Clinical Trials Register

Summary
EudraCT Number:	2016-002620-92
Sponsor's Protocol Code Number:	Pennsaid-C-2016/P-3-02
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:	2016-08-05
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

2016-002620-92

A.3

Full title of the trial

A multi-centre, randomised, controlled, double-blind, parallel-group study on the efficacy and safety of Pennsaid-2% topical skin solution in patients with Grade I-II ankle sprain

Multizentrische, randomisierte, kontrollierte, doppelblinde Parallelgruppen-studie zur Untersuchung der Wirksamkeit und Sicherheit von topischer Penn-said-2% Lösung in Patienten mit Grad I-II Sprunggelenkverstauchung

A.3.1

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

Clinical study to evaluate the efficacy and safety of a 2% Diclofenac cutaneous solution vs. placebo in the treatment of acute uncomplicated
unilateral ankle sprain

Klinische Studie zur Bewertung der Wirksamkeit und Sicherheit der Anwendung einer 2%-Diclofenac Lösung gegenüber Placebo zur Behandlung von akuter, unkomplizierter, einseitiger Sprunggelenksverstauchung

A.4.1

Sponsor's protocol code number

Pennsaid-C-2016/P-3-02

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	Nuvo Pharmaceuticals Inc.
B.1.3.4	Country	Canada
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	Nuvo Pharmaceuticals Inc.
B.4.2	Country	Canada
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Bundesinstitut für Arzneimittel und Medizinprodukte
B.5.2	Functional name of contact point	Bundesinstitut
B.5.3	Address:
B.5.3.1	Street Address	Kurt-Kiesinger Allee 3
B.5.3.2	Town/ city	Bonn
B.5.3.3	Post code	53175
B.5.3.4	Country	Germany
B.5.4	Telephone number	+49228207 4318
B.5.5	Fax number	+49228207 4355
B.5.6	E-mail	ct@bfarm.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	No
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	Pennsaid 2 % cutanous solution
D.3.4	Pharmaceutical form	Cutaneous solution
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	Diclofenac
D.3.9.1	CAS number	15307-79-6
D.3.9.3	Other descriptive name	Diclofenac Sodium
D.3.9.4	EV Substance Code	SUB01674MIG
D.3.10	Strength
D.3.10.1	Concentration unit	% (W/W) percent weight/weight
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2
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	Cutaneous solution
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

Treatment of pain and Inflammation associated Acute Soft Tissue Injury/Ankle Sprain

Behandlung von Schmerzen und Entzündungen bei akuter Weichteilverletzung/Knöchelverstauchung

E.1.1.1

Medical condition in easily understood language

To assess the efficacy of diclofenac sodium 2% w/w cutaneous solution for treatment of Pain and Inflammation associated with acute soft tissue injury/ankle sprain

Beurteilung der Wirksamkeit von topischer Diclofenac-Natrium-Lösung 2 % w/w zur Behandlung von Schmerzen und Entzündung bei akuter Weichteilverletzung/Sprunggelenkverstauchung.

E.1.1.2

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	19.1
E.1.2	Level	LLT
E.1.2	Classification code	10002549
E.1.2	Term	Ankle sprain
E.1.2	System Organ Class	100000004863

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 primary objective of this study is:
To assess the efficacy of diclofenac sodium 2% w/w cutaneous solution for the treatment of Pain and Inflammation associated with acute soft tissue injury/ankle sprain

Die primäre Zielsetzung dieser Studie ist:
Die Bewertung der Wirksamkeit von Diclofenac 2%-Lösung bei Patienten mit akuter Sprunggelenkverstauchung, insbesondere in Bezug auf die Schmerz- und Entzündungslinderung.

E.2.2

Secondary objectives of the trial

To assess the safety and tolerability of diclofenac sodium 2% w/w cutaneous solution for treatment of Pain and Inflammation associated with acute soft tissue injury/ankle sprain.

Beurteilung der Sicherheit und Verträglichkeit von topischer Diclofenac-Natrium-Lösung 2 % w/w zur Behandlung von Schmerzen und Entzündung bei akuter Weichteilverletzung/Knöchelverstauchung.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Experiencing an acute grade I or II sprain of the lateral ankle as assessed by the investigator within 12hrs of injury.
2. Male or female aged 18 – 75 years
3. Have POM of > 50mm on a 100mm visual analogue scale (VAS) and no use of pain medication within 12hrs preceding randomization
4. Willing and able to provide informed consent

1.Eine akute Verstauchung 1. oder 2. Grades des äußeren Knöchels haben, die vom Prüfarzt innerhalb von 12 Std. nach der Verletzung festgestellt wurde.
2.Männlich oder weiblich und im Alter von 18 bis 75 Jahren sein.
3.Einen POM von > 50 mm auf einer 100-mm visuellen Analogskala (VAS) aufweisen und dürfen innerhalb von 12 Std. vor der Randomisierung keine Schmerzmittel eingenommen haben.
4.Bereit und in der Lage sein, eine Einwilligungserklärung abzugeben.

E.4

Principal exclusion criteria

1 Previous participation in any investigational trial with diclofenac containing topical medications
2 Previous participation in any investigational trial within the last 30 days
3 Ankle sprain requiring an orthopaedic or surgical treatment
4 Abrasion, any lesion or wound of the skin at either side of the affected ankle
5 Any concurrent injury affecting the lower extremities that is painful at rest or on movement that could affect mobilisation of the patient
6 Use of any topical analgesic or anti-inflammatory medication on the affected ankle during the previous 30 days; use of any systemic analgesic or anti-inflammatory medication within the last one week (including the time since the present injury)
7 A grade I sprain of the same ankle within 3 months
8 A grade II or III sprain or any other significant injury or surgery of the same ankle/foot within 6 months of study start
9 Pain or instability of the affected ankle attributable to previous ankle sprain
10 Any other trauma or ankle sprain attributed to a known disease affecting the ligaments
11 Subjects with known hypersensitivity to diclofenac, aspirin (acetylsalicylic acid [ASA]) or any other NSAID, dimethyl sulfoxide (DMSO), or ethanol. This includes subjects exhibiting aspirin or other NSAID-induced reactions such as bronchospasm, rhinitis, and urticaria or other NSAID-induced allergic symptoms
12 Any chronic disease, which may impair the subject's ability to participate in the trial (i. e. severe congestive heart failure, active gastric or duodenal ulcer, etc.).
13 Use of prohibited medications or of possibly confounding pain-relieving measures / interventions
14 Malignant disease other than basalioma
15 Subjects lacking fluency in German to such extent that they need to be assumed having difficulties understanding the patient information, the instructions for orderly use of the investigational trial medication and the visit/diary questions with regard to their well-being and the intensity of their symptoms
16 Patients who are staff or close relatives of the Investigator or CRO
17 Unreliable subjects including non-compliant subjects, subjects with known or suspected alcoholism or drug abuse or with a history of a serious psychiatric disorder

If female – Additional exclusion criteria: pregnant, lactating, or of child-bearing potential and not using adequate contraction

1 Vorherige Teilnahme an jeglicher klinischen Prüfung mit experimenteller Anwendung einer topischen diclofenac-haltigen Prüfmedikation;
2 Teilnahme an jeglicher sonstigen klinischen Prüfung innerhalb der letzten dreißig Tage;
3 Sprunggelenkverstauchung, die einer orthopädischen oder chirurgischen Behandlung bedarf;
4 Hautabschürfung oder jegliche Läsion der Haut einer oder beider Seiten des verletzten Sprunggelenkes;
5 Jegliche Begleitverletzung der unteren Extremitäten, die Schmerzen in Ruhe oder bei Bewegung auslöst oder die die Mobilisierung des Patienten beeinträchtigt;
6 Jegliche topische Anwendung eines schmerzlindernden oder anti-entzündlichen Arzneimittels innerhalb der letzten 30 Tage; Anwendung eines systemischen schmerzlindernden oder anti-entzündlichen Arzneimittels innerhalb der letzten Woche (inkl. des Zeitintervalls seit der jetzigen Verletzung);
7 Grad I Verstauchung desselben Sprunggelenkes innerhalb der letzten 3 Monate;
8 Grad II oder III Verstauchung, bedeutsame Verletzung oder chirurgischer Eingriff desselben Sprunggelenkes innerhalb der letzten 6 Monate;
9 Schmerzen oder Instabilität des verletzten Sprunggelenkes, die auf eine frühere Verstauchung zurückzuführen ist;
10 Vorheriges Trauma oder Verstauchung, die aus einer bekannten Erkrankung der Ligamente hervorgeht;
11 Bekannte Überempfindlichkeit gegen Diclofenac, Aspirin (Acetylsalicylsäure [ASA]) oder ein sonstiges NSAID, Dimethylsulphoxid (DMSO), oder Äthanol inklusive Patienten mit ASA- oder NSAID-bedingten Reaktionen, Bronchospasmen, Rhinitis, Urticaria oder sonstigen NSAID-bedingten allergischen Beschwerden;
12 Jegliche chronische Erkrankung, die die Fähigkeit des Patienten, an der Studie teilzunehmen, beeinträchtigt (z.B. hochgradige kongestive Herzinsuffizienz, Magen- oder Duodenalulkus, usw.);.
13 Anwendung untersagter Medikamente oder möglicherweise störender schmerzlindernder Maßnahmen (siehe Kapitel 5.8)
14 Malignität (mit Ausnahme eines Basalioms);
15 Patienten mit ungenügenden Deutschkenntnissen, so dass angenommen werden muss, dass sie bedeutsame Schwierigkeiten empfinden könnten, die Patienteninformation oder die Anweisungen zu einer ordnungsgemäßen Anwendung der Prüfmedikation zu verstehen oder das Tagebuch mit den Angaben zu ihrem Wohlbefinden oder zu der Ausprägung ihrer Schmerzen zu führen;
16 Mitarbeiter oder nahe Verwandte des Prüfarztes bzw. Mitarbeiter des Auftragsforschungsinstitutes;
17 Unzuverlässige Patienten, Patienten mit einer möglichen ungenügenden Compliance, Hinweis oder Verdacht auf Alkohol- oder Drogenabhängigkeit sowie schwerwiegende psychische Erkrankung.

Zusätzliche Ausschlusskriterien für Frauen: Schwangerschaft, Stillen, oder – falls nicht postmenopausal – ungenügende Verhütung.

E.5 End points

E.5.1

Primary end point(s)

Pain on movement (POM) on D03

POM am Tag 3

E.5.1.1

Timepoint(s) of evaluation of this end point

Day 03 (D01-adjusted estimate)

Day 03 (D01-adjustiert)

E.5.2

Secondary end point(s)

POM on D05 and D08
Percentage of subjects reaching ≥ 50% improvement in POM on D03, D05, and D08
Cumulative Proportion of Responders Analysis (CPRA) on D03 and D05
Numbers needed to treat (NNT) for reaching ≥ 50% improvement in POM on D03 and D05
Pain at rest (PAR) on D03, D05, D08
Ankle swelling on D03, D05, D08
Ankle tenderness on D03, D05, D08
Ankle function (Karlsson score) on D03, D05, D08
PGAB (Patient Global Assessment of Benefit)
PGAS (Patient Global Assessment of Satisfaction)
Use of rescue medication

Schmerz bei kontrollierter Bewegung (POM) am Tag D05 und D08
Anteil der Patienten, die eine mindestens 50%-ige POM-Verbesserung am D03, D05, und D08 erzielen
Analyse der kumulativen Responderrate ("Cumulative Proportion of Responders Analysis": CPRA) am D03 und D05
Anzahl der notwendigen Behandlungen ("Number needed to treat": NNT) für eine mindestens 50%-ige POM-Verbesserung zum Tag D03 und D05
Ruheschmerz ("pain-at-rest": PAR) am Tag D03, D05 und D08
Sprunggelenkschwellung am Tag D03, D05 und D08
Druckempfindlichkeit des Sprunggelenkes ("tenderness") am Tag D03, D05 und D08
Funktionseinschränkung des Sprunggelenkes (Karlsson score) am Tag D03, D05 und D08
Gesamtbewertung des therapeutischen Nutzens seitens des Patienten ("Patient Global Assessment of Benefit": PGAB)
Gesamtbewertung der Zufriedenheit mit der Behandlung des Patienten ("Patient Global Assessment of Satisfaction": PGAS)
Anwendung von Notfallmedikation

E.5.2.1

Timepoint(s) of evaluation of this end point

D01, D03, D05, D08: POM, PAR, tenderness, ankle swelling and ankle function
Use of rescue medication: throughout

Tag 1, 3, 5 und 8: POM, PAR, Druckempfindlichkeit, Schwellung und Funktion des Knöchels
an allen Tagen Verwendung von Reservemedikation

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

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

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

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:

100

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

126

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

2016-09-21

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-10-07

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2017-03-30

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