Caplyta (lumateperone) - 2 indications

Scroll down for more information on each indication:

• for the treatment of schizophrenia in adults; approved December of 2019
• for the treatment of depressive episodes associated with bipolar I or II disorder in adults, as monotherapy and as adjunctive therapy with lithium or valproate; approved December of 2021

General Information

Caplyta (lumateperone) is an atypical antipsychotic.

Caplyta is specifically indicated for:

• the treatment of schizophrenia in adults
• the treatment of depressive episodes associated with bipolar I or II disorder in adults, as monotherapy and as adjunctive therapy with lithium or valproate

Caplyta is supplied as a capsule for oral administration. The recommended dosage of Caplyta is 42 mg administered orally once daily with food. Dose titration is not required.

Mechanism of Action

Caplyta (lumateperone) is an atypical antipsychotic. The mechanism of action of lumateperone in the treatment of schizophrenia is unknown. However, the efficacy of lumateperone could be mediated through a combination of antagonist activity at central serotonin 5-HT2A receptors and postsynaptic antagonist activity at central dopamine D2 receptors.

Side Effects

Adverse effects associated with the use of Caplyta may include, but are not limited to, the following:

• somnolence/sedation
• dry mouth

The Caplyta drug label comes with the following Black Box Warning: Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. CAPLYTA is not approved for the treatment of patients with dementia-related psychosis.

Indication 1 - the treatment of schizophrenia in adults

approved December of 2019

Clinical Trial Results

The FDA approval of Caplyta was based on two placebo-controlled trials. 

Study 1 was a four-week, randomized, double-blind, placebo-controlled, multi-center study in adult patients with a diagnosis of schizophrenia according to the DSM-IV-TR criteria. The primary efficacy measure was the Positive and Negative Syndrome Scale (PANSS) total score. The PANSS is a 30-item scale used to measure symptoms of schizophrenia. Each item is rated by a clinician on a seven-point scale. A score of 1 indicates the absence of symptoms, and a score of 7 indicates extremely severe symptoms. The PANSS total score may range from 30 to 210 with higher scores reflecting greater overall symptom severity. A total of 335 patients were randomized to receive Caplyta 42 mg, Caplyta 84 mg (two times the recommended daily dose), an active comparator, or placebo. The study was not designed to allow for efficacy comparison of Caplyta and the active comparator. 
Compared to the placebo group, patients randomized to Caplyta 42 mg showed a statistically significant reduction from baseline to Day 28 in the PANSS total score. The treatment effect in the Caplyta 84 mg group (vs. placebo) was not statistically significant.  

Study 2 was a four-week, randomized, double-blind, placebo-controlled, multi-center study in adult patients with a diagnosis of schizophrenia according to the DSM-5 criteria. The primary efficacy measure was the PANSS total score. A total of 450 patients were randomized to receive Caplyta 28 mg (two-thirds the recommended daily dose), Caplyta 42 mg, or placebo. Compared to the placebo group, patients randomized to Caplyta 42 mg showed a statistically significant reduction from baseline to Day 28 in the PANSS total score.  The treatment effect in the Caplyta 28 mg group (vs. placebo) was not statistically significant.

In pooled data from short term studies, mean changes from baseline in weight gain, fasting glucose, triglycerides and total cholesterol were similar between Caplyta and placebo. The incidence of extrapyramidal symptoms was 6.7% for Caplyta and 6.3% for placebo. 

Indication 2 - for the treatment of depressive episodes associated with bipolar I or II disorder in adults, as monotherapy and as adjunctive therapy with lithium or valproate

approved December of 2021

Clinical Trial Results

The FDA approval for Caplyta was based on two positive Phase 3 placebo-controlled bipolar depression studies. The studies evaluated the effects of Caplyta on depression in adult patients with bipolar I or bipolar II disorder both as monotherapy (Study 404) and as adjunctive therapy with lithium or valproate (Study 402). In these studies, the efficacy of Caplyta 42 mg was established by demonstrating statistically significant improvements over placebo for the change from baseline in the Montgomery-Asberg Depression Rating scale (MADRS) total score at week 6. Caplyta 42 mg also showed a statistically significant improvement in the key secondary endpoint relating to clinical global impression of bipolar disorder in each study.