Clinical Trials Register

Summary
EudraCT Number:	2016-003962-24
Sponsor's Protocol Code Number:	6632-9050-04
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:	2016-11-15
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

2016-003962-24

A.3

Full title of the trial

A multi-centre, randomized, placebo-controlled, double-blind, parallel-group study investigating safety and efficacy of a sore throat lozenge in the symptomatic treatment of patients with acute pharyngitis.

Multizentrische, randomisierte, Placebo-kontrollierte, doppelblinde Parallelgruppenstudie zur Untersuchung der Sicherheit und Wirksamkeit einer Halstablette zur symptomatischen Behandlung von Patienten mit akuter Rachenentzündung

A.3.1

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

A.3.2

Name or abbreviated title of the trial where available

DoriPha II

A.4.1

Sponsor's protocol code number

6632-9050-04

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	Medice Arzneimittel Pütter 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	Medice Arzneimittel Pütter 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	Medice Arzneimitel Pütter GmbH & Co. KG
B.5.2	Functional name of contact point	Klinische Forschung
B.5.3	Address:
B.5.3.1	Street Address	Kuhloweg 37
B.5.3.2	Town/ city	Iserlohn
B.5.3.3	Post code	58638
B.5.3.4	Country	Germany
B.5.4	Telephone number	0049023719370
B.5.5	Fax number	004902371937106
B.5.6	E-mail	R.Ammer@medice.de

D. IMP Identification
D.IMP: 1
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	Dorithricin® Halstabletten Classic
D.2.1.1.2	Name of the Marketing Authorisation holder	Medice 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.3.4	Pharmaceutical form	Lozenge
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oropharyngeal use
D.3.11 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

Acute Pharyngitis

E.1.1.1

Medical condition in easily understood language

Acute throat infection

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

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

Safety and efficacy of Dorithricin® Halstabletten Classic (lozenges)

E.2.2

Secondary objectives of the trial

Not applicable

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• male and female outpatients aged ≥18 years
• signed informed consent form
• clinically diagnosed acute pharyngitis (Tonsillo-Pharyngitis Assessment (TPA) ≥5)
• recent onset of symptoms (≤24 hours)
• pain intensity of ≥8 on a 11-point numeric rating scale
• difficulty in swallowing (100-mm VAS ≥50 mm)

E.4

Principal exclusion criteria

•patients with strong suspicion of streptococcus A infection (McIsaac Score ≥3)
•another acute episode of pharyngitis within the last 7 days prior to screening (the current acute pharyngitis which started within the last 24 hours is not meant)
•positive rapid streptococcus A test (rapid antigen detection test) to exclude the major bacterial pathogen responsible for sore throat
•purulent tonsillitis
•severe inflammations of the throat or throat pain that are accompanied by high fever (≥ 38,5°C, oral (sublingual)), headache, nausea and/or vomiting
•the use of systemic antibiotics / local antibiotics in the throat area during the study and within the previous 7 days prior to screening
•the use of any systemic analgesics / local analgesics in the throat area (e.g. non-steroidal drugs, ASA (> 100 mg), paracetamol) during the study or within the previous 36 hours prior to screening
•the use of any systemic anti-inflammatory drug / local anti-inflammatory drug in the throat area (e.g. glucocorticoids) during the study or within the previous 4 weeks prior to screening
•the use of local anesthetics for treatment of sore throat during the study or within the previous 2 days prior to screening
•the use of any other ‘sore throat medication’ (e.g. lozenges, drops, sprays) or other “cold medication” that could interfere the study results during the study and within the previous 7 days prior to screening
•the use of any systemic or local (i.e. in the throat area) antihistamines started within 2 weeks prior to screening
•major wounds of the mouth and throat
•immunodeficiency disorders (e.g. organ transplantation, HIV infection)
•severe neurologic and/or psychiatric disorders (including acute depressive mood / acute episode of depression)
•malignant ENT disorders within the previous 5 years
•known hypersensitivity to any of the ingredients of the study medication
•fructose intolerance
•women of child-bearing potential who do not use a highly effective method of contraception, that is the case when the Pearl Index of the contraceptive measure is ≥1
•pregnancy and lactation
•participation in another clinical study during the study and within the previous 30 days prior to screening
•presence of drug or alcohol abuse
•persons who are institutionalized by court order or regulatory action
•patients, who are members of the staff of the study center, staff of the sponsor or involved Clinical Research Organization (CRO), the investigator him- / herself or close relatives of the investigator
•legal incapacity and/or other circumstances rendering the subject unable to understand the nature, scope and possible impact of the study

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint variable is defined as the percentage of total responders assessed at Visit 2 (approx. 72 hrs after first application of treatment).

E.5.1.1

Timepoint(s) of evaluation of this end point

At Visit 2 / T72 hrs. Analysis will be done after last patient last
visit, data cleaning, data base lock and unblinding.

E.5.2

Secondary end point(s)

1)Analysis of throat pain:
a)Percentage of symptom-free patients in throat pain at Visit 2 (approx. 72 hrs after first application of treatment)
b)Baseline difference in throat pain (11-point NRS) at Visit 2 (approx. 72 hrs after first application of treatment)
2)Analysis of difficulties in swallowing:
a)Percentage of symptom-free patients in difficulty in swallowing at Visit 2 (approx. 72 hrs after first application of treatment)
b)Baseline difference in difficulty in swallowing (100-mm VAS) at Visit 2 (approx. 72 hrs after first application of treatment)
3)Evaluation of diary documentation:
a)Percentage of early responders in both pharyngitis symptoms assessed at 48 hrs after first application of treatment
A patient is defined as early responder, if both pharyngitis symptoms throat pain and difficulty in swallowing were symptom-free 48 hrs after first application of treatment and remained symptom free until end of study. This means no throat pain (score=0 on the 11-point NRS scales and absence of throat pain in the “yes/no” questions) and no difficulty in swallowing (score=0 mm on the 100-mm VAS scales and absence of difficulty in swallowing in the “yes/no” questions) is documented after 48 hrs neither in the diary nor at the assessment at Visit 2.
b)Percentage of symptom-free patients in throat pain at 48 hrs after first application of treatment
A patient is defined as symptom-free in throat pain at 48 hrs after first application of treatment in case of a complete resolution of throat pain at that time point and remained symptom free until the end of study. This means no throat pain (score=0 on the 11-point NRS scales and absence of throat pain in the “yes/no” questions) is documented after 48 hrs neither in the diary nor at the assessment at Visit 2.
c)Percentage of symptom-free patients in difficulty in swallowing at 48 hrs after first application of treatment
A patient is defined as symptom-free in difficulty in swallowing at 48 hrs after first application of treatment in case of a complete resolution of difficulty in swallowing at this time point and remained symptom free until end of study. This means no difficulty in swallowing (score=0 mm on the 100-mm VAS scales and absence of difficulty in swallowing in the “yes/no” questions) is documented after 48 hrs neither in the diary nor at the assessment at Visit 2.
4)Time to free of symptom(s) of
-throat pain and difficulty in swallowing (both must be symptom-free)
-throat pain
-difficulty in swallowing
5)Symptom relief direct after first application of treatment:
a)Throat pain intensity
b)Difficulty in swallowing intensity
c)Mean of throat pain intensity will be graphically displayed
d)Mean of difficulty in swallowing will be graphically displayed
e)Time till reduction of throat pain by at least one NRS score point
f)Time till reduction of difficulty in swallowing by at least one VAS score point
g)Sum of throat pain intensity differences over 2 hrs after application of treatment
h)Sum of difficulty in swallowing differences over 2 hrs after application of treatment
i)Percentage of patients who reduced their baseline throat pain NRS score by at least 50% during 2 hrs after first application of treatment
j)Percentage of patients who reduced their baseline difficulty in swallowing VAS score by at least 50% during 2 hrs after first application of treatment
The endpoints 5 g – j will in addition be analysed in the subgroup of patients who documented their symptom relief during the complete 2 hrs after first application of treatment.

E.5.2.1

Timepoint(s) of evaluation of this end point

Analysis of throat pain/ difficulties in swallowing: Visit 2/ 72 hrs after start of treatment
Evaluation of diary documentation: early responders/ symptom-free patients 48 hrs after start of treatment
Efficacy - Endpoints with respect to symptom relief in the first two hours
after first intake: 2 hrs after start of treatment
All analyses will be done after last patient last visit, data cleaning, data
base lock and unblinding.

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

Yes

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

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

End of clinical trial: last patient last visit

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:

320

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

320

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

320

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)

If
- symptoms worsen during the clinica trial or
- there is no response to treatment or
- the patient discontues prematurely,
then (if necessary) a standard treatment for the respective disease
pattern will be initiated by the investigator

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

2016-12-14

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-12-27

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2017-07-02

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