Efficacy in Adult Patients

A Comprehensive Clinical Program

LATUDA efficacy in adults with schizophrenia established at doses ranging from 40 mg/day to 160 mg/day

Efficacy_Chart2

SD: standard deviation; SE: standard error; LS Mean: least-squares mean; CI: confidence interval, unadjusted for multiple comparisons.
PANSS=Positive and Negative Syndrome Scale. BPRSd=Brief Psychiatric Rating Scale derived from PANSS total score.
aDifference (drug minus placebo) in least-squares mean change from baseline.
bIncluded for assay sensitivity.1
*Doses statistically significantly superior to placebo.

Significant Improvement in Adults with Schizophrenia Symptoms

LATUDA 40 mg/day and 120 mg/day significantly improved PANSS total scores vs placebo in adult patients

3.8_PANSS_Chart

 

Clinical Study Design Overview

Study 3 (Meltzer et al.) was a 6-week, randomized, double-blind, placebo- and active-controlled trial (N=478) designed to evaluate the efficacy and safety of 2 fixed once-daily doses of LATUDA (40 mg/day, 120 mg/day) in adult patients.

Study 3 was 1 of 5 pivotal, short-term (6-week) placebo-controlled studies in adult patients (mean age of 37.7 years, range 18–68 years) who met DSM-IV criteria for schizophrenia.

Active-control olanzapine 15 mg/day was included for purposes of establishing assay sensitivity.

Primary endpoint: change in PANSS total score from baseline at Week 6, MMRM analysis. Mean baseline PANSS total scores: LATUDA 40 mg/day 96.6; LATUDA 120 mg/day 97.9; olanzapine 15 mg/day 96.3; placebo 95.8. Key secondary endpoint: mean change in CGI-S score from baseline at Week 6, MMRM analysis. Mean baseline CGI-S scores: LATUDA 40 mg/day 5.0; LATUDA 120 mg/day 5.0; olanzapine 15 mg/day 4.9; placebo 4.9.1,4

References:
1.
 Latuda® (lurasidone HCl) prescribing information. Sunovion Pharmaceuticals Inc. February 2017.
2. Ogasa M, Kimura T, Nakamura M, Guarino J. Lurasidone in the treatment of schizophrenia: a 6‑week, placebo‑controlled study.Psychopharmacol. 2013;225(3):519-530.
3. Nakamura M, Ogasa M, Guarino J, et al. Lurasidone in the treatment of acute schizophrenia: a double-blind, placebo-based controlled trial. J Clin Psychiatry. 2009;70:829-836.
4. Meltzer HY, Cucchiaro J, Silva R, et al. Lurasidone in the treatment of schizophrenia: a randomized, double-blind, placebo- and olanzapine-controlled study. Am J Psychiatry. 2011;168:957-967.
5. Nasrallah HA, Silva R, Phillips D, et al. Lurasidone for the treatment of acutely psychotic patients with schizophrenia: a 6-week, randomized, placebo-controlled study. J Psychiat Res. 2013;47:670-677.
6. Loebel A, Cucchiaro J, Sarma K, et al. Efficacy and safety of lurasidone 80 mg/day and 160 mg/day in the treatment of schizophrenia: a randomized, double-blind, placebo- and active-controlled trial. Schizophr Res. 2013;145:101-109.

 

LATUDA 40 mg/day and 120 mg/day significantly improved Clinical Global Impression - Severity (CGI-S) scores vs placebo in adult patients

 

3.8_CGI-S_Chart

Clinical Study Design Overview

Study 3 (Meltzer et al.) was a 6-week, randomized, double-blind, placebo- and active-controlled trial (N=478) designed to evaluate the efficacy and safety of 2 fixed once-daily doses of LATUDA (40 mg/day, 120 mg/day) in adult patients.

Study 3 was 1 of 5 pivotal, short-term (6-week) placebo-controlled studies in adult patients (mean age of 37.7 years, range 18−68 years) who met DSM-IV criteria for schizophrenia. Active-control olanzapine 15 mg/day was included for purposes of establishing assay sensitivity.

Primary endpoint: change in PANSS total score from baseline at Week 6, MMRM analysis. Mean baseline PANSS total scores: LATUDA 40 mg/day 96.6; LATUDA 120 mg/day 97.9; olanzapine 15 mg/day 96.3; placebo 95.8. Key secondary endpoint: mean change in CGI-S score from baseline at Week 6, MMRM analysis. Mean baseline CGI-S scores: LATUDA 40 mg/day 5.0; LATUDA 120 mg/day 5.0; olanzapine 15 mg/day 4.9; placebo 4.9.1,4

References:
1.
 Latuda® (lurasidone HCl) prescribing information. Sunovion Pharmaceuticals Inc. February 2017.
2. Ogasa M, Kimura T, Nakamura M, Guarino J. Lurasidone in the treatment of schizophrenia: a 6‑week, placebo‑controlled study.Psychopharmacol. 2013;225(3):519-530.
3. Nakamura M, Ogasa M, Guarino J, et al. Lurasidone in the treatment of acute schizophrenia: a double-blind, placebo-based controlled trial. J Clin Psychiatry. 2009;70:829-836.
4. Meltzer HY, Cucchiaro J, Silva R, et al. Lurasidone in the treatment of schizophrenia: a randomized, double-blind, placebo- and olanzapine-controlled study. Am J Psychiatry. 2011;168:957-967.
5. Nasrallah HA, Silva R, Phillips D, et al. Lurasidone for the treatment of acutely psychotic patients with schizophrenia: a 6-week, randomized, placebo-controlled study. J Psychiat Res. 2013;47:670-677.
6. Loebel A, Cucchiaro J, Sarma K, et al. Efficacy and safety of lurasidone 80 mg/day and 160 mg/day in the treatment of schizophrenia: a randomized, double-blind, placebo- and active-controlled trial. Schizophr Res. 2013;145:101-109.

LATUDA 80 mg/day significantly improved BPRSd scores vs placebo in adult patients

3.8_BPRSd_Chart

Clinical Study Design Overview

Study 2 was a 6-week, randomized, double-blind, placebo-controlled trial (N=180) designed to evaluate the efficacy and safety of LATUDA 80 mg/day (once daily) vs placebo in adult patients.

Study 2 was 1 of 5 pivotal, short-term (6-week) placebo-controlled studies in adult patients (mean age of 40.8 years, range 21−63 years) who met DSM-IV criteria for schizophrenia.

Primary endpoint: mean change from baseline in BPRS, derived from the PANSS, at Week 6, ANCOVA LOCF analysis. Mean baseline BPRSd scores: LATUDA 80 mg/day 55.1, placebo 56.1.1,4

References:
1.
 Latuda® (lurasidone HCl) prescribing information. Sunovion Pharmaceuticals Inc. February 2017.
2. Ogasa M, Kimura T, Nakamura M, Guarino J. Lurasidone in the treatment of schizophrenia: a 6‑week, placebo‑controlled study.Psychopharmacol. 2013;225(3):519-530.
3. Nakamura M, Ogasa M, Guarino J, et al. Lurasidone in the treatment of acute schizophrenia: a double-blind, placebo-based controlled trial. J Clin Psychiatry. 2009;70:829-836.
4. Meltzer HY, Cucchiaro J, Silva R, et al. Lurasidone in the treatment of schizophrenia: a randomized, double-blind, placebo- and olanzapine-controlled study. Am J Psychiatry. 2011;168:957-967.
5. Nasrallah HA, Silva R, Phillips D, et al. Lurasidone for the treatment of acutely psychotic patients with schizophrenia: a 6-week, randomized, placebo-controlled study. J Psychiat Res. 2013;47:670-677.
6. Loebel A, Cucchiaro J, Sarma K, et al. Efficacy and safety of lurasidone 80 mg/day and 160 mg/day in the treatment of schizophrenia: a randomized, double-blind, placebo- and active-controlled trial. Schizophr Res. 2013;145:101-109.

IMPORTANT SAFETY INFORMATION AND INDICATIONS FOR LATUDA

INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS; and SUICIDAL THOUGHTS AND BEHAVIORS

Increased Mortality in Elderly Patients with Dementia-Related Psychosis
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. LATUDA is not approved for the treatment of patients with dementia-related psychosis.

Suicidal Thoughts and Behaviors
Antidepressants increased the risk of suicidal thoughts and behaviors in patients aged 24 years and younger. Monitor for clinical worsening and emergence of suicidal thoughts and behavior. LATUDA is not approved for use in pediatric patients with depression.

 

CONTRAINDICATIONS: LATUDA is contraindicated in the following:

Cerebrovascular Adverse Reactions, Including Stroke: In clinical trials, elderly subjects with dementia randomized to risperidone, aripiprazole, and olanzapine had a higher incidence of stroke and transient ischemic attack, including fatal stroke. LATUDA is not approved for the treatment of patients with dementia-related psychosis.

Neuroleptic Malignant Syndrome (NMS): NMS is a potentially fatal symptom complex, reported with administration of antipsychotic drugs. Clinical signs of NMS are hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability. Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. Manage NMS with immediate discontinuation of antipsychotic drugs, including LATUDA, intensive symptomatic treatment, and monitoring.

Tardive Dyskinesia (TD): The risk of developing TD (a syndrome of abnormal involuntary movements) and the potential for it to become irreversible are believed to increase as the duration of treatment and total cumulative dose of antipsychotic increase. The syndrome can develop, although much less commonly, after relatively brief treatment periods at low doses. There is no known treatment for established TD, although the syndrome may remit, partially or completely, if antipsychotic treatment is withdrawn.

Metabolic Changes Atypical antipsychotic drugs have caused metabolic changes including:

Hyperglycemia and Diabetes Mellitus: Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients treated with atypical antipsychotics. Patients with diabetes should be regularly monitored for worsening of glucose control; those with risk factors for diabetes should undergo fasting blood glucose testing at the beginning of and periodically during treatment. Any patient treated with atypical antipsychotics should be monitored for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. Patients who develop symptoms of hyperglycemia should undergo fasting blood glucose testing. In some cases, hyperglycemia has resolved when the atypical antipsychotic was discontinued; however, some patients required continuation of anti-diabetic treatment despite discontinuation of the suspect drug.

Dyslipidemia: Undesirable alterations in lipids have been observed in patients treated with atypical antipsychotics.

Weight Gain: Weight gain has been observed with atypical antipsychotic use. Clinical monitoring of weight is recommended.

Hyperprolactinemia: As with other drugs that antagonize dopamine D2 receptors, LATUDA elevates prolactin levels. Galactorrhea, amenorrhea, gynecomastia, and impotence have been reported in patients receiving prolactin-elevating compounds.

Leukopenia, Neutropenia, and Agranulocytosis: Leukopenia/neutropenia has been reported with antipsychotics. Agranulocytosis (including fatal cases) has been reported with other agents in the class. Monitor complete blood count in patients with a pre-existing low white blood cell count (WBC)/absolute neutrophil count (ANC) or history of drug-induced leukopenia/neutropenia. Discontinue LATUDA at the first sign of a decline in WBC in the absence of other causative factors.

Orthostatic Hypotension and Syncope: Atypical antipsychotics cause orthostatic hypotension and syncope. Generally, the risk is greatest at the beginning of treatment and when increasing the dose. Monitor patients vulnerable to hypotension and those with cardiovascular and cerebrovascular disease.

Falls: Antipsychotics may cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls causing fractures or other injuries. For patients with disease, conditions, or medications that could exacerbate these effects, complete fall risk assessments when initiating treatment and recurrently during therapy.

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

Potential for Cognitive and Motor Impairment: Patients should be cautioned about operating hazardous machinery, including motor vehicles, until they are reasonably certain that therapy with LATUDA does not affect them adversely.

Body Temperature Regulation: Use LATUDA with caution in patients who may experience conditions that increase body temperature (e.g., exercising strenuously, exposure to extreme heat, concomitant medication with anticholinergic activity, or being subject to dehydration).

Dysphagia: Antipsychotics, including LATUDA, have been associated with esophageal dysmotility and aspiration, and should be used with caution in patients at risk for aspiration pneumonia.

Most Commonly Observed Adverse Reactions: Commonly observed adverse reactions (≥5% incidence and at least twice the rate of placebo) for LATUDA:

To report SUSPECTED ADVERSE REACTIONS, contact Sunovion Pharmaceuticals Inc. at 877-737-7226 or FDA at 1-800-FDA-1088 (www.fda.gov/medwatch).

Indications

LATUDA is indicated for:

Before prescribing LATUDA, please read the full Prescribing Information, including Boxed Warnings.