Clinical Trials Register

Summary
EudraCT Number:	2012-001039-30
Sponsor's Protocol Code Number:	BetHäm2012
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2012-11-16
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

Germany - BfArM

A.2

EudraCT number

2012-001039-30

A.3

Full title of the trial

BetHäm2012: A monocenter, single-blind, randomized, 2-armed, placebo-controlled, cross-over study to investigate coagulation markers in patients with haemophilia A after administration of Betain

BetHäm2012: Monozentrische, einfach verblindete, randomisierte, 2- armige, placebokontrollierte Cross-over Studie zur Untersuchung der Gerinnung bei Patienten mit Hämophilie A unter Einnahme von Betain

A.3.1

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

Betain and haemophilia A

Betain und Hämophilie A

A.4.1

Sponsor's protocol code number

BetHäm2012

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	Hospital of Goethe-Universitiy
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	center of hemophilia, Hospital of goethe-university
B.4.2	Country	Germany
B.4.1	Name of organisation providing support	Ethic Committee, Hospital Goethe-University
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	Hospital of Goethe-University
B.5.2	Functional name of contact point	Dr. med. W. Miesbach, Med. Klinik I
B.5.3	Address:
B.5.3.1	Street Address	Theodor-Stern-Kai 7
B.5.3.2	Town/ city	Frankfurt am Main
B.5.3.3	Post code	60590
B.5.3.4	Country	Germany
B.5.4	Telephone number	00496963017788
B.5.5	Fax number	00496963016738
B.5.6	E-mail	wolfgang.miesbach@kgu.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	Cystadane
D.2.1.1.2	Name of the Marketing Authorisation holder	Orphan Europe SARL
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Betaine anhydrous
D.3.4	Pharmaceutical form	Powder for oral solution
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	Betaine anhydrous
D.3.9.1	CAS number	107-43-7
D.3.9.3	Other descriptive name	BETAINE
D.3.9.4	EV Substance Code	SUB13055MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	3.0
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	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	Yes
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	Powder for oral solution
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

In this study patients with haemophilia A are included.

Bei den Studienpatienten handelt es sich um Patienten mit Hämophilie A.

E.1.1.1

Medical condition in easily understood language

Hemophilia A is an inherited bleeding disorder caused by a deficiency of coagulation factor VIII with an occurrence of spontaneous bleeding, especially in the joints.

Bei der Hämophilie A handelt es sich um eine angeborene Blutungsneigung, die auf einem Mangel des Gerinnungsfaktor VIII beruht. Hierdurch können spontane Blutungen insbes. in die gr. Gelenke auftreten

E.1.1.2

Therapeutic area

Diseases [C] - Blood and lymphatic diseases [C15]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	18.1
E.1.2	Level	LLT
E.1.2	Classification code	10018937
E.1.2	Term	Haemophilia A
E.1.2	System Organ Class	100000004850

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Primary endpoint is FVIII activity

Primärer Endpunkt ist die FVIII Aktivität

E.2.2

Secondary objectives of the trial

Secondary endpoints are
aPTT
VWF-Ag
VWF-Akt
FIX:C
FVIII inhibitor
Methionin level
CAT
Absence of adverse events

Sekundäre Endpunkte sind:
• aPTT
• VWF-Ag
• VWF:Akt
• FIX:C
• FVIII-Hemmkörper
• Methionin-Spiegel
• Thrombingeneration, CAT
• Verträglichkeit, d.h. Abwesenheit von Adverse Events

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Male patients with moderate or mild haemophilia A at the age of 18 – 70 years without an inhibitor against FVIII
Written informed consent
No need for regularly prophylactic treatment with FVIII product
Complaince of the patient

• Männliche Patienten mit Hämophilie A im Alter von 18 - 70 Jahren ohne Nachweis eines Antikörpers gegen den Gerinnungsfaktor VIII (Hemmkörpers) mit mittelschwerer (FVIII-Gehalt von 1 – 5 %) oder milder Hämophilie A (Faktor VIII über 5 %).
• Informed consent unterschrieben
• Keine Notwendigkeit zur regelmäßigen, prophylaktischen Therapie mit einem Faktor VIII-Präparat.
• Bei den Patienten bekanntermaßen vorliegende Compliance

E.4

Principal exclusion criteria

Patients without haemophilia A or patients with haemophilia A at the age of under 18 years or older than 70 years
Known adverse reactions against Betain substrate or components of Betain or placebo
Known history of cerebral oedema
Legal incompetence
Participating in other clinical studies
Comedication which would interfere to administration of Betain

• Patienten ohne Hämophilie A oder Patienten mit Hämophilie A in einem Alter von unter 18 Jahren bzw. über 70 Jahren.
• Bekannte Betain-Unverträglichkeit oder Überempfindlichkeit oder Unverträglichkeit gegen andere Bestandteile des Präparats oder Zusammensetzung des Placebos
• Vorgeschichte eines Hirnödems
• Nicht geschäftsfähige Patienten
• Teilnahme an einer anderen Studie
• Jegliche nötige Begleitmedikation, die laut Fachinformation einer Einnahme von Betain entgegensteht.

E.5 End points

E.5.1

Primary end point(s)

Primary endpoint is FVIII activity

Primärer Endpunkt ist die FVIII Aktivität

E.5.1.1

Timepoint(s) of evaluation of this end point

Screening
day start of IMP-intake (U1)
day 1 after start of IMP-intake (U2)
day 3 after start of IMP-intake (U3)
day 7 after start of IMP-intake (U4)
day 14 after start of IMP-intake (U5)
day 1 after start wash-out (U6)
day 3 after start wash-out (U7)
day 7 after start wash-out (U8)
day start IMP2-intake (U9)
day 1 after start of IMP2-intake (U10)
day 3 after start of IMP2-intake (U11)
day 7 after start of IMP2-intake (U12)
day 14 after start of IMP2-intake (U13)
day 1 after end of IMP-intake (U14)
day 3 after end of IMP-intake (U15)

Screening
Tag Start IMP-Einnahme (U1)
Tag 1 nach Start IMP-Einnahme (U2)
Tag 3 nach Start IMP-Einnahme (U3)
Tag 7 nach Start IMP-Einnahme (U4)
Tag 14 nach Start IMP-Einnahme (U5)
Tag 1 nach Start Auswaschphase (U6)
Tag 3 nach Start Auswaschphase (U7)
Tag 7 nach Start Auswaschphase (U8)
Tag Start IMP2-Einnahme (U9)
Tag 1 nach Start IMP2-Einnahme (U10)
Tag 3 nach Start IMP2-Einnahme (U11)
Tag 7 nach Start IMP2-Einnahme (U12)
Tag 14 nach Start IMP2-Einnahme (U13)
Tag 1 nach Ende IMP-Einnahme (U14)
Tag 3 nach Ende IMP-Einnahme (U15)

E.5.2

Secondary end point(s)

Secondary endpoints are
aPTT
VWF-Ag
VWF-Akt
FIX:C
FVIII inhibitor
Methionin level
CAT
Absence of adverse events

Sekundäre Endpunkte sind:
• aPTT
• VWF-Ag
• VWF:Akt
• FIX:C
• FVIII-Hemmkörper
• Methionin-Spiegel
• Thrombingeneration, CAT
• Verträglichkeit, d.h. Abwesenheit von Adverse Events

E.5.2.1

Timepoint(s) of evaluation of this end point

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

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)

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

clinical trial with an authorized active substance in another indication

klinische Studie eines bereits zugelassenen Wirkstoffs in einer anderen Indikation

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

Yes

E.8.1.4

Double blind

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

Yes

E.8.4

The trial involves multiple sites in the 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

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)

The subjects are patients in the study center; so also after the poststudy-visit the patients will come to the center.

Da die Studienteilnehmer bereits Patienten im Studienzentrum sind, werden diese auch nach der post-study-visit weiter im Zentrum vorstellig werden.

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

2013-03-06

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-03-05

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

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