UMIN-CTR Clinical Trial

Public title

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)

Acronym

Study of the Efficacy of Lurasidone in Cognitive Functioning in Bipolar Patients (ELICE_BD)

Scientific Title

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)

Scientific Title:Acronym

Study of the Efficacy of Lurasidone in Cognitive Functioning in Bipolar Patients (ELICE_BD)

Region

Japan	North America	Europe

Condition

Bipolar Disorder

Classification by specialty

Psychiatry

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

The primary objective of this study is to compare changes in cognitive function in euthymic bipolar patients who are treated with 20 to 80 mg/day of Lurasidone vs Placebo adjunctive therapy over a 6 week period.

Basic objectives2

Efficacy

Basic objectives -Others

Trial characteristics_1

Confirmatory

Trial characteristics_2

Pragmatic

Developmental phase

Phase III

Primary outcomes

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.

Key secondary outcomes

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.

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Double blind -all involved are blinded

Control

Placebo

Stratification

NO

Dynamic allocation

NO

Institution consideration

Institution is not considered as adjustment factor.

Blocking

NO

Concealment

Central registration

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

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.

Interventions/Control_2

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.

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

19

years-old

<=

Age-upper limit

65

years-old

>=

Gender

Male and Female

Key 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.

Key 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.

Target sample size

150

Name of lead principal investigator

1st name	Lakshmi
Middle name
Last name	Yatham

Organization

University of British Columbia

Division name

Regional Head and Program Medical Director, Mental Health and Addictions, Vancouver Coastal Health and Providence Health Care

Zip code

V6T 2B5, CANADA

Address

2215 Wesbrook Mall Vancouver, British Columbia V6T 2B5, CANADA

TEL

604-822-0562

Email

yatham@mail.ubc.ca

Name of contact person

1st name	Nazlin
Middle name
Last name	Walji

Organization

University of British Columbia

Division name

Mood Disorders Centre at UBC Hospital UBC Department of Psychiatry

Zip code

BC V6T 2A1

Address

2255 Wesbrook Mall Vancouver, BC V6T 2A1

TEL

604-822-7294

Homepage URL

Email

nazlin.walji@ubc.ca

Institute

University of British Columbia

Institute

Department

Personal name

Organization

Sumitomo Dainippon Pharma Co., Ltd.

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Japan

Co-sponsor

Kazuyuki Nakagome (National Center of Neurology and Psychiatry Hospital; 4-1-1 Ogawahigashi-cho, Kodaira, Tokyo 187-8551)

Name of secondary funder(s)

Organization

NCNP Ethics Committee

Address

4-1-1 Ogawahigashi-cho, Kodaira, Tokyo

Tel

042-341-2711

Email

rinri-jimu@ncnp.go.jp

Secondary IDs

YES

Study ID_1

NCT02731612

Org. issuing International ID_1

U.S. National Institutes of Health

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

British Columbia大学病院（British Columbia、Canada）、Mount Sinai病院（New York, USA）、Case Western Reserve大学病院（Ohio、USA）、Barcelona大学病院（Catalonia、Spain）、King's College大学病院（London、UK）、国立精神・神経医療研究センター病院（東京都）、北海道大学病院（北海道）、藤田医科大学病院（愛知県）、関西医科大学総合医療センター（大阪府）、産業医科大学病院（福岡県）、杏林大学医学部付属病院（東京都）、市ヶ谷ひもろぎクリニック（東京都）

Date of disclosure of the study information

2016

Year

12

Month

07

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Open public recruiting

Date of protocol fixation

2016

Year

06

Month

17

Day

Date of IRB

Anticipated trial start date

2018

Year

12

Month

01

Day

Last follow-up date

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2016

Year

12

Month

07

Day

Last modified on

2019

Year

12

Month

18

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000028947