In a new study, investigators found that 40 mg and 60 mg lumateperone is clinically safe to treat schizophrenia.
Cristoph U. Correll, MD
While it is notoriously difficult to treat schizophrenia, investigators are hopeful lumateperone could be the answer.
Investigators, led by Cristoph U. Correll, MD, professor of Psychiatry at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, examined the efficacy and safety of lumateperone, a serotonin, dopamine, and glutamate modulator, for the short-term treatment of schizophrenia.
In a randomized, double-blind, placebo-controlled, phase 3 clinical trial that took place between November 13, 2014 and July 20, 2015, investigators examined 450 patients with schizophrenia between 18-60 years old who were experiencing an acute exacerbation of psychosis at 12 clinical sites in the US.
Lumateperone is the active free base form of the drug administered orally as a tosylate salt (lumateperone tosylate, also known as ITI-007) in capsule form.
The mean age in the study was 42.4 years old and 346 patients were male.
In the study, 150 patients were randomly selected to receive 60 mg of lumateperone tosylate, 40 mg of lumateperone tosylate, or a placebo daily for 4 weeks.
In a previous study, investigators discovered that a higher dose of 84 mg of lumateperone was not effective.
The primary efficacy end point was the mean change from baseline to day 28 on the Positive and Negative Syndrome Scale (PANSS) total score compared to placebo. The secondary efficacy measure was the Clinical Global Impression-Severity of Illness (CGI-S) score.
The PANSS subscale scores, social function, safety, and tolerability were also assessed.
The mean baseline PANSS score was 89.8, while the mean baseline CGI-S score was 4.8.
The investigators found that 42 mg of lumateperone met the primary and key secondary efficacy objectives, demonstrating a statistically significant improvement compared to placebo from baseline to day 28 on the PANSS total score (least-squares mean difference [LSMD], −4.2; 95% CI, −7.8 to −.6; P =.02; effect size [ES], −.3) and the CGI-S (LSMD, −.3; 95% CI, −.5 to −.1; P =.003; ES, −.4).
For the group that received 28 mg of lumateperone daily, the LSMD from baseline to day 28 was −2.6 (95% CI, −6.2-1.1; P =.16; ES, −.2) on the PANSS total score and −.2 (95% CI, −0.5-0.0; P =.02; ES, −.3) on the CGI-S.
“Both lumateperone doses were well tolerated without clinically significant treatment- emergent motor adverse effects or changes in cardiometabolic or endocrine factors vs placebo,” the authors wrote. “Lumateperone demonstrated efficacy for improving the symptoms of schizophrenia and had a favorable safety profile.”
There is currently an unmet medical need to treat the broad range of symptoms without increasing adverse effects of antipsychotics, including risk of EPS, parkinsonism and akathisia, hyperprolactinemia, weight gain, dyslipidemia, diabetes, and cardiovascular disease.
Also, tolerability and safety issues with the current antipsychotic choices often leads to nonadherence.
In an accompanying editorial, Joshua T. Kantrowitz, MD, Assistant Professor of Clinical Psychiatry, Columbia University Department of Psychiatry, explained how the future role of lumateperone could be crucial in treating schizophrenia patients.
“The results of this phase 3 study of lumateperone extend those of the previously reported phase 2 study, demonstrating anti-psychotic efficacy and a favorable safety profile,” Kantrowitz said. “However, the questions of relative efficacy and whether its mechanism of action is truly novel remains unanswered.”
Kantrowitz said some of the reasons why lumateperone could usher in a new wave of antipsychotics because they have a wider separation between its affinity for D2 and 5-HT2A receptors, with a ratio of D2 to 5-HT2A affinity of 60:1, which could lead to decreased extrapyramidal symptoms at a therapeutic dose.
Lumateperone is also a presynaptic D2 partial agonist and a postsynaptic D2 antagonist.