Clinical Trials Register

Summary
EudraCT Number:	2011-004697-28
Sponsor's Protocol Code Number:	523001.01.099
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-03-27
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

Czechia - SUKL

A.2

EudraCT number

2011-004697-28

A.3

Full title of the trial

Randomised, double-blind trial to compare the treatment effects of Ginkgo biloba extract EGb 761® and pentoxifylline in patients with sub-chronic and chronic tinnitus focussing on psycho-social problems

Randomizovaná, dvojitě zaslepená klinická studie ke srovnání léčebného účinku speciálního extraktu Ginkgo biloby – EGb 761®
a pentoxifyllinu u pacientů se subchronickým a chronickým tinnitem se zaměřením na psychosociální problémy

A.3.1

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

Clinical study to investigate the treatment effects of a Ginkgo biloba extract in comparison to the standard medication Pentoxifylline in patients with chronic or subchronic tinnitus (ear noises)

A.3.2

Name or abbreviated title of the trial where available

Tinnitus Czech Republic

A.4.1

Sponsor's protocol code number

523001.01.099

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. W. Schwabe GmbH & Co. KG
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. W. Schwabe GmbH & Co. KG
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	Dr. W. Schwabe GmbH & Co. KG
B.5.2	Functional name of contact point	Clinical Research
B.5.3	Address:
B.5.3.1	Street Address	Willmar-Schwabe-Str. 4
B.5.3.2	Town/ city	Karlsruhe
B.5.3.3	Post code	76227
B.5.3.4	Country	Germany
B.5.4	Telephone number	+497214005508
B.5.5	Fax number	+4972140058508
B.5.6	E-mail	susanne.kraft@schwabe.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	Tebonin® intens 120 mg
D.2.1.1.2	Name of the Marketing Authorisation holder	Dr. W. Schwabe GmbH & Co. KG
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.3.1	Product name	Ginkgo biloba special extract EGb 761®
D.3.2	Product code	EGb 761®
D.3.4	Pharmaceutical form	Film-coated 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	NA
D.3.9.1	CAS number	90045-36-6
D.3.9.2	Current sponsor code	EGb 761
D.3.9.3	Other descriptive name	STANDARDISED GINKGO BILOBA EXTRACT
D.3.9.4	EV Substance Code	SUB16390MIG
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	120
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.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
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	Pentoxifylline 600 mg retard
D.2.1.1.2	Name of the Marketing Authorisation holder	ratiopharm GmbH, Ulm
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.3.1	Product name	Pentoxifylline 600 mg retard
D.3.4	Pharmaceutical form	Film coated gastro-resistant 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	PENTOXIFYLLINE
D.3.9.1	CAS number	06/05/6493
D.3.9.2	Current sponsor code	Pentoxifylline 600 mg prolonged release tablets
D.3.9.3	Other descriptive name	NA
D.3.9.4	EV Substance Code	SUB09705MIG
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	600
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	Film coated gastro-resistant 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

chronic or sub-chronic tinnitus

subchronickým a chronickým tinnitem

E.1.1.1

Medical condition in easily understood language

chronic ear noises

E.1.1.2

Therapeutic area

Diseases [C] - Ear, nose and throat diseases [C09]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	PT
E.1.2	Classification code	10043882
E.1.2	Term	Tinnitus
E.1.2	System Organ Class	10013993 - Ear and labyrinth 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 compare the treatment effects of Ginkgo biloba extract EGb 761® and pentoxifylline in patients with sub-chronic or chronic tinnitus focussing on psycho-social problems

Porovnání léčebného efektu speciálního extraktu Ginkgo biloby (EGb 761®) a pentoxifilinu u pacientů s chronickým a subchronickým tinnitem se zaměřením na psychosociální problém

E.2.2

Secondary objectives of the trial

To underline the safety and tolerability of EGb 761®

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Outpatients aged ≥ 40 with unilateral or bilateral, sub-chronic or chronic tinnitus (duration > 3 months)
2. Tinnitus is the main complaint, other cochlear or vestibular symptoms may be present but less annoying
3. Tinnitus is maskable with noise masking.
4. Annoyance rated at least 3 on the 11-Point Box Scale of tinnitus annoyance at screening and baseline.
5. Abridged Tinnitus Questionnaire (Mini-TQ) total score rated ≥ 5 at baseline.
6. Written informed consent to participate in the clinical trial, to randomized treatment and to data recording in accordance with applicable laws

1. Ambulantní pacienti ve věku ≥ 40 s jednostranným a/nebo oboustranným tinnitem (doba trvání > 3 měsíce)
2. Tinnitus je hlavní problém, ostatní kochleární příznaky mohou být přítomny, ale jsou méně obtěžující
3. Tinnitus je maskovatelný šumem
4. Obtížnost tinnitu je na 11 bodové škále vyjadřující jeho obtížnost označena nejméně čísle „3“
5. Celkové skore zkrácené verze dotazníku (Mini - TQ) je udáno u základní čáry hodnotou ≥ 5
6. Písemný souhlas odpovídá platným zákonům klinických zkoušek, randomizaci a též zanášení dat.

E.4

Principal exclusion criteria

1. Participation in another experimental drug trial at the same time or within the past 4 weeks before enrolment
2. Currently taking any treatments for tinnitus
3. Acute or chronic otitis media or vestibular neuritis
4. Drug-induced tinnitus
5. Significant cardiac or circulatory disorder
• severe (Canadian Cardiovascular Society stage IV) or unstable angina pectoris
• decompensated congestive heart failure (NYHA stage IV)
• significant coronary sclerosis or history of myocardial infarction
• uncontrolled hypertension with systolic blood pressure above 180 mmHg and/or diastolic blood pressure above 115 mmHg
• hypotension with systolic blood pressure below 110 mmHg and/or diastolic blood pressure below 70 mmHg
• clinically significant cardiac arrhythmias (Lown classes IVb and V, bifascicular bundle branch block)
6. Any acute or recent event of bleeding or history of bleeding (in particular intracerebral or retinal bleeding or bleeding from any organ), haemorrhagic diathesis, intake of anticoagulants
7. Any surgery within the last 3 months before the start of randomised treatment
8. Severe renal or hepatic dysfunction (serum creatinine or serum ASAT, ALAT or gamma-GT above 3 times the upper limit of the reference range)
9. Insulin-dependent or drug-dependent diabetes mellitus
10. Systemic lupus erythemathosus (SLE)
11. Intake of drugs not permitted during participation in the study, in particular anticoagulants, antidiabetic drugs, insulin, theophylline, cimetidine, psychoactive drugs, other perfusion-enhancing drugs, cognition enhancing drugs or anti-cholinergic drugs (for details see section 6 of protocol)
12. Active malignant disease (exception: prostate cancer which does not require other than hormone treatment within the next 6 months)
13. Known hypersensitivity to Ginkgo biloba extract, pentoxifylline or other methylxanthine substances, or to excipients contained in the tablets
14. Active peptic ulcer disease or any gastrointestinal disease with potential impairment of the absorption of orally applied drugs (e.g. Billroth I/II, Crohn's disease, ulcerative colitis, any kind of enterectomy)
15. Female patients of childbearing potential without safe contraception (hormonal contraception, oral or transdermal, is considered sufficiently safe; child-bearing potential can be denied in case of postmenopausal state for at least 2 years, hysterectomy, bilateral tubal ligation or bilateral oophorectomy)

1. Současná či v období posledních 4 týdnů účast na jiném experimentálním lékovém výzkumu
2. Současné používání jiných léků proti tinnitus
3. Akutní či chronická otitis nebo neuronitis vestibularis
4. Medikamentózně indukovaný tinnitus
5. Průkazná srdeční a/nebo oběhová nedostatečnost
• Těžká či nestabilní angina pectoris (stadium IV dle Kanadské kardiovaskulární společnosti)
• Dekompenzovaná kongestivní srdeční nedostatečnost (NYHA Stadium IV)
• Signifikantní koronární skleróza s infarktem myokardu v anamnéze
• Dekompenzovaný krevní tlak se systolickými hodnotami přes 180 mm a/nebo diastolickým tlakem přes 115 mmHg
• Nízký krevní tlak se systolickým tlakem pod 110 mmHg a/nebo diastolickým tlakem pod 70 mmHg
• Klinicky signifikantní porucha srdečního rytmu (Lowm klasifikace IVb a V, bifascikulární Schenkelův blok)
6. Každé akutní krvácení či stav po něm v anamneze (zejména intracerebrální nebo retinální či každá forma orgánového krvácení) hemoragické diatezy, užívání antikoagulancií
7. Každý chirurgický zákrok v období posledních 3 měsíců před počátkem randomizace
8. Těžké ledvinové či jaterní poruchy (sérový kreatinin a/nebo sérum-ASAT, ALAT nebo Gamma - GT vice jak třikrát zvýšené nežli normální hodnoty)
9. Diabetes mellitus inzulin dependentní či závislý na diabetické medikaci
10. Systémový Lupus erytematodes (SLE)
11. Používání medikace, která není během klinických zkoušek povolena, zejména antikoagulancia, antidiabetika, insulin, theophylin, cimetidine, psychoaktivní preparáty, léky zvyšující kognitivní funkce anebo anticholinergní působící preparáty (detaily viz. kap.6)
12. Aktivní maligní onemocnění (výjimka: karcinom prostaty, který během posledních 6 měsíců je léčen pouze hormonálně)
13. Přecitlivělost na extrakty Ginkgo biloba, pentoxifyllin, jiný metyl xantinové substance anebo proti jednotlivým komponentám tablet
14. Aktivní žaludeční či dvanáctníkový vřed nebo gastrointestinální onemocnění, které může potenciálně ovlivňovat absorpci perorálně podávaných medikamentů (např.Billroth II/II, Morbus Crohn, ulcerózní colitis, jakákoliv resekce střevní)
15. Pacientky ve fertilním věku bez bezpečné antikoncepce ( orání či trans dermální hormonální antikoncepce je považována za bezpečnou, za nefertilní stav lze považovat menopauzu trvající nejméně dva roky, stav po hysterektomii, bilaterální ligaturu vejcovodů, či adnexetomii)

E.5 End points

E.5.1

Primary end point(s)

the changes of the 11-point box scales for tinnitus loudness and annoyance and the changes of the Mini-TQ total score during the 12 weeks of treatment;

E.5.1.1

Timepoint(s) of evaluation of this end point

comparison after 12 weeks of treatment

E.5.2

Secondary end point(s)

none

E.5.2.1

Timepoint(s) of evaluation of this end point

none

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

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

dvojitě zaslepená

double dummy technique

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

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

December 2013 (Last patient out)

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:

150

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

200

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)

none

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

2012-06-01

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-04-04

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2014-04-09

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