Select therapeutic use:

Mood disorders:

Indications for: CAPLYTA

Depressive episodes associated with bipolar I or II disorder (bipolar depression) in adults, as monotherapy and as adjunctive therapy with lithium or valproate.

Clinical Trials:

The approval was supported by data from 2 global randomized, double-blind, placebo-controlled phase 3 studies (Study 404 [ClinicalTrials.gov: NCT03249376] and 402 [ClinicalTrials.gov: NCT02600507]) that evaluated the efficacy and safety of Caplyta as monotherapy and adjunctive therapy with lithium or valproate, respectively, in adults with bipolar depression. 

In Study 404, 381 patients were randomly assigned 1:1 to receive Caplyta 42mg orally once daily or placebo; Study 402 included 529 patients who were randomly assigned 1:1:1 to receive Caplyta 42mg, 28mg, or placebo. 

The primary endpoint for both studies was the improvement in depression from baseline to week 6, as assessed by the Montgomery-Åsberg Depression Rating Scale (MADRS). A key secondary end point included the Clinical Global Impression Scale for Bipolar for Severity of Illness-Depression subscale (CGI-BP-S).

Results from Study 404 showed that Caplyta was associated with a statistically significant improvement on the MADRS total score, with a mean reduction of 16.7 points compared with 12.1 points for placebo, (least squares [LS] mean difference, -4.6 points [95% CI, -6.3, -2.8]; P <.001). Additionally, Caplyta treatment led to statistically significant improvements on the CGI-BP-S depression score.

In Study 402, Caplyta 42mg was associated with a statistically significant improvement on the MADRS total score, with a mean reduction of 16.9 points compared with 14.5 points for placebo (LS mean difference, -2.4 points [95% CI, -4.4, -0.4]; P =.0206). Caplyta 42mg also met the key secondary end point of statistically significant improvement on the CGI-BP-S depression score. The treatment effect in the Caplyta 28mg group (vs placebo) was not statistically significant.

Adult Dosage:

42mg once daily. Moderate to severe hepatic impairment, or concomitant with moderate CYP3A4 inhibitors: reduce dose to 21mg once daily. Concomitant strong CYP3A4 inhibitors: reduce dose to 10.5mg once daily.

Children Dosage:

Not established.

Boxed Warning:

Increased mortality in elderly patients with dementia-related psychosis. Suicidal thoughts and behaviors.

CAPLYTA Warnings/Precautions:

Elderly with dementia-related psychosis (not approved use); increased risk of death or cerebrovascular events (eg, stroke, TIA). Increased risk of suicidal thoughts and behavior in children, adolescents, and young adults; monitor closely for worsening or unusual changes in all patients. Discontinue immediately if neuroleptic malignant syndrome is suspected. Cardio- or cerebrovascular disease. Risk for hypotension, aspiration, seizures, or diabetes (do baseline fasting blood sugar). Pre-existing low WBC or ANC, or a history of leukopenia/neutropenia; monitor CBC during 1st few months of treatment; consider discontinuing at 1st sign of significant decline in WBC occurs in absence of other causative factors. Exposure to extreme heat. Dehydration. Hypovolemia. Perform fall risk assessments when initiating and recurrently on long-term therapy. Monitor for hyperglycemia, dyslipidemia, weight gain. Reevaluate periodically. Write ℞ for smallest practical amount. Moderate to severe hepatic impairment: reduce dose (see Adult). Neonates: risk for extrapyramidal and/or withdrawal symptoms post delivery (due to exposure during 3rd-trimester pregnancy). Pregnancy. Nursing mothers.

CAPLYTA Classification:

Atypical antipsychotic.

CAPLYTA Interactions:

Potentiated by moderate or strong CYP3A4 inhibitors (eg, diltiazem, itraconazole); reduce dose (see Adult). Antagonized by CYP3A4 inducers (eg, rifampin); avoid. Caution with drugs that interfere with temperature regulation (eg, anticholinergics).

Adverse Reactions:

Somnolence/sedation, dry mouth, dizziness, nausea; tardive dyskinesia (consider discontinuation if occurs), neutropenia, orthostatic hypotension, syncope.

Note:

Register patients in the National Pregnancy Registry for Atypical Antipsychotics (866) 961-2388.

Metabolism:

Lumateperone is extensively metabolized. Uridine 5'- diphospho-glucuronosyltransferases (UDP-glucuronosyltransferase, UGT) 1A1, 1A4, and 2B15, aldoketoreductase (AKR)1C1, 1B10, and 1C4, and cytochrome P450 (CYP) 3A4, 2C8, and 1A2, are involved in the metabolism of lumateperone.

Drug Elimination:

Renal (58%), fecal (29%). Terminal half-life is ~18 hours. 

 

Generic Drug Availability:

NO

How Supplied:

Caps—30

Psychosis:

Indications for: CAPLYTA

Schizophrenia.

Clinical Trials:

Approval was based on results from 2 double-blind, placebo-controlled trials (Study 1:  ClinicalTrials.gov Identifier: NCT01499563 [N=335] and Study 2: ClinicalTrials.gov Identifier: NCT02282761 [N=450]), which evaluated the efficacy of Caplyta in patients with schizophrenia for 28 days. 

Study 1: Median age was 42 years (range 20 to 55 years). 17% were female, 19% were Caucasian, and 78% were African American.

Study 2: Median age was 44 years (range 19 to 60 years); 23% were female, 26% were Caucasian and 66% were African American.

Primary endpoint: Change from baseline in the Positive and Negative Syndrome Scale (PANSS) total score at week 4. The PANSS is a 30-item scale used to measure symptoms of schizophrenia. Each item is rated by a clinician on a 7-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.

Findings from Study 1 and Study 2 showed that Caplyta 42mg once daily demonstrated a statistically significant reduction from baseline to day 28 in the PANSS total score with a placebo-subtracted difference of -5.8 (95% CI, -10.5, -1.1) and -4.2 (95% CI, -7.8, -0.6), respectively.

Studies 1 and 2 did not include any patients aged 65 or older.

Adult Dosage:

42mg once daily. Moderate to severe hepatic impairment, or concomitant with moderate CYP3A4 inhibitors: reduce dose to 21mg once daily. Concomitant strong CYP3A4 inhibitors: reduce dose to 10.5mg once daily.

Children Dosage:

Not established.

Boxed Warning:

Increased mortality in elderly patients with dementia-related psychosis. Suicidal thoughts and behaviors.

CAPLYTA Warnings/Precautions:

Elderly with dementia-related psychosis (not approved use); increased risk of death or cerebrovascular events (eg, stroke, TIA). Increased risk of suicidal thoughts and behavior in children, adolescents, and young adults; monitor closely for worsening or unusual changes in all patients. Discontinue immediately if neuroleptic malignant syndrome is suspected. Cardio- or cerebrovascular disease. Risk for hypotension, aspiration, seizures, or diabetes (do baseline fasting blood sugar). Pre-existing low WBC or ANC, or a history of leukopenia/neutropenia; monitor CBC during 1st few months of treatment; consider discontinuing at 1st sign of significant decline in WBC occurs in absence of other causative factors. Exposure to extreme heat. Dehydration. Hypovolemia. Perform fall risk assessments when initiating and recurrently on long-term therapy. Monitor for hyperglycemia, dyslipidemia, weight gain. Reevaluate periodically. Write ℞ for smallest practical amount. Moderate to severe hepatic impairment: reduce dose (see Adult). Neonates: risk for extrapyramidal and/or withdrawal symptoms post delivery (due to exposure during 3rd-trimester pregnancy). Pregnancy. Nursing mothers.

CAPLYTA Classification:

Atypical antipsychotic.

CAPLYTA Interactions:

Potentiated by moderate or strong CYP3A4 inhibitors (eg, diltiazem, itraconazole); reduce dose (see Adult). Antagonized by CYP3A4 inducers (eg, rifampin); avoid. Caution with drugs that interfere with temperature regulation (eg, anticholinergics).

Adverse Reactions:

Somnolence/sedation, dry mouth, dizziness, nausea; tardive dyskinesia (consider discontinuation if occurs), neutropenia, orthostatic hypotension, syncope.

Note:

Register patients in the National Pregnancy Registry for Atypical Antipsychotics (866) 961-2388.

Metabolism:

Lumateperone is extensively metabolized. Uridine 5'- diphospho-glucuronosyltransferases (UDP-glucuronosyltransferase, UGT) 1A1, 1A4, and 2B15, aldoketoreductase (AKR)1C1, 1B10, and 1C4, and cytochrome P450 (CYP) 3A4, 2C8, and 1A2, are involved in the metabolism of lumateperone.

Drug Elimination:

Renal (58%), fecal (29%). Terminal half-life is ~18 hours. 

 

Generic Drug Availability:

NO

How Supplied:

Caps—30