Clinical Trials Register

Summary
EudraCT Number:	2013-002970-32
Sponsor's Protocol Code Number:	KKL072012
National Competent Authority:	Slovenia - JAZMP
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-11-21
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

Slovenia - JAZMP

A.2

EudraCT number

2013-002970-32

A.3

Full title of the trial

A COMPARISON OF THERAPEUTIC EQUIVALENCE BETWEEN THE TEST AND THE REFERENCE FORMULATION OF FIXED COMBINATION OF CETYLPYRIDINIUM CHLORIDE 1.0 mg/BENZYDAMINE HYDROCHLORIDE 3 mg IN SUBJECTS WITH SORE THROAT ASSOCIATED WITH UPPER RESPIRATORY TRACT INFECTIONS

PRIMERJALNA RAZISKAVA TERAPEVTSKE EKVIVLENCE MED TESTNO IN REFERENČNO FORMULACIJO FIKSNE KOMBINACIJE 1,0 mg CETILPIRIDINIJEVEGA KLORIDA IN 3 mg BENZIDAMINIJVEGA HIDROKLORIDA PRI PREIZKUŠANCIH Z BOLEČINO V ŽRELU, POVEZANO Z OKUŽBAMI ZGORNJIH DIHAL

A.3.1

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

A comparison of effIcacy and safety between the two drugs in patients
with sore throat in order to demonstrate that their efficacy and safety is equivalent

Primerjava učinkovitosti in varnosti med dvemi zdravili za boleče žrelo z namenom, da bi pokazali, da sta po učinku in varnosti enakovredni.

A.4.1

Sponsor's protocol code number

KKL072012

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	KRKA, tovarna zdravil, d. d., Novo mesto
B.1.3.4	Country	Slovenia
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	KRKA, tovarna zdravil, d. d., Novo mesto
B.4.2	Country	Slovenia
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	KRKA, tovarna zdravil, d. d., Novo mesto
B.5.2	Functional name of contact point	Info točka raziskave
B.5.3	Address:
B.5.3.1	Street Address	Dunajska 56
B.5.3.2	Town/ city	Ljubljana
B.5.3.3	Post code	1000
B.5.3.4	Country	Slovenia
B.5.4	Telephone number	0038614751489
B.5.5	Fax number	0038614361266
B.5.6	E-mail	marko.boh@krka.biz

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	Septolete total
D.3.4	Pharmaceutical form	Lozenge
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oropharyngeal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	CETYLPYRIDINIUM CHLORIDE
D.3.9.1	CAS number	123-03-5
D.3.9.3	Other descriptive name	CETYLPYRIDINIUM CHLORIDE
D.3.9.4	EV Substance Code	SUB07460MIG
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	1
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	BENZYDAMINE
D.3.9.1	CAS number	642-72-8
D.3.9.4	EV Substance Code	SUB05770MIG
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	3
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	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	Gola action
D.2.1.1.2	Name of the Marketing Authorisation holder	Iodosan S.p.A.
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	Gola action
D.3.4	Pharmaceutical form	Orodispersible tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oropharyngeal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	BENZYDAMINE
D.3.9.1	CAS number	642-72-8
D.3.9.4	EV Substance Code	SUB05770MIG
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	3
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	CETYLPYRIDINIUM CHLORIDE
D.3.9.1	CAS number	123-03-5
D.3.9.3	Other descriptive name	CETYLPYRIDINIUM CHLORIDE
D.3.9.4	EV Substance Code	SUB07460MIG
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	1
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	Lozenge
D.8.4	Route of administration of the placebo	Oropharyngeal use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Sore throat associated with upper respiratory infections

E.1.1.1

Medical condition in easily understood language

Sore throat

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	16.1
E.1.2	Level	LLT
E.1.2	Classification code	10041368
E.1.2	Term	Sore throat NOS
E.1.2	System Organ Class	10038738 - Respiratory, thoracic and mediastinal disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	16.1
E.1.2	Level	PT
E.1.2	Classification code	10068319
E.1.2	Term	Oropharyngeal pain
E.1.2	System Organ Class	10038738 - Respiratory, thoracic and mediastinal 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 demonstrate the equivalence of the treatment effect between test and reference product in terms of the sore throat pain intensity difference at the predefined time point compared to baseline .
_WIthin the main objective a superiority of the treatment effect of both test and reference treatment over placebo treatment is to be demonstrated in terms of sore throat pain intensity difference at the predefined time point compared to baseline.

E.2.2

Secondary objectives of the trial

-to assess the safety profile of test in comparison with reference IMP and placebo
- to demonstrate similar safety profile in test and reference IMP infections.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Subjects with a sore throat associated with upper respiratory trat infection
• Onset of sore throat ≤ 6 days
• Both sexes, age range 18-65 years
• ≥ 4 points on the 10 point Tonsillopharyngitis assessment (TPA) score
• Moderate to severe sore throat pain defined as a score ≥ 60 mm on
the 100 mm Sore Throat Pain Intensity Scale

E.4

Principal exclusion criteria

• Pregnancy or lactation or unreliable contraceptive method
• Subjects with any evidence of mouth breathing or coughing which could compromise respiratory function and worsen sore throat
• Severe streptococcal tonsillitis assessed by rapid antigen detection test (RADT)
• Increased body temperature that needs antipyretic treatment (more than 38.5 C)
• Recurrent (chronic) sore throat
• Other severe respiratory tract diseases (pneumonia, infectious mononucleosis, asthma or difficulty in breathing, peritonsillar abscess etc.)
• Oropharyngeal lesions (tumours, purulent necrotic process, aphtous ulcers, etc.)
• Pharmacological therapy with:
- Antibiotics currently,
- oral antiseptics and demulcents in the form of sprays, gargles, lozenges or drops within 3 h before the initial dose,
- short-acting analgesics within 6 hours before the initial dose,
- long-acting or slow-release analgesic within 24 hours before the initial dose,
- local anaesthetics within 4 hours before the initial dose,
- antihistamines within 12 hours before the initial dose,
- nasal decongestants, anti-tussives or expectorants including their fixed combinations within 8 hours before the initial dose.
• Any chronic disease which requires long-term use of oral analgesics, NSAIDs, antihistamines and local anaesthetics
• Previously diagnosed hypersensitivity to benzydamine, other NSAIDs, cetylpyridinium chloride or any other component of study drugs including the rescue medication (paracetamol)
• Subject is currently participating in another clinical trial
• Excessive alcohol consumption, drug abuse or drug addiction
• Subject refuses to participate with the investigator

E.5 End points

E.5.1

Primary end point(s)

• Sore throat pain intensity (STPI) difference at 1 hour after the IMP administration (STPID1h).
Defined as the mean difference between STPI score at 1 hour after the IMP administration and the baseline STPI score, assessed before the IMP administration at Visit 1.
STPI is assessed by visual analogue scale ( VAS)

E.5.1.1

Timepoint(s) of evaluation of this end point

60 minutes

E.5.2

Secondary end point(s)

1. Percent of responders after the initial single IMP dose (% RESP).
Defined as the share of subjects who respond to the therapy with respect to the total number of subjects taking the same IMP
2. Mean sore throat pain intensity STPI) difference at 2 hours after the IMP administration (STPID2h).
Defined as the mean difference between STPI score at 2 hours after the IMP administration and the baseline STPI score, assessed before the IMP administration at Visit 1. STPI is assessed by visual analogue scale ( VAS)
3. Mean sore throat pain intensity STPI) difference at 3 hours after the IMP administration (STPID3h).
Defined as the mean difference between STPI score at 3 hours after the IMP administration and the baseline STPI score, assessed before the IMP administration at Visit 1. STPI is assessed by visual analogue scale ( VAS)
4. Total pain relief over the time interval of 15 min to 180 minutes after the IMP administration at Visit 1 (TOTPAR).
Defined as mean area under the curve (AUC) of sore throat pain relief (STPAR) scores. These scores are assessed by the STPAR scale.
5. Time to Sore Throat Pain relief (TSTPAR). Defined as the time in minutes to at least 1 point increase on the STPAR scale followed by at least 3-point STPAR score on at least two consecutive measurements.

E.5.2.1

Timepoint(s) of evaluation of this end point

1. 180 min
2. 120 min
3. 180 min
4. 15, 30, 45, 60, 75, 90, 105, 120, 135, 150, 165 and 180
min
5. 15, 30, 45, 60, 75, 90, 105, 120, 135, 150, 165 and 180
min

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

Double blind refers only to test product and placebo

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

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

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Russian Federation

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

E.8.9.2

In all countries concerned by the trial months

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:

340

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

340

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.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

340

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)

The treatment plan after the end of trial participation is not different
from expected normal treatment of the condition

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2013-12-23

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-09-27

P. End of Trial
P.	End of Trial Status	Completed

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