Study of the Efficacy of Lurasidone in Cognitive Functioning in Bipolar Patients (ELICE-BD)

JRCT ID: jRCTs031180065

Registered date:27/12/2018

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Bipolar Disorder
• Date of first enrollment: 08/01/2019
• Target sample size: 150
• Countries of recruitment: Canada,Japan,United States,Japan,United Kingdom,Japan
• Study type: Interventional

Intervention(s)

Intervention group: Lurasidone 20 mg tablets, 6 weeks, daily oral administration starting at 20 mg, increasing to 40 mg at Day 7, and recommended to increase to 60 mg at Week 3 depending on the subject's performance on the WAIS-3 Coding subtest. The dose may be further increased to a maximum dose of 80 mg if there are no tolerability issues based on investigator's discretion.
Control group: matching placebo, 6 weeks, daily oral administration starting at 20 mg, increasing to 40 mg at Day 7, and recommended to increase to 60 mg at Week 3 depending on the subject's performance on the WAIS-3 Coding subtest. The dose may be further increased to a maximum dose of 80 mg if there are no tolerability issues based on investigator's discretion.

Outcome(s)

• Primary Outcome: The primary efficacy measure for the study will be improvement in cognitive performance, as measured by changes in composite cognitive score from baseline to endpoint, extracted from the International Society for Bipolar Disorders-Battery for Assessment of Neurocognition. The coprimary efficacy measure will include changes in functioning from baseline to endpoint measured using UCSD based performance skills assessment-brief version.
• Secondary Outcome: Secondary efficacy measures will include: a) improvement in mood scores, based on Montgomery Asberg Depression Rating Scale(MADRS) and Young Mania Rating Scale(YMRS); b) improvement in overall psychiatric status, defined as change from baseline to endpoint in score on the Clinical Global Improvement Scale, Bipolar Version, Severity and Change Subscales; c) frequency and severity of side effects of lurasidone as reported by patients or determined by investigators; d) improvement in quality of life, defined as change from baseline to endpoint in scores on the Quality of Life, Bipolar Version, global and subscale ratings; e) improvement in subjective-rated cognitive functioning, defined as change from baseline to endpoint in scores on the cognitive complaints in bipolar disorder rating assessment(COBRA); f) improvement in daily functioning, defined as change from baseline to endpoint in scores on the Functioning Assessment Short Test(FAST), Sheehan Disability Scale(SDS); and g) study completion rates.

Key inclusion & exclusion criteria

• Age minimum: >= 19age old
• Age maximum: <= 65age old
• Gender: Both

Include criteria

1. Males or females aged 19 to 65 years.
2. DSM-5 diagnosis of BP I or II Disorder. BP II patients must have had 2 definite periods of hypomania in the last 5 years.
3. All patients must be taking either a mood stabilizer (lithium or valproate) (lamotrigine for BP II only) or an atypical antipsychotic or a combination of these except for two atypical antipsychotics. Medications and therapeutic doses are: lithium, 0.6-1.2 mEq/L; divalproex/sodium valproate, 350-700 mM/L(45-125 mcg/ml); risperidone 1-6 mg/day; olanzapine 5-30 mg/day; quetiapine IR or XR 300-900 mg/day; aripiprazole 10-30 mg/day; and ziprasidone 80-160 mg/day. Combinations of any of them with lamotrigine 100-400 m/day, or the combination of a mood stabilizer plus asenapine 5-20 mg/day, are also permitted.
4. All concomitant medication must be at a stable dose for 2 weeks prior to the randomization.
5. Clinically stable during the last 4 weeks as assessed by clinical interview.
6. A MADRS and YMRS score less than or equal to 8.
7. Patients who show cognitive impairments, defined as 0.5 standard deviations below the mean or worse(z = - 0.5 or lower), on either the WAIS-III - Coding subtest, or the Rey Auditory Verbal Learning Test(RAVLT) total learning score on trials 1-5 or immediate recall trial, at screening visit.
8. WAIS-III vocabulary scaled score >6 (equivalent to estimated IQ 80 or greater).
9. Sufficient level of Japanese language.
10. Females who are postmenopausal for at least 1 year before the screening visit (confirmed by FSH test) or are surgically sterile. Females of childbearing potential who are taking contraceptive pills or agree to practice 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.
11. 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.

Exclude criteria

1. 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.
2. Patients taking procognitive medications, clozapine, tricyclic antidepressants, first-generation antipsychotics, and cogentin.
3. Those taking two or more antipsychotics.
4. Anticholinergics and stimulants that increase dopamine levels are not permitted.
5. Cognitive remediation therapy within 3 months prior to entry or during the double blind phase.
6. Neuromodulation treatment with ECT or rTMS or tDCS or DBS within eight weeks or treatment with an experimental drug within 30 days.
7. 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.
8. History of nonresponse or intolerance to lurasidone.
9. Psychotic disorder other than Bipolar Disorder.
10. Patients who currently meet criteria for anxiety disorder (GAD, OCD, Panic disorder, PTSD).
11. Those with a documented current or lifetime diagnosis of ADHD or other learning disorders.
12. Axis I diagnosis of alcohol/substance abuse or dependence within the past month.
13. Significant risk of harm to self or others.
14. Pregnancy or lactation.
15. Liver function tests (AST and ALT) three times the upper limit of normal.

Related Information

• Primary Sponsor: Nakagome Kazuyuki
• Secondary Sponsor: Yatham Lakshmi
• Source(s) of Monetary Support: University of British Columbia
• Secondary ID(s): NCT02731612 UMIN000025167