Poster
106
(#106) Switching From Antipsychotic Agents to Ulotaront in Participants With Schizophrenia: A Phase 3 Open-Label Study
Psych Congress 2025
Abstract: Introduction: Ulotaront is a trace amine-associated receptor 1 (TAAR1) agonist with no dopamine D2 receptor blockade in development for schizophrenia. Phase 2 studies demonstrated efficacy and a distinct, well-tolerated safety profile. This study evaluated the safety, tolerability, and effectiveness of switching clinically stable adults with schizophrenia from a typical/atypical antipsychotic to ulotaront.
Methods: This 8-week, Phase 3 study (NCT05628103) evaluated flexible-dose ulotaront (50-100 mg/day) in adults with schizophrenia requiring a change in antipsychotic(s) due to intolerability/lack of efficacy. Participants had a ≤4 Clinical Global Impression-Severity (CGI-S) and ≤80 Positive and Negative Syndrome Scale (PANSS) score, with no recent changes in antipsychotic(s). Prior antipsychotics were discontinued by the end of Weeks 2-6; ulotaront continued until Week 8. The primary endpoint was discontinuation due to clinical reasons (adverse events [AEs]/lack of efficacy); the secondary endpoint was discontinuation for any reason. Other endpoints included AE incidence, and PANSS and CGI-S score change from baseline to Week 8.
Results: Of the 101 adults enrolled (71.3% male; 63.4% Black/African American; mean age: 48.1 years), 83 (82.2%) completed the study. Eight (7.9%) discontinued due to clinical reasons (7 AEs, 1 lack of efficacy). Eighteen (17.8%) discontinued study due to any reason. Overall, 41.6% experienced ≥ 1 AE; most were mild-moderate and unrelated to ulotaront. PANSS and CGI-S scores generally remained stable.
Conclusions: Discontinuation rate due to clinical reasons was low and was comparable to discontinuation rates in similar studies. No new safety signals were identified, and treatment effectiveness remained stable during switch.
Short Description: Ulotaront is a trace amine-associated receptor 1 (TAAR1) agonist, representing a new mechanism of action under development for the treatment of schizophrenia. This study evaluated the safety, tolerability, and effectiveness of switching clinically stable adults with schizophrenia from a prior antipsychotic to ulotaront. Findings indicated a low discontinuation rate comparable to similar switch studies. No new safety signals were identified, and treatment effectiveness remained stable throughout the transition period.
Name of Sponsoring Organization(s): Otsuka Pharmaceutical Development & Commercialization, Inc
Methods: This 8-week, Phase 3 study (NCT05628103) evaluated flexible-dose ulotaront (50-100 mg/day) in adults with schizophrenia requiring a change in antipsychotic(s) due to intolerability/lack of efficacy. Participants had a ≤4 Clinical Global Impression-Severity (CGI-S) and ≤80 Positive and Negative Syndrome Scale (PANSS) score, with no recent changes in antipsychotic(s). Prior antipsychotics were discontinued by the end of Weeks 2-6; ulotaront continued until Week 8. The primary endpoint was discontinuation due to clinical reasons (adverse events [AEs]/lack of efficacy); the secondary endpoint was discontinuation for any reason. Other endpoints included AE incidence, and PANSS and CGI-S score change from baseline to Week 8.
Results: Of the 101 adults enrolled (71.3% male; 63.4% Black/African American; mean age: 48.1 years), 83 (82.2%) completed the study. Eight (7.9%) discontinued due to clinical reasons (7 AEs, 1 lack of efficacy). Eighteen (17.8%) discontinued study due to any reason. Overall, 41.6% experienced ≥ 1 AE; most were mild-moderate and unrelated to ulotaront. PANSS and CGI-S scores generally remained stable.
Conclusions: Discontinuation rate due to clinical reasons was low and was comparable to discontinuation rates in similar studies. No new safety signals were identified, and treatment effectiveness remained stable during switch.
Short Description: Ulotaront is a trace amine-associated receptor 1 (TAAR1) agonist, representing a new mechanism of action under development for the treatment of schizophrenia. This study evaluated the safety, tolerability, and effectiveness of switching clinically stable adults with schizophrenia from a prior antipsychotic to ulotaront. Findings indicated a low discontinuation rate comparable to similar switch studies. No new safety signals were identified, and treatment effectiveness remained stable throughout the transition period.
Name of Sponsoring Organization(s): Otsuka Pharmaceutical Development & Commercialization, Inc
