Study of the Efficacy of Lurasidone in Cognitive Functioning in Bipolar Patients

Study Overview
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Brief Summary
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This is a randomized, double-blind, placebo-controlled, multicentre, parallel-group study to assess the cognitive effects of lurasidone in bipolar I and II patients (manic depression) who are in remission from an episode. Participants who show cognitive impairment at the screening visit will be enrolled into the study and randomized at the baseline visit to receive either lurasidone or placebo adjunctive therapy in a 1:1 ratio for 6 weeks.

Official Title
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A 6-Week Randomised, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy of Lurasidone Adjunctive Therapy in Improving Cognitive Functioning in Euthymic Bipolar Disorder Patients (ELICE-BD)

Conditions
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Bipolar Disorder

Intervention / Treatment
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* Drug: lurasidone
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females aged 19 to 65 years inclusive. Diagnostic and Statistical Manual of Mental Disorder, 5th Edition (DSM.5) diagnosis of Bipolar Type I or Type II Disorder, with or without a history of psychosis. BP II patients must have had 2 definite periods of hypomania in the last 5 years. All patients must be taking either a mood stabilizer (i.e. lithium or valproate) (lamotrigine as a mood stabilizer is acceptable for bipolar 2 disorder patients only and not for bipolar I disorder) or an atypical antipsychotic or a combination of these (two mood stabilizers or a mood stabilizer plus an atypical antipsychotic), at therapeutic doses, for mood stabilization. Those taking two atypical antipsychotics are excluded. Combinations of these medications as outlined above, or the combination of any of them with lamotrigine 100-400 mg daily, or the combination of a mood stabilizer plus asenapine 5-20 mg/day, are also permitted. All concomitant medication must be at a stable dose for two weeks prior to the randomization visit. Clinically stable during the last 4 weeks as assessed by clinical interview. A Montgomery Asberg Depression Rating Scale(MADRS) and Young Mania Rating Scale (YMRS) score less than or equal to 8. Patients who show cognitive impairments (-0.50 SD or below) on either the Wechsler Adult Intelligence Scale-IV (WAIS-IV) -Coding subtest, or the Rey Auditory Verbal Learning Test (RAVLT) total learning score on trials 1 to 5 or immediate recall, at screening visit. A WAIS-IV vocabulary scaled score >5 (equivalent to estimated IQ 80 or greater). A sufficient level of the English or Japanese language. Females who are postmenopausal for at least 1 year before the screening visit (confirmed by an FSH test) or are surgically sterile. Females of childbearing potential who are taking contraceptive pills or agree to practice effective double barrier methods of contraception, from the time of signing the informed consent up to the last dose of study drug, and for 7 days after dosing stops, or who agree to completely abstain from heterosexual intercourse. Capability of understanding, consenting to, and complying with study requirements, study visits, and to return to the clinic for follow-up evaluations as specified by the protocol. Exclusion Criteria: A history of unstable or inadequately treated medical illnesses including moderate to severe brain injury, or neurological illnesses impacting cognitive function. Patients with a personal or family history of cardiac problems will need to undergo EKG at screen visit, and will be excluded if results are abnormal. Patients taking procognitive medications, clozapine, tricyclic antidepressants, first-generation antipsychotics, and cogentin. Those taking two or more antipsychotics. Those taking strong CYP3A4 inhibitors (e.g. clarithromycin, nefazodone, grapefruit juice) or strong CYP3A4 inducers (e.g. carbamazepine, St John's wort (Hypericum perforatum). Please refer to the current Lurasidone SmPC for further listed contraindications. Anticholinergics and stimulants that increase dopamine levels are not permitted Cognitive remediation therapy within 3 months prior to entry or during the double blind phase. Neuromodulation treatment with ECT or rTMS or tDCS or DBS within eight weeks or treatment with an experimental drug within 30 days. History of nonresponse or intolerance to lurasidone. Psychotic disorder other than Bipolar Disorder. Patients who currently meet criteria for anxiety disorder (GAD, OCD, Panic disorder, PTSD). Those with a current or lifetime diagnosis of ADHD or other learning disorders. Axis I diagnosis of alcohol/substance abuse or dependence within the past month. Significant risk of harm to self or others. Pregnancy or lactation. Liver function tests (AST and ALT) three times the upper limit of normal.

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lurasidone<br>Lurasidone 20 - 80 mg / day added to current treatment for 6 weeks. | Drug: lurasidone<br>* Atypical Antipsychotic<br>* Other names: Latuda;|
| Placebo Comparator: Placebo<br>Placebo added to current treatment for 6 weeks | Other: Placebo<br>* Inactive substance<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in cognitive performance in Euthymic bipolar patients treated with Lurasidone vs Placebo adjunctive therapy. | Cognitive improvement will be measured by changes in composite cognitive score from baseline to endpoint, extracted from the International Society for Bipolar Disorders-Battery for Assessment of Neurocognition. | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Depression | Montgomery Asberg Depression Rating Scale (MADRS) will be used to assess changes in bipolar depression from baseline to endpoint. | 6 weeks | 
| Change in Mania | The Young Mania Rating Scale (YMRS) will be used to assess changes in mania from baseline to endpoint. | 6 weeks | 
| Improvement in overall psychiatric status | Clinical Global Improvement Scale will be used to assess change from baseline to endpoint in overall psychiatric status. | 6 weeks | 
| Improvement in Quality of Life | Quality of Life, Bipolar Version Scale will be used to assess improvement in quality of life from baseline to endpoint. | 6 weeks | 
| Improvement in Subjective-rated Cognitive Functioning | Cognitive Complaints in Bipolar Disorder Rating Assessment (COBRA) will be used to assess changes in subjective cognitive functioning from baseline to endpoint. | 6 weeks | 
| Improvement in Objectively Rated Daily Functioning | Functioning Assessment Short Test (FAST) will be used to assess improvement in objectively rated daily functioning, defined as change in scores from baseline to endpoint. | 6 weeks | 
| Improvement in Subjectively Rated Daily Functioning | Sheehan Disability Scale (SDS) will be used to assess improvement in subjectively rated daily functioning, defined as change in scores from baseline to endpoint. | 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cognition, Bipolar Disorder, Euthymic, Lurasidone