Clinical Trials Register

Summary
EudraCT Number:	2013-003038-34
Sponsor's Protocol Code Number:	D1002001
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:	2015-06-01
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

2013-003038-34

A.3

Full title of the trial

A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study of SM-13496 for the Treatment of Bipolar I Depression

Randomizované, dvojito zaslepené, placebom kontrolované skúšanie SM-13496 v paralelných skupinách pre liečbu depresívnej fázy pri bipolárnej afektívnej poruche 1. typu

A.3.1

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

A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study of SM-13496 for the Treatment of Bipolar I Depression

A.3.2

Name or abbreviated title of the trial where available

A Phase III Study of SM-13496 in Patients With Bipolar I Depression.

A.4.1

Sponsor's protocol code number

D1002001

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01986101

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	Sumitomo Dainippon Pharma Co., Ltd.
B.1.3.4	Country	Japan
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	Sumitomo Dainippon Pharma Co., Ltd.
B.4.2	Country	Japan
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Sumitomo Dainippon Pharma Co., Ltd.
B.5.2	Functional name of contact point	Kantaro Ushiroda
B.5.3	Address:
B.5.3.1	Street Address	1-17-10 Kyobashi, Chuo-ku
B.5.3.2	Town/ city	Tokyo
B.5.3.3	Post code	104-0031
B.5.3.4	Country	Japan
B.5.4	Telephone number	+8135159 2519
B.5.5	Fax number	+8135159 2549
B.5.6	E-mail	kantaro-ushiroda@ds-pharma.co.jp

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	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
D.3.9.1	CAS number	367514-88-3
D.3.9.2	Current sponsor code	SM-13946
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	range
D.3.10.3	Concentration number	20 to 120
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

Bipolar I depression

E.1.1.1

Medical condition in easily understood language

Bipolar depression

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	18.0
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

The primary objective is to compare the efficacy of SM-13496 monotherapy with that of placebo in patients with depressive symptoms associated with bipolar I disorder by assessing the change from baseline in the Montgomery-Ǻsberg Depression Rating Scale (MADRS) total score at Week 6.

E.2.2

Secondary objectives of the trial

1) To evaluate the efficacy of SM-13496 monotherapy in patients with depressive symptoms associated with bipolar I disorder
2) To evaluate the time course of efficacy of SM-13496 monotherapy in patients with depressive symptoms associated with bipolar I disorder
3) To evaluate the following
- The efficacy for anxiety symptoms associated with bipolar I disorder by assessing the change from baseline in the Hamilton Rating Scale for Anxiety (HAM-A) total score at Week 6
- The efficacy for manic symptoms associated with bipolar I disorder by assessing the change from baseline in the Young Mania Rating Scale (YMRS) total score at Week 6
4) To evaluate the overall safety of SM-13496
5) To evaluate the influence on the extrapyramidal symptoms
6) To evaluate the influence on the following
- QTc
- Body weight
- Prolactin
- Glucose metabolism
- Lipid metabolism

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1) Patients who were fully informed of and understand the objectives, procedures, and possible benefits and risks of the study and who provided written voluntary consent to participate in the study. If the patient is a minor at the time of consent, written consent should be obtained from a legally acceptable representative (guardian) in addition to the patient him/herself.
2) Outpatients aged 18 through 74 years at informed consent.
3) Patients with bipolar I disorder, most recent episode depressed, with or without rapid cycling disease course (≥ 4 episodes of mood disturbance but < 8 episodes in the 12 months prior to screening), and without psychotic features (diagnosed by the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, Text Revision [DSM-IV-TR] criteria and confirmed by the Mini International Neuropsychiatric Interview [MINI]).
4) Patients who have a history of at least one manic or mixed episode (preferably with confirmation by a reliable informant, such as a family member or caregiver)
5) Patients whose current major depressive episode is ≥ 4 weeks and < 12 months in duration at screening.
6) Patients with a rater-administered MADRS total score of ≥ 20 and a computer-administered MADRS total score of ≥ 20 at both screening and baseline.
7) Patients with a YMRS total score of ≤ 12 at both screening and baseline.
8) Patients with a negative pregnancy test at screening, when the patients are female and of childbearing potential.
9) Patients who agree to use appropriate contraception to prevent pregnancy in female patients and the female partners of patients, when the patients or their partners are of childbearing potential.
10) Patients whose dosage of the following concomitant drugs remains unchanged
for the specified duration as follows:
- The dose of oral hypoglycemic drugs or antihypertensive drugs remained unchanged for at least 30 days prior to screening.
- The dose of thyroid hormone (replacement therapy) remained unchanged for at least 90 days prior to screening.
- The dose of drugs for complications (other than the above-mentioned drugs) have been stable (within ± 25%) for at least 30 days prior to screening.
- The content of psychotherapy and cognitive behavioral therapy remained unchanged for at least 12 weeks prior to screening.

E.4

Principal exclusion criteria

1) Patients who were diagnosed as having an Axis I or Axis II disorder (DSM-IV-TR criteria) other than bipolar I disorder that is the primary focus of treatment within 3 months prior to screening.
2) Patients with a score of ≥ 4 on the MADRS item 10 (suicidal thoughts) at screening or baseline.
3) Patients with a “Yes” response to the Columbia-Suicide Severity Rating Scale (C-SSRS) item 4 (active suicidal ideation with some intent to act, without specific plan) or item 5 (active suicidal ideation with specific plan and intent) at
screening (within 6 months prior to screening) or baseline.
4) Patients with imminent risk of suicide or injury to self, others, or property.
5) Patients for whom diagnostic agreement (based on the Bipolarity Index) between the investigator and Bracket (Pennsylvania, the United States), the agency for computerized diagnosis, cannot be reached.
6) Patients with a history of non-response to 6-week trial of 3 or more antidepressants (with or without concomitant use of mood stabilizers) during the current episode.
7) Patients who had been hospitalized because of a manic or mixed episode within 60 days prior to screening.
8) Patients who received monoamine oxidase (MAO) inhibitor within 21 days prior to screening.
9) Patients who received fluoxetine or a combination of olanzapine and fluoxetine within 28 days prior to screening.
10) Patients who received any depot antipsychotics (sustained-release formulation) within 90 days prior to screening.
11) Patients who received clozapine within 120 days prior to screening.
12) Patients who received electroconvulsive therapy within 90 days prior to screening.
13) Patients with a ≥ 25% reduction in the MADRS total score between screening and baseline.
14) Patients with a history of HIV seropositivity.
15) Patients with a history of alcohol/drug abuse (DSM-IV-TR criteria) within 3 months prior to screening or of alcohol/drug dependence (DSM-IV-TR criteria) within 12 months prior to screening. Exceptions include caffeine or nicotine
abuse/dependency.
16) Patients with a history of hypersensitivity (eg, drug-induced anaphylaxis, rash, urticaria, or other allergic reactions) to more than one distinct chemical class of drug.
17) Patients with previous or existing clinically significant complications, such as serious nervous system, endocrine system (eg, type I diabetes mellitus), hepatic, renal, hematological, respiratory, cardiovascular (eg, unstable angina, congestive
heart failure), gastrointestinal, urological, or other diseases. Patients who have a history of any of such diseases and who are considered ineligible for the study by the investigator.
18) Patients with acute hepatitis, severe chronic hepatitis or marked hepatic dysfunction. When the hepatitis screening test is positive, the investigator should evaluate carefully patient eligibility on the basis of his or her medical history or other laboratory data.
19) Patients with a gastrointestinal disease or a surgical history that may affect drug absorption, distribution, metabolism, or excretion.
20) Patients with any chronic organic disease of the central nervous system (ie, tumor, inflammation, convulsive seizure, vascular disorders, Parkinson’s disease, Alzheimer’s disease or other type of dementia, myasthenia gravis, or other
degenerative diseases) .
21) Patients with any mental retardation or persistent neurological findings due to serious head injury.
22) Patients with a BMI of ≤ 18 kg/m2 or ≥ 40 kg/m2 at screening.
23) Patients with previous or existing macular or retinal pigment changes.
24) Patients with a previous (within 5 years prior to screening) or existing malignant tumor (excluding appropriately treated basal cell carcinoma of the skin, squamous cell carcinoma, and uterine cervix cancer).
25) Patients with a history of neuroleptic malignant syndrome.
26) Patients with severe tardive dyskinesia, severe dystonia, or other severe motor dysfunction.
27) Patients with an HbA1c (NGSP) value of 8.4% or higher at screening.
28) Patients with a history or presence of clinically significant ECG abnormality.
29) Patients who have received the study medication (including placebo) in a previous clinical study of SM-13496.
30) Patients who are breastfeeding.
31) Patients who are currently participating or participated in a clinical study with an investigational or marketed compound or device within 3 months prior to screening or who participated in 3 or more clinical studies within 12 months
prior to screening.
32) Patients who are otherwise considered ineligible for the study by the investigator.

E.5 End points

E.5.1

Primary end point(s)

The primary variable of the study is the change from baseline in the MADRS total score at Week 6

E.5.1.1

Timepoint(s) of evaluation of this end point

Baseline, 1, 2, 3, 4, 5 and 6 weeks

E.5.2

Secondary end point(s)

- Change from baseline in the MADRS total score at each assessment
- Change from baseline in the CGI-BP-S (depression) score at Week 6 and each
assessment point
- Change from baseline in the SDS total score at Week 6
- Change from baseline in the YMRS total score at Week 6 and each assessment
point
- Change from baseline in the HAM-A total score at Week 6
- Treatment response rate (proportion of patients who achieve a ≥ 50% reduction
from baseline in the MADRS total score) at Week 6
- Symptom remission rate (proportion of patients who achieve a MADRS total
score of ≤ 12) at Week 6

E.5.2.1

Timepoint(s) of evaluation of this end point

Baseline, 1, 2, 3, 4, 5 and 6 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

Yes

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

Yes

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

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

Japan

Malaysia

Philippines

Russian Federation

Taiwan

Ukraine

E.8.7

Trial has a data monitoring committee

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 last subject (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.1.1.1

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:

476

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

120

F.4.2.2

In the whole clinical trial

501

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

See protocol

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2015-07-28

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-06-25

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2017-02-16

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