Clinical Trials Register

Summary
EudraCT Number:	2012-003226-25
Sponsor's Protocol Code Number:	Abifood01
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:	2012-12-21
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

2012-003226-25

A.3

Full title of the trial

Phase I, randomized, open design trial to evaluate the effect of food (fasting, fat meal and standard meal) on the pharmacokinetics of abiraterone acetate at reduced doses, compared with conventional-dose abiraterone acetate administered fasting in patients with metastatic prostatic cancer resistant to castration that have progressed to docetaxel.

Ensayo fase I, randomizado y abierto para evaluar el efecto de la comida (ayunas y comida estándar y rica en grasas) en los parámetros farmacocinéticos de acetato de abiraterona a dosis reducidas, frente a acetato de abiraterona administrado en ayunas a dosis convencional, en pacientes con cáncer de próstata avanzado resistente a la castración que han progresado a docetaxel.

A.3.1

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

Study to evaluate the effect of food on the availability of the drug abiraterone administered at low doses with food (standard and fat food) before fasting normal dose in patients with advanced prostatic cancer resistant to castration that have progressed to docetaxel.

Estudio para evaluar el efecto de la comida en la disponibilidad del fármaco abiraterona administrado a bajas dosis con comida normal o grasa frente a dosis normal en ayunas en pacientes con cáncer de próstata avanzado resistente a la castración que han progresado a docetaxel.

A.4.1

Sponsor's protocol code number

Abifood01

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	Fundacion Publica Andaluza para la Gestion de la Investigacion en Salud de Sevilla
B.1.3.4	Country	Spain
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	NA
B.4.2	Country	Spain
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Unidad de investigación Clínica y ensayos Clínicos
B.5.2	Functional name of contact point	Unidad de Investigación Clínica
B.5.3	Address:
B.5.3.1	Street Address	Avda. Manuel Siurot, s/n
B.5.3.2	Town/ city	Seville
B.5.3.3	Post code	41013
B.5.3.4	Country	Spain
B.5.4	Telephone number	0034955013414
B.5.5	Fax number	0034954232992
B.5.6	E-mail	claram.rosso.sspa@juntadeandalucia.es

D. IMP Identification
D.IMP: 1
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	ZYTIGA (Abiraterone Acetate)
D.2.1.1.2	Name of the Marketing Authorisation holder	Janssen-Cilag International NV
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.3.1	Product name	ZYTIGA (Abiraterone Acetate)
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	ZYTIGA (ABIRATERONE ACETATE)
D.3.9.1	CAS number	154229-18-2
D.3.9.3	Other descriptive name	ABIRATERONE ACETATE
D.3.9.4	EV Substance Code	SUB31647
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	250
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	Yes
D.2.1.1.1	Trade name	ZYTIGA (abiraterone acetate)
D.2.1.1.2	Name of the Marketing Authorisation holder	Jansen-Cilag International NV
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.3.1	Product name	ZYTIGA(abiraterone Acetate)
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	ZYTIGA (ABIRATERONE ACETATE)
D.3.9.1	CAS number	154229-18-2
D.3.9.3	Other descriptive name	ABIRATERONE ACETATE
D.3.9.4	EV Substance Code	SUB31647
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	250
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

metastatic prostatic cancer after castration-resistant progression to docetaxel

cáncer de próstata avanzado resistente a la castración tras progresión a docetaxel

E.1.1.1

Medical condition in easily understood language

patients with metastatic prostatic cancer unresponsive to docetaxel

pacientes con cáncer de próstata avanzado sin respuesta a docetaxel

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	16.0
E.1.2	Level	LLT
E.1.2	Classification code	10036947
E.1.2	Term	Prostatic cancer metastatic
E.1.2	System Organ Class	100000004864

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 describe the pharmacokinetics of abiraterone acetate administered at reduced doses with meals, compared to abiraterone acetate administered conventional-dose fasting .

Describir los parámetros farmacocinéticos de acetato de abiraterona a dosis reducidas administrado junto con las comidas, frente a acetato de abiraterona administrado en ayunas a dosis convencional.

E.2.2

Secondary objectives of the trial

- To describe the tolerance and adverse event profile of abiraterone acetate administered at reduced doses with meals and compare the safety profile of the dose and the conventional dosing regimen. Adverse events were assessed according to Common Terminology Criteria for Adverse Events (CTCAE) of the National Cancer Institute (NCI), (version 4).
- To compare the costs of resources used between the two treatment groups.
- To describe efficacy parameters, progression-free survival (PFS) and overall survival (OS), PSAquantification and monitoring, efficacy on pain control and disease progression.
- To assess the impact of abiraterone acetate plus prednisone on the quality of life (QOL) related to health.
- To evaluate the possible effect of the usual diet in pharmacokinetic parameters in medical abiraterone acetate kinetic points defined.

- Describir la tolerancia y el perfil de acontecimientos adversos de acetato de abiraterona a dosis reducidas administrado junto con las comidas y compararlo con el perfil de seguridad de la dosis y el régimen de administración convencional. Los acontecimientos adversos se evaluarán de acuerdo con los Criterios de Terminología Común para Acontecimientos Adversos (CTCAE) del National Cancer Institute (NCI), (versión 4).
- Describir parámetros de eficacia; supervivencia libre de progresión (SLP) y supervivencia global (SG), cuantificación y seguimiento de PSA, eficacia sobre el control del dolor y progresión de la enfermedad.
- Evaluar el impacto de acetato de abiraterona más prednisona sobre la calidad de vida (CdV) relacionada con la salud.
- Evaluar el posible efecto de la dieta habitual en los parámetros farmacocinéticos de acetato abiraterona medicos en los puntos cinéticos definidos.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Patients with prostatic adenocarcinoma histologically or cytologically confirmed without neuroendocrine differentiation or small cell histology.
- At least one, but no more than 2, cytotoxic chemotherapy regimens for metastatic prostatic cancer resistant to castration. At least one regimen must have contained docetaxel. If docetaxel chemotherapy was used more than once, be considered as only regime.
- Men of 18 or more years old.
- Progression criteria according to the recommendations of the Prostate Cancer Working Group. For inclusion progression is considered to have two consecutive elevated PSA measurements over a baseline or radiological evidence of progression in soft tissue or bone (according to modified RECIST criteria) with or without progression based on PSA value
- Androgen deprivation present with testosterone levels <50 ng / dl or <2.0 nmol / l).
- ECOG performance status (Eastern Cooperative Oncology Group) <2.
- Adequate organ function, defined by: absolute neutrophil count (ANC) ? 1.5 × 109 / L (1500/mm3), platelet count ? 100 × 109 / L (100.000/mm3), hemoglobin ? 9.0 g / dL (90 g / L), serum creatinine ? 1.5 × ULN, total bilirubin ? 1.5 × ULN (allowed <2 × ULN if Gilbert syndrome known) AST and ALT ? 2.5 × ULN (up to 5 x ULN if liver metastases).
- Accept the use of barrier contraception throughout the study: to use condoms in combination with another effective contraceptive method.
- Able to swallow study medication whole.
- Informed consent signed to participate in the study.

- Pacientes adenocarcinoma de próstata confirmado histológicamente o citológicamente sin diferenciación neuroendocrina o histología de células pequeñas.
- Al menos uno, pero no más de 2, regímenes de quimioterapia citotóxica para cáncer de próstata metastásico resistente a la castración. Al menos un régimen debe haber contenido docetaxel. Si se usó quimioterapia con docetaxel más de una vez, se considerará como un régimen.
- Hombres de 18 o mas años de edad.
- Criterios de progresión de acuerdo a las recomendaciones del Prostate Cancer Working Group. Para la inclusión se considera progresión el tener dos mediciones consecutivas de PSA elevados respecto a un valor basal ó evidencia radiológica de progresión en tejidos blandos o hueso (de acuerdo a criterios RECIST modificados) con o sin progresión basada en el valor de PSA
- Deprivación androgénica presente con niveles de testosterona de < 50 ng/dl o < 2.0 nmol /l).
- Estado funcional del ECOG (Eastern Cooperative Oncology Group) < 2.
- Función orgánica adecuada, definida por: recuento absoluto de neutrófilos (RAN) ? 1,5 × 109/L (1500/mm3), recuento de plaquetas ? 100 × 109/L (100.000/mm3), hemoglobina ? 9,0 g/dL (90 g/L), creatinina sérica ? 1,5 × LSN, bilirrubina total ? 1,5 × LSN (se permite < 2 × LSN en caso de síndrome de Gilbert conocido) AST y ALT ? 2,5 × LSN (hasta 5 x LSN si hay metástasis hepáticas).
- Aceptar el uso de métodos anticonceptivos de barrera durante todo el estudio: debe utilizar preservativo conjuntamente con otro método anticonceptivo eficaz.
- Capaz de tragar el fármaco del estudio entero.
- Firma del consentimiento informado para participar en el estudio.

E.4

Principal exclusion criteria

- Uncontrolled or severe non-malignant coexisting disease, including active and uncontrolled infection.
- Known or suspected allergy to abiraterone acetate or related compounds with this kind of medication.
- Inability or unwillingness to swallow tablets.
- Other malignancy (except nonmelanoma skin cancer), with a probability ? 30% recurrence in 12 months.
- Brain metastases known
- Important chronic gastrointestinal disorder with diarrhea as the main symptom (Crohn's disease, ulcerative colitis, malabsorption or ? grade 2 diarrhea of ??any etiology at baseline).
- Surgery or local prostatic intervention within 30 days before the first dose. Further, any clinically relevant sequelae of surgery must be resolved before day 1 of cycle 1.
- Radiotherapy, chemotherapy or immunotherapy within 30 days before or single fraction of palliative radiotherapy within 14 days prior to the administration of the day 1del cycle 1.
- Patients with uncontrolled hypertension (systolic BP> 160 mm Hg or diastolic BP> 95 mmHg), clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the last 6 months, severe or unstable angina, heart failure Class III or IV New York Heart Association heart failure or ejection fraction <50%, active or symptomatic viral hepatitis, chronic liver disease, adrenal or pituitary dysfunction clinically significant. (Patients with hypertension controlled with medication are allowed)
- Any acute toxicity from chemotherapy and / or previous radiation therapy has not been resolved to grade ? 1 of the NCI CTCAE (version 4). Allowed alopecia and grade 2 peripheral neuropathy induced by chemotherapy.
- Any condition which in the opinion of the investigator would put the patient at significant risk, may confound the results of the study or would significantly interfere with patient participation in the study.
- Previous treatment with abiraterone acetate

- Enfermedad no maligna coexistente grave o no controlada, incluida infección activa y no controlada.
- Alergia conocida o sospechada a acetato de abiraterona o a otros compuestos relacionados con esta clase de medicación.
- Incapacidad o falta de disposición para tragar comprimidos.
- Otro tumor maligno, (excepto cáncer de piel no melanoma), con una probabilidad ? 30% de recidiva en 12 meses.
- Metástasis cerebrales conocidas
- Trastorno gastrointestinal crónico importante con diarrea como síntoma principal (enfermedad de Crohn, colitis ulcerosa, malabsorción o diarrea de grado ? 2 de cualquier etiología en el momento basal).
- Cirugía o intervención prostática local dentro de los 30 días previos a la primera dosis. Además, cualquier secuela clínicamente relevante de la cirugía se debe haber resuelto antes del día 1 del ciclo 1.
- Radioterapia, quimioterapia o inmunoterapia dentro de los 30 días anteriores o fracción única de radioterapia paliativa dentro de los 14 días previos a la administración del día 1del ciclo 1.
- Pacientes con hipertensión no controlada (PA sistólica > 160 mm Hg O PA diastólica >95 mmHg), cardiopatía clínicamente significativa evidenciada por infarto de miocardio, o episodios trombóticos arteriales en los últimos 6 meses, angina grave o inestable, insuficiencia cardiaca de Clase III o IV de la New York Heart Association o fracción de eyección cardiaca < 50%, hepatitis vírica activa o sintomática, insuficiencia hepática crónica, disfunción adrenal o hipofisiaria clínicamente significativa. (Los pacientes con hipertensión arterial controlada con fármacos están permitidos)
- Cualquier toxicidad aguda debida a la quimioterapia y/o la radioterapia previas que no se haya resuelto a grado ? 1 de los CTCAE del NCI (versión 4). Se permiten la alopecia y la neuropatía periférica de grado 2 inducidas por la quimioterapia.
- Cualquier condición que en opinión del investigador podría poner al paciente en un riesgo significativo, podría confundir los resultados del estudio o podría interferir significativamente con la participación del paciente en el estudio.
- Tratamiento previo con Acetato de Abiraterona

E.5 End points

E.5.1

Primary end point(s)

Abiraterone pharmacokinetic parameters: AUC0-t and AUC0-?, Cmax, Tmax with effect from the administration of food.

Parámetros farmacocinéticos en los distintos puntos: AUC0-t y AUC0-∞, Cmáx, Tmáx con efecto de la administración de la comida.

E.5.1.1

Timepoint(s) of evaluation of this end point

At the end or treatment

Al final del tratamiento

E.5.2

Secondary end point(s)

- PSA levels at baseline and follow-up until disease progression.
- Response rate according to RECIST 1.1
- Pain scales: pain is measured by the BPI-SF scale (Brief Pain Inventory-Short Form, 0-10 points scale where 0 to 3 is no pain, and 4 to 10 indicates the intensity of pain).
- Analgesics use: the need for rescue analgesic use associated with pain, analgesic and collect the required DDT.
- habitual diet by the patient at home

- Niveles de PSA basales y en el seguimiento hasta progresión de la enfermedad.
- Tasa de respuesta segun los criterios recist 1.1
- Escalas de dolor: se valorará el dolor mediante la escala BPI-SF (Brief Pain Inventory-Short Form, escala de 0-10 puntos donde 0 - 3 es ausencia de dolor, y de 4 a 10 indica la intensidad del dolor).
- Uso de analgésicos: necesidad de utilización de analgésicos de rescate asociados al dolor, se recogerá el analgésico y DDT requerida.
- Dieta habitual realizada por el paciente en domicilio.

E.5.2.1

Timepoint(s) of evaluation of this end point

All visits

todas las visitas del estudio

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

Yes

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

Yes

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

Yes

E.7.1.3.1

Other trial type description

Pharmacokinetic

Farmacocinática

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

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)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

dosis reducida

reduced dosis

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

At final visit of last patient

En la 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

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)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

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.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)

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

2013-07-12

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-12-20

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

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