SUMMARY  

• The recommended CAPLYTA dosage is 42 mg administered orally once daily with or without food. Dose titration is not needed.¹ 
• Ingestion of a high-fat meal with CAPLYTA lowered lumateperone mean peak drug concentration (C_max) by 33% and increased mean area under the plasma concentration time curve (AUC) by 9%. Median time of maximum observed plasma drug concentration (T_max) was delayed about 1 hour (from 1 hour at fasted state to 2 hours in the presence of food).¹ 
• A two-part, phase 1, open-label, single-dose, pharmacokinetic study evaluating the effects of a Food and Drug Administration (FDA)-defined high-fat, high-calorie (HFHC) meal on lumateperone tosylate 60 mg (equivalent to CAPLYTA 42 mg) concentrations demonstrated a decreased C_max after food (geometric least square mean [GLSM] ratio, 0.673; 90% confidence interval [CI], 0.566-0.800).² 
  • Area under the plasma concentration time curve through the last measurable concentration (AUC_0-t) and area under the plasma concentration time curve extrapolated to infinity (AUC_0-∞) did not show a food effect (AUC_0-t GLSM ratio: 1.070, 90% CI, 0.954-1.199; AUC_0-∞ GLSM ratio: 1.089; 90% CI, 0.971-1.222).  
  • The incidence rate of treatment-emergent adverse events (TEAEs) was higher in the fasted groups compared to the HFHC group: 75.0%, 66.7%, and 34.8% in the one capsule/fasted, one over-encapsulated (OE) tablet/fasted, and one capsule/HFHC groups, respectively.
    • Higher rates of dizziness (45.8%, 45.8%, 13.0%), nausea (16.7%, 33.3%, 8.7%), dry mouth (12.5%, 12.5%, 0%), and vomiting (16.7%, 16.7%, 0%) were observed in the fasted groups vs the HFHC group.

PRODUCT LABELING

Recommended Dosage

The recommended CAPLYTA dosage is 42 mg administered orally once daily with or without food. Dose titration is not needed.¹ 

Effect of Food

Ingestion of a high-fat meal with CAPLYTA lowered lumateperone mean C_max by 33% and increased mean AUC by 9%. Median T_max was delayed about 1 hour (from 1 hour at fasted state to 2 hours in the presence of food).¹ 

CLINICAL DATA

Pharmacokinetic Study

A two-part, Phase 1, open-label, single-dose, single-center, crossover study was conducted in 2 groups of healthy subjects to compare the bioavailability of lumateperone tosylate formulated capsules to that of lumateperone tosylate OE tablets and determine the effects of an FDA-defined HFHC meal on the pharmacokinetics of a single oral administration of a lumateperone tosylate 60 mg capsule.²

Study Design

• Healthy subjects ≥18 and ≤50 years of age, with a body mass index ≥18 kg/m² and ≤32 kg/m², and a minimum body weight of 50 kg were included in this study.
• In part A, subjects were randomized to receive 1 of 2 treatment sequences of lumateperone tosylate 40 mg on day 1 of period 1 and day 2 of period 2 in a crossover manner according to their randomized sequence, with a minimum of 7 days separating day 1 of each period:
  • One 40-mg capsule while fasted.
  • Two 20-mg OE tablets while fasted.
  • Note: Lumateperone tosylate 40 mg is equivalent to lumateperone 28 mg.
• In part B, subjects were randomized to receive 1 of 6 treatment sequences of lumateperone tosylate 60 mg on day 1 of period 1, period 2, and period 3 in a crossover manner according to their randomized sequence, with a minimum of 7 days separating day 1 of each period:
  • One 60-mg capsule while fasted.
  • One 60-mg OE tablet while fasted.
  • One 60-mg capsule after an FDA-defined HFHC meal.
  • Note: Lumateperone tosylate 60 mg is equivalent to CAPLYTA 42 mg.
• Blood samples for pharmacokinetic analysis of lumateperone tosylate and its metabolites were analyzed at timepoints until 48 hours post-dose.

Results

• A total of 24 subjects in part A and 25 subjects in part B were analyzed.  
• A summary of lumateperone tosylate bioavailability parameters are reported in Lumateperone Tosylate 40 mg GLSM and GLSM Ratios for Part A and Lumateperone Tosylate 60 mg GLSM and GLSM Ratios for Part B.

Safety

Part A

• The incidence rate of TEAEs was similar across treatment groups (one capsule, 62.5%; two OE tablets, 50%), with all TEAEs considered mild or moderate in severity.
• In the one capsule group, there were higher rates of dizziness (29.2% vs 20.8%), nausea (12.5% vs 8.3%), and vomiting (12.5% vs 0%) compared to the two OE tablet group.

Part B

• The incidence rate of TEAEs in the one capsule/fasted, one OE tablet/fasted, and one capsule/HFHC groups were 75%, 66.7%, and 34.8%, respectively.
• Higher rates of dizziness (45.8%, 45.8%, 13%), nausea (16.7%, 33.3%, 8.7%), dry mouth (12.5%, 12.5%, 0%), and vomiting (16.7%, 16.7%, 0%) were observed in the fasted groups vs the HFHC group.
• All TEAEs were considered mild or moderate in severity.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 12 September 2025.