Clinical Trials Register

Summary
EudraCT Number:	2021-002126-24
Sponsor's Protocol Code Number:	SEP380-301
National Competent Authority:	Slovakia - SIDC (Slovak)
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2022-09-09
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

2021-002126-24

A.3

Full title of the trial

A Multi-region, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study Evaluating SEP-4199 Controlled Release (CR) for the Treatment of Major Depressive Episode Associated with Bipolar I Disorder (Bipolar I Depression)

Multiregionálna, multicentrická, randomizovaná, dvojito zaslepená, placebom kontrolovaná štúdia paralelných skupín hodnotiaca SEP-4199 s riadeným uvoľňovaním (CR) na liečbu veľkej depresívnej epizódy spojenej s bipolárnou poruchou typu I (bipolárna depresia I)

A.3.1

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

Research study to evaluate the effectiveness of SEP-4199 CR in patients with major depressive episodes associated with Bipolar I Disorder.

A.4.1

Sponsor's protocol code number

SEP380-301

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	SUNOVION PHARMACEUTICALS INC.
B.5.2	Functional name of contact point	Dr Steven Szabo
B.5.3	Address:
B.5.3.1	Street Address	84 Waterford Drive
B.5.3.2	Town/ city	Marlborough, Massachusetts
B.5.3.3	Post code	071752
B.5.3.4	Country	United States
B.5.4	Telephone number	+1508787-4227

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	SEP-4199 CR 200mg
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	Aramisulpride
D.3.9.1	CAS number	71675-90-6
D.3.9.2	Current sponsor code	SEP-380262
D.3.9.4	EV Substance Code	SUB216374
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	170
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Esamisulpride
D.3.9.1	CAS number	71675-92-8
D.3.9.2	Current sponsor code	SEP-380255
D.3.9.4	EV Substance Code	SUB216375
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	30
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

Major Depressive Episode Associated with Bipolar I Disorder

E.1.1.1

Medical condition in easily understood language

Depression in Bipolar Disorder

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10004939
E.1.2	Term	Bipolar I 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 objective of Study SEP380-301 is to evaluate the efficacy, safety, and tolerability of SEP 4199 controlled release (CR) formulation given as monotherapy at fixed doses of 200 mg/day and 400 mg/day compared with placebo in the treatment of subjects with Major Depressive Episode associated with Bipolar I Disorder (Bipolar I Depression).

Primary Efficacy:
Evaluate the efficacy of SEP-4199 CR in the reduction of depression symptoms, as measured using the Montgomery-Asberg Depression Rating Scale (MADRS).

E.2.2

Secondary objectives of the trial

Secondary Efficacy:
Evaluate the efficacy of SEP-4199 CR in global improvement of bipolar depression severity, as measured using the Clinical Global Impression-Bipolar Version-Severity of Illness, Depression scale (CGI-BP-S depression).

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 or legally acceptable representative must possess an
educational level and degree of understanding of English or the local
language that enables them to communicate suitably with the
Investigator and the study coordinator.
3. Subject is 18 to 65 years of age, inclusive, at the time of informed
consent.
4. Subject meets DSM-5 criteria, based on the SCID-5-CT, for bipolar I
disorder, current episode depressed with or without rapid cycling disease course (≥ 4 episodes of mood disturbance but < 8 episodes in
the previous 12 months) with or without psychotic features.
5. Subject has a lifetime history of at least 1 manic episode or manic
episode with mixed features corroborated by at least one of the
following: medical records, documented correspondence with a treating psychiatrist or mental healthcare provider/staff, or information from a reliable informant who is familiar with the subject's psychiatric history. The adequacy of the information will be assessed by the Sponsor
Eligibility Committee.
6. Attempts should be made to obtain supporting information regarding
the subject's current major depressive episode from additional sources.
This may include relevant medical records and/or documented
correspondence with a treating psychiatrist or mental healthcare
provider/staff if the subject has been evaluated during the current MDD
episode, or information from a reliable informant who is familiar with the
subject's recent psychiatric history.
7. Subject's current major depressive episode is ≥ 4 weeks and less than
12 months in duration at Screening.
8. Subject has a MADRS-S total score ≥ 22 at Screening.
9. Subject has a MADRS total score ≥ 22 at both Screening and Baseline.
10. Subject has a CGI-BP-S depression score ≥ 4 at both Screening and
Baseline.
11. Subject has a YMRS total score ≤ 12 at both Screening and Baseline.
12. Subjects meets an additional inclusion criterion at Baseline that will
remain blinded to clinical site Investigators and staff.
Please refer to Protocol for the complete list.

E.4

Principal exclusion criteria

1. Subject currently has any DSM-5 defined psychiatric diagnosis other
than bipolar I disorder that was the primary focus of treatment or is
currently being treated with concomitant medication.
2. Subject has a lifetime history of, or symptoms consistent with,
schizophrenia, schizoaffective disorder, or a major psychiatric diagnosis
other than bipolar I disorder that is judged to pose risk to the study
scientific objectives based on the judgement of the Investigator or the
Sponsor Eligibility Committee. A lifetime history of anxiety disorders,
attention-deficit/hyperactivity disorder (ADHD), and post-traumatic
stress disorder (PTSD) are not exclusionary if the disorder does not meet
Exclusion Criterion 1. (Note: Subjects with a previous diagnosis of major
depressive disorder or bipolar II disorder that was subsequently
changed to bipolar I disorder are allowed.)
3. Subject has a history within the past 12 months prior to Screening of
substance use disorder.
4. Subject has confirmed or suspected borderline personality disorder.
5. Subject demonstrates a decrease (improvement) of ≥ 25% in MADRS
total score from Screening to Baseline.
6. Subject is considered by the Investigator to be at imminent risk of
suicide or injury to self or others, or has a score ≥ 4 on MADRS item 10
(suicidal ideation) or answers "yes" to "suicidal ideation" item (active
suicidal ideation with some intent to act, without specific plan) or item 5
(active suicidal ideation with specific plan and intent) on the C-SSRS
assessment at the Screening Visit (in the past 3 months [90 days]) or at
Baseline.
7. Subject has received any psychotropic medication or herbal
supplement within 3 days or 5 half-lives (whichever is longer) prior to
Baseline or anticipates the need for psychotropic medications or herbal
supplements during participation in this study, with the exception of the
medications specified in Protocol Section 10.3. The following treatments
have additional restrictions as specified below:
a. Monoamine oxidase inhibitors (MAOIs) must be discontinued at least
28 days prior to Baseline.
b. Fluoxetine, and olanzapine/fluoxetine combination must be
discontinued at least 28 days prior to Baseline.
c. Clozapine used at 200 mg/day or less for insomnia, agitation, or
anxiety must be discontinued at least 28 days prior to Baseline. Subjects
with a history of treatment with clozapine for any reason at doses
greater than 200 mg/day or at doses less than or equal to 200 mg/day
for a usage other than insomnia, agitation, or anxiety are excluded from
study participation.
d. Depot neuroleptics must have been discontinued at least one
treatment cycle or at least 30 days (whichever is longer) prior to
Baseline.
e. Subjects with a history of treatment with ketamine, esketamine,
arketamine, or psychedelic therapies (eg, psilocybin,
methylenedioxymethamphetamine [MDMA]) for MDD or any psychedelic
treatment.
f. Electroconvulsive therapy (ECT) or repetitive transcranial magnetic
stimulation (rTMS) within 90 days prior to Baseline.
g. Subjects with a history of treatment with vagus nerve stimulation
(VNS) or deep brain stimulation (DBS) are excluded from study
participation.
8. Subject initiated a new psychotherapeutic intervention (eg,
psychotherapy) focused on treatment of bipolar I depression within the
past 12 weeks prior to Screening. (Note: Subjects who have participated
in ongoing psychotherapy treatment for at least 12 weeks prior to
Screening will be permitted to continue this treatment during the study.)
9. Subject has a history of non-response to an adequate (6-week) trial of
3 or more antidepressants (with or without mood stabilizers) during the
current major depressive episode.
10. Subject was hospitalized during the Screening Period without explicit
approval by the Medical Monitor. (Note: Hospitalization during the
Screening Period will not be allowed, except where required by local
regulations, or when determined to be clinically indicated based on the
subject's psychiatric history and current psychiatric symptoms. Medical
justification must be provided to the Medical Monitor and the Medical
Monitor must approve the request for hospitalization.)
11. Subject has any clinically significant unstable medical condition or
any clinically significant chronic disease that would pose a risk to the
subject or that might confound the results of the study. (Note: Active
medical conditions that are minor or well-controlled are not exclusionary
if they do not affect risk to subject or study results. In cases in which the
impact of the condition upon risk to subject or study results is unclear,
the Medical Monitor should be consulted.)
Please refer to Protocol for the complete list.

E.5 End points

E.5.1

Primary end point(s)

Primary Efficacy Endpoint:
•Change from Baseline to Week 6 in MADRS total score

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 6

E.5.2

Secondary end point(s)

Secondary Efficacy Endpoints:
•Change from Baseline to Week 6 in CGI-BP-S depression score

E.5.2.1

Timepoint(s) of evaluation of this end point

Week 6

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

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

Yes

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

Colombia

Japan

Mexico

United States

France

Bulgaria

Romania

Croatia

Russian Federation

Slovakia

Turkey

Ukraine

Serbia

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

LPLV

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:

512

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

127

F.4.2.2

In the whole clinical trial

522

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)

None.

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

2022-12-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-11-03

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2023-10-10

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