Weight, metabolic parameters, and prolactin^1,2

For bipolar I and II depression in adults

Weight change was similar to placebo in 6‑week trials and not common in a 6‑month, open‑label safety trial^1,2

Mean weight change from baseline^1,2

Monotherapy: 6 weeks

Adjunctive
(with Lithium or Valproate): 6 weeks

Open-label,
monotherapy: 6 months

Weight change (lbs)	CAPLYTA (n=338)	Placebo (n=356)	CAPLYTA (n=166)	Placebo (n=170)	CAPLYTA (n=127)
Weight change (lbs)	+0.1	+0.4	0.0	+0.5	-0.02

Monotherapy: 6 weeks

Weight change (lbs)	CAPLYTA (n=338)	Placebo (n=356)
Weight change (lbs)	+0.1	+0.4

Adjunctive (with Lithium or Valproate): 6 weeks

Weight change (lbs)	CAPLYTA (n=166)	Placebo (n=170)
Weight change (lbs)	0.0	+0.5

Open-label, monotherapy: 6 months

Weight change (lbs)	CAPLYTA (n=127)
Weight change (lbs)	-0.02

99% of participants receiving CAPLYTA did not experience clinically
significant weight gain²*

*Defined as ≥7% increase from baseline to 6 weeks.

Antipsychotic drugs have been reported to cause metabolic changes, including weight gain. Measure weight when initiating CAPLYTA and monitor periodically during long-term treatment.

Please see additional Important Safety Information, including Boxed WARNINGS, below.

Study design

Monotherapy study: 6-week study that randomized 381 patients to either CAPLYTA 42 mg or placebo. Patients were generally moderately to markedly ill. Median age was 45 years (range 18-72 years). 58% were female, 91% were Caucasian, and 8% were African American.¹ The primary efficacy measure was the change from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) total score.

Adjunctive therapy study: 6-week study that randomized 529 patients to lithium or valproate with either CAPLYTA 28 mg (two-thirds of the recommended daily dose), CAPLYTA 42 mg, or placebo. Patients were generally moderately to markedly ill. Median age was 46 years (range 18 to 75 years). 58% were female, 88% were Caucasian, and 11% were African American. The treatment effect in the CAPLYTA 28 mg group (vs placebo) was not statistically significant.¹

Long-term study: An open-label study of 127 patients to determine the safety and tolerability of CAPLYTA 42 mg administered orally once daily for up to approximately 6 months in patients with bipolar depression.¹

Full chart description

This chart depicts weight change in clinical trials at 6 weeks in patients taking CAPLYTA as monotherapy or adjunctive therapy (with lithium or valproate) and weight change at 6 months for people taking CAPLYTA as monotherapy.

Across the monotherapy arm of the study, placebo (n=356) and CAPLYTA (n=338), patients experienced, respectively, +0.4 pounds weight change vs +0.1 pounds weight change. Across the adjunctive (with lithium or valproate) arm of the study, placebo (n=170) and CAPLYTA (n=166), patients experienced, respectively, +0.5 pounds weight change vs 0.0 pounds weight change. In the open-label, long-term monotherapy study, CAPLYTA (n=127), patients experienced -0.02 pounds weight change.

Change in metabolic parameters in 6‑week trials and in a 6‑month, open‑label safety trial^1,2

Mean change from baseline in metabolic parameters^1,2†

Monotherapy: 6 weeks

Adjunctive
(with Lithium or Valproate): 6 weeks

Open-label,
monotherapy: 6 months

Metabolic parameters	CAPLYTA (n=372)	Placebo (n=374)	CAPLYTA (n=177)	Placebo (n=175)	CAPLYTA
Glucose (mg/dL)	+0.1	0.0	+1.2	+0.8	+2.1 (n=112)
Insulin (mIU/L)	-0.8	+0.6	+3.5	+0.4	+0.7 (n=111)
Hemoglobin A1c (%)					0.0 (n=96)
Total cholesterol (mg/dL)	-0.6	-1.1	-6.5	-0.7	-2.4 (n=117)
LDL cholesterol (mg/dL)	-0.7	-0.6	-5.9	-0.6	-5.1 (n=117)
HDL cholesterol (mg/dL)	+0.4	0.0	-0.6	-0.2	+0.9 (n=117)
Triglycerides (mg/dL)	-1.4	-4.0	-1.6	-1.2	+2.3 (n=112)

Monotherapy: 6 weeks

Metabolic parameters	CAPLYTA (n=372)	Placebo (n=374)
Glucose (mg/dL)	+0.1	0.0
Insulin (mIU/L)	-0.8	+0.6
Hemoglobin A1c (%)
Total cholesterol (mg/dL)	-0.6	-1.1
LDL cholesterol (mg/dL)	-0.7	-0.6
HDL cholesterol (mg/dL)	+0.4	0.0
Triglycerides (mg/dL)	-1.4	-4.0

Adjunctive (with Lithium or Valproate): 6 weeks

Metabolic parameters	CAPLYTA (n=177)	Placebo (n=175)
Glucose (mg/dL)	+1.2	+0.8
Insulin (mIU/L)	+3.5	+0.4
Hemoglobin A1c (%)
Total cholesterol (mg/dL)	-6.5	-0.7
LDL cholesterol (mg/dL)	-5.9	-0.6
HDL cholesterol (mg/dL)	-0.6	-0.2
Triglycerides (mg/dL)	-1.6	-1.2

Open-label, monotherapy: 6 months

Metabolic parameters	CAPLYTA
Glucose (mg/dL)	+2.1 (n=112)
Insulin (mIU/L)	+0.7 (n=111)
Hemoglobin A1c (%)	0.0 (n=96)
Total cholesterol (mg/dL)	-2.4 (n=117)
LDL cholesterol (mg/dL)	-5.1 (n=117)
HDL cholesterol (mg/dL)	+0.9 (n=117)
Triglycerides (mg/dL)	+2.3 (n=112)

In 6‑week trials, metabolic parameters were similar to placebo¹

LDL=low-density lipoprotein; HDL=high-density lipoprotein.

^†n=number of subjects with data. Baseline is defined as last non-missing pretreatment measurement.

Antipsychotic drugs have been reported to cause metabolic changes, including hyperglycemia, diabetes mellitus, and dyslipidemia. Assess fasting plasma glucose and lipids when initiating CAPLYTA and monitor periodically during long-term treatment.

Please see additional Important Safety Information, including Boxed WARNINGS, below.

Full chart description

This chart depicts mean baseline change in levels of specific metabolic parameters of CAPLYTA vs. Placebo at 6 weeks, as well as CAPLYTA alone at 6 months.

Across the monotherapy arm of the study, placebo (n=374) and CAPLYTA (n=372) patients respectively experienced the following: glucose (mg/dL), 0.0 vs 0.1; insulin (mIU/L), 0.6 vs -0.8; total cholesterol (mg/dL), -1.1 vs -0.6; LDL cholesterol (mg/dL), -0.6 vs -0.7; triglycerides (mg/dL), -4.0 vs -1.4. Across the adjunctive therapy (with lithium or valproate) arm of the study, placebo (n=175) and CAPLYTA (n=177) patients respectively experienced the following: glucose (mg/dL), 0.8 vs 1.2; insulin (mIU/L), 0.4 vs 3.5; total cholesterol (mg/dL), -0.7 vs -6.5; LDL cholesterol (mg/dL), -0.6 vs -5.9; triglycerides (mg/dL), -1.2 vs -1.6.

At 6 months, CAPLYTA demonstrated the following changes: glucose (mg/dL), 2.1 (n=112); insulin (mIU/L), 0.7 (n=111); hemoglobin A1c (%), 0.0 (n=96); total cholesterol (mg/dL), -2.4 (n=117); LDL cholesterol (mg/dL), -5.1 (n=117); HDL cholesterol (mg/dL), 0.9 (n=117); triglycerides (mg/dL), 2.3 (n=112).

Prolactin levels in 6‑week trials and in a 6‑month, open‑label safety trial^1,2

Prolactin levels in clinical trials^1,2

Monotherapy: 6 weeks

Adjunctive
(with Lithium or Valproate): 6 weeks

Open-label,
monotherapy: 6 months

Prolactin	CAPLYTA(n=372)	Placebo(n=374)	CAPLYTA(n=164)	Placebo(n=170)	CAPLYTA(n=115)
Mean change from baseline (µg/L)	-0.2	+1.1	+0.63	+1.78	+1.09

Monotherapy: 6 weeks

Prolactin	CAPLYTA(n=372)	Placebo(n=374)
Mean change from baseline (µg/L)	-0.2	+1.1

Adjunctive (with Lithium or Valproate): 6 weeks

Prolactin	CAPLYTA(n=164)	Placebo(n=170)
Mean change from baseline (µg/L)	+0.63	+1.78

Open-label, monotherapy: 6 months

Prolactin	CAPLYTA(n=115)
Mean change from baseline (µg/L)	+1.09

Prolactin-related TEAE levels in clinical trials^1,2

Monotherapy: 6 weeks

Adjunctive
(with Lithium or Valproate): 6 weeks

Prolactin-related TEAEs	CAPLYTA(n=372)	Placebo(n=374)	CAPLYTA(n=177)	Placebo(n=175)
Blood prolactin increased	1.3%	0.3%	2.3%	0.0%
Hyperprolactinemia	0.3%	0.8%	0.6%	3.4%

Monotherapy: 6 weeks

Prolactin-related TEAEs	CAPLYTA(n=372)	Placebo(n=374)
Blood prolactin increased	1.3%	0.3%
Hyperprolactinemia	0.3%	0.8%

Adjunctive (with Lithium or Valproate): 6 weeks

Prolactin-related TEAEs	CAPLYTA(n=177)	Placebo(n=175)
Blood prolactin increased	2.3%	0.0%
Hyperprolactinemia	0.6%	3.4%

Clinically significant elevation of prolactin levels in clinical trials^1,2

Monotherapy: 6 weeks

Adjunctive
(with Lithium or Valproate): 6 weeks

Clinically significant elevations	CAPLYTA(n=335)	Placebo(n=355)	CAPLYTA(n=162)	Placebo(n=170)
Prolactin (≥5x upper limit of normal)	0.3%	0.6%	1.2%	1.2%

Monotherapy: 6 weeks

Clinically significant elevations	CAPLYTA(n=335)	Placebo(n=355)
Prolactin (≥5x upper limit of normal)	0.3%	0.6%

Adjunctive (with Lithium or Valproate): 6 weeks

Clinically significant elevations	CAPLYTA(n=162)	Placebo(n=170)
Prolactin (≥5x upper limit of normal)	1.2%	1.2%

TEAEs=treatment-emergent adverse events.

In 6‑week trials, prolactin levels were similar to placebo¹

WARNINGS & PRECAUTIONS: Antipsychotic drugs have been reported to cause:

Metabolic Changes, including hyperglycemia, diabetes mellitus, dyslipidemia, and weight gain. Hyperglycemia, in some cases extreme and associated with ketoacidosis, hyperosmolar coma or death, has been reported in patients treated with antipsychotics. Measure weight and assess fasting plasma glucose and lipids when initiating CAPLYTA and monitor periodically during long-term treatment.

Please see additional Important Safety Information, including Boxed WARNINGS, below.

Full chart description

This chart depicts prolactin levels with CAPLYTA vs placebo at 6 weeks and prolactin levels with CAPLYTA at 6 months.

At 6 weeks, across the monotherapy arm of the study, placebo (n=374) and CAPLYTA (n=372), patients experienced prolactin mean change from baseline (µg/L), respectively: 1.1 vs -0.2; patients experienced the following prolactin-related TEAEs, respectively: blood prolactin increased, 0.3% vs 1.3%; hyperprolactinemia, 0.8% vs 0.3%; placebo (n=355) and CAPLYTA (n=335), patients experienced clinically significant elevations, prolactin (≥5x upper limit of normal), respectively, 0.6% vs 0.3%. Across the adjunctive (with lithium or valproate) arm of the study, placebo (n=170) and CAPLYTA (n=164), patients experienced prolactin mean change from baseline (µg/L), respectively: 1.78 vs 0.63; placebo (n=175) and CAPLYTA (n=177), patients experienced the following prolactin-related TEAEs, respectively: blood prolactin increased, 0.0% vs 2.3%; hyperprolactinemia, 3.4% vs 0.6%; placebo (n=170) and CAPLYTA (n=162), patients experienced clinically significant elevations, prolactin (≥5x upper limit of normal), respectively, 1.2% vs 1.2%.

At 6 months, patients taking CAPLYTA experienced prolactin mean change from baseline (µg/L) of 1.09 (n=115).

CAPLYTA demonstrated safety in 2,664 adult patients
with schizophrenia and bipolar depression¹

Most Common
Adverse Reactions

Weight, metabolic parameters, and prolactin1,2

For bipolar I and II depression in adults

Weight change was similar to placebo in 6‑week trials and not common in a 6‑month, open‑label safety trial1,2

Mean weight change from baseline1,2

Monotherapy: 6 weeks

Adjunctive (with Lithium or Valproate): 6 weeks

Open-label, monotherapy: 6 months

Monotherapy: 6 weeks

Adjunctive (with Lithium or Valproate): 6 weeks

Open-label, monotherapy: 6 months

View study design & full chart description

Change in metabolic parameters in 6‑week trials and in a 6‑month, open‑label safety trial1,2

Mean change from baseline in metabolic parameters1,2†

Monotherapy: 6 weeks

Adjunctive (with Lithium or Valproate): 6 weeks

Open-label, monotherapy: 6 months

Monotherapy: 6 weeks

Adjunctive (with Lithium or Valproate): 6 weeks

Open-label, monotherapy: 6 months

View full chart description

Prolactin levels in 6‑week trials and in a 6‑month, open‑label safety trial1,2

Prolactin levels in clinical trials1,2

Monotherapy: 6 weeks

Adjunctive (with Lithium or Valproate): 6 weeks

Open-label, monotherapy: 6 months

Monotherapy: 6 weeks

Adjunctive (with Lithium or Valproate): 6 weeks

Open-label, monotherapy: 6 months

Prolactin-related TEAE levels in clinical trials1,2

Monotherapy: 6 weeks

Adjunctive (with Lithium or Valproate): 6 weeks

Monotherapy: 6 weeks

Adjunctive (with Lithium or Valproate): 6 weeks

Clinically significant elevation of prolactin levels in clinical trials1,2

Monotherapy: 6 weeks

Adjunctive (with Lithium or Valproate): 6 weeks

Monotherapy: 6 weeks

Adjunctive (with Lithium or Valproate): 6 weeks

View full chart description

Weight, metabolic parameters, and prolactin^1,2

Weight change was similar to placebo in 6‑week trials and not common in a 6‑month, open‑label safety trial^1,2

Mean weight change from baseline^1,2

Adjunctive
(with Lithium or Valproate): 6 weeks

Open-label,
monotherapy: 6 months

Change in metabolic parameters in 6‑week trials and in a 6‑month, open‑label safety trial^1,2

Mean change from baseline in metabolic parameters^1,2†

Adjunctive
(with Lithium or Valproate): 6 weeks

Open-label,
monotherapy: 6 months

Prolactin levels in 6‑week trials and in a 6‑month, open‑label safety trial^1,2

Prolactin levels in clinical trials^1,2

Adjunctive
(with Lithium or Valproate): 6 weeks

Open-label,
monotherapy: 6 months

Prolactin-related TEAE levels in clinical trials^1,2

Adjunctive
(with Lithium or Valproate): 6 weeks

Clinically significant elevation of prolactin levels in clinical trials^1,2

Adjunctive
(with Lithium or Valproate): 6 weeks