Phase 3 LATUDA Data Demonstrates Bipolar Depression Symptom Improvement

Sunovion Pharmaceuticals Inc. has announced post-hoc analysis results of a positive phase 3 placebo-controlled clinical study, and interim data from a long-term open-label extension study, evaluating lurasidone HCI (LATUDA) in children and adolescents with major depressive episodes associated with bipolar I disorder.

Study results showed that 6 weeks of treatment with LATUDA was associated with statistically significant and clinically meaningful improvement in a wide range of depressive symptoms, compared to the placebo.

“Depressive symptoms can be severely debilitating to schoolwork and social activities in children and adolescents living with bipolar disorder, which is recognized as the fourth leading cause of disability among children and adolescents around the world,” Kiki Chang, MD, clinical study investigator, said in a statement. “The findings presented today are encouraging, as we need additional treatment options that are well tolerated and can be used on an ongoing basis by children and adolescents who live with bipolar depression.”

The trial studied 347 children and adolescents 10—17 years of age with bipolar depression. Participants received once-daily LATUDA, flexibly dosed 20–80 mg/day, or placebo.

The LATUDA arm participants associated with statistically significant and clinically meaningful improvement in symptoms compared to placebo, based on primary efficacy endpoint data from baseline to week 6 on the Children’s Depression Rating Scale, Revised (CDRS-R) total score.

Compared to the placebo, patients randomized to LATUDA demonstrated greater improvement on 13 of the 17 CDRS-R items including social withdrawal, sleep disturbance, listless speech, depressed facial effect, excessive guilt, difficult having fun, depressed feelings, low self-esteem, excessive weeping, hypoactivity, impaired schoolwork, irritability and appetite disturbance.

Changes were not significant between the LATUDA group and the placebo group in 4 items, including excessive fatigue, physical complains, morbid ideation and suicidal ideation.

Long-term treatment for 28 weeks was well tolerated and continued to improve depressive symptoms with minimal effect on weight and metabolic parameters in children and adolescents with bipolar depression.

The most common side effects with an incidence greater than 5% of LATUDA-treated patients included nausea, somnolence, weight increase, vomiting, dizziness and insomnia.

The long-term open label extension study focused on 223 participants who completed the 6-week trial. The 2-year, open-label, flexible dose, extension study showed that among the 155 people who completed 28 weeks of treatment, LATUDA was generally well-tolerated with similar adverse effects reported in the 6-week pivotal trial.

The most common adverse effects greater than 10% were headache, 19.7%, somnolence 18.5%, nausea 14.3%.

At 28 weeks, participants who were treated with LATUDA throughout the initial 6-week trial had continued improvement in the CDRS-R total score in the extension phase. Continued improvement in the open-label phase was similarly observed on the Clinical Global Impression-Bipolar Version, Severity of Illness (CGI-BP-S) depression score.

A supplemental New Drug Application (sNDA) has been submitted to the US Food and Drug Administration (FDA) for the use of LATUDA in children and adolescents with bipolar depression that was accepted for review June 30.

LATUDA is an atypical antipsychotic agent approved in the US for the treatment of bipolar depression as monotherapy and as adjunctive therapy with lithium or valproate in adults, and for the treatment of schizophrenia in adults and adolescents.

The most common side effects include sleepiness or drowsiness, akathisia, difficulty moving, slow movements, muscle stiffness or tremor, nasal inflammation, and nausea.

A press release was made available.

The study, “Efficacy and Safety of Lurasidone in Children and Adolescents with Bipolar I Depression: A Double-Blind, Placebo-Controlled Study,” can be found in the Journal of the American Academy of Child and Adolescent Psychiatry.