Clinical Trials Register

Summary
EudraCT Number:	2017-003044-20
Sponsor's Protocol Code Number:	CASK0117
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:	2017-08-24
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

2017-003044-20

A.3

Full title of the trial

A Randomised, Double-blind, Placebo-controlled, Multi-centre Clinical Study to Investigate the Efficacy and Safety of Three Doses of Cineole in Subjects with Severe Acute Bronchitis with or without Associated Common Cold

A.3.1

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

A study of the effectiveness and safety of Cineole in patients suffering from severe bronchitis with or without associated common cold

A.4.1

Sponsor's protocol code number

CASK0117

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	Cassella-med 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	Cassella-med 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	Cassella-med GmbH & Co. KG
B.5.2	Functional name of contact point	Clinical Operations
B.5.3	Address:
B.5.3.1	Street Address	Gereonsmuehlengasse 1
B.5.3.2	Town/ city	Cologne
B.5.3.3	Post code	50670
B.5.3.4	Country	Germany
B.5.4	Telephone number	492211652658
B.5.5	Fax number	492211652525
B.5.6	E-mail	anja.berwanger@klosterfrau.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	Yes
D.2.1.1.1	Trade name	Soledum® Kapseln 100 mg
D.2.1.1.2	Name of the Marketing Authorisation holder	Casella-med 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	Gastro-resistant capsule, soft
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	cineole
D.3.9.1	CAS number	470-82-6
D.3.9.3	Other descriptive name	CINEOLE
D.3.9.4	EV Substance Code	SUB20486
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	100
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	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	Soledum® Kapseln forte 200 mg
D.2.1.1.2	Name of the Marketing Authorisation holder	Casella-med 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	Gastro-resistant capsule, soft
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	cineole
D.3.9.1	CAS number	470-82-6
D.3.9.3	Other descriptive name	CINEOLE
D.3.9.4	EV Substance Code	SUB20486
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	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	Capsule
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule
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

Severe acute bronchitis with or without associated common cold

E.1.1.1

Medical condition in easily understood language

Severe bronchitis with or without common cold

E.1.1.2

Therapeutic area

Body processes [G] - Circulatory and Respiratory Physiological Phenomena [G09]

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	10000687
E.1.2	Term	Acute bronchitis
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

The primary objective is the dose-response behaviour of 600 mg, 900 mg and 1200 mg cineole in subjects with severe acute bronchitis with or without associated common cold.

E.2.2

Secondary objectives of the trial

Secondary objectives are the efficacy and safety of 3 different doses of cineole compared with placebo in the treatment of severe acute bronchitis.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Age between 18 and 65 years
2. Acute bronchitis since ≤ 48 hours, with or without associated common cold
3. Women of childbearing potential are allowed only with negative pregnancy test and effective contraception
4. Subjects able to follow the instructions given by the investigator
5. Signed informed consent
6. BSS > 12, indicating severe or very severe bronchitis.

E.4

Principal exclusion criteria

1. Chronic bronchitis (WHO Definition) and chronic obstructive pulmonary disease (COPD)
2. Bronchial asthma
3. Allergic rhinitis
4. Chronic rhinitis with or without nasal polyp(s)
5. Cystic fibrosis
6. Pneumonia and/or indication for treatment with antibiotics
7. Pertussis and/or pseudo-croup
8. Subjects treated with antibiotics, glucocorticosteroids (systemic or per inhalation), β2-mimetics, theophylline, expectorants/mucolytics, antitussives, cineole, or other etheric oils (systemic or per inhalation) within 7 days prior to study start or at the time of study start
9. Known hypersensitivity to cineole or any of the other compounds of Soledum® Kapseln/ Soledum® Kapseln forte
10. Known serious concomitant disease that can influence the course of the bronchitis
11. Clinically relevant renal and/or liver diseases
12. Smoking at the time of enrolment into the trial or in the last 6 months prior to the enrolment into the trial
13. Immunosuppressive states, e.g. malignancy, autoimmune diseases, AIDS
14. Pregnancy, lactation. Women without reliable contraception
15. Dependency from alcohol or drugs
16. Insufficient knowledge of local language endangering compliance
17. Subjects participating in another study or who participated in clinical studies within the last 30 days

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy variable is the sum score of the Bronchitis Severity Scale (BSS) taking into account the change/course of the sum score from start of treatment (Study Day 1) until Study Day 5 and Study Day 8. The BSS comprises the following criteria: cough, sputum production (expectoration), rales/rhonchi, chest pain when coughing and dyspnoea. Each of these 5 criteria is to be assessed by the investigator on a 5-step rating scale with the following steps: 0 = symptom not present, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe. The BSS sum score is the sum of the scores for each of the 5 criteria.

E.5.1.1

Timepoint(s) of evaluation of this end point

Study Days 1, 5 and 8

E.5.2

Secondary end point(s)

Secondary efficacy variables are:
- The course of the scores for each of the individual criteria of the BSS (which are cough, sputum production (expectoration), rales/rhonchi, chest pain when coughing and dyspnoea) from start of treatment (Study Day 1) until Study Day 5 and Study Day 8. The criterion rales/rhonchi can be assessed only based on auscultation. Therefore this criterion is assessed by investigator, but not by the subject. Hence, the individual criteria of the BSS assessed by the subject include cough, sputum production (expectoration), chest pain when coughing and dyspnoea.
- Complete remission: a BSS sum score of ≤ 2: A sum score of the BSS ≤ 2 assessed by the investigator indicates complete remission.
- Severity of cough measured on a 100 mm Visual Analogue Scale (VAS) (ranging from 0 mm = no cough to 100 mm = worst cough ever) every day from inclusion (Study Day 1) to Study Day 8
- Body temperature (measured with ear thermometer) assessed by the investigator at inclusion (Study Day 1) and Study Day 8 and assessed by the subject every day from Study Day 2 to Study Day 7, inclusively
- Treatment failure: hospitalisation due to worsening of bronchitis and / or prescription and subsequent use of any available product for bronchitis/sinusitis/common cold
- Use of antibiotics
- Assessment of the efficacy of the study medication by investigator and by subject on a verbal rating scale: 3 = very good, 2 = good, 1 = satisfactory, 0 = bad
- Use of rescue medication

Safety Assessment:
- Adverse events
- General physical examination at inclusion and at Study Day 8
- Laboratory parameters: Haematology including erythrocyte count, platelet count, white blood cell count with differential white blood cell count (WBC), liver panel with gamma-glutamyl transferase (GGT), alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), alkaline phosphatase (ALP), creatinine, C-reactive protein (CRP), vitamin D (25OH).
- Assessment of the tolerability of the study medication by investigator and by subject on a verbal rating scale; 3 = very good; 2 = good; 1 = satisfactory; 0 = bad.

E.5.2.1

Timepoint(s) of evaluation of this end point

BSS: Study Days 1, 5 8

Severity of cough: Study Days 1 to 8

Body temperature, laboratory parameters and general physical examination: Study Days 1 and 8 (and subject self assesses body temperature daily from Study Days 2 to 7)

Efficacy and safety assessment on verbal rating scale: Study Days 5, 8 and 14

Others: ongoing throughout study participation

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

Yes

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

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

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial 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:

205

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

210

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

2017-10-25

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-11-27

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2018-05-11

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