Clinical Trials Register

Summary
EudraCT Number:	2015-005751-27
Sponsor's Protocol Code Number:	X213220
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2016-03-18
Trial 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

2015-005751-27

A.3

Full title of the trial

A Multi-Center, Open-Label, Randomized, Single-Dose, Controlled Trial of Intravenously Administered XOMA 213 in Suppression of Lactation after Delivery in Postpartum Women

Ensayo multicéntrico, abierto, aleatorizado, de dosis única, controlado, de XOMA 213 administrado por vía intravenosa a mujeres después del parto para la supresión de la lactancia

A.3.1

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

A study of XOMA 213 in the reduction of breast milk production in women after child birth.

Estudio de XOMA 213 en la reducción de la producción de leche materna en mujeres después del parto.

A.4.1

Sponsor's protocol code number

X213220

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	XOMA (US) LLC
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	XOMA (US) LLC
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	León Research S.L
B.5.2	Functional name of contact point	Regulatory Affairs
B.5.3	Address:
B.5.3.1	Street Address	Ordoño II, 37- 2° Dcha
B.5.3.2	Town/ city	León / León
B.5.3.3	Post code	24001
B.5.3.4	Country	Spain
B.5.4	Telephone number	0034987261064
B.5.5	Fax number	0034987216243
B.5.6	E-mail	iminguez@leonresearch.es

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.3.2	Product code	XOMA 213
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	XOMA 213
D.3.9.2	Current sponsor code	XOMA 213
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
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	Comparator
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	Yes
D.2.1.1.1	Trade name	DOSTINEX 0,5 mg COMPRIMIDOS
D.2.1.1.2	Name of the Marketing Authorisation holder	Pfizer, S.L.
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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.3.4	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	cabergoline
D.3.9.1	CAS number	81409-90-7
D.3.9.2	Current sponsor code	cabergoline
D.3.9.3	Other descriptive name	CABERGOLINE
D.3.9.4	EV Substance Code	SUB06041MIG
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	0.5
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

Suppression of Lactation after Delivery in Postpartum Women

Supresión de la lactancia después del parto en mujeres después del parto

E.1.1.1

Medical condition in easily understood language

Inhibition of breast milk production after childbirth

La inhibición de la producción de leche materna después del parto

E.1.1.2

Therapeutic area

Body processes [G] - Reproductive physiologi cal processes [G08]

MedDRA Classification

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, tolerability, and pharmacokinetics of a single intravenous dose of XOMA 213 administered postpartum in women who wish to suppress lactation immediately postpartum.
? To evaluate the pharmacodynamics of XOMA 213 as measured by changes in milk secretion, breast engorgement, pain and tenderness, and rebound symptomology.

?Evaluar la seguridad, la tolerabilidad y la farmacocinética de una dosis intravenosa única de XOMA 213 administrada después del parto a mujeres que desean suprimir la lactancia inmediatamente después del parto.

?Evaluar la farmacocinética de XOMA 213, medida según las variaciones de la secreción de leche, la congestión de las mamas, el dolor y la hiperestesia, y los síntomas de rebote.

E.2.2

Secondary objectives of the trial

Not applicable

No aplica

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Subjects may be included in the study if ALL of the following criteria are met:
1. Provide written informed consent before any study specific procedures are performed
2. Female, aged 18 to 45 years, pregnant with a gestational age of at least 36 weeks, and expected to deliver within 21 days of study Screening
3. Wishing to suppress lactation immediately after delivery
4. Willing to be hospitalized for 3 consecutive days immediately after delivery
5. For female subjects with reproductive potential (ie, fertile, following menarche and until becoming post-menopausal unless permanently sterile), a willingness to use highly effective* contraceptive measures adequate to prevent a new pregnancy for at least 3 months after administration of study drug. For women with reproductive potential who use a hormonal method of contraception, concurrent use of a second (barrier) method is recommended.

Se incluirá en el estudio a las mujeres que cumplan TODOS los criterios siguientes:
1. Consentimiento informado por escrito antes de realizar cualquier procedimiento específico del estudio
2. Mujeres embarazadas de 18 a 45 años con una edad de gestación de al menos 36 semanas, cuyo parto esté previsto en los 21 días siguientes a la selección del estudio
3. Deseo de suprimir la lactancia inmediatamente después del parto
4. Aceptación de permanecer en el hospital durante 3 días seguidos inmediatamente después del parto
5. En el caso de las mujeres en edad fértil (es decir, fértiles, después de la primera menstruación y antes de la menopausia, salvo que sean estériles de forma definitiva), compromiso de utilizar medidas anticonceptivas de gran eficacia* adecuadas para evitar un nuevo embarazo durante al menos 3 meses después de la administración del fármaco del estudio. En las mujeres en edad fértil que utilicen un método anticonceptivo hormonal se recomienda el uso simultáneo de un segundo método (de barrera).

E.4

Principal exclusion criteria

Subjects will be excluded from the study if ANY of the following criteria are met:
1. History of mastitis
2. History of pituitary disease
3. History of intrauterine fetal death, bleeding disorder, pre-eclampsia, liver or kidney impairment, or any severe complication associated with the current or prior pregnancies
4. History of pregnancy-related hypertension, (eg, preeclampsia, eclampsia, or post partum hypertension), which are contraindications to cabergoline
5. Major general surgery (including C-section) within 3 months before study entry or anticipated during the study period
6. Seropositivity for HIV antibody, hepatitis B surface antigen, or hepatitis C antibody
7. Treatment within 30 days before study entry or concurrent treatment during the study with any drug, other than study drug, that affects prolactin levels or lactation (eg, cabergoline, bromocriptine, other dopamine agonists, or antidepressants)
8. History of severe allergic or anaphylactic reaction to monoclonal antibodies
9. Any out-of-range laboratory value at Screening that has not been reviewed, approved, and documented as not clinically significant by the Investigator
10. Presence of clinically significant cardiac disease or failure, renal insufficiency, hepatic insufficiency, chronic obstructive pulmonary disease, anemia, or uncontrolled hypertension
11. History of malignancy within 3 years before study entry other than carcinoma in situ of the cervix or adequately treated nonmetastatic squamous or basal cell carcinoma of the skin
12. Known allergy or sensitivity to XOMA 213 or any component of the study drug or known contraindications to treatment with cabergoline
13. Treatment with an investigational drug or device within 30 days or 5 half-lives of the investigational drug, whichever is longer, before Day 1. Participation in registries and purely diagnostic studies is allowed.
14. Any condition that, in the opinion of the investigator, would jeopardize the subject’s safety after exposure to the study drug. Any condition (eg, psychiatric illness, severe alcoholism, or drug abuse) or situation that may compromise the ability of the subject to give written informed consent, may put the subject at significant risk, may confound the study results, or may interfere significantly with the subject’s participation in the study.

Se excluirá del estudio a las mujeres que cumplan CUALQUIERA de los criterios siguientes:
1. Antecedente de mastitis
2. Antecedente de enfermedad hipofisaria
3. Antecedentes de muerte fetal intrauterina, trastornos hemorrágicos, preeclampsia, insuficiencia hepática o renal o de cualquier complicación grave relacionada con embarazos actuales o anteriores
4. Antecedentes de hipertensión gestacional (p. ej., preeclampsia, eclampsia o hipertensión puerperal) para los que está contraindicada la administración de cabergolina
5. Intervención general de cirugía mayor (incluida la cesárea) en los 3 meses previos a la inclusión en el estudio o prevista durante el periodo del ensayo
6. Seropositividad del anticuerpo contra el VIH, el antígeno de superficie de la hepatitis B o el anticuerpo de la hepatitis C
7. Tratamiento en los 30 días previos a la entrada en el estudio o tratamiento concurrente durante el estudio con cualquier medicamento que no sea el fármaco del estudio que afecte a las concentraciones de prolactina o la lactancia (p. ej., cabergolina, bromocriptina, otros agonistas de la dopamina o antidepresivos)
8. Antecedente de reacción alérgica o anafiláctica grave a anticuerpos monoclonales
9. Cualquier valor analítico fuera de los límites en la selección que no se haya revisado, aprobado y documentado como clínicamente no significativo por el investigador
10. Presencia de insuficiencia cardíaca o cardiopatía, insuficiencia renal, insuficiencia hepática, enfermedad pulmonar obstructiva crónica, anemia o hipertensión no controlada clínicamente importantes
11. Antecedente de neoplasia maligna en los 3 años previos a la inclusión en el estudio, distinta de carcinoma in situ del cuello uterino o carcinoma basocelular o espinocelular no metastásico de la piel tratado adecuadamente
12. Alergia o sensibilidad conocida a XOMA 213 o a cualquier componente del fármaco del estudio o motivos conocidos por los que esté contraindicado el tratamiento con cabergolina
13. Tratamiento con un fármaco o producto sanitario experimental en 30 días o 5 semividas del fármaco experimental, lo que sea más largo, antes del día 1. Se permite la participación en registros y estudios exclusivamente diagnósticos.
14. Cualquier proceso o situación que, en opinión del investigador, afecte a la seguridad de las participantes después de la exposición al fármaco del estudio. Cualquier proceso (p. ej., enfermedad psiquiátrica, alcoholismo grave o toxicomanía) o situación que pueda afectar a la capacidad de la participante de otorgar el consentimiento informado por escrito, suponga un riesgo importante para ella, confunda los resultados del estudio o dificulte significativamente la participación en el ensayo.

E.5 End points

E.5.1

Primary end point(s)

Biological:
? Assessment of change from baseline milk secretion, breast engorgement, and pain and tenderness at Days 1, 2, 3, 5, 8, and 21 post-dose.
? Concomitant medications (such as analgesics) and other non-medication treatment measures (such as ice compresses) for relief of pain
Safety:
? Safety will be assessed through an examination of the incidence, severity, and type of treatment-emergent adverse events and changes from baseline vital signs, physical examination results, lab values, ECG results, and infusion site reactions.
Pharmacokinetics:
? Blood samples will be collected after dosing to determine concentration of XOMA 213 in serum. The following noncompartmental PK parameters will be calculated: Cmax, Tmax, CEOI, t1/2, AUC0-t, AUC0-inf, CL, Vz, and VSS.

Biológicos:
? Evaluación de la variación de la secreción de leche, la congestión de las mamas y el dolor y la hiperestesia los días 1, 2, 3, 5, 8 y 21 después de la dosis con respecto al momento basal. (Véase la Tabla 2.)
? Medicamentos concomitantes (como analgésicos) y otras medidas terapéuticas no farmacológicas (como compresas de hielo) para aliviar el dolor
Seguridad:
? La seguridad se evaluará examinando la incidencia, la intensidad y el tipo de acontecimientos adversos surgidos durante el tratamiento y las alteraciones de las constantes vitales, los resultados de la exploración física, los valores analíticos y los resultados del ECG con respecto al momento basal y las reacciones en el lugar de infusión.
Farmacocinética:
? Se obtendrán muestras de sangre después de la dosis para determinar la concentración sérica de XOMA 213. Se calcularán los siguientes parámetros FC no compartimentales: Cmáx, Tmáx, CFDI, t1/2, AUC0-t, AUC0-inf, CL, Vz y VSS.

E.5.1.1

Timepoint(s) of evaluation of this end point

Days 1, 2, 3, 5, 8, and 21 post-dose

Días 1, 2, 3, 5, 8, y 21 después de la dosis

E.5.2

Secondary end point(s)

Not applicable

No aplica

E.5.2.1

Timepoint(s) of evaluation of this end point

Not applicable

No aplica

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

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)

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

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

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)

Yes

E.8.2.2

Placebo

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

E.8.6.2

Trial being conducted completely outside of the EEA

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

última visita del último paciente

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:

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

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

Yes

F.3.3.7.1

Details of other specific vulnerable populations

Pregnant women who expect to deliver within 21 days of study entry and wish to suppress lactation

F.4 Planned number of subjects to be included

F.4.1

In the member state

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

Ninguna

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

2016-05-18

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-05-11

P. End of Trial
P.	End of Trial Status	Completed

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