Clinical Trials Register

Summary
EudraCT Number:	2019-002813-20
Sponsor's Protocol Code Number:	331-201-00242
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2019-11-13
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

Germany - BfArM

A.2

EudraCT number

2019-002813-20

A.3

Full title of the trial

A Multicenter, Randomized, Flexible-dose, Double-blind Trial of Brexpiprazole Versus Placebo for the Treatment of Adults With Borderline Personality Disorder

Eine multizentrische, randomisierte, doppelblinde Studie mit flexibler Dosierung zu Brexpiprazol im Vergleich zu Placebo bei der Behandlung Erwachsener mit Borderline-Persönlichkeitsstörung

A.3.1

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

A Trial of Brexpiprazole in the Treatment of Borderline Personality Disorder

A.3.2

Name or abbreviated title of the trial where available

A Trial of Brexpiprazole in the Treatment of Borderline Personality Disorder

A.4.1

Sponsor's protocol code number

331-201-00242

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT04100096

A.5.4

Other Identifiers

Name:

IND

Number:

141091

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	Otsuka Pharmaceutical Development & Commercialization, 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	Otsuka Pharmaceutical Development & Commercialization, 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	Otsuka Pharmaceutical Development & Commercialization, Inc.
B.5.2	Functional name of contact point	Heather Sutton
B.5.3	Address:
B.5.3.1	Street Address	2440 Research Boulevard
B.5.3.2	Town/ city	Rockville
B.5.3.3	Post code	20850
B.5.3.4	Country	United States
B.5.4	Telephone number	+14436210289
B.5.6	E-mail	heather.sutton-cw@otsuka-us.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	Brexpiprazole
D.3.2	Product code	OPC-34712
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	BREXPIPRAZOLE
D.3.9.1	CAS number	913611-97-9
D.3.9.2	Current sponsor code	OPC-34712
D.3.9.3	Other descriptive name	BREXPIPRAZOLE
D.3.9.4	EV Substance Code	SUB91646
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	1
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.IMP: 2
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	Brexpiprazole
D.3.2	Product code	OPC-34712
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	BREXPIPRAZOLE
D.3.9.1	CAS number	913611-97-9
D.3.9.2	Current sponsor code	OPC-34712
D.3.9.3	Other descriptive name	BREXPIPRAZOLE
D.3.9.4	EV Substance Code	SUB91646
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	2
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.IMP: 3
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	Brexpiprazole
D.3.2	Product code	OPC-34712
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	BREXPIPRAZOLE
D.3.9.1	CAS number	913611-97-9
D.3.9.2	Current sponsor code	OPC-34712
D.3.9.3	Other descriptive name	BREXPIPRAZOLE
D.3.9.4	EV Substance Code	SUB91646
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	3
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

Borderline Personality Disorder

E.1.1.1

Medical condition in easily understood language

Borderline Personality 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	10006034
E.1.2	Term	Borderline personality disorder
E.1.2	System Organ Class	10037175 - Psychiatric disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10006033
E.1.2	Term	Borderline personality
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

To compare the efficacy of brexpiprazole versus placebo for the treatment of subjects with a diagnosis of BPD.

E.2.2

Secondary objectives of the trial

To evaluate the safety and tolerability of brexpiprazole for the treatment of subjects with a diagnosis of BPD

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Male or female subjects, ages 18 to 65, inclusive, at the time of informed consent
- Subjects with a primary DSM-5 diagnosis of BPD confirmed by the SCID-5-PD at screening.
- At screening and Day 0, subjects must have a total score ≥ 12 on the ZAN-BPD scale.
- Subjects who, in the investigator's judgment, require treatment with a medication for BPD.
- Subjects willing to discontinue all prohibited medications to meet protocol-required washouts prior to and during the trial period.

E.4

Principal exclusion criteria

- Sexually active males or females of childbearing potential who do not agree to practice 2 different methods of birth control or remain abstinent during the trial and for 30 days after the last dose of IMP. Male or female subjects identifying as homosexual with exclusively homosexual partners may not be required to practice birth control methods following discussion with the investigator and medical monitor. Male subjects must also agree not to donate sperm from trial screening through 30 days after the last dose of IMP.
- Women who are breastfeeding and/or who have a positive pregnancy test result prior to receiving IMP.
- Subjects with a concurrent DSM-5 diagnosis of schizophrenia or schizoaffective disorder. Also, subjects with a concurrent diagnosis of bipolar I disorder, bipolar II disorder, delirium, dementia, amnesia, eating disorder, antisocial personality disorder, or other cognitive disorders. Subjects with MDD, PTSD, ADHD, panic disorder, or generalized anxiety can be included if symptoms have been stable, these disorders are not the primary focus of treatment and changes in any treatment for these disorders would not likely be required for the duration of the trial.
- Subjects currently in psychotherapy specifically used to target BPD symptoms at time of screening.
- Subjects who have had electroconvulsive treatment or transcranial magnetic stimulation.
- Subjects with a current diagnosis of substance or alcohol use disorder within 90 days prior to screening visit.
- Subjects who fulfill the following criteria related to suicide and/or suicidal ideation are excluded:
- Subjects who have a significant risk of committing violent acts, serious self-harm, or suicide based on history or routine psychiatric status examination, or those who are homicidal or considered to be a high risk to others, or subjects with a response of "yes" on the C-SSRS Suicidal Ideation Item 5, OR
- Subjects with a response of "yes" on the C-SSRS Suicidal Behavior Items, OR
- Subjects who have had 3 suicide attempts, OR,
- Subjects who have had 3 or more hospitalizations due to suicidal behavior. Note that subjects who have engaged in non-suicidal self-injurious behavior within the 90 days prior to screening or at Day 0 are eligible, unless the behavior is better described as an actual attempt, interrupted attempt, or aborted attempt according to C-SSRS definition and/or investigator judgment and therefore exclusionary.
Subjects with a response of "yes" on the C-SSRS Suicidal Ideation Item 4 within the 90 days prior to screening or at Day 0 may be included following discussion with a medical monitor.
- Subjects with hypothyroidism or hyperthyroidism or an abnormal result for free T4 at screening.
- Subjects who currently have clinically significant neurological, hepatic, renal, metabolic, hematological, immunological, cardiovascular, pulmonary, or gastrointestinal disorders.
- Subjects with uncontrolled hypertension, symptomatic hypotension, or orthostatic hypotension.
- Subjects with epilepsy or a history of seizures, except for a single seizure episode.
- Subjects who received brexpiprazole in any prior clinical trial or subjects who have taken or are taking commercially available brexpiprazole (Rexulti®).
- Subjects with a history of neuroleptic malignant syndrome, serotonin syndrome, or clinically significant tardive dyskinesia.
- Subjects with a history of true allergic response to more than 1 class of medication.
- Subjects who are currently either inpatient or partially hospitalized.
- Subjects who participated in a clinical trial within 90 days prior to screening or who participated in more than 2 clinical trials within a year prior to screening.

E.5 End points

E.5.1

Primary end point(s)

1. Change from baseline in the Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD) total score
A clinician-administered scale with a total score range of 0 to 36. A higher score represents a higher severity of disease symptoms.

E.5.1.1

Timepoint(s) of evaluation of this end point

Time Frame: Up to 12 weeks

E.5.2

Secondary end point(s)

1. Change from baseline in the Clinical Global Impression - Severity of Illness (CGI-S) score
An observer-rated scale with a total score range of 0 to 7. A higher score represents a worse outcome.

2. Change from baseline in the Patient's Global Impression of Severity (PGI-S) for each trial visit during the double-blind treatment period
A 7-point single-item self-report scale for the patient to rate the severity of symptoms of BPD. A higher score denotes more severe symptoms.

3. Patient's Global Impression of Change (PGI-C) Scale Score
A 7-point single-item self-report scale depicting a subject's rating of overall change in their condition since starting trial medication. With a higher score denoting a worse outcome.

4. Clinical Global Impression - Improvement (CGI-I) Scale Score
An observer-rated scale with a total score of 0 to 7. A higher score represents a worse outcome.

E.5.2.1

Timepoint(s) of evaluation of this end point

Time Frame: Up to 12 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

Yes

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

Yes

E.6.10

Pharmacogenetic

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

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

Germany

Spain

Ukraine

United States

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

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

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:

240

F.1.3

Elderly (>=65 years)

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

F.4.2.2

In the whole clinical trial

240

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)

Subjects who complete all trial visits through Week 12 with no major protocol deviations may be offered entry into an open-label extension trial.

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

2020-03-06

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-03-16

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2020-08-19

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