Benzinga | Jan 21, 2021 08:13AM EST

Intra-Cellular Therapies Highlights CAPLYTA Open-Label Safety Switching Study In Patients With Schizophrenia Published In Journal, Schizophrenia Research

Patients with stable symptoms of schizophrenia were switched from previous antipsychotic medications with no dose titration to CAPLYTA 42 mg for a 6-week treatment duration, then switched back to previous or another approved antipsychotic.



In patients with stable symptoms of schizophrenia, CAPLYTA was well-tolerated with low rates of metabolic and extrapyramidal symptoms (EPS) adverse events; schizophrenia symptoms remained stable and did not worsen from baseline.

NEW YORK, Jan. 21, 2021 (GLOBE NEWSWIRE) -- Intra-Cellular Therapies, Inc. (NASDAQ:ITCI), a biopharmaceutical company focused on the development and commercialization of therapeutics for central nervous system (CNS) disorders, today announced the publication of results from the CAPLYTA clinical trial (ITI-007-303) in adult patients with schizophrenia. The article, "Safety and tolerability of lumateperone 42 mg: An open-label antipsychotic switch study in outpatients with stable schizophrenia" (Correll et al. 2021), was recently published online in Schizophrenia Research and is available here.

The objective of this 6-week open-label study was to evaluate the safety and tolerability of CAPLYTA with stable schizophrenia patients switched from another antipsychotic treatment. The most common drug-related treatment emergent adverse events during CAPLYTA treatment were somnolence (6.6%), headache (5.3%) and dry mouth (5.3%). Reports of EPS were low (1%).

After 6 weeks of CAPLYTA treatment, it was observed that the mean total cholesterol, low-density lipoprotein (LDL) cholesterol, body weight and prolactin levels decreased from baseline. At the conclusion of the treatment period with CAPLYTA, patients were switched back to their previous or another approved antipsychotic. In a prespecified secondary safety analysis, conducted 2 weeks after discontinuing CAPLYTA, it was observed that the mean total cholesterol, LDL cholesterol, body weight and prolactin levels increased. In this study, patients' schizophrenia symptoms remained stable and did not worsen from baseline.

These data further support the safety, tolerability and effectiveness of CAPLYTA in patients with schizophrenia and provide important information to clinicians.

"Weight gain and metabolic side effects or motor disturbances are leading reasons for healthcare providers to switch antipsychotics. Scientific results from studies that resemble a real world clinical setting and published in the medical literature provide important information for clinicians to make informed treatment decisions," said Dr. Christoph Correll, Professor of Psychiatry and Molecular Medicine at the Zucker School of Medicine at Hofstra/Northwell, New York. "CAPLYTA is a valuable addition to the armamentarium to help treat this challenging mental illness."

About ITI-007-303

ITI-007-303 is an open label, multicenter study conducted in the United States to investigate the safety and effectiveness of up to 1 year of treatment with CAPLYTA 42 mg in 301 stable patients with schizophrenia after switching from previous antipsychotic medications with no dose titration to CAPLYTA 42 mg. The study was conducted in 2 parts.

In Part 1, patients were eligible for participation if they had stable psychopathology and were able to be treated on an outpatient basis after Day 5. Entering the screening period on an existing antipsychotic was not a requirement of the study; therefore, medication history could not always be verified.

Patients meeting entry criteria were required to discontinue previous antipsychotics, tapering as appropriate, prior to starting CAPLYTA 42 mg with no dose titration. The primary objective assessed adverse events (AE), vital signs, laboratory tests, and extrapyramidal symptoms (EPS). Three hundred and one patients received CAPLYTA in the study and the 6-week treatment was completed by 218 (72.2%) of patients. The most common reason for treatment discontinuation was adverse events (8.9%). At the conclusion of the treatment period with CAPLYTA, patients were switched to their previous or another approved antipsychotic and a follow-up safety assessment was conducted approximately 2 weeks later.

In Part 2 of this study, patients were treated for up to 1 year and the favorable safety profile was maintained. Data from Part 2 of the study will be published in a separate report.

CAPLYTA(r) (lumateperone) is indicated for the treatment of schizophrenia in adults. CAPLYTA is available in 42 mg capsules.

Important Safety Information

Boxed Warning: Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. CAPLYTA is not approved for the treatment of patients with dementia-related psychosis.

Contraindications: CAPLYTA is contraindicated in patients with known hypersensitivity to lumateperone or any components of CAPLYTA. Reactions have included pruritus, rash (e.g. allergic dermatitis, papular rash, and generalized rash), and urticaria.

Warnings & Precautions: Antipsychotic drugs have been reported to cause:

* Cerebrovascular Adverse Reactions in Elderly Patients with Dementia-Related Psychosis, including stroke and transient ischemic attack. See Boxed Warning above.

* Neuroleptic Malignant Syndrome (NMS), which is a potentially fatal reaction. Signs and symptoms include: high fever, stiff muscles, confusion, changes in breathing, heart rate, and blood pressure, elevated creatinine phosphokinase, myoglobinuria (and/or rhabdomyolysis), and acute renal failure. Patients who experience signs and symptoms of NMS should immediately contact their doctor or go to the emergency room.

* Tardive Dyskinesia, a syndrome of uncontrolled body movements in the face, tongue, or other body parts, which may increase with duration of treatment and total cumulative dose. TD may not go away, even if CAPLYTA is discontinued. It can also occur after CAPLYTA is discontinued.

* 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.

* Leukopenia, Neutropenia, and Agranulocytosis (including fatal cases). Complete blood counts should be performed in patients with pre-existing low white blood cell count (WBC) or history of leukopenia or neutropenia. CAPLYTA should be discontinued if clinically significant decline in WBC occurs in absence of other causative factors.

* Decreased Blood Pressure & Dizziness. Patients may feel lightheaded, dizzy or faint when they rise too quickly from a sitting or lying position (orthostatic hypotension). Heart rate and blood pressure should be monitored and patients should be warned with known cardiovascular or cerebrovascular disease. Orthostatic vital signs should be monitored in patients who are vulnerable to hypotension.

* Falls. CAPLYTA may cause sleepiness or dizziness and can slow thinking and motor skills, which may lead to falls and, consequently, fractures and other injuries. Patients should be assessed for risk when using CAPLYTA.

* Seizures. CAPLYTA should be used cautiously in patients with a history of seizures or with conditions that lower seizure threshold.

* Sleepiness and Trouble Concentrating. Patients should use caution when operating machinery or motor vehicles until they know how CAPLYTA affects them.

* Body Temperature Dysregulation. CAPLYTA should be used with caution in patients who may experience conditions that may increase core body temperature such as strenuous exercise, extreme heat, dehydration, or concomitant anticholinergics.

* Dysphagia. CAPLYTA should be used with caution in patients at risk for aspiration.

Drug Interactions: CAPLYTA should not be used with CYP3A4 inducers, moderate or strong CYP3A4 inhibitors and UGT inhibitors.

Special Populations: Newborn infants exposed to antipsychotic drugs during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. Breastfeeding is not recommended. Use of CAPLYTA should be avoided in patients with moderate or severe liver problems.

Adverse Reactions: The most common adverse reactions in clinical trials with CAPLYTA vs. placebo were somnolence/sedation (24% vs. 10%) and dry mouth (6% vs. 2%).

Please click here to see full Prescribing Information including Boxed Warning.