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Ulotaront Misses Primary Endpoint in 2 Phase 3 Trials of Adults With Schizophrenia
Ulotaront failed to meet its primary endpoint in 2 phase 3 clinical trials of adults with schizophrenia and acute psychosis, makers Sumitomo Pharma Co. and Otsuka Pharmaceutical Co. recently announced. Ulotaront is a trace amine-associated receptor 1 (TAAR1) agonist with 5-HT1A agonist activity that was granted Breakthrough Therapy Designation by the US Food and Drug Administration (FDA) for the treatment of schizophrenia in May 2019.
The multicenter, phase 3 trials — DIAMOND (Developing Innovative Approaches for Mental Disorders) 1 and DIAMOND 2 — evaluated the efficacy, safety, and tolerability of ulotaront compared with placebo over 6 weeks.
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DIAMOND 1 randomized 435 adults with schizophrenia and acute psychosis to ulotaront 50 mg/day, ulotaront 75 mg/day, or placebo. Although all 3 groups showed a reduction in the Positive and Negative Syndrome Scale (PANSS) total score over time, neither ulotaront treatment group was superior to placebo on the primary endpoint of change from baseline in PANSS total score at week 6. Least squares [LS] means were -16.9 with ulotaront 50 mg/day, -19.6 with ulotaront 75 mg/day, and -19.3 with placebo.
DIAMOND 2 randomized 464 adults with schizophrenia and acute psychosis to ulotaront 75 mg/day, ulotaront 100 mg/day, or placebo. Again, neither ulotaront treatment group demonstrated statistically significant improvement compared with placebo on the primary endpoint at week 6. However, in this trial both ulotaront groups showed numerically larger mean reductions in PANSS total score compared with placebo: LS means were -16.4 with ulotaront 75 mg/day, -18.1 with ulotaront 100 mg/day, and -14.3 with placebo.
Ulotaront was generally safe and well-tolerated in both trials.
A large placebo effect may have masked the molecule’s therapeutic effect in the studies, according to the drug’s developers.
“High placebo responses, like those seen in DIAMOND 1 and DIAMOND 2, are well documented in psychiatric clinical studies. The placebo response in DIAMOND 1 was particularly high…,” said Hiroshi Nomura, president and CEO of Sumitomo Pharma. “We continue to work closely with Otsuka and analyze the data to determine our next steps and plan to discuss with the FDA how to proceed based on these results.”
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