Clinical Trials Register

Summary
EudraCT Number:	2005-003777-24
Sponsor's Protocol Code Number:	PKU-006
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:	2006-01-19
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

2005-003777-24

A.3

Full title of the trial

Estudio fase 3, multicéntrico, aleatorizado, doble ciego y controlado con placebo para evaluar la seguridad y la eficacia de PhenoptinTM en dosis de 20 mg/kg/dia para aumentar la tolerancia a la fenilalanina en niños fenilcetonúricos que siguen dietas restrictivas en fenilalanina.

A.4.1

Sponsor's protocol code number

PKU-006

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	BioMarin Pharmaceutical 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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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	Information not present in EudraCT
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EMEA/OD/077/03
D.3 Description of the IMP
D.3.1	Product name	Phenoptin
D.3.2	Product code	T1401
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	Sapropterin
D.3.9.1	CAS number	69056-38-8
D.3.9.2	Current sponsor code	T1401
D.3.9.3	Other descriptive name	Sapropterin dihydrochloride
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	not less then
D.3.10.3	Concentration number	100
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.8	Extractive medicinal product	Information not present in EudraCT
D.3.11.9	Recombinant medicinal product	Information not present in EudraCT
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	Yes
D.3.11.13.1	Other medicinal product type	Synthetic Drug Product

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

Fenilcetonuria (Phenylketonuria-PKU)

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	6.1
E.1.2	Classification code	10034872

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

Valorar la capacidad de Phenoptin para aumentar la tolerancia a la fenilalanina (Phe) en niños fenilcetonúricos que siguen dietas restrictivas en Phe.

E.2.2

Secondary objectives of the trial

1.Valorar la capacidad de Phenoptin para reducir las concentraciones de Phe sanguínea en niños fenilcetonúricos que siguen dietas restrictivas en Phe.

2.Comparar la capacidad de Phenoptin frente a un placebo para aumentar la tolerancia a la Phe en niños fenilcetonúricos que siguen dietas restrictivas en Phe.

3.Valorar la seguridad de Phenoptin frente a un placebo en esta población de sujetos.

4.Investigar la posible reducción en los gastos originados por alimentos médicos y preparados exentos de Phe.

E.2.3

Trial contains a sub-study

Information not present in EudraCT

E.3

Principal inclusion criteria

·Diagnóstico clínico de PKU con hiperfenilalaninemia (HPA) documentada mediante al menos una determinación de Phe sanguínea ³ 360 μmol/l (6 mg/dl).
·Control alimentario con una dieta restrictiva en Phe, demostrado por:· Tolerancia a Phe calculada £ 000 mg/día.
·Al menos 6 meses de control de Phe sanguínea (concentración media £ 480 μmol/l) antes de inscribirse en el estudio.
·Concentración de Phe sanguínea £ 480 μmol/l en el momento de la selección.
·Edad entre 4 y 12 años inclusive en el momento de la selección.
·Las niñas en edad fértil (en la opinión del investigador principal) deben presentar una prueba sanguínea o urinaria de embarazo negativa en el momento del ingreso (antes de recibir la primera dosis). Nota: Debe advertirse a todas las niñas en edad fértil y a los varones que hayan llegado a la madurez sexual que practiquen un método anticonceptivo aceptable a lo largo del estudio. Además, las niñas en edad fértil deben estar dispuestas a someterse a pruebas periódicas de embarazo en el transcurso del estudio.
·Voluntad y capacidad para cumplir con los procedimientos del estudio.
·Voluntad para proporcionar un asentimiento por escrito (si corresponde) y un consentimiento informado por escrito firmado por el padre, madre o tutor legal una vez que se explique la naturaleza del estudio y antes de que se realice algún procedimiento relacionado con la investigación.

E.4

Principal exclusion criteria

·Se vea afectado por cualquier circunstancia que, en la opinión del IP, lo exponga a un alto riesgo si cumple con el tratamiento y/o finaliza el estudio.
·Tenga antecedentes de trasplante de órganos.
·Sea considerado como poco fiable o no disponible para participar en el estudio, o tenga padres o tutores legales que sean considerados como poco fiables o no disponibles.
·Haya recibido algún tratamiento experimental los 30 días anteriores a la visita de selección, o requiera algún tratamiento o vacuna experimentales antes de finalizar todas las valoraciones previstas para el estudio.
·Tenga un valor de ALT más de 2 veces mayor que el límite superior de normalidad (es decir, de grado 1 o superior según los criterios de toxicidad de la Organización Mundial de la Salud; apéndice 2) en la visita de selección.
·Sufra una enfermedad o afección simultánea capaz de interferir en su participación en el estudio o su seguridad (por ej., trastornos convulsivos, asma dependiente de esteroides orales u otra afección que requiera la administración de corticosteroides orales o parenterales, o diabetes insulinodependiente).
·Sufra una patología neuropsiquiátrica grave (por ej., depresión importante) que no esté bajo tratamiento médico actual.
·Necesite tratamiento concomitante con cualquier medicamento que haya demostrado inhibir la síntesis de folato (por ej., metotrexato).
·Esté tomando levodopa.
·Tenga un diagnóstico clínico de deficiencia primaria de BH4.

E.5 End points

E.5.1

Primary end point(s)

El criterio principal de valoración de eficacia será el aporte de Phe alimentaria que el sujeto tolere durante el tratamiento con Phenoptin en comparación con el valor previo al tratamiento, mientras mantiene un control adecuado de su Phe sanguínea.

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

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Information not present in EudraCT

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

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

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.8.3

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.8.5

The trial involves multiple Member States

Yes

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

Information not present in EudraCT

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

E.8.7

Trial has a data monitoring committee

Information not present in EudraCT

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

Última visita del último paciente que este llevando a cabo el estudio.

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 months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

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)

Yes

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.2

Adults (18-64 years)

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

Information not present in EudraCT

F.3.3.1

Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2006-01-19.

Yes

F.3.3.2

Women of child-bearing potential using contraception

Information not present in EudraCT

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Al ser sujetos menores de 18 años, el menor otorgará su consentimiento por escrito (si es requerido) y siempre tendrán que otorgar consentimiento escrito los padres o representante legal del paciente una vez explicada la naturaleza del estudio.

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

150

F.4.2.2

In the whole clinical trial

300

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

2006-03-01

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2005-12-30

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2006-11-06

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