Clinical Trials Register

Summary
EudraCT Number:	2019-002897-30
Sponsor's Protocol Code Number:	331-201-00195
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2020-01-10
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

Spain - AEMPS

A.2

EudraCT number

2019-002897-30

A.3

Full title of the trial

A Multicenter, Open-label Trial to Evaluate the Safety and Tolerability of Brexpiprazole in the Treatment of Adult Subjects With Borderline Personality Disorder

Ensayo multicéntrico en abierto para evaluar la seguridad y tolerabilidad de brexpiprazol en el tratamiento de sujetos adultos con trastorno límite de la personalidad”

A.3.1

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

Open-label Trial of Brexpiprazole in the Treatment of Borderline Personality Disorder

Ensayo en abierto de brexpiprazol en el tratamiento del trastorno límite de la personalidad

A.4.1

Sponsor's protocol code number

331-201-00195

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	Otsuka Call Center
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	844-687-8522
B.5.6	E-mail	OtsukaRMReconciliation@rmpdc.org

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	up to
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

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

Trastorno límite de la personalidad

E.1.1.1

Medical condition in easily understood language

Borderline Personality Disorder

Trastorno límite de la personalidad

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

Evaluar la seguridad y tolerabilidad de brexpiprazol para el tratamiento de sujetos con diagnóstico de TLP.

E.2.2

Secondary objectives of the trial

Exploratory Efficacy

Eficacia exploratoria

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1) Subjects, who completed the last treatment visit of the previous double-blind brexpiprazole BPD trial and who, in the opinion of the investigator, could potentially benefit from administration of brexpiprazole for the treatment of BPD.
2) Male or female outpatients, ages 18 to 65 years, inclusive, at the time of informed consent of the previous double-blind brexpiprazole BPD trial.
3) Subjects who are able to complete the consent process and/or consent obtained from a legally acceptable representative (as required by the institutional review board [IRB]/independent ethics committee [IEC]) prior to the initiation of any protocol-required procedures.
4) Ability, in the opinion of the principal investigator, to understand the nature of the trial and follow protocol requirements, including the prescribed dosage regimens, tablet ingestion, and discontinuation of prohibited medication, and to read and understand the written word in order to be reliably rated on assessment scales.

1) Pacientes que completaron la última visita de tratamiento del anterior ensayo doble ciego con brexpiprazol para el TLP y que, a criterio del investigador, podrían llegar a beneficiarse de la administración de brexpiprazol para el tratamiento contra el TLP.
2) Pacientes ambulatorios, de ambos sexos, de entre 18 y 65 años de edad (inclusive) en el momento del consentimiento informado del anterior ensayo doble ciego con brexpiprazol contra el TLP.
3) Pacientes que puedan completar el proceso de consentimiento u obtención del consentimiento de un representante legal (según lo exija el Comité de Revisión Institucional [CRI]/Comité de Ética Independiente [CEI]), antes de comenzar ningún procedimiento que requiera el protocolo.
4) Capacidad, a criterio del investigador principal, de comprender la naturaleza del ensayo y de cumplir los requisitos del protocolo, inclusive las pautas posológicas prescritas, la toma de comprimidos y la suspensión de los medicamentos prohibidos, además de capacidad de leer y comprender textos escritos para poder disponer de una puntuación fiable en las escalas de evaluación.

E.4

Principal exclusion criteria

1) Sexually active males or females of childbearing potential (FOCBP) 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. If employing birth control, 2 of the following precautions must be used: vasectomy, tubal ligation, intrauterine device, birth control pill, birth control implant, birth control depot injection, condom with spermicide, sponge with spermicide, or occlusive cap (vaginal diaphragm or cervical/vault cap) with spermicide. Male or female subjects identifying as homosexual with exclusively same-sex 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/baseline through 30 days after the last dose of IMP.
2) Women who are breastfeeding and/or who have a positive pregnancy test result prior to receiving IMP.
3) Subjects who fulfill the following criteria related to suicide and/or suicidal ideation at entry are excluded:
- Subjects who have a significant risk of committing violent acts, serious self-harm, or suicide, or those who are homicidal or considered to be a high
risk to others, or subjects with a response of “yes” on the Columbia-Suicide Severity Rating Scale (C-SSRS) Suicidal Ideation Item 5 (Active Suicidal
Ideation with Specific Plan and Intent), OR
- Subjects with a response of “yes” on the C-SSRS Suicidal Behavior Items Actual Attempt, Interrupted Attempt, or Aborted Attempt
- Subjects who endorse engaging in preparatory acts and/or non-suicidal self-injury may be included according to investigator judgment, provided the
behavior has not increased significantly in frequency or severity during the preceding double-blind trial period, and after discussion and approval by the medical monitor.
4) Subjects with abnormal laboratory tests results, vital signs results, or electrocardiogram (ECG) findings, unless, based on the investigator’s judgment, the findings are not medically significant and would not impact the safety of the subject or the interpretation of the trial results. The medical monitor should be contacted to discuss individual cases, as needed. In addition, subjects with the following laboratory test and ECG results at
screening must be excluded from the trial:
 Platelets ≤ 75000/mm3
 Hemoglobin ≤ 9 g/dL
 Neutrophils, absolute ≤ 1000/mm3
 Aspartate aminotransferase (AST) > 2 × the upper limit of normal (ULN)
 Alanine aminotransferase (ALT) > 2 × ULN
 Creatine phosphokinase (CPK) > 3 × ULN, unless discussed with and approved by the medical monitor
 Creatinine ≥ 2 mg/dL
 QT interval corrected for heart rate using Fridericia’s formula (QTcF) ≥ 450 msec in men and ≥ 470 msec in women, unless due to ventricular
pacing. Tests with exclusionary results should be repeated to ensure reproducibility of the abnormality before excluding a subject based on the criteria noted above. For ECGs, perform 3 consecutive recordings. If 2 of the 3 remain exclusionary then the subject must be excluded.

1) Hombres sexualmente activos o mujeres en edad fértil que no acepten la utilización de 2 métodos distintos de control anticonceptivo o la abstinencia durante el ensayo y durante los 30 días siguientes a la última dosis del PEI. Si se utiliza algún método anticonceptivo, deben usarse dos de los siguientes métodos: vasectomía, ligadura de trompas, dispositivo intrauterino, píldora anticonceptiva, implante anticonceptivo, inyecciones anticonceptivas de depósito, preservativo o esponja con espermicida o capuchón oclusivo (diafragma vaginal o capuchón cervical/cúpula vaginal) con espermicida. Es posible que, tras comentarlo con el investigador y el supervisor médico, no se exija que utilicen métodos anticonceptivos a los participantes que se identifiquen como homosexuales con parejas exclusivamente del mismo sexo.
Los pacientes hombres deben estar de acuerdo, además, en no donar esperma desde la selección/el inicio del ensayo y durante los 30 días siguientes a la administración de la última dosis del PEI.
2) Mujeres en período de lactancia o que hayan obtenido un resultado positivo en alguna prueba de embarazo antes de recibir el PEI.
3) Se excluirá a los pacientes que cumplan con los siguientes criterios relacionados con el suicidio o las tendencias suicidas en el momento de su incorporación:
- Pacientes que presenten un riesgo considerable de cometer actos violentos, autolesionarse gravemente o suicidarse, o los que presenten tendencias homicidas o se consideren un gran riesgo para otras personas, así como pacientes con una respuesta afirmativa en el ítem 5 sobre ideación suicida de la Escala de puntuación de la intensidad de las intenciones suicidas de Columbia (Columbia-Suicide Severity Rating Scale, C-SSRS; ideación suicida activa con plan específico e intención); O
- Pacientes con una respuesta afirmativa a los ítems de conducta suicida de la C-SSRS, intento real, intento interrumpido o intento abortado;
- Podrá incluirse a los pacientes que apoyen la participación en actos preparatorios o autolesiones no suicidas, a criterio del investigador, siempre y cuando la frecuencia o gravedad de tal conducta no hayan aumentado de modo considerable durante el período del anterior ensayo doble ciego y tras comentarlo con el supervisor médico y recibir su aprobación.
4) Pacientes con anomalías en los resultados de los análisis de laboratorio, las constantes vitales o los resultados de los electrocardiogramas (ECG) a menos que, según el criterio del investigador, los resultados no sean clínicamente importantes y no afecten a la seguridad del paciente ni a la interpretación de los resultados del ensayo. Se deberá consultar con el supervisor médico para comentar los casos particulares, según sea necesario. Además, debe excluirse del ensayo a los pacientes con los siguientes resultados en las pruebas analíticas y los ECG en el momento de la selección:
Plaquetas ≤ 75 000/mm3
Hemoglobina ≤ 9 g/dl
Neutrófilos, cantidad absoluta, ≤ 1000/mm3
Aspartato aminotransferasa (AST) > 2 veces el límite superior de la normalidad (LSN)
Alanina aminotransferasa (ALT) > 2 veces el LSN
Creatinfosfocinasa (CPK) > 3 veces el LSN, salvo que se haya consultado con el supervisor médico y lo haya aprobado
Creatinina ≥ 2 mg/dl
Intervalo QT corregido para la frecuencia cardíaca mediante la fórmula de Fridericia (QTcF) ≥ 450 ms en hombres y ≥ 470 ms en mujeres, a menos que dispongan de estimulación ventricular. Antes de excluir a un paciente basándose en los criterios señalados antes, deben repetirse una vez las pruebas con resultados excluyentes para garantizar la reproducibilidad de la anomalía. En el caso de los ECG, deben realizarse 3 pruebas consecutivas. Si dos de las 3 continúan siendo excluyentes, deberá excluirse al paciente.

E.5 End points

E.5.1

Primary end point(s)

Frequency and severity of AEs.

Frecuencia y gravedad de los EA

E.5.1.1

Timepoint(s) of evaluation of this end point

Up to 12 weeks

Hasta 12 semanas

E.5.2

Secondary end point(s)

 Changes in: ECGs, vital signs, clinical laboratory tests including prolactin, changes in body weight, and physical examinations;
 EPS: SAS, AIMS, and BARS;
 Suicidal ideation and behavior will be assessed using the C-SSRS.
 Change from baseline in the ZAN-BPD total score by trial visit and at the last visit (ie, Week 12/ET);
 Change from baseline in the ZAN-BPD sector scores by trial visit and at the last visit (ie, Week 12/ET);
 Change from baseline in the CGI-S score, by trial visit and at the last visit (ie, Week 12/ET);
 CGI-I score;
 Change from baseline in the PGI-S (ie, Week 12/ET);
 PGI-C score;
 Change from baseline in the HADS-A and HADS-D score (ie, Week 12/ET);
 Change from baseline in the WHODAS 2.0 score (ie, Week 12/ET);
 Change from baseline in the CGI-SS-extended scale (ie, Week 12/ET).

Cambios en los ECG, las constantes vitales, los análisis clínicos de laboratorio (incluida la prolactina), el peso corporal y las exploraciones físicas;
SEP: SAS, AIMS y BARS;
Las ideas y la conducta suicidas se evaluarán mediante la escala C-SSRS.
Variación con respecto al valor inicial en la puntuación total de ZAN-BPD, por visita del estudio y en la última visita (es decir, semana 12/FA);
Variación con respecto al valor inicial en las puntuaciones de sectores de ZAN-BPD, por visita del estudio y en la última visita (es decir, semana 12/FA);
Variación con respecto al valor inicial de la puntuación de la CGI-S, por visita del estudio y en la última visita (es decir, semana 12/FA);
Puntuación en la escala CGI-I;
Variación con respecto al valor inicial de la puntuación de la PGI-S (es decir, semana 12/FA);
Puntuación en el cuestionario PGIC;
Variación con respecto al valor inicial de la puntuación de HADS-A y HADS-D (es decir, semana 12/FA)
Variación con respecto al valor inicial de la puntuación de WHODAS (es decir, semana 12/FA)
Variación con respecto al valor inicial de la puntuación de la escala CGI-SS-extendida (es decir, semana 12/FA)

E.5.2.1

Timepoint(s) of evaluation of this end point

Up to 12 weeks

Hasta 12 semanas

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

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

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

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

E.8.2.3

Other

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:

195

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

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

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 will be entered into post-treatment follow-up period for up to 24 days.

Los pacientes que completen todas las visitas del ensayo hasta la semana 12 sin desviaciones importantes del protocolo pasarán al período de seguimiento posterior al tratamiento durante un máximo de 24 días.

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

2020-02-19

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-02-17

P. End of Trial
P.	End of Trial Status	Ongoing

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