Clinical Trials Register

Summary
EudraCT Number:	2012-005003-40
Sponsor's Protocol Code Number:	BTS651/12
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:	2012-11-23
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

Germany - BfArM

A.2

EudraCT number

2012-005003-40

A.3

Full title of the trial

Effects of Wobenzym® plus in healthy, sportive people after eccentric exercise - a randomized, two-stage, double-blind, placebo-controlled cross-over trial

Wirkung von Wobenzym® plus bei gesunden Sportlern nach exzentrischer Belastung – eine randomisierte, zweiphasige, doppel-blinde, placebo-kontrollierte cross-over Studie.

A.3.1

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

Effects of Wobenzym® plus in healthy, sportive people after muscular load - a randomized, two-stage, double-blind, placebo-controlled cross-over trial

Wirkung von Wobenzym® plus bei gesunden Sportlern nach muskulärer Belastung – eine randomisierte, zweiphasige, doppel-blinde, placebo-kontrollierte cross-over Studie.

A.4.1

Sponsor's protocol code number

BTS651/12

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	MUCOS Pharma 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	MUCOS Pharma 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	BioTeSys GmbH
B.5.2	Functional name of contact point	Clinical Trial Information
B.5.3	Address:
B.5.3.1	Street Address	Schelztorstraße 54-56
B.5.3.2	Town/ city	Esslingen
B.5.3.3	Post code	73728
B.5.3.4	Country	Germany
B.5.4	Telephone number	004971131057147
B.5.5	Fax number	004971131057151
B.5.6	E-mail	c.reule@biotesys.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	Wobenzym® plus
D.2.1.1.2	Name of the Marketing Authorisation holder	MUCOS Pharma 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	Wobenzym® plus
D.3.4	Pharmaceutical form	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.3.9.1	CAS number	9001-00-7
D.3.9.3	Other descriptive name	BROMELAINS
D.3.9.4	EV Substance Code	SUB13124MIG
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	90
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	9002 –07-7
D.3.9.3	Other descriptive name	TRYPSIN
D.3.9.4	EV Substance Code	SUB12616MIG
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	48
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	RUTOSIDE
D.3.9.1	CAS number	153-18-4
D.3.9.4	EV Substance Code	SUB10407MIG
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	100
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	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	Wobenzym® plus is an orally applied enzyme-rutoside combination product (bromelain, trypsin, rutoside)

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	Coated 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

"Healthy volunteers"
Influence of the product on exercise induced muscle damage, noticable in temporal strength loss and muscle soreness. The indication is as defined in the SmPC: Swelling and inflammtion caused by injuries/ Trauma. in this case injury of the muscle.

E.1.1.1

Medical condition in easily understood language

Healthy volunteers
Influence of the product on exercise induced temporal strength loss and muscle soreness. The indication is as defined in the SmPC: Swelling and inflammtion caused by injuries

E.1.1.2

Therapeutic area

Not possible to specify

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The aim of the current study is to investigate the therapeutic effect of Wobenzym® plus, an anti-inflammatory drug containing proteolytic enzymes, on exercise induced muscle damage (eiMD) and recovery time in male amateur sportsmen with medium proficiency level compared to placebo.
As primary objective, the reduction of maximal isokinetic strength after exercise in the stronger leg and subjective pain after exercise are assumed to be the most promising parameters. Therefore these parameters are combined in a multidimensional approach summarizing different parameters and points of time to strengthen the power.
The period after the stress test will be separately calculated for the acute phase (3h, 6h) and the recovery phase (24h-48h).

E.2.2

Secondary objectives of the trial

The 0h (immideately post) 72h (long term) will be analyzed exploratory. Secondary objectives are the difference in delayed onset muscle soreness (DOMS) by using a visual analogue scale and the retrospective pain scale (Likert Scale). In addition, the difference of sensitivity against pressure will be analysed before and after exercise. Different biomarkers giving information about inflammatory response, metabolic fatigue, immunological response and anti-oxidative potential will be assessed at different points of time, too.
Additionally, a global assessment of the effects of the study preparation at the end will be evaluated as secondary objective.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

•Subject is able and willing to sign the Informed Consent Form prior to screening evaluations
•Subject is in good physical and mental health as established by medical history, physical examination, vital signs, results of biochemistry, haematology
•Not anticipating any planned changes in lifestyle regarding activity and nutrition for the duration of the study
•Non smoker
•Men with strength training experience
•Age: 35-45 years
• BMI ≥20 kg/m2 and ≤ 32 kg/m2
• medium concentric strength ability (180-300 Nm)

E.4

Principal exclusion criteria

•Relevant history or presence of any medical disorder, potentially interfering with this trial (e.g. volunteers having experienced any cardiovascular events such as infarction, angina, surgical endocoronary intervention, stroke or volunteers suffering from diabetes as well as acute or chronic injury of the musculo-skeletal system, e.g. cruciate ligament rupture.
•No intake of anti-inflammatory medication/ food supplements or intake of medications that directly affect parameters of muscle function or performance within 4 weeks prior to visit 1 or during the trial
•Subjects not willing to abstain from intake of analgesic medication 24 hours prior to and during visit 1 and 2.
•For this trial clinically relevant abnormal laboratory, vital signs or physical findings at screening
•Known hypersensitivity to the study preparation or to single ingredients
•Drug, alcohol and medication abuse
•Known HIV-infection
•Known acute or chronic hepatitis B and C infection
•Participation in another clinical trial within the last 4 weeks and concurrent participation in another clinical trial

E.5 End points

E.5.1

Primary end point(s)

The ensemble of appropriate single efficacy criteria shall be tested by a multivariate, directional test approach, reflecting the “global status after eccentric exercise” at different points in time:

Recovery Phase:

•Reduction of maximal isokinetic strength after stress test at 24h, 48h
•Movement induced pain (VAS after performing a deep lunge of 90° for both legs) at 24h and 48h
•Pressure induced pain: Nm/cm2 measured with algometry (in the middle of the muscle belly, m. rectus femoris) at 24h, 48h.

Acute Phase:

•Reduction of maximal isokinetic strength after stress test at 3h, 6h
•Movement induced pain (VAS after performing a deep lunge of 90° for both legs) at 3h, 6h
•Pressure induced pain: Nm/cm2 measured with algometry (in the middle of the muscle belly, m. rectus femoris) at 3h, 6h

For all primary analyses the leg with maximum initial strength at baseline will remain primary leg for all analyses.

E.5.1.1

Timepoint(s) of evaluation of this end point

Immediately before eccentric exercise (day 4 and 32) - pre
Immediately after eccentric exercise (day 4 and 32) - 0h
3 hours after eccentric exercise (day 4 and 32) - 3h
6 hours after eccentric exercise (day 4 and 32) - 6h
24 hours after eccentric exercise (day 5 and 33) - 24h
48 hours after eccentric exercise (day 6 and 34) - 48h
72 hours after eccentric exercise (day 7 and 35) - 72h

E.5.2

Secondary end point(s)

•Primary leg (maximum initial strength at baseline): primary efficacy criteria at 0h (immediately post exercise) and 72h (longterm effect)
•Retrospective pain: Likert scale at 24h, 48h, 72h
•Inflammatory response
oIL-6 (pre, 0h, 3h, 24h post)
oProstaglandin E metabolite derived from Cyclooxygenase 2
(pre, 0h, 3h, 6h, 24h post)
•Metabolic marker
oCreatin kinase (all time-points)
oLDL (all time-points)
oLactate (pre, 10 min and 30 min post )
•Redox-status
oTOS (pre, 3h, 6h, 24h)
oTAS (pre, 3h, 6h, 24h)

•Immunological response
oNK-cell-test (pre, 3h, 24h)

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

E.6.4

Safety

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)

E.7.4

Therapeutic use (Phase IV)

Yes

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
The study will be terminated prematurely by intervention of the sponsor and/or investigator if during the study any suspect arises that the safety of the human subjects could be endangered, e.g. occurrence of serious or unexpected adverse events or newly published toxicological (human health relevant) findings.
In case of protocol violations which could cause potential harming or limit scientific statement, sponsor and investigator decide about remedy.

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)

F.2 Gender

F.2.1

Female

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

Yes

F.3.2

Patients

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)

In the current trail only healthy volunteers will be included to the trial. The IMP is an approved drug without serious side effects. The research areas exercise induced muscle damage and muscle soreness are natural reactions of the body to unusual or heavy muscular load and heals spontaneously after 3-7 days. Therefore there will be no need of further treatment after the subject has ended the trial. For all unexpected events the subjects will be insured by volunteer insurance

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

2013-01-21

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-01-08

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2013-08-13

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