Clinical Trials Register

Summary
EudraCT Number:	2011-000986-10
Sponsor's Protocol Code Number:	D1050296
National Competent Authority:	Slovakia - SIDC (Slovak)
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-09-22
Trial results	View 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

Slovakia - SIDC (Slovak)

A.2

EudraCT number

2011-000986-10

A.3

Full title of the trial

A RANDOMIZED, DOUBLE-BLIND, PLACEBOCONTROLLED,
FLEXIBLE-DOSE, PARALLEL-GROUP
STUDY OF LURASIDONE ADJUNCTIVE TO LITHIUM OR
DIVALPROEX FOR THE PREVENTION OF RECURRENCE
IN SUBJECTS WITH BIPOLAR I DISORDER

A.3.1

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

A.3.2

Name or abbreviated title of the trial where available

PERSIST

A.4.1

Sponsor's protocol code number

D1050296

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	Sunovion Pharmaceuticals Inc.
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Sunovion Pharmaceuticals Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	inVentiv Health Clinical (UK) Limited
B.5.2	Functional name of contact point	N/A
B.5.3	Address:
B.5.3.1	Street Address	N/A
B.5.3.2	Town/ city	N/A
B.5.3.3	Post code	N/A
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	001512347-2692
B.5.6	E-mail	RegOpsEurope@inventivhealth.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	No
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	lurasidone HCl
D.3.2	Product code	SM-13496
D.3.4	Pharmaceutical form	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	(3aR,4S,7R,7aS)-2-{(1R,2R)-2-[4-(1,2-benzisothiazol-3-yl)piperazin-1- ylmethyl]cyclohexylmethyl}hexahydro-4,7-methano-2H-isoindole-1,3-dione HCl
D.3.9.1	CAS number	367514-88-3
D.3.9.2	Current sponsor code	SM-13496
D.3.9.3	Other descriptive name	Lurasidone Hydrochloride
D.3.9.4	EV Substance Code	SUB34204
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	40
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	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

bipolar disorder I depression

E.1.1.1

Medical condition in easily understood language

A mental illness characterized by the occurrence of one or more manic episodes, or mixed episodes. There is also a history of one or more major depressive episodes

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	17.1
E.1.2	Level	LLT
E.1.2	Classification code	10004936
E.1.2	Term	Bipolar depression
E.1.2	System Organ Class	100000004873

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate the efficacy and safety of lurasidone (in combination with lithium or divalproex) for the maintenance treatment of bipolar I disorder in subjects with or without rapid cycling and/or psychotic features.

E.2.2

Secondary objectives of the trial

Global severity, assessed by the Clinical Global Impression Bipolar
Version, Severity of Illness (CGI-BP-S) score (overall)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Subject provides written informed consent and is willing and able to comply with the protocol in the opinion of the Investigator.
2. Subject is at least 18 years of age, with bipolar I disorder, most recent episode manic,
mixed manic, hypomanic, or depressed, with or without rapid cycling disease course (≥ 4 episodes of mood disturbance but < 8 episodes in the previous 12 months), and/or psychotic features (diagnosed by DSM-IV-TR criteria and confirmed by the SCID-CT).
3. Subject has experienced at least one manic, mixed, or depressed episode in the past 2 years. It is strongly recommended that a reliable informant (eg, family member,
caregiver, or treating health professional) be available to confirm this history.
4. If currently experiencing a major depressive episode, should be < 12 months in duration.
5. At screening and at open-label baseline, YMRS or MADRS total score ≥ 14 if receiving lithium or divalproex; ≥ 18 if not currently on lithium or divalproex.
6. Subjects not being treated with lithium or divalproex at screening must be willing to initiate lithium or divalproex treatment for the duration of the study.
7. Subject is not pregnant (must have a negative serum pregnancy test at screening) or nursing (must not be lactating) and is not planning pregnancy within the projected duration of the study.
8. Female subject who is of reproductive potential agrees to remain abstinent or use adequate and reliable contraception throughout the study and for at least 30 days after the last dose of lurasidone has been taken. In the Investigator’s judgment, the subject will adhere to this requirement.
9. Adequate contraception is defined as continuous use of either two barrier methods (eg, condom and spermicide or diaphragm with spermicide) or a hormonal contraceptive. Acceptable hormonal contraceptives include the following: a) contraceptive implant (such as Norplant®) implanted at least 90 days prior to screening; b) injectable contraception (such as medroxyprogesterone acetate injection) given at least 14 days
prior to screening; or c) oral contraception taken as directed for at least 30 days prior to screening.
10. Subjects who are of non-reproductive potential, ie, subject who is surgically sterile, has undergone tubal ligation, or is postmenopausal (defined as at least 12 months of spontaneous amenorrhea or between 6 and 12 months of spontaneous amenorrhea with follicle stimulating hormone concentrations within postmenopausal range as determined by laboratory analysis) are not required to remain abstinent or use adequate
contraception.
11. Subject is in good physical health on the basis of medical history, physical examination, and laboratory screening.
12. Subject who requires concomitant medication treatment with the following agents may be included if they have been on stable doses for the specified times: 1) oral hypoglycemics and antihypertensive agents: must be stabilized for at least 30 days prior to screening; 2) thyroid hormone replacement: must be stable for at least 90 days prior to screening.

E.4

Principal exclusion criteria

Open-label Phase:
a. Diagnosis of an Axis I or Axis II disorder, other than bipolar I
disorder, that is the primary focus of treatment within 3 months of
screening
b. Subjects for whom diagnostic agreement between the Investigator
and Bracket cannot be reached
c. Ultra-fast rapid cycling (defined as ≥ 8 mood episodes over the
previous 12-month period)
d. Subjects who test positive for drugs of abuse at screening. In the
event a subject tests positive for cannabinoids (tetrahydrocannabinol),
the Investigator will evaluate the subject's ability to abstain from
cannabis during the study
e. Unstable/inadequately treated medical illness
f. The subject answers "yes" to "Suicidal Ideation" items 4 or 5 on the CSSRS (at time of evaluation)

Double-blind Phase:
a. Subjects who in the Investigator's judgment have not been compliant with study medication during the stabilization phase
b. Subjects who have not stabilized during the open-label phase (within
20 weeks)
c. Subjects who test positive for drugs of abuse at double-blind phase
baseline. In the event a subject tests positive for cannabinoids
(tetrahydrocannabinol), the Investigator will evaluate the subject's
ability to abstain from cannabis during the study

E.5 End points

E.5.1

Primary end point(s)

Primary Efficacy Endpoint:
- Time to recurrence of any mood event (from double-blind phase baseline); mood event is
defined as any of the following:
- Fulfilled DSM-IV-TR criteria for manic, mixed manic, hypomanic, or depressive episode
- Required treatment intervention for manic, mixed manic, hypomanic, or depressive symptoms with any antipsychotic (other than study drug), antidepressant, mood stabilizer (other than lithium or divalproex), anxiolytic agents, benzodiazepine
(beyond dosage allowed for anxiety, agitation or insomnia)
- Psychiatric hospitalization for any bipolar mood episode
- YMRS or MADRS total score ≥ 18 or CGI-BP-S score ≥ 4 at at two consecutive assessments no more than 10 days apart
- Discontinuation from the study because of a mood event (as determined by the Investigator)
Subject meeting criteria for a mood event must be discontinued from the study.

E.5.1.1

Timepoint(s) of evaluation of this end point

Visit 13-20 (at every visit; visit schedule – every 4 weeks)

E.5.2

Secondary end point(s)

1. Time to all-cause discontinuation
2. Time to recurrence of a manic, mixed manic, hypomanic, or depressed episode
3. Proportion of subjects who experience a recurrence of a manic, mixed manic, hypomanic, or depressed episode
4. Change from double-blind phase baseline (final visit in the open-label phase) to endpoint in Global severity, assessed by the Clinical Global Impression Bipolar Version, Severity of
Illness (CGI-BP-S) score (overall, depression, mania), YMRS, MADRS, Quick Inventory of Depressive Symptomatology – Self Report (QIDS-SR16) total score, and Positive and
Negative Syndrome Scale Positive Subscale (PANSS-P)
5. Subject self-report of functional impairment associated with symptoms of bipolar disorder, assessed by the Sheehan Disability Scale (SDS) total score and SDS subscales
6. Quality of life assessed by Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF)
7. Sleep quality assessed by the Pittsburgh Insomnia Rating Scale (PIRS-2)
8. Health outcome measures: Health Services Utilization Questionnaire (HSUQ) and the SF-12 Health Survey
9. Medication Satisfaction Questionnaire (MSQ)

E.5.2.1

Timepoint(s) of evaluation of this end point

Visit 13-20 (at every visit; visit schedule – every 4 weeks)

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

Yes

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

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Argentina

Australia

Bulgaria

Chile

Croatia

Czech Republic

France

Hungary

India

Poland

Russian Federation

Serbia

Slovakia

Spain

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

Last visit of the last patient undergoing the trial

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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

2025

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

225

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception