Bipolar Disorder
Conditions
Interventions
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 subjec
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 sub
Sponsors
University of British Columbia
Kazuyuki Nakagome (National Center of Neurology and Psychiatry Hospital
4-1-1 Ogawahigashi-cho, Kodaira, Tokyo 187-8551)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Aged 19 to 65 years. 2. DSM-5 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 or lamotrigine) or an atypical antipsychotic or a combination of these in therapeutic doses 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); lamotrigine 100-400mg/day; 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. Combination of a mood stabilizer plus asenapine 5-20 mg/day is also permitted. Lamotrigine as a single agent therapy is only allowed for BP II patients. 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 SD below the mean or worse(z =-0.5 or lower), on either the WAIS-III-Coding subtest, or the Rey Auditory Verbal Learning Test total learning score on trials 1-5 or immediate recall trial, at screening visit. 8. WAIS-III vocabulary scaled score >5. 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. Capable 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
Exclusion criteria: Subjects meeting any of the following criteria are not eligible to participate in the trial: 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 childhood 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 co-primary efficacy measure will include changes in functioning from baseline to endpoint measured using UCSD-based performance skills assessment-brief version. | — |
Secondary
| Measure | Time frame |
|---|---|
| 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. | — |
Countries
Japan,North America,Europe
Contacts
Public ContactNazlin Walji
University of British Columbia Mood Disorders Centre at UBC Hospital UBC Department of Psychiatry
Outcome results
None listed