Clinical Trials Register

Summary
EudraCT Number:	2011-004094-93
Sponsor's Protocol Code Number:	PAFCUTIII
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-01-27
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

Germany - BfArM

A.2

EudraCT number

2011-004094-93

A.3

Full title of the trial

Double-blind, three-way cross-over, placebo controlled study to assess the efficacy, safety and mechanisms of treatment with rupatadine 20 and 40mg in cold contact urticaria (CCU)

A.3.1

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

Efficacy of rupatadine in cold contact urticaria

A.3.2

Name or abbreviated title of the trial where available

PAFCUTIII

A.4.1

Sponsor's protocol code number

PAFCUTIII

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	Allergie-Centrum Charité
B.1.3.4	Country	Germany
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	J. Uriach Cia., S.A.
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	Charité-Universitätsmedizin Berlin
B.5.2	Functional name of contact point	Allergie-Centrum Charité
B.5.3	Address:
B.5.3.1	Street Address	Charitéplatz 1
B.5.3.2	Town/ city	Berlin
B.5.3.3	Post code	10117
B.5.3.4	Country	Germany
B.5.4	Telephone number	+4930518 043
B.5.5	Fax number	+4930518 972
B.5.6	E-mail	marcus.maurer@charite.de

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	Yes
D.2.1.1.1	Trade name	Rupafin
D.2.1.1.2	Name of the Marketing Authorisation holder	J. Uriach Cia., S.A.
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	Rupatadine
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	10
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	Yes
D.3.11.13.1	Other medicinal product type	Antihistamine

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

Cold contact urticaria

E.1.1.1

Medical condition in easily understood language

Cutaneous condition characterized by wheals, and occurs in rainy, windy weather, and after contact with cold objects

E.1.1.2

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

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	10009869
E.1.2	Term	Cold urticaria
E.1.2	System Organ Class	10040785 - Skin and subcutaneous tissue 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 assess the effects of rupatadine 20 mg and 40 mg on symptom
development during the induction of skin lesions in CCU patients
challenged with defined temperatures using Temptest® 3.0

E.2.2

Secondary objectives of the trial

To assess the effects of rupatadine on mast cell mediator release in blood during the induction of skin lesions in CCU patients challenged with cold water bath provocation with defined temperatures. Mediator measurements will include histamine and other mast cell-derived inflammation markers (e.g. PAF/LysoPAF, PGD2)
To assess the effect of rupatadine on mast cell activation in the skin of CCU patients
To assess the safety and tolerability of rupatadine

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Informed consent signed and dated.
• Reliable method of contraception for women of childbearing potential during the study and 3 months thereafter.
• Outpatients with CCU for more than 6 weeks confirmed by
positive response with wheal and itch on Temptest®.
• Age 18 and above years.
• No participation in other clinical trials 1 month before and after
participation in this study.

E.4

Principal exclusion criteria

• Subjects who are inmates of psychiatric wards, prisons, or other state institutions. Existing or planned placement in an institution after ruling according to § 40 passage 1, number 4 AMG (Arzneimittelgesetz).
• The presence of permanent severe diseases, especially those affecting the immune system, except urticaria and cold urticaria.
• The presence of permanent gastrointestinal condition which may
influence the oral therapy (chronic diarrhoea diseases, congenital
malformations or surgical mutilations of gastrointestinal tract).
• History or presence of epilepsy, significant neurological disorders,
cerebrovascular attacks or ischemia.
• History or presence of myocardial infarction or cardiac arrhythmia
which requires drug therapy.
• ECG alterations of repolarisation (QTc prolongations > 450ms).
• Blood pressure >180/100 mmHg and/or heart rate >100/min.
• Evidence of significant hepatic or renal disease (GOT and/or GPT 3 times above the upper reference value, serum creatinine 1.5 times above the upper reference value).
• History of hypersensitivity or allergic reaction to rupatadine or any other antihistamine compounds.
• Presence of active cancer which requires chemotherapy or radiation therapy.
• Presence of lactose and galactose intolerance or glucose-galactose malabsorption.
• Simultaneous chronic spontaneous or physical urticaria that could interfere CCU clinical assessment.
• Intake of antihistamines or antileukotrienes within 7 days before
beginning of the study.
• Intake of oral or depot corticosteroids within 14 days prior to
screening visit.
• Use of systemic immunosupressants/immunomodulators like
cyclosporine A, dapsone, methotrexate, mycophenolate, chloroquine, and comparable drugs within 28 days prior to screening visit.
• Use of ketoconazole, erythromycin or potential inhibitors of the
isoenzyme CYP3A4 of the cytochrome P450.
• Currently abusing drugs or alcohol.
• Unwilling or unable to comply with the protocol.
• Pregnancy or breast-feeding.

E.5 End points

E.5.1

Primary end point(s)

- Change in critical stimulation time thresholds (CSTT) and critical
temperature thresholds (CTT) after treatment with different dosages of rupatadine (20 mg and 40 mg) measured by Temptest® 3.0

E.5.1.1

Timepoint(s) of evaluation of this end point

Visit 2, Visit 3, Visit 4, Visit 5

E.5.2

Secondary end point(s)

- Change in mast cell mediator release, including histamine,
PAF/LysoPAF and PGD2 after treatment with rupatadine (20 and 40 mg) compared to placebo
- Change in mast cell activation (measured by intracutaneous codeine,histamine, PAF and saline injection)
- Safety and tolerability: This includes physical examination, routine safety laboratory assessments, clinical observation, vital signs and adverse event reporting

E.5.2.1

Timepoint(s) of evaluation of this end point

Visit 3, Visit 4, Visit 5

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

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

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

E.8.1.6

Cross over

Yes

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.8.2.4

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

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

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

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

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 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 2012-01-27.

Yes

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

F.4.2.2

In the whole clinical trial

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)

All patients will be offered a follow up visit at the out-patients clinic of the corresponding study place to receive best medical care after having participated in the study.

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2012-04-19

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-03-29

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2013-07-02

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