SUMMARY

• Vanover et al (2019)¹ conducted an open-label, positron emission tomography (PET) study to evaluate the dopamine D2 receptor occupancy (D2RO) at plasma steady state following 2 weeks of treatment with 42 mg of CAPLYTA daily in the morning in patients with schizophrenia (N=10).
  • Following administration of a CAPLYTA dose of 42 mg, the highest D₂RO level in the dorsal striatum was observed 1 hour after dosing, with a mean±standard deviation (SD) occupancy of 39%±12% (n=6).
• Davis et al (2015)² conducted an open-label, PET study to evaluate the receptor occupancy profile of lumateperone in 16 healthy volunteers. Participants received different doses of lumateperone as follows: 10 mg, n=2; 20 mg, n=4; 30 mg, n=4; and 40 mg, n=2.
  • Lumateperone showed peak striatal D₂RO within 30 minutes to 1 hour after administration.
  • At the 10 mg dose, lumateperone showed a high occupancy (>80%) of the cortical serotonin 5-HT_2A receptors about 30 minutes after administration.

BACKGROUND

Receptor occupancy studies of CAPLYTA were conducted in healthy volunteers and patients with schizophrenia. Specifically, dopamine D₂ and serotonin 5-HT_2A receptor occupancy were evaluated using PET.^1,2 

CLINICAL DATA

Vanover et al (2019)¹ conducted an open-label, PET study to evaluate the D₂RO at plasma steady state following 2 weeks of treatment with 42 mg of CAPLYTA daily in the morning in patients with schizophrenia (N=10; age [mean±SD], 39.3±9.1 years). All enrolled patients discontinued their previous antipsychotic medication to establish a drug-free baseline using a 2-week washout period. During the study, 9 patients received lorazepam as a concomitant psychotropic medication.

D₂RO Following CAPLYTA Treatment

• Following administration of a CAPLYTA dose of 42 mg, the highest D₂RO level in the dorsal striatum was observed at 1 hour, with a mean±SD occupancy of 39%±12% (n=6).
• The mean±SD dorsal striatal D₂RO gradually decreased from 34%±8% at 3 to 4 hours after dosing to 19%±10% at 7.5 hours after dosing, and 7%±7% at 24 to 27 hours after dosing (n=4).
• Combined data from all patients at 1 or 3 hours revealed a mean D₂RO of 37%, with an associated mean total plasma level of 49.3 ng/mL. A statistically significant correlation was observed between D₂RO and total plasma concentration (r²=0.6; P=0.0077).

Safety

• No clinically significant changes were reported in vital signs, electrocardiograms (ECGs), or clinical laboratory parameters.
• No adverse events (AEs) of akathisia, other extrapyramidal motor AEs, or motor disturbances with CAPLYTA were reported.
• The most frequent (reported in >2 patients) AEs possibly related to CAPLYTA were mild to moderate headache (40%) and mild sedation (40%).

Davis et al (2015)² conducted an open-label, PET study to evaluate the receptor occupancy profile of lumateperone in 16 healthy volunteers (age [mean±SD], 30.7±6.4 years). Participants received different doses of lumateperone as follows: 10 mg, n=2; 20 mg, n=4; 30 mg, n=4; and 40 mg, n=2.

• At the 10 mg dose, lumateperone showed a high occupancy (>80%) of the cortical serotonin 5-HT_2A receptors about 30 minutes after administration. At the 40 mg dose, the mean striatal serotonin transporter occupancy of lumateperone ranged from 19.3% to 27.5% about 30 minutes after administration.
• Lumateperone showed peak striatal D₂RO within 30 minutes to 1 hour following administration. A dose-dependent increase in striatal D₂RO was seen with lumateperone; see Table: Lumateperone Striatal D₂RO at Different Doses and Times.

• During the study, no clinically significant changes were reported in vital signs, ECG measures, QT interval, or clinical laboratory parameters.
• Additionally, no dose-dependent or serious AEs were reported with lumateperone.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 18 August 2025.