Clinical Trials Register

Summary
EudraCT Number:	2017-003980-36
Sponsor's Protocol Code Number:	IIT15419
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2017-11-14
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

UK - MHRA

A.2

EudraCT number

2017-003980-36

A.3

Full title of the trial

A single-Centre, open-label, exploratory study of the effect of 20 mg ambroxol hydrochloride on cough reflex sensitivity in patients with acute cough.

A.3.1

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

The effect of 20 mg ambroxol on artificially induced cough

A.3.2

Name or abbreviated title of the trial where available

A study of the effect of 20 mg ambroxol hydrochloride on cough refex

A.4.1

Sponsor's protocol code number

IIT15419

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Hull and East Yorkshire Hospitals NHS Trust
B.1.3.4	Country	United Kingdom
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	Sanofi-Aventis group
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	University of Hull
B.5.2	Functional name of contact point	Caroline Wright
B.5.3	Address:
B.5.3.1	Street Address	Respiratory Medicine
B.5.3.2	Town/ city	Castle Hill Hospital, Cottingham
B.5.3.3	Post code	HU16 5JQ
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	01482624067
B.5.5	Fax number	01482624068
B.5.6	E-mail	c.e.wright@hull.ac.uk

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	lysopaine
D.2.1.1.2	Name of the Marketing Authorisation holder	Sanofi-Aventis
D.2.1.2	Country which granted the Marketing Authorisation	France
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	lysopaine
D.3.2	Product code	NA
D.3.4	Pharmaceutical form	Lozenge
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oromucosal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ambroxol hydrochloride
D.3.9.1	CAS number	238728-92-4
D.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	2-Amino-3,5-dibromo-N-(trans-4-hydroxycyclohexyl)benzylamine
D.3.9.4	EV Substance Code	AS1
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	20
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

acute cough assouciated with URTI

E.1.1.1

Medical condition in easily understood language

cough associated with a cold

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10066522
E.1.2	Term	Acute cough
E.1.2	System Organ Class	100000004855

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 assess the effect of a single dose of 20 mg ambroxol lozenge on cough reflex sensitivity in patients with acute cough. Cough sensitivity will be measured using an artificially induced cough model, stimulating cough with four different types of challenge agents (citric acid,capsaicin,ATP and distilled water).

E.2.2

Secondary objectives of the trial

•To determine the effect of single dose of 20 mg ambroxol lozenge on cough severity VAS and urge-to-cough VAS in subjects with acute cough associated with URTI
•To evaluate changes in cough reflex sensitivity during acute cough associated with URTI in relation to the healthy (post-recovery) state.
•To assess the safety and tolerability of ambroxol

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1 Be informed of the nature of the study and have provided written informed voluntary consent;
2 Be able to speak, read, and understand English;
3 Be males or females, of any race, between 18 and 80 years of age, inclusive;
4 Subject has an acute cough and other symptoms consistent with a common cold /acute upper respiratory tract infection (URTI) diagnosis as deemed by the investigator or qualified designee based on findings from medical history review, full physical examination and vital signs;
5 The onset of symptoms must be within 72 h of study enrolment;
6 Have a Cough Severity VAS ≥ 40 mm at Screening;
7 Be in good general health (other than URTI) with no clinically relevant abnormalities based on the medical history, physical examination, and 12 lead electrocardiogram;
8 Cough at least twice to all cough challenge Agents-citric acid, Capsaicin, ATP and distilled water cough challenges at baseline.
9 If a female of child-bearing potential (i.e., have not undergone a hysterectomy or bilateral oophorectomy) or not post-menopausal (defined as no menses for at least 12 months), agree to use 2 forms of acceptable birth control from Screening through the Follow Up Visit; or if a male, they and/or their partner of child-bearing potential agree to use 1 form of acceptable birth control from Screening through the Follow Up Visit;
10 Be able to communicate effectively with the Investigator and other study centre personnel and agree to comply with the study procedures and restrictions.

E.4

Principal exclusion criteria

11 History of asthma or other respiratory related disease
12 Symptoms of runny nose, stuffy nose, sore throat, or sneezing due to any condition other than URTI or common cold (e.g., seasonal or perennial allergic rhinitis, sinusitis, strep throat, vasomotor rhinitis, etc.) as established by the investigator
13 Clinical features of a complication of the common cold during the physical examination at screening (e.g., otitis media, sinusitis, or pneumonia) with or without the need for systematic antibiotics
14 Evidence of a possible bacterial infection i.e. sinus pain, purulent nasal discharge or pleuritic pain.
15 Evidence of chest infection or pneumonia
16 Fever greater than 39ºC (102ºF oral temperature) at the time of screening if, in the judgment of the investigator, the individual is too ill to participate in the study or the fever is due to reasons other than URTI
17 Demonstrate more than two coughs to inhalation of the normal saline solution during baseline challenge
18 Current smoker or individuals who have given up smoking within the past 6 months or those with >20 pack-year smoking history;
19 Treatment with an ACE-inhibitor during the study or within 4 weeks prior to Screening
20 History of opioid use within 1 week prior to baseline;
21 Requiring concomitant therapy with prohibited medications (see Section 7.5)
22 History of known or suspected allergy or hypersensitivity reactions to ambroxol (e.g., asthma, urticaria or allergic type any of the non-medicinal ingredients contained in study investigational products.
23 Clinically significant abnormal electrocardiogram (ECG) at Screening;
24 Personal or family history of congenital long QT syndrome or family history of sudden death;
25 Pregnant or breastfeeding;
26 Treatment with an investigational drug or biologic within 30 days preceding the first dose of study medication or plans to take another investigational drug or biologic within 30 days of study completion;
27 Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results and, in the judgment of the Investigator or Sponsor, would make the subject inappropriate for entry into this trial

E.5 End points

E.5.1

Primary end point(s)

•To assess the effect of single dose of 20 mg ambroxol lozenge on cough reflex sensitivity to four different types of challenge agents in acute cough associated with URTI.

E.5.1.1

Timepoint(s) of evaluation of this end point

30 mibn and 90 min post dose

E.5.2

Secondary end point(s)

• To determine the effect of single dose of 20 mg ambroxol lozenge on cough severity VAS and urge-to-cough VAS in subjects with acute cough associated with URTI
• To evaluate changes in cough reflex sensitivity during acute cough associated with URTI in relation to the healthy (post-recovery) state.
• To assess the safety and tolerability of ambroxol

E.5.2.1

Timepoint(s) of evaluation of this end point

Vas- at baseline, 30 min and 90 min post dose and between baseline and follow-up (approx 4 weeks).
Cough refelx-baseline and followup (approx 4 weeks)

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

E.6.5

Efficacy

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

Yes

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)

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

E.8.1.1

Randomised

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

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

E.8.2.3

Other

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.8.4.1

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 trial will be 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

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