Caplyta

• Indications and Usage, adjunctive treatment of major depressive disorder                     11/2025

CAPLYTA is indicated for:

• Treatment of schizophrenia in adults 
  [see Clinical Studies (14.1)]
  .
• Treatment of depressive episodes associated with bipolar I or II disorder (bipolar depression) in adults, as monotherapy and as adjunctive therapy with lithium or valproate 
  [see Clinical Studies (14.2)]
  .
• Adjunctive therapy with antidepressants for the treatment of major depressive disorder (MDD) in adults  

  [see

  14.3 Adjunctive Treatment of Major Depressive Disorder
  in Adults

  Studies 5 and 6 Designs:

  The effectiveness of CAPLYTA, as adjunctive therapy with antidepressants, for the treatment of major depressive disorder (MDD) in adults was established in two 6-week, randomized, double-blind, placebo-controlled, multi-center trials in adult patients who met DSM-5 criteria for MDD, with or without symptoms of anxiety who had inadequate response to one to two courses of prior antidepressant therapy (ADT) (Study 5 NCT04985942 and Study 6 NCT05061706).  Inadequate response to ADT was defined as having less than 50% improvement after at least six weeks of treatment with selective serotonin or serotonin norepinephrine reuptake inhibitors or bupropion at the minimum effective ADT dosage or greater. Patients were randomized to receive oral CAPLYTA 42 mg or placebo once daily and all patients continued their background ADT.

  Studies 5 and 6 Endpoints:

  In Study 5 and 6, the primary endpoint was change from baseline to Week 6 in the Montgomery-Asberg Depression Rating Scale (MADRS) total score

  [see Clinical Studies (14.2)]

  in the CAPLYTA + ADT group compared to the placebo + ADT group.  The key secondary endpoint was the change from baseline to Week 6 in the Clinical Global Impression Scale-Severity (CGI-S) score. The CGI-S is a validated clinician-rated scale that measures the patient’s current illness state on a 1 (normal, not at all ill) to 7-point (extremely ill) scale.

  Studies 5 and 6 Baseline Demographics:

  • In Study 5, a total of 485 patients were randomized to receive CAPLYTA 42 mg + ADT or placebo + ADT. Demographic and baseline characteristics were similar for the CAPLYTA and placebo groups. Median age was 46 (range 18 to 65). 66% were female, 77% were White, 15% were Asian, and 7% were Black.
  • In Study 6, a total of 480 patients were randomized to receive CAPLYTA 42 mg + ADT or placebo + ADT. Demographic and baseline characteristics were similar for the CAPLYTA and placebo groups. Median age was 48 (range 18 to 65). 70% were female, 95% were White.

  Studies 5 and 6 Efficacy Results:

  In Studies 5 and 6, patients randomized to CAPLYTA 42 mg + ADT showed a statistically significant improvement from baseline to day 43 in the MADRS total score and CGI-S score compared to the placebo + ADT group. The results of Study 5 and Study 6 are shown in Table 11.

  Examination of subgroups by age, sex, race, and ADT class did not suggest differences in response in these studies.

  Table 11: Primary Efficacy Results from Adjunctive MDD Trials (Studies 5 and 6)

  			Primary Efficacy Endpoint: MADRS Total Score
  Study Number	Treatment Group	N	Mean Baseline Score (SD)	LS Mean Change from Baseline (SE)	Placebo-subtracted Differencea (95% CI)
  5	CAPLYTA (42 mg) + ADT*	239	30.4 (3.75)	-14.7 (0.54)	-4.9 (-6.38, -3.44)
  	Placebo + ADT	242	30.1 (3.50)	-9.8 (0.53)
  6	CAPLYTA (42 mg) + ADT*	232	30.8 (3.88)	-14.7 (0.56)	-4.5 (-6.03, -3.02)
  	Placebo + ADT	237	31.5 (3.97)	-10.2 (0.54)

  The MADRS total score ranges from 0 to 60; higher scores reflect greater symptom severity
  
  SD: standard deviation; SE: standard error; LS Mean: least squares mean; CI: confidence interval
  
  ^aDifference (CAPLYTA + ADT minus placebo + ADT) in LS mean change from baseline
  
  ^*CAPLYTA + ADT statistically significantly superior to placebo + ADT.

  The change from baseline in MADRS total score over time in adult patients who received adjunctive treatment for MDD in Study 5 is displayed in Figure 3.

  Figure

  3. Change from Baseline in MADRS Total Score by Time (Weeks) in Patients with MDD (Adjunctive Treatment) in Study 5

  

  
  
  

  Figure 3

  14.3 Adjunctive Treatment of Major Depressive Disorder
  in Adults

  Studies 5 and 6 Designs:

  The effectiveness of CAPLYTA, as adjunctive therapy with antidepressants, for the treatment of major depressive disorder (MDD) in adults was established in two 6-week, randomized, double-blind, placebo-controlled, multi-center trials in adult patients who met DSM-5 criteria for MDD, with or without symptoms of anxiety who had inadequate response to one to two courses of prior antidepressant therapy (ADT) (Study 5 NCT04985942 and Study 6 NCT05061706).  Inadequate response to ADT was defined as having less than 50% improvement after at least six weeks of treatment with selective serotonin or serotonin norepinephrine reuptake inhibitors or bupropion at the minimum effective ADT dosage or greater. Patients were randomized to receive oral CAPLYTA 42 mg or placebo once daily and all patients continued their background ADT.

  Studies 5 and 6 Endpoints:

  In Study 5 and 6, the primary endpoint was change from baseline to Week 6 in the Montgomery-Asberg Depression Rating Scale (MADRS) total score

  [see Clinical Studies (14.2)]

  in the CAPLYTA + ADT group compared to the placebo + ADT group.  The key secondary endpoint was the change from baseline to Week 6 in the Clinical Global Impression Scale-Severity (CGI-S) score. The CGI-S is a validated clinician-rated scale that measures the patient’s current illness state on a 1 (normal, not at all ill) to 7-point (extremely ill) scale.

  Studies 5 and 6 Baseline Demographics:

  • In Study 5, a total of 485 patients were randomized to receive CAPLYTA 42 mg + ADT or placebo + ADT. Demographic and baseline characteristics were similar for the CAPLYTA and placebo groups. Median age was 46 (range 18 to 65). 66% were female, 77% were White, 15% were Asian, and 7% were Black.
  • In Study 6, a total of 480 patients were randomized to receive CAPLYTA 42 mg + ADT or placebo + ADT. Demographic and baseline characteristics were similar for the CAPLYTA and placebo groups. Median age was 48 (range 18 to 65). 70% were female, 95% were White.

  Studies 5 and 6 Efficacy Results:

  In Studies 5 and 6, patients randomized to CAPLYTA 42 mg + ADT showed a statistically significant improvement from baseline to day 43 in the MADRS total score and CGI-S score compared to the placebo + ADT group. The results of Study 5 and Study 6 are shown in Table 11.

  Examination of subgroups by age, sex, race, and ADT class did not suggest differences in response in these studies.

  Table 11: Primary Efficacy Results from Adjunctive MDD Trials (Studies 5 and 6)

  			Primary Efficacy Endpoint: MADRS Total Score
  Study Number	Treatment Group	N	Mean Baseline Score (SD)	LS Mean Change from Baseline (SE)	Placebo-subtracted Differencea (95% CI)
  5	CAPLYTA (42 mg) + ADT*	239	30.4 (3.75)	-14.7 (0.54)	-4.9 (-6.38, -3.44)
  	Placebo + ADT	242	30.1 (3.50)	-9.8 (0.53)
  6	CAPLYTA (42 mg) + ADT*	232	30.8 (3.88)	-14.7 (0.56)	-4.5 (-6.03, -3.02)
  	Placebo + ADT	237	31.5 (3.97)	-10.2 (0.54)

  The MADRS total score ranges from 0 to 60; higher scores reflect greater symptom severity
  
  SD: standard deviation; SE: standard error; LS Mean: least squares mean; CI: confidence interval
  
  ^aDifference (CAPLYTA + ADT minus placebo + ADT) in LS mean change from baseline
  
  ^*CAPLYTA + ADT statistically significantly superior to placebo + ADT.

  The change from baseline in MADRS total score over time in adult patients who received adjunctive treatment for MDD in Study 5 is displayed in Figure 3.

  Figure

  3. Change from Baseline in MADRS Total Score by Time (Weeks) in Patients with MDD (Adjunctive Treatment) in Study 5

  

  
  
  

  Figure 3

  14.3 Adjunctive Treatment of Major Depressive Disorder
  in Adults

  Studies 5 and 6 Designs:

  The effectiveness of CAPLYTA, as adjunctive therapy with antidepressants, for the treatment of major depressive disorder (MDD) in adults was established in two 6-week, randomized, double-blind, placebo-controlled, multi-center trials in adult patients who met DSM-5 criteria for MDD, with or without symptoms of anxiety who had inadequate response to one to two courses of prior antidepressant therapy (ADT) (Study 5 NCT04985942 and Study 6 NCT05061706).  Inadequate response to ADT was defined as having less than 50% improvement after at least six weeks of treatment with selective serotonin or serotonin norepinephrine reuptake inhibitors or bupropion at the minimum effective ADT dosage or greater. Patients were randomized to receive oral CAPLYTA 42 mg or placebo once daily and all patients continued their background ADT.

  Studies 5 and 6 Endpoints:

  In Study 5 and 6, the primary endpoint was change from baseline to Week 6 in the Montgomery-Asberg Depression Rating Scale (MADRS) total score

  [see Clinical Studies (14.2)]

  in the CAPLYTA + ADT group compared to the placebo + ADT group.  The key secondary endpoint was the change from baseline to Week 6 in the Clinical Global Impression Scale-Severity (CGI-S) score. The CGI-S is a validated clinician-rated scale that measures the patient’s current illness state on a 1 (normal, not at all ill) to 7-point (extremely ill) scale.

  Studies 5 and 6 Baseline Demographics:

  • In Study 5, a total of 485 patients were randomized to receive CAPLYTA 42 mg + ADT or placebo + ADT. Demographic and baseline characteristics were similar for the CAPLYTA and placebo groups. Median age was 46 (range 18 to 65). 66% were female, 77% were White, 15% were Asian, and 7% were Black.
  • In Study 6, a total of 480 patients were randomized to receive CAPLYTA 42 mg + ADT or placebo + ADT. Demographic and baseline characteristics were similar for the CAPLYTA and placebo groups. Median age was 48 (range 18 to 65). 70% were female, 95% were White.

  Studies 5 and 6 Efficacy Results:

  In Studies 5 and 6, patients randomized to CAPLYTA 42 mg + ADT showed a statistically significant improvement from baseline to day 43 in the MADRS total score and CGI-S score compared to the placebo + ADT group. The results of Study 5 and Study 6 are shown in Table 11.

  Examination of subgroups by age, sex, race, and ADT class did not suggest differences in response in these studies.

  Table 11: Primary Efficacy Results from Adjunctive MDD Trials (Studies 5 and 6)

  			Primary Efficacy Endpoint: MADRS Total Score
  Study Number	Treatment Group	N	Mean Baseline Score (SD)	LS Mean Change from Baseline (SE)	Placebo-subtracted Differencea (95% CI)
  5	CAPLYTA (42 mg) + ADT*	239	30.4 (3.75)	-14.7 (0.54)	-4.9 (-6.38, -3.44)
  	Placebo + ADT	242	30.1 (3.50)	-9.8 (0.53)
  6	CAPLYTA (42 mg) + ADT*	232	30.8 (3.88)	-14.7 (0.56)	-4.5 (-6.03, -3.02)
  	Placebo + ADT	237	31.5 (3.97)	-10.2 (0.54)

  The MADRS total score ranges from 0 to 60; higher scores reflect greater symptom severity
  
  SD: standard deviation; SE: standard error; LS Mean: least squares mean; CI: confidence interval
  
  ^aDifference (CAPLYTA + ADT minus placebo + ADT) in LS mean change from baseline
  
  ^*CAPLYTA + ADT statistically significantly superior to placebo + ADT.

  The change from baseline in MADRS total score over time in adult patients who received adjunctive treatment for MDD in Study 5 is displayed in Figure 3.

  Figure

  3. Change from Baseline in MADRS Total Score by Time (Weeks) in Patients with MDD (Adjunctive Treatment) in Study 5

  

  
  
  

  Figure 3

  ].

• Recommended oral dosage of CAPLYTA is 42 mg once daily with or without food. (
  2.1 Recommended Dosage

  The recommended CAPLYTA dosage is 42 mg administered orally once daily with or without food. Dose titration is not needed.
  )
• Moderate hepatic impairment or severe hepatic impairment: Recommended dosage is 21 mg once daily. (
  2.3 Dosage Recommendations for Patients with Hepatic
  Impairment

  For patients with moderate hepatic impairment (HI) (Child-Pugh class B) or severe HI (Child-Pugh class C), the recommended CAPLYTA dosage is 21 mg once daily

  [see Use in Specific Populations (8.6)]

  .  The recommended CAPLYTA dosage in patients with mild HI is the same as those with normal hepatic function.
  ,
  8.6 Hepatic Impairment

  Patients with moderate hepatic impairment (HI) (Child-Pugh class B) and severe HI (Child-Pugh class C) generally had higher exposure to lumateperone than patients with normal hepatic function; therefore, the recommended CAPLYTA dosage in patients with moderate or severe HI is lower than those with normal hepatic function

  [see

  Dosage and Administration (

  2.3

  )

  and

  Clinical Pharmacology (

  12.3

  )

  ]

  .

  The recommended dosage in patients with mild HI (Child-Pugh class A) is the same as those with normal hepatic function.
  )

CAPLYTA capsules are available in three strengths:

• 42 mg: Blue cap and opaque white body imprinted with “ITI-007 42 mg”
• 21 mg: Opaque white cap and body imprinted with “ITI-007 21 mg”
• 10.5 mg: Opaque light pink cap and body imprinted with “ITI-007 10.5 mg”