lipsmeier F, Bamdadian A, Lindemann M. Deep Learning-Based Human Activity Recognition for Continuous Activity and Gesture Monitoring for Schizophrenia Patients With Negative Symptoms. Front Psychiatry. 2020 Sep 16;11:574375. doi: 10.3389/fpsyt.2020.574375. eCollection 2020. |