Clinical Trials Register

Summary
EudraCT Number:	2018-001395-37
Sponsor's Protocol Code Number:	Repha_1430
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:	2018-06-05
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

2018-001395-37

A.3

Full title of the trial

Investigation of the efficacy and safety of ANGOCIN® Anti-Infekt N versus placebo in adult patients with acute bronchitis. A multicenter,
randomized, double-blind, placebo-controlled, parallel-group phase
IV clinical trial.

Untersuchung der Wirksamkeit und Sicherheit von Angocin® Anti-Infekt N im Vergleich zu Placebo in erwachsenen Patienten mit akuter Bronchitis.
Eine multizentrische, randomisierte, doppelblinde, Placebo-kontrollierte, Parallelgruppen- Phase IV Studie.

A.3.1

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

Investigation of the efficacy and safety of ANGOCIN® Anti-Infekt N versus placebo in adult patients with acute bronchitis.

Untersuchung der Wirksamkeit und Sicherheit von Angocin® Anti-Infekt N im Vergleich zu Placebo bei Erwachsenen mit akuter Bronchitis.

A.3.2

Name or abbreviated title of the trial where available

ANGOCOUGH

A.4.1

Sponsor's protocol code number

Repha_1430

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	Repha GmbH
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	Repha GmbH, Langenhagen
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	Mediconomics GmbH
B.5.2	Functional name of contact point	Clinical Research
B.5.3	Address:
B.5.3.1	Street Address	Misburger Straße 81 B
B.5.3.2	Town/ city	Hannover
B.5.3.3	Post code	30625
B.5.3.4	Country	Germany
B.5.4	Telephone number	004905115609980
B.5.5	Fax number	0049051156099820
B.5.6	E-mail	info@mediconomics.com

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	Angocin Anti-Infekt N
D.2.1.1.2	Name of the Marketing Authorisation holder	Repha GmbH
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	Film-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.3.8	INN - Proposed INN	Horseradish root powder
D.3.9.3	Other descriptive name	HORSERADISH
D.3.9.4	EV Substance Code	SUB130891
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	80
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Kapuzinerkressenkrautpulver
D.3.9.3	Other descriptive name	NASTURTIUM HERB POWDER
D.3.9.4	EV Substance Code	SUB176175
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	200
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	Yes
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	Film-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

acute bronchitis

Akute Bronchitis

E.1.1.1

Medical condition in easily understood language

acute bronchitis

Akute Bronchitis

E.1.1.2

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	LLT
E.1.2	Classification code	10006452
E.1.2	Term	Bronchitis acute
E.1.2	System Organ Class	100000004862

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Comparison of the Change within the mean BSSinv (Baseline to Day 7) between both Treatment groups

Vergleich der Veränderung des mittleren Symptomscores BSSinv von Baseline zu Tag 7 zwischen den beiden Behandlungsgruppen.

E.2.2

Secondary objectives of the trial

Change of single symptoms BSSinv between V1, V2, V3 and V4 within the course of the study
Change of single symptoms BSSinv between V1, V2, V3 and V4 and within the course of the study
rate of AB taking patients between V1 and V4
rate of cured patients between V1-V4 (responder)
comparison of non-responder rate between V1 and V4
Evaluation of efficacy by the investigator (V2, V3, V4)
Change in CAT during Treatment course
Change in SF-12 during Treatment course

Differenz des mittleren Symptomscores BSSinv zwischen V1 (baseline) und jeweils V2, V3 und V4 und im Laufe der Studie
Veränderung der einzelnen Symptome des BSSinv zwischen V1 (baseline) und jeweils V2, V3 und V4 und im Laufe der Studie
Rate der Patienten, die zwischen V1 und V4 einer Antibiotikatherapie zur Behandlung der akuten Bronchitis unterzogen wurden (AB-Rate)
Rate der geheilten Patienten im Zeitraum V1 – V4 (Responder)
Vergleich der Rate an Non-Respondern zwischen V1 und V4
Generelle Beurteilung der Wirksamkeit durch den Prüfarzt zu V2, V3 und V4
Veränderung des CAT im Verlauf der Behandlung
Veränderung des SF-12 im Verlauf der Behandlung

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. signed informed consent
2. male and female outpatients aged ≥18 und ≤75 Jahre
3. diagnosis of acute (or recurrend acute) bronchitis:
- characterized by the main symptoms with an BSSinv Score ≥ 5
- symptoms occured ≤ 48 h before study enrolment

1. Unterschriebene Einwilligungserklärung
2. Männliche und weibliche Patienten in ambulanter Behandlung, zwischen ≥18 und ≤75 Jahre
3. Diagnose einer akuten (oder wiederkehrenden, akuten) Bronchitis:
- charakterisiert durch die Hauptsymptome mit einem BSSinv Score ≥ 5
- mit Auftreten der Symptome ≤ 48 h vor Einschluss in die Studie

E.4

Principal exclusion criteria

a) Diseases
1. Chronic Bronchitis (i.e. all forms and causes of persistent chronic bronchitis)
2. Patients with severe respiratory infections, requiring treatment with antibiotics
3. Diagnosed Asthmatics or patients with diagnosed allergic bronchial Asthma (severity in adults: ligth to severe according to S2k guidance for asthmatics diagnosis), diagnosed bronchietktase, and diagnosed chronic obstructive pulmonary disease (COPD, GOLD I-IV)
4. Cystic fibrosis
5. Known hypersensitivity to study medication / placebo or respective excipients
6. Any contraindications to the study medication
7. known immune deficient patients, known progressive autoimmune diseases
8. Signs or symptoms of fulminant bacterial Bronchitis (fever > 38.5°C)
9. Diagnosed severe heart diseases NYHA class >/= 2(e. g. myocardial infarction, coronary heart disease)
10. Diagnosed severe diseases of the liver (e. g. fatty liver, liver cirrhosis)
11. Diagnosed severe diseases of the kidney (serum creatinine > 1.4 mg/dL)
12. Severe somatopathic, neurological and / or psychiatric diseases making it difficult for the Patient to decide to consent to Trial participation
13.Patients with malignant growth processes or cancer treatment within the last five years (head / neck Treatments) and / or within the last 2
years (other body regions) prior to study inclusion with further hazardous potential
14. Any condition which might interfere with study objectives or that would limit the patients ability to complete the study as judged by the
investigator
15. Exisiting habits of alcohol or drug abuse

b) Medication
1. Treatment with immunosuppressive medication 8 weeks prior to screening
2. Treatment with systemic or inhalative antibiotics or nasal or systemic / inhalative corticosteroids within the last 30 days prior to study inclusion
3. Systemic or inhalative antiviral treatment such as aciclovir; zanamivir, or oseltamivir within 30 days prior to visit 1.
4. Treatment with registered alternative medicinal preparations for treatment of common cold like symptoms or with immunomodulating properties,
within the last 7 days prior to study inclusion
5. Treatment with bronchodilatators within the last 7 days prior to study enrolment
6. Treament with expectorants or antitussives within the last 3 days before study enrolment
7. Patients requiring antibiotic treatment for any condition at study entry

c) General
1. Parallel participation in any other clinical study, participation in
another study within less than 6 weeks prior to study entry, or previous
participation in this same study
2. Pregnant, lactating women or women capable of bearing children
rejecting the use of reliable contraceptives (Pearl-lndex < 1)
3. Legal incapacity and / or other circumstances rendering the patient
unable to understand the nature, scope and possible impact of the study
4. Patients in custody by juridical or official order
5. Uncooperative patients
6. Patients who have difficulties in understanding the language
(German) in which the patient information is given
7. Patients who are in a dependent relationship with the Sponsor, the
investigator, other study team members, or the study center

a) Erkrankungen
1. Chronische Bronchitis (sämtliche Formen und Ursachen einer persistierenden, chronischen Bronchitis)
2. Patienten mit schwerwiegenden Atemwegsinfektionen, welche eine Antibiotikabehandlung erfordern
3. Diagnostizierte Asthmatiker, Patienten mit diagnostiziertem allergischen Bronchialasthma (Schweregrade Erwachsene leicht bis schwer, gemäß S2k-Leitlinie zur Diagnostik und Therapie von Patienten mit Asthma), diagnostizierte Bronchietktasie, Patienten mit diagnostizierter chronisch obstruktiver Lungenerkrankung (COPD, GOLD I – IV)
4. Zystische Fibrose
5. Bekannte Überempfindlichkeit gegen Meerrettichwurzel, Kapuzinerkresse oder einen der Hilfsstoffe von ANGOCIN® Anti-Infekt N oder des Placebo
6. Patienten mit in der Packungsbeilage genannten Kontraindikationen
7. Bekannt immungeschwächte Patienten bzw. bekannte progressive Autoimmunerkrankungen
8. Anzeichen oder Symptome einer fulminanten (plötzlich, schnell und schwerwiegend beginnenden) bakteriellen Bronchitis (Fieber > 38.5 °C)
9. Diagnostizierte schwere Erkrankungen des Herzens ab NYHA-Klasse II (z. B. Myokardinfarkt, Koronare Herzkrankheit)
10. Diagnostizierte schwere Erkrankungen der Leber (z. B. Fettleber, Leberzirrhose)
11. Diagnostizierte schwere Beeinträchtigungen der Nierenfunktion (Kreatinin im Serum > 1,4 mg/dL)
12. Schwere diagnostizierte somatopathische, neurologische und/ oder psychiatrische Erkrankungen, die es dem Patienten erschweren, eine fundierte Entscheidung über die Einwilligung zur Teilnahme in der klinischen Prüfung zu treffen. Die Beurteilung liegt im Ermessen des behandelnden Prüfarztes.
13. Patienten mit malignen Entartungen oder Krebsbehandlungen im Kopf- / Hals-Bereich in den letzten 5 Jahren, sowie in allen anderen Bereichen des Körpers in den letzten 2 Jahren vor Einschluss in die Studie mit weiterhin bestehendem Gefährdungspotential
14. Patienten mit einer Erkrankung oder in einer Situation, die nach Meinung des Prüfers den Patienten einem signifikanten Risiko aussetzen, die Studienergebnisse beeinträchtigen oder diese erheblich beeinflussen könnten
15. Bestehender Alkoholabusus bzw. Medikamenten- oder Drogenmissbrauch

b) Medikation
1. Behandlung mit immunsuppressiven Medikamenten innerhalb von 8 Wochen vor dem Screening
2. Behandlung mit systemischen oder inhalativen Antibiotika, oder systemischen oder inhalativen Corticosteroiden in den letzten 30 Tagen vor Einschluss in die Studie
3. Systemische oder inhalative antivirale Behandlungen wie etwa Aciclovir, Zanamivir oder Oseltamivir innerhalb der letzten 30 Tage vor Visite 1
4. Behandlung mit zugelassenen Homöopathika zur Bekämpfung von Erkältungssymptomen oder mit Medikamenten mit immunmodulatorischen Eigenschaften, innerhalb der letzten 7 Tage vor Einschluss in die Studie
5. Behandlung mit Bronchodilatoren innerhalb der letzten 7 Tage vor Einschluss in die Studie
6. Behandlung mit Schleimlösern oder Antitussiva innerhalb der letzten 3 Tage vor Einschluss in die Studie
7. Patienten, die zum Zeitpunkt des Einschlusses antibiotische Behandlung benötigen

Anamnese
c) Allgemeine Anamnese
1. Patienten, welche 6 Wochen vor erstmaliger Einschlussuntersuchung
oder während der klinischen Prüfung an anderen Arzneimittelstudien
teilnahmen oder teilnehmen, oder vorher in der gleichen Studie
teilgenommen haben
2. Schwangere, stillende Mütter oder gebärfähige Frauen, die die
Anwendung einer zuverlässigen Verhütungsmethode (Pearl-lndex < 1)
ablehnen
3. Rechtsunfähigkeit und/ oder andere Umstände, die den Patienten davon abhalten, das Wesen, Ziel und Auswirkungen der Studie zu verstehen
4. Personen, die aufgrund behördlicher oder gerichtlicher Anordnung in einer Anstalt untergebracht wurden
5. Unkooperative Patienten
6. Patienten, die der deutschen Sprache nicht mächtig sind (Einverständniserklärung)
7. Patienten, die in einem Abhängigkeitsverhältnis zu Sponsor, Prüfarzt, anderem Studienpersonal oder dem Prüfzentrum stehen

E.5 End points

E.5.1

Primary end point(s)

Comparison of the Change within the mean BSSinv (Baseline to Day 7) between both Treatment groups

Vergleich der Veränderung des mittleren Symptomscores BSSinv von Baseline zu Tag 7 zwischen den beiden Behandlungsgruppen.

E.5.1.1

Timepoint(s) of evaluation of this end point

day 7

Tag 7

E.5.2

Secondary end point(s)

E.5.2.1

Timepoint(s) of evaluation of this end point

After Treatment Phase (max. 12 days)

Nach Abschluss der Behandlungsphase (max. 12 Tage)

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

E.6.5

Efficacy

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

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

Yes

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:

300

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

380

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.

Keine (Generell besteht für alle Patienten die Möglichkeit, nach
Beendigung der Teilnahme an der klinischen Prüfung, soweit
erforderlich, individuell entsprechend ihrer Symptomatik nach Maßgabe
des sie betreuenden Arztes weiter behandelt zu werden.)

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

2018-07-30

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-07-04

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2020-12-10

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