Clinical Trials Register

Summary
EudraCT Number:	2011-002754-31
Sponsor's Protocol Code Number:	NUC-3/PSC
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:	2012-07-19
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2011-002754-31

A.3

Full title of the trial

Double-blind, randomized, placebo-controlled, phase II dose-finding study comparing different doses of norursodeoxycholic acid capsules with placebo in the treatment of primary sclerosing cholangitis

Ensayo clínico doble ciego, randomizado, controlado con placebo, fase II de búsqueda de dosis, comparando dosis diferentes de ácido nor-ursodeoxicólico en cápsulas versus placebo, en el tratamiento de colangitis esclerosante primaria

A.3.1

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

Double-blind (neither physician nor patient knows of the actual treatment which can be with or without active substance), randomized (patient will be allocated to a certain treatment group by chance), placebo-controlled (tested against capsules without active substance), phase II dose-finding study comparing different doses of norursodeoxycholic acid capsules with placebo (without active substance) in the treatment of PSC (inflammation of the bile ducts with scar formation)

EC doble ciego (ni médico ni el paciente saben el tratamiento real, que puede ser con o sin sust activa), randomizado (el paciente será asignado a un grupo de tratamiento al azar), controlado con placebo (Probado frente a cápsulas sin sust activa), fase II de búsqueda de dosis, comparando dosis diferentes de ácido nor-ursodeoxicólico en cápsulas vs placebo (sin sust activa), en el tratamiento de colangitis esclerosante primaria (inflamación de los conductos biliares con formación de cicatrices)

A.3.2

Name or abbreviated title of the trial where available

Norursodeoxycholic acid vs. Placebo in PSC

Ácido nor-ursodeoxicólico vs. Placebo en CEP (Colangitis Esclerosante Primaria)

A.4.1

Sponsor's protocol code number

NUC-3/PSC

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	Dr. Falk Pharma GmbH
B.1.3.4	Country	Germany
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	Dr. Falk Pharma GmbH
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	SERMES CRO
B.5.2	Functional name of contact point	Dña Lena Erbiti
B.5.3	Address:
B.5.3.1	Street Address	C/ Rufino González, 14. 2ª planta
B.5.3.2	Town/ city	Madrid
B.5.3.3	Post code	28037
B.5.3.4	Country	Spain
B.5.4	Telephone number	+3491375. 69 .30134
B.5.5	Fax number	+3491754.27.21
B.5.6	E-mail	lena_erbiti@sermes.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	norursodeoxycholic acid
D.3.4	Pharmaceutical form	Capsule
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	norursodeoxycholic acid
D.3.9.1	CAS number	99697-24-2
D.3.9.3	Other descriptive name	NorUDCA
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule
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

primary sclerosing cholangitis

colangitis esclerosante primaria

E.1.1.1

Medical condition in easily understood language

Orphan chronic liver disease with inflammation of the bile ducts.

Enfermedad Hepática crónica rara con inflamación de los conductos biliares

E.1.1.2

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10036732
E.1.2	Term	Primary sclerosing cholangitis
E.1.2	System Organ Class	10019805 - Hepatobiliary disorders

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

To evaluate the efficacy of three doses of norUDCA vs. placebo for the treatment of PSC;
To identify efficacious norUDCA dose(s) for the treatment of PSC for further evaluation in phase III

Evaluar la eficacia de tres dosis de norUDCA versus placebo para el tratamiento de la CEP
Identificar la dosis eficaz de norUDCA para el tratamiento de la CEP para su posterior evaluación en la Fase III

E.2.2

Secondary objectives of the trial

To study safety and tolerability (adverse events, laboratory parameters) of norUDCA;

To assess quality of life

Estudiar la seguridad y tolerabilidad (acontecimientos adversos, parámetros de laboratorio) de norUDCA
Evaluar la calidad de vida.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Signed informed consent,
2. Male or female patients ? 18 and < 80 years,
4. Alkaline Phosphatase ? 1.5 x ULN at baseline,
6. Women of child-bearing potential have to apply during the entire
duration of the study a highly effective method of birth control, which is
defined as one which results in a low failure rate (i.e., less than 1% per
year) when used constantly and correctly such as implants, injectables,
combined oral contraceptive method, or some IUDs. Women of nonchildbearing potential may be included if surgically sterile or postmenopausal for at least 2 years. The investigator is responsible for
determining whether the subject has this adequate birth control for
study participation.

1. Consentimiento informado firmado
2. Pacientes varones o mujeres de 18 años o mayores, y menores de 80 años
4. Fosfatasa alcalina ? 1,5 x LSN al inicio
6. Las mujeres en edad fértil deben emplear un método anticonceptivo altamente eficaz en todo momento durante el estudio, el cual por definición será aquel que presente una baja tasa de fallos (es decir, menos del 1% por año) al utilizarse de forma constante y correcta, como los implantes, inyectables, anticonceptivos orales combinados, o algunos dispositivos intrauterinos. Las mujeres que no estén en edad fértil pueden incluirse si se les ha practicado una esterilización quirúrgica, o han pasado por lo menos 2 años después de la menopausia. El investigador es responsable de determinar si el sujeto está empleando el anticonceptivo adecuado para la participación en el estudio.

E.4

Principal exclusion criteria

1. History or presence of other concomitant liver diseases including:
? Positive hepatitis B or C serology (Hbs Ag+, anti-HBc+, anti-HCV;
Note: Patients who present with anti-HBc+ only, may be included if they
are HBV-DNA negative)
? Primary Biliary Cirrhosis, (AMA-positive)
? Wilson's Disease
? Haemochromatosis
? Autoimmune Hepatitis
? Chronic alcoholic consumption (daily consumption >30g/d)
? Biopsy proven NASH
? Cholangiocarcinoma,
2. Treatment with any of the following drugs within the last 3 months
prior to baseline: any glucocorticosteroids (including budesonide),
azathioprine or other immunosuppressive drugs (e.g. cyclophosphamide,
cyclosporine, methotrexate, tacrolimus, 6-mercaptopurine),
chlorambucil, pentoxyfylline, penicillamine, pirfenidone, fibrates,
biologics (e.g., anti-tumor necrosis factor-alpha therapy), or rifampicin,
5. Child B/C liver cirrhosis,
12. Total bilirubin > 3.0 mg/dl (> 50 ?mol/L), at screening or baseline,
13. Rise in total bilirubin by at least 50% within the last 6 months prior
to baseline,
14. Albumin < 36 g/L, at screening or baseline,
16. Any relevant systemic disease (e.g., AIDS),
17. Abnormal renal function (Cystatin C > ULN) at screening and/or at
baseline visit,
18. TSH > ULN at screening,
20. Any active malignant disease,
21. Known intolerance/hypersensitivity to study drug, or drugs of
similar chemical structure or pharmacological profile

1. Historial o presencia de otras enfermedades hepáticas concomitantes, incluyendo:
? Serología positiva para la Hepatitis B o C (HBsAg +, anti-HBc +,
anti-HCV; Nota: Los pacientes que son anti-HBc + solamente,
pueden ser incluidos si son HBV-DNA negativos)
? Cirrosis biliar primaria (AMA-positivos)
? Enfermedad de Wilson
? Hemocromatosis
? Hepatitis Autoinmune
? Consumo crónico de alcohol (consumo diario de más de 30 g/día)
? Biopsia probada de NASH
? Colangiocarcinoma,
2.Tratamiento con cualquiera de los siguientes medicamentos dentro de los últimos 3 meses antes del inicio: cualquier glucocorticosteroide (incluyendo budesonida), azatioprina u otros medicamentos inmunosupresores (por ejemplo, ciclofosfamida, ciclosporina, metotrexato, tacrólimus, 6-mercaptopurina), clorambucil, pentoxifilina, penicilamina, pirfenidona, fibratos, agentes biológicos (por ejemplo, terapia con anti-factor de necrosis tumoral (TNF) alfa), o rifampicina
5. Cirrosis hepática infantil por virus B/C
12. Bilirrubina total > 3,0 mg/dl (> 50 µmol/L), en la selección o inicio,
13. Aumento de la bilirrubina total de al menos un 50% en los últimos 6 meses anteriores al inicio
14. Albúmina < 36 g/L, en la selección o inicio
16. Cualquier enfermedad sistémica importante (por ejemplo, SIDA)
17. Función renal anormal (Cistatina C> LSN) en la selección y/o al inicio
18. TSH> LSN en la selección
20. Cualquier enfermedad maligna activa
21. Intolerancia/hipersensibilidad conocida al medicamento en estudio, o a los medicamentos de estructura química o perfil farmacológico similar

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint is the change in serum alkaline phosphatase.

La variable principal es el cambio en la fosfatasa alcalina del suero

E.5.1.1

Timepoint(s) of evaluation of this end point

At the EOT visit.

En la Visita de Final de Tratamiento

E.5.2

Secondary end point(s)

Secondary efficacy endpoints are:

· s-ALP at each study visit (screening to follow-up)

· ?-GT, AST, ALT and serum bilirubin levels at each study visit (screening to follow-up)

· Course of pruritus (measured by VAS): absolute change in the pruritus score from baseline to EOT, and from EOT to the follow-up visit

Las variables secundaria son:
S-ALP en cada visita de estudio (Selección hasta seguimiento)

· ?-GT, AST, ALT y los niveles séricos de bilirrubina en cada visita de estudio (selección hasta seguimiento)

· Curso de prurito (medido por EVA): el cambio absoluto en la puntuación de prurito desde el inicio hasta el fin de tratamiento, y de fin de tratamiento a la visita de seguimiento.

E.5.2.1

Timepoint(s) of evaluation of this end point

Timepoints of evaluation are included in the description of endpoints in E.5.2.

Los tiempos de evaluación están incluidos en la descripción de las variables de evaluación en la sección E.5.2

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

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

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

Yes

E.8.2.3.1

Comparator description

Diferentes dosis de medicamento

Different dosages of IMP

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the 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

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

Yes

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

last visit of the last subject

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

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:

120

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

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

160

F.4.2.2

In the whole clinical trial

160

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)

Planned Treatment during Follow-up and after Study End
In cases, where a patient still shows clinical symptoms at EOT/withdrawal visit, the patient may receive symptomatic treatment in the choice of the investigator during the follow-up phase. For all patients, treatment after study end (after V9 [follow-up visit]) is left to investigator?s discretion.

Tratamiento planeado durante el seguimiento y después del fin del estudio.
En los casos en los que el paciente al fin de estudio/ abandono, todavía muestra sintomas clínicos, el paciente puede recibir tratamiento sintomatico a elección del investigador durante la fase de seguimiento. Para todos los pacientes, después del fin del estudio ( después del la Visita 9 [visita de seguimiento]) el tratamiento se deja a criterio del Investigador

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

2012-11-12

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-09-07

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

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials