Clinical Trials Register

Summary
EudraCT Number:	2013-000107-17
Sponsor's Protocol Code Number:	EAT2TREAT
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:	2013-04-05
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

2013-000107-17

A.3

Full title of the trial

Pharmacological therapy of episodic ataxia type 2: a placebo-controlled comparison of the efficacy of 4-aminopyridine sustained-release (Fampyra TM) and acetazolamide (Acemit TM)

Pharmakologische Therapie der Episodischen Ataxie Typ 2: Placebokontrollierter Vergleich der Wirksamkeit von retardiertem 4-Aminopyridin (Fampyra®) und Acetazolamid (Acemit®)

A.3.1

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

Comparsion of the therapy with Fampyra and Acemit in patients with episodic ataxia type 2

A.3.2

Name or abbreviated title of the trial where available

4-aminopyridine sustained-release (Fampyra TM) and acetazolamide (Acemit TM) in patients with EA2

4-Aminopyridin-R (Fampyra®) und Acetazolamid (Acemit®) bei Episodischer Ataxie Typ 2

A.4.1

Sponsor's protocol code number

EAT2TREAT

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 the University of Munich, Grosshadern
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	Bundesministerium für Bildung und Forschung (BMBF)
B.4.2	Country	Germany
B.4.1	Name of organisation providing support	Biogen Idec International GmbH
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Hospital of the University of Munich
B.5.2	Functional name of contact point	DSGZ
B.5.3	Address:
B.5.3.1	Street Address	Marchioninistr. 15
B.5.3.2	Town/ city	Munich
B.5.3.3	Post code	81377
B.5.3.4	Country	Germany
B.5.4	Telephone number	00498970956987
B.5.5	Fax number	00498970958795

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	Fampyra TM
D.2.1.1.2	Name of the Marketing Authorisation holder	Biogen Idec Ltd.
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	Prolonged-release 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	FAMPRIDINE
D.3.9.1	CAS number	504-24-5
D.3.9.4	EV Substance Code	SUB07505MIG
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	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	Acemit TM
D.2.1.1.2	Name of the Marketing Authorisation holder	medphano Arzneimittel GmbH
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	ACETAZOLAMIDE
D.3.9.1	CAS number	59-66-5
D.3.9.4	EV Substance Code	SUB05219MIG
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	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
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

Familial episodic ataxia (EA) represents a genetically and phenotypically diverse group of rare autosomal dominant hereditary disorders characterized by episodes of imbalance and incoordination that are variably associated with interictal neurological signs and typically triggered by physical exertion and emotional stress. Episodic ataxia type 2 (EA2) with associated interictal nystagmus and other ocular motor abnormalities is the most common and the best characterized of all EA syndromes.

E.1.1.1

Medical condition in easily understood language

Episodic ataxia type 2 is a hereditary disorder characterized by attacks with imbalance, vertigo and abnormal eye movements lasting up to days.

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

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	10067447
E.1.2	Term	Episodic ataxia
E.1.2	System Organ Class	100000004850

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

Primary objective:
1) Analysis of the efficacy of the two active IMPs (4-aminopyridine sustained-released, acetazolamide) regarding reduction of the frequency of attacks compared to placebo
2) Quantifying the differences between the two IMPs (4-aminopyridine sustained-released, acetazolamide) regarding reduction of the frequency of attacks

E.2.2

Secondary objectives of the trial

Secondary objective:
1) Quantitative description and comparison of the median duration and intensity of attacks under 4-aminopyridine sustained-released vs. acetazolamide vs. placebo measured within the last 30 days of a 12-week treatment phase
2) Quantitative description and comparison of the gait variability at maximum walking speed at the end of a 12-week treatment phase under 4-aminopyridine sustained-released vs. acetazolamide vs. placebo
3) Analysis of the absolute change of the SARA scores and quality of life scores in the 3 treatment groups compared to the baseline score of each phase
4) Comparison of the frequency of (S)AEs under 4-aminopyridine sustained-released vs. acetazolamide vs. placebo

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Subjects will only be randomized in the study if they meet all of the following criteria:

1. Written informed consent of the subject
2. Patients (male or female) aged 18 years or older
3. Genetically confirmed episodic ataxia type 2 or a familial history of ataxia with clinical picture of episodic ataxia type 2 starting in childhood
4. Subjects, with the ability to follow study instructions and likely to attend and complete all required visits (Compliance)

E.4

Principal exclusion criteria

Subjects will not be randomized in the study if any of the following criteria applies:

1. Weight of 40 kg or less
2. Pregnancy or breast-feeding
3. Concurrend treatment with inhibitors of organic cation transporter 2 (OCT2), e.g. cimetidine
4. Known hypersensitivity to aminopyridine and/or acetazolamide/sulfonamide
5. Cardiovascular diseases e.g. recent heart attack (within the last 3 months), cardiac arrhythmia (QTc interval > 500 ms, atrial fibrillation, AV block grade ≥ II), unstable angina pectoris, severe heart failure (NYHA class IV), severe arterial hypertension (grade III according to the guidelines of the German society of cardiology, 2008)
6. Recently occurred stroke (within the last 3 months)
7. Epileptic seizure currently or in the past
8. Asthma (severity ≥ grade III)
9. Obstructive lung disease (e.g. pulmonary emphysema)
10. Liver insufficiency defined as GOT/GPT/total bilirubin > 3 x upper range
(e.g. cirrhosis of the liver)
11. Milde or severe renal failure (Creatinine Clearance ≤ 80ml/min)
12. Addison's disease
13. Unadjusted thyroid dysfunction
14. Acute gastric and intestinal ulcer
15. Known hyperchloremic acidosis
16. Depressed sodium and/or potassium blood serum levels
17. Chronic noncongestive glaucoma
18. Hypercalcaemia
19. Articular gout
20. Known African anaemia
21. Diabetes mellitus type I/II
22. Other acute, serious illness of the subject
23. Subject is unable to understand the scope, significance and consequences of this clinical trial and is unable to comply with the study design
24. Previous participation in this clinical trial or participation in any clinical trial taking an investigational medicinal product within 30 days prior to written informed consent for this clinical trial

E.5 End points

E.5.1

Primary end point(s)

Primary endpoint:
number of attacks within the last 30 days of each 12-week treatment phase

E.5.1.1

Timepoint(s) of evaluation of this end point

12 weeks after treatment with IMP (for each treatment phase)

E.5.2

Secondary end point(s)

Secondary endpoint:
1) Median duration and intensity of the attacks within the last 30 days of each 12-week treatment
phase
2) Change (relative change, log scale) of the gait variability (CV) at maximum walking speed measured at the end of a 12-week treatment phase (Visit 3, 6 and 9) as well as 4 weeks after taking the last IMP (follow-up visit) compared to the beginning of a 12-week tratment phase (Visit 1, 4 and 7)
3) Absolute change of VDADL and EQ-5D-5L (quality of life scores) measured at the end of a 12-week treatment phase (Visit 3, 6 and 9) as well as 4 weeks after taking the last IMP (follow-up visit) compared to the beginning of a12-week treatment phase (Visit 1, 4 and 7)
4) Absolute change of SARA scores measured at the end of a 12-week treatment phase (Visit 3, 6 and 9) as well as 4 weeks after taking the last IMP (follow-up visit) compared to the beginning of the respective 12-week treatment phase (Visit 1, 4 and 7)

E.5.2.1

Timepoint(s) of evaluation of this end point

Regrading end point 1:
At the beginning and 12 weeks after treatment with IMP (for each treatment phase)
Regarding end point 2, 3 and 4:
At the beginning and 12 weeks after treatment with IMP (for each treatment phase) as well as 4 weeks after taking the last IMP (follow-up)

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)

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

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.1.3

Elderly (>=65 years)

Yes

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.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)

4 weeks after last administration of IMP, there will be a follow-up visit.
After the clinical trial, patients will have the opportunity to make regular appointments and to get medical advice in the german center of vertigo and balance disorders.

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

2013-05-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-05-15

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-10-06

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Orphan Designation Number:
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