Clinical Trials Register

Summary
EudraCT Number:	2019-002213-19
Sponsor's Protocol Code Number:	ELICE-BD-O1
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	GB - no longer in EU/EEA
Date on which this record was first entered in the EudraCT database:	2019-11-05
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2019-002213-19

A.3

Full title of the trial

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)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A randomised study to evaluate Lurasidone versus Placebo in improving cognitive functioning in patients with Bipolar Disorder

A.3.2

Name or abbreviated title of the trial where available

ELICE-BD

A.4.1

Sponsor's protocol code number

ELICE-BD-O1

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02731612

A.5.4

Other Identifiers

Name:	Latuda FDA (NDA) number	Number:	200603
Name:	Health Canada NOL Control Number	Number:	193350

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	University of British Columbia
B.1.3.4	Country	Canada
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	University of British Columbia
B.4.2	Country	Canada
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Tailored Clinical Research Solutions
B.5.2	Functional name of contact point	Yeung
B.5.3	Address:
B.5.3.1	Street Address	Tailored Clinical Research Solutions, R
B.5.3.2	Town/ city	Regal Court Business Centre, 42-44 High St
B.5.3.3	Post code	SL1 1EL
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	07776070005
B.5.5	Fax number	00000000
B.5.6	E-mail	davy.yeung@tcr-solutions.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Latuda
D.2.1.1.2	Name of the Marketing Authorisation holder	Sunovion Pharmaceuticals Europe Ltd
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Latuda
D.3.2	Product code	n/a
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Lurasidone Hydrochloride
D.3.9.1	CAS number	367514-87-2
D.3.9.4	EV Substance Code	AS1
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Euthymic Bipolar disorder

E.1.1.1

Medical condition in easily understood language

Bipolar Disorder

E.1.1.2

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10057667
E.1.2	Term	Bipolar disorder
E.1.2	System Organ Class	10037175 - Psychiatric disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of the study is to assess changes in cognitive function (i.e, concentration, memory) in euthymic (relatively stable mood state) Bipolar patients (type I & II) who are treated with 20 to 80 mg/day of Lurasidone (Latuda) adjunctive therapy over a 6 week period in comparison to those euthymic patients who will be treated with Placebo add-on.

E.2.2

Secondary objectives of the trial

To measure the improvement in patients' mood scores and overall psychiatric status.
To look at the number and severity of study drug side effects (safety).
To look at the improvement in quality of life of the patients.
To look at the improvement in subjective-rated cognitive and daily functioning.
To look at the number of patients completing the study (study completion rates)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Patients who meet all of the following criteria are eligible to participate in this trial:

1. Males or females aged 19 to 65 years inclusive.
2. DSM.5 diagnosis of Bipolar Type I or Type II Disorder, with or without a
history of Psychosis. Bipolar Type 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 (i.e. Lithium or
Valproate) (Lamotrigine as a mood stabilizer is acceptable for Bipolar II
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.
Medications and therapeutic doses are: lithium, serum level 0.6-1.2 mEq/L;
divalproex/sodium valproate, serum level 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 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.
4. All concomitant medication must be at a stable dose for two weeks prior to the
randomization visit.
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-IV – 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. A WAIS-IV vocabulary scaled score >5 (equivalent to estimated IQ 80 or
greater).
9. A sufficient level of English or Spanish or Japanese language.
10. Females who are postmenopausal for at least 1 year before the screening visit
(confirmed by an FSH test) or are surgically sterile.
11. 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.
12. 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.

E.4

Principal exclusion criteria

Patients 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. 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.

5. Anticholinergics and stimulants that increase dopamine levels are not permitted
6. Cognitive remediation therapy within 3 months prior to entry or during the
double blind phase.
7. Neuromodulation treatment with ECT or rTMS or tDCS or DBS within eight weeks or
treatment with an experimental drug within 30 days.
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.

E.5 End points

E.5.1

Primary end point(s)

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.

E.5.1.1

Timepoint(s) of evaluation of this end point

At the end of the study.

E.5.2

Secondary end point(s)

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)
g) study completion rates

E.5.2.1

Timepoint(s) of evaluation of this end point

At the end of the study.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1