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

NCT02731612 | Completed Phase 3 FDA Drug

• 1 other identifier: H16-00129
• Study Type: interventional
• Target: 100
• Locations: 4 countries
• Sites: 9

Brief Summary

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.

Conditions

Bipolar Disorder

Keywords

Bipolar Disorder; Cognition; Euthymic; Lurasidone

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Change in Depression

  6 weeks

• Change in Mania

  6 weeks

• Improvement in overall psychiatric status

  6 weeks

• Improvement in Quality of Life

  6 weeks

• Improvement in Subjective-rated Cognitive Functioning

  6 weeks

Study Arms (2)

Lurasidone

EXPERIMENTAL

Lurasidone 20 - 80 mg / day added to current treatment for 6 weeks.

Drug: lurasidone

Placebo

PLACEBO COMPARATOR

Placebo added to current treatment for 6 weeks

Other: Placebo

Interventions

lurasidone DRUG

Atypical Antipsychotic

Also known as: Latuda

Lurasidone

Placebo OTHER

Inactive substance

Placebo

Eligibility Criteria

• Age: 19 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Lakshmi N Yatham: lead

Study Sites (9)

The Brigham and Women's Hospital, Department of Psychiatry

Boston, Massachusetts, 02115, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

UBC Mood Disorders Center

Vancouver, British Columbia, V6T 1Z3, Canada

Location

Department of Psychiatry, University of Occupational and Environmental Health

Kitakyushu, Fukuoka, 807-8555, Japan

Location

Department of Neuropsychiatry, Kansai Medical University

Moriguchi-shi, Osaka, 570-8506, Japan

Location

Department of Psychiatry, Hokkaido University Graduate School of Medicine

Kita-ku, Sapporo, 060-8638, Japan

Location

National Center of Neurology and Psychiatry

Kodaira, Tokyo, 187-8551, Japan

Location

Department of Psychiatry, Fujita Health University School of Medicine

Aichi, Toyoake, 470-1192, Japan

Location

Institute of Psychiatry, Psychology and Neuroscience,King's College London

London, England, SE5 8AF, United Kingdom

Location

MeSH Terms

Conditions

Bipolar Disorder

Interventions

Lurasidone Hydrochloride

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Lakshmi N Yatham, MBBS,MRCPsy

  University of British Columbia, Department of Psychiatry

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prinicipal Investigator

Study Record Dates

• First Submitted: March 23, 2016
• First Posted: April 7, 2016
• Study Start: May 8, 2017
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: February 14, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

JP (5); US (2); GB (1); CA (1)