CAPLYTA®
(lumateperone)
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CAPLYTA® (lumateperone)
Medical Information
CAPLYTA - Comparison With Other Atypical Antipsychotics
Last Updated: 12/08/2025
SUMMARY
- A randomized, double‑blind, parallel‑group, placebo‑ and active-controlled, multicenter, phase 3 study (study 302) evaluated the efficacy and safety of CAPLYTA in patients with schizophrenia (N=696).1
- The least-square (LS) mean (standard error [SE]) change in the Positive and Negative Syndrome Scale (PANSS) total score from baseline to day 42 was -14.6 (1.23) for CAPLYTA 42 mg, -15 (1.27) for lumateperone 14 mg, -20.5 (1.33) for risperidone 4 mg, and -15.1 (1.21) for placebo.
- The rate of treatment-emergent adverse events (TEAEs) related to the study treatment was 52.3% for CAPLYTA 42 mg, 33.7% for lumateperone 14 mg, 57.2% for risperidone 4 mg, and 45.5% for placebo.
- A randomized, double-blind, placebo- and active-controlled, multicenter, phase 2 study (study 005) evaluated the efficacy and safety of CAPLYTA in patients with schizophrenia (N=335).2
- The LS mean (standard error of the mean) change from baseline to day 28 in the PANSS total score in the CAPLYTA 42 mg, lumateperone 84 mg, risperidone 4 mg, and placebo groups was -13.2 (1.69), -8.3 (1.68), -13.4 (1.72), and -7.4 (1.68), respectively.
- The relative risk of experiencing any TEAE was 1.14 (95% confidence interval [CI], 0.89-1.46) with CAPLYTA 42 mg, which was not significantly different from that with placebo (P=0.346). The relative risk of experiencing any TEAE vs placebo was 1.3 with lumateperone 84 mg (P=0.024) and 1.25 with risperidone 4 mg (P=0.077).
CLINICAL DATA
A randomized, double‑blind, parallel‑group, placebo‑ and active-controlled, multicenter, phase 3 study (study 302) evaluated the efficacy and safety of CAPLYTA in patients with schizophrenia (N=696). Patients were randomized 1:1:1:1 to receive CAPLYTA 42 mg (n=174), lumateperone 14 mg (n=174), risperidone 4 mg (n=174), or placebo (n=174) for 6 weeks.1
Efficacy
- The LS mean (SE) change in the PANSS total score from baseline to day 42 was -14.6 (1.23; 95% CI, -17 to -12.18) for CAPLYTA 42 mg, -15 (1.27; 95% CI, -17.49 to -12.49) for lumateperone 14 mg, -20.5 (1.33; 95% CI, -23.08 to -17.85) for risperidone 4 mg, and -15.1 (1.21; 95% CI, -17.42 to -12.68) for placebo.
Safety
- TEAEs reported in ≥5% of patients in any treatment group during the study are summarized in Table: TEAEs Reported in ≥5% of Patients. The rate of TEAEs related to the study treatment was 52.3% for CAPLYTA 42 mg, 33.7% for lumateperone 14 mg, 57.2% for risperidone 4 mg, and 45.5% for placebo.
- Treatment withdrawal due to TEAEs was reported in no patient on CAPLYTA 42 mg, 5 patients (2.9%) on lumateperone 14 mg, 10 patients (5.8%) on risperidone 4 mg, and 1 patient (0.6%) on placebo.
| n (%) | CAPLYTA 42 mg (n=172) | Lumateperone 14 mg (n=172) | Risperidone 4 mg (n=173) | Placebo (n=178) |
|---|---|---|---|---|
| Patients with ≥1 TEAE | 115 (66.9) | 88 (51.2) | 119 (68.8) | 108 (60.7) |
| Headache | 36 (20.9) | 16 (9.3) | 36 (20.8) | 25 (14) |
| Somnolence | 31 (18) | 19 (11) | 30 (17.3) | 11 (6.2) |
| Nausea | 16 (9.3) | 7 (4.1) | 15 (8.7) | 8 (4.5) |
| Constipation | 12 (7) | 10 (5.8) | 7 (4) | 17 (9.6) |
| Dyspepsia | 9 (5.2) | 6 (3.5) | 3 (1.7) | 10 (5.6) |
| Dry mouth | 9 (5.2) | 4 (2.3) | 7 (4) | 0 |
| Sedation | 7 (4.1) | 11 (6.4) | 14 (8.1) | 5 (2.8) |
| Toothache | 7 (4.1) | 5 (2.9) | 8 (4.6) | 11 (6.2) |
| Weight increased | 3 (1.7) | 5 (2.9) | 11 (6.4) | 4 (2.2) |
| Abbreviation: TEAE, treatment-emergent adverse event. | ||||
Lieberman et al (2016)2 conducted a phase 2, randomized, double-blind, placebo- and active-controlled, multicenter clinical study (study 005) to evaluate the efficacy and safety of CAPLYTA in patients with schizophrenia (N=335). Patients were randomized 1:1:1:1 to receive CAPLYTA 42 mg (n=84), lumateperone 84 mg (n=84), risperidone 4 mg (n=82), or placebo (n=85) for 4 weeks.
Efficacy
- Patients on CAPLYTA 42 mg showed a significant improvement in the PANSS total score on day 28; see Table: Changes in PANSS Score.
| CAPLYTA 42 mg | Lumateperone 84 mg | Risperidone 4 mg | Placebo | |
|---|---|---|---|---|
| PANSS total score | n=76 | n=80 | n=75 | n=80 |
| LS mean (SEM) change from baseline to day 28 | -13.2 (1.69) | -8.3 (1.68) | -13.4 (1.72) | -7.4 (1.68) |
| LS mean difference from placebo (rounded) | -5.8 | -0.9 | -6 | NA |
| P value, effect size | 0.017, 0.42 | 0.708, 0.07 | 0.013, 0.44 | NA |
| Abbreviations: LS, least squares; NA, not applicable; PANSS, Positive and Negative Syndrome Scale; SEM, standard error of mean. | ||||
- The relative risk of experiencing any TEAE was 1.14 (95% CI, 0.89-1.46) with CAPLYTA 42 mg, which was not significantly different from that with placebo (P=0.346). The relative risk of experiencing any TEAE vs placebo was 1.3 with lumateperone 84 mg (P=0.024) and 1.25 with risperidone 4 mg (P=0.077).
- Treatment discontinuation due to adverse events was reported in 5 patients: 2 patients in the CAPLYTA group (dry mouth, n=1; worsening of schizophrenia, n=1) and 3 patients in the risperidone group (akathisia, n=2; blood creatine phosphokinase increase, n=1).
- TEAEs reported during the study are summarized in Table: Treatment-Emergent Adverse Events.
- Post hoc comparisons with risperidone treatment revealed that CAPLYTA 42 mg and lumateperone 84 mg treatments resulted in statistically significantly lower levels of total cholesterol (CAPLYTA 42 mg, P=0.012; lumateperone 84 mg, P=0.004), prolactin (CAPLYTA 42 mg, P<0.001; lumateperone 84 mg, P<0.001), fasting glucose (CAPLYTA 42 mg, P=0.007; lumateperone 84 mg, P=0.023), and triglycerides (CAPLYTA 42 mg, P=0.074; lumateperone 84 mg, P=0.002).
| CAPLYTA 42 mg (n=84) | Lumateperone 84 mg (n=83) | Risperidone 4 mg (n=82) | Placebo (n=85) | |
|---|---|---|---|---|
| TEAEs reported in ≥5% of patientsa | ||||
| Sedation/somnolence | 14 (16.7) | 27 (32.5) | 17 (20.7) | 11 (12.9) |
| Dry mouth | 4 (4.8) | 7 (8.4) | 5 (6.1) | 2 (2.4) |
| Nausea | 5 (6) | 4 (4.8) | 4 (4.9) | 1 (1.2) |
| Dizziness | 4 (4.8) | 7 (8.4) | 1 (1.2) | 1 (1.2) |
| Other TEAEs common with risperidone, n (%) | ||||
| Akathisia | 1 (1.2) | 2 (2.4) | 6 (7.3) | 2 (2.3) |
| Tachycardia | 1 (1.2) | 0 | 4 (4.9) | 0 |
| Change in body weightb | 2±3.10 | 1.9±3.35 | 3±3.69 | 0.8±3.46 |
| Abbreviations: SD, standard deviation; TEAE, treatment-emergent adverse event.aTEAEs reported in patients in either CAPLYTA group and considered possibly related to study treatment.bChange from screening (day -7) to day 28. | ||||
Literature Search
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