Clinical Trials Register

Summary
EudraCT Number:	2020-001032-99
Sponsor's Protocol Code Number:	DRO-200-III-20-1
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:	2020-06-02
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

2020-001032-99

A.3

Full title of the trial

Randomized, controlled, double-blind, multi-center trial to evaluate the efficacy and safety of “Lixim 70 mg wirkstoffhaltiges Pflaster” (etofenamate 70 mg medicated plaster) applied once daily (every 24 hours) or twice daily (every 12 hours) vs. matching placebo in the short-term symptomatic treatment of local pain in acute uncomplicated ankle sprains in adults

Randomisierte, kontrollierte, doppelblinde, multizentrische Studie zur Bewertung der Wirksamkeit und Sicherheit von „Lixim 70 mg wirkstoffhaltiges Pflaster“(Etofenamat 70 mg wirkstoffhaltiges Pflaster) angewendet entweder einmal täglich (alle 24 Stunden) oder zweimal täglich (alle 12 Stunden) im Vergleich zu einem entsprechenden Placebo in der kurzzeitigen symptomatischen Behandlung lokaler Schmerzen bei akuten unkomplizierten Sprunggelenksverstauchungen Erwachsener.

A.3.1

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

The main purpose of this placebo-controlled clinical trial is to compare the efficacy and safety of "Lixim 70 active-substance patch" (Lixim patch), which is applied once daily with the efficacy and safety of the same active ingredient patch applied twice daily in the treatment of acute uncomplicated ankle sprains (distorsions).

Hauptzweck dieser Placebo kontrollierten klinischen Prüfung ist der Vergleich der Wirksamkeit und Sicherheit von „Lixim 70 wirkstoffhaltiges Pflaster“(Lixim Pflaster), welches einmal täglich aufgetragen wird mit der Wirksamkeit und Sicherheit des gleichen wirkstoffhaltigen Pflasters, welches zweimal täglich aufgetragen wird bei der Behandlung von akuten unkomplizierten Sprunggelenkverstauchungen (Distorsionen).

A.4.1

Sponsor's protocol code number

DRO-200-III-20-1

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	Drossapharm AG
B.1.3.4	Country	Switzerland
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	Drossapharm AG
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	Clinsearch GmbH
B.5.2	Functional name of contact point	Prof. Dr. Bruno Giannetti
B.5.3	Address:
B.5.3.1	Street Address	Zugerstrasse 80A
B.5.3.2	Town/ city	Walchwill
B.5.3.3	Post code	6318
B.5.3.4	Country	Switzerland
B.5.4	Telephone number	41417116376
B.5.5	Fax number	41417101977
B.5.6	E-mail	info@clinsearch.ch

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	Lixim 70 mg wirkstoffhaltiges Pflaster
D.2.1.1.2	Name of the Marketing Authorisation holder	Drossapharm AG
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	Etofenamate
D.3.4	Pharmaceutical form	Medicated plaster
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Cutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Lixim 70mg wirkstoffhaltiges Pflaster
D.3.9.1	CAS number	30544-47-9
D.3.9.3	Other descriptive name	ETOFENAMATE
D.3.9.4	EV Substance Code	SUB07319MIG
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	70
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	Medicated plaster
D.8.4	Route of administration of the placebo	Cutaneous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Acute ankle sprain, Grade I

E.1.1.1

Medical condition in easily understood language

Acute ankle sprain

E.1.1.2

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

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

To demonstrate that the Lixim plaster applied once every 24 hours is superior to matching placebo plasters, in particular with regard to pain relief.

E.2.2

Secondary objectives of the trial

• To demonstrate that the Lixim plaster applied once every 12 hours is superior to matching placebo plasters, in particular with regard to pain relief.
• To assess relative efficacy (non-inferiority) of the Lixim plaster applied once every 24 hours with the same medicated plaster applied once every 12 hours.
• To assess the safety (including local tolerability) of both Lixim plaster treatment regimens (once/twice a day) compared with placebo.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Acute uncomplicated unilateral ankle sprain, Grade I
2. Enrolment within 12 hours of the injury
3. Baseline VAS score for (investigator manipulated) pain on movement (POM) of injured ankle > 50 mm on a 100 mm VAS
4. Adult male or female patients
5. Age 18 to 60 years
6. Having given written informed consent
7. Satisfactory health as determined by the Investigator based on medical history and physical examination.

E.4

Principal exclusion criteria

1. Serious injury in the area of the foot or ankle, including fracture, nerve injury, ligament disruption, tear of muscle or cartilage, or open wound.
2. Excessively hairy skin at application site.
3. Chronic skin disorder at application site.
4. History of excessive sweating inclusive of application site.
5. Intake of NSAIDs or analgesics within 36 hours, opioids within 7 days, or corticosteroids within 60 days of clinical trial start.
6. Intake of long-acting NSAIDs or application of topical medication since the injury (RICE allowed).
7. Participation in a clinical trial within 30 days before entry or concomitantly.
8. Drug or alcohol abuse in the opinion of the investigator.
9. Pregnant and lactating women.
10. Women of child-bearing potential without medically accepted contraception.
11. Known hypersensitivity to etofenamate or one of the excipients of the medicated plaster.
12. History of previous grade I ankle sprain (same ankle) within 6 months, or previous grade II sprain, or other significant injury to the same ankle or foot within 6 months.
13. Patients with history of previous grade III ankle sprain (same ankle).
14. Patients with a disease affecting the same ankle, such as synovitis, rheumatoid arthritis, arthrosis, etc.
15. Patients suffering from symptoms of an infectious disease including swelling of any joint of the affected lower limb.
16. Patients who had surgery of the affected lower limb within one year of clinical trial entry.
17. Patients with significant diseases (defined as a disease which, in the opinion of the investigator, may either put the patient at risk because of participation in the clinical trial or a disease which may influence the results of the clinical trial or the patient’s ability to participate in the clinical trial; includes patients with a history of gastrointestinal bleeding, significant cardiovascular, liver or renal disease).
18. Patients with a blood coagulation disorder.
19. Patients who use any impermissible medication
20. Patients with a history of analgesic-induced asthma

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy outcome is change from baseline of ankle pain-on-movement (POM) assessed by Visual Analogue Scale (VAS) at Visit 5

E.5.1.1

Timepoint(s) of evaluation of this end point

72 hours after initiating treatment

E.5.2

Secondary end point(s)

• POM on VAS at Visits 3, 4 and 6 (24, 48 and 96 hours after initiating treatment).
• POM on VAS at Visit 7 (Day 8 (±1)).
• Pain at Rest at Visit 5 (72 hours after beginning of treatment)
• AUC of POM VAS pain scores over the 0-24, 0-48, 0-72 and 0-96 hours
• Circumference measurement of swelling (compared to non-affected side) by “Figure-of-eight-method” at all visits.
• Global efficacy assessments at Visit 5 and 7 (72 hours after initiating treatment and Day 8 (±1)).

Additional outcomes
• Use of rescue medication
• used any rescue medication (Y/N),
• the average over Days 1-8 of number of tablets used per day,
• the total number of tablets used by day,
• the total number of days on which rescue medication was used.
Outcomes will be compared for all use of rescue medication and separately for use to treat ankle pain. Day 1 and the day of the final visit will count as full days for all comparisons.
• Pain at Rest at Visit 4 (24 and 48 hours after initiating treatment)
• Time to meaningful/optimal reduction of pain defined as 30% (meaningful) and 50% (optimal) reduction of baseline VAS for POM. Both time points will be calculated
• Responder Rate: Will be defined as the number of patients reaching 50% of pain reduction at Visit 5 (72 hours)
• Time to full return to normal (daily) activities
• Plaster adhesion assessment
• Assessment of local tolerability according to a numerical scale

E.5.2.1

Timepoint(s) of evaluation of this end point

24, 48, 72 and 96 hours after initiating treatment

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

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

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

LPLV

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:

224

F.1.3

Elderly (>=65 years)

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

Information not present in EudraCT

F.4 Planned number of subjects to be included

F.4.1

In the member state

224

F.4.2

For a multinational trial

F.4.2.1

In the EEA

224

F.4.2.2

In the whole clinical trial

224

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)

No continuation supplies will be made available for the patients as no further treatment is expected to be necessary at the end of the clinical trial. However, if necessary, the Investigator will continue to treat the patient with other medications until the injury is resolved. Alternatively, the Investigator will inform the patient’s general practitioner (GP) at the end of the clinical trial period and the patient will then be advised to visit his GP directly.

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	IL-CSM CLINICAL SUPPLIES MANAGEMENT
G.4.3.4	Network Country	Germany
G.4 Investigator Network to be involved in the Trial: 2
G.4.1	Name of Organisation	Grieshaber Logistics Group AG
G.4.3.4	Network Country	Germany
G.4 Investigator Network to be involved in the Trial: 3
G.4.1	Name of Organisation	Teikoku Seiyaku Co., Ltd.
G.4.3.4	Network Country	Japan
G.4 Investigator Network to be involved in the Trial: 4
G.4.1	Name of Organisation	Untersuchungsinstitut Heppeler GmbH
G.4.3.4	Network Country	Germany
G.4 Investigator Network to be involved in the Trial: 5
G.4.1	Name of Organisation	Vektor Pharma TF GmbH
G.4.3.4	Network Country	Germany
G.4 Investigator Network to be involved in the Trial: 6
G.4.1	Name of Organisation	Ivers-Lee AG
G.4.3.4	Network Country	Switzerland

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2020-09-03

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-07-02

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2021-05-04

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