Clinical Trials Register

Summary
EudraCT Number:	2012-002699-14
Sponsor's Protocol Code Number:	DPM-CF-204
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-09-20
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

France - ANSM

A.2

EudraCT number

2012-002699-14

A.3

Full title of the trial

A randomised, multicentre, double-blind, placebo-controlled, crossover trial determining the efficacy of dry powder mannitol in improving lung function in subjects with Cystic Fibrosis aged six to seventeen years

A.3.1

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

Trial of inhaled mannitol in children with cystic fibrosis

A.3.2

Name or abbreviated title of the trial where available

DPM-CF-204 mannitol in CF aged 6-17 years

A.4.1

Sponsor's protocol code number

DPM-CF-204

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	Pharmaxis Ltd.
B.1.3.4	Country	Australia
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	Pharmaxis Ltd.
B.4.2	Country	Australia
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Pharmaxis Pharmaceuticals Ltd
B.5.2	Functional name of contact point	European Regional Director
B.5.3	Address:
B.5.3.1	Street Address	Pharmaxis Pharmaceuticals Limited
B.5.3.2	Town/ city	Burnham, Buckinghamshire
B.5.3.3	Post code	SL1 7LW
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	4401628902121
B.5.5	Fax number	4401628669355
B.5.6	E-mail	stephen.doyle@pharmaxis.co.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	Bronchitol
D.2.1.1.2	Name of the Marketing Authorisation holder	Pharmaxis Pharmaceuticals Ltd.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU 3/05/325
D.3 Description of the IMP
D.3.1	Product name	Bronchitol
D.3.2	Product code	N/A
D.3.4	Pharmaceutical form	Inhalation powder, hard capsule
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Inhalation use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	mannitol
D.3.9.1	CAS number	69-95-8
D.3.9.2	Current sponsor code	N/A
D.3.9.3	Other descriptive name	N/A
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	400
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	Inhalation powder, hard capsule
D.8.4	Route of administration of the placebo	Inhalation use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Cystic fibrosis in children aged 6 to 17 years

E.1.1.1

Medical condition in easily understood language

Cystic fibrosis in children aged 6 to 17 years

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	15.0
E.1.2	Level	PT
E.1.2	Classification code	10011762
E.1.2	Term	Cystic fibrosis
E.1.2	System Organ Class	10010331 - Congenital, familial and genetic disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

To determine the effect of eight weeks of twice-daily treatment with inhaled dry powder mannitol on lung function (FEV1) in subjects with CF who are aged six to seventeen years

E.2.2

Secondary objectives of the trial

•To determine the effect of inhaled mannitol on FVC;
•To determine the effect of inhaled mannitol on FEF25-75 (exploratory objective) and
•To assess the safety of inhaled mannitol.
•To evaluate the difference in treatment induced sputum weight in patients treated with inhaled mannitol compared to those treated with placebo

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Personally provide, or have a legal guardian provide written informed consent to participate in the trial, according to local regulations;
2. rhDNase and maintenance antibiotic use is allowed but treatment must have been established at least 3months prior to screening. The subject must remain on rhDNase and / or maintenance antibiotics for the duration of the trial. The subject must not commence treatment with rhDNase or maintenance antibiotics during the trial;
3. Have a confirmed diagnosis of cystic fibrosis (sweat test result >= 60 mEq/L chloride and/or genotyping showing two identifiable mutations consistent with a diagnosis of cystic fibrosis);
4. Be aged >= 6 years and < 18 years;
5. Have a percentage of predicted FEV1 of >= 30% and < 90% at Screening (Visit 0). Percentage of predicted FEV1 will be calculated using Wang for children aged < 8 years, and using NHanes III for those >= 8 years; and
6. Be able to perform all the techniques necessary to measure lung function.

E.4

Principal exclusion criteria

1. Be using maintenance nebulised hypertonic saline Be considered “terminally ill”; eligible for lung transplantation, or have received a lung transplant previously;
2. Require home oxygen or assisted ventilation;
3. Have had an episode of massive haemoptysis defined as acute bleeding ≥240 ml in a 24-hour period and/or recurrent bleeding ≥100 ml/day over several days in the three-months prior to Screening (Visit 0);
4. Have a known intolerance to mannitol;
5. Be taking non-selective beta blockers;
6. In the three months prior to Screening (Visit 0) have had a myocardial infarction; a cerebral vascular accident; major ocular, abdominal, chest or brain surgery;
7. Have a known cerebral, aortic or abdominal aneurysm;
8. Be currently participating in, or have participated in another investigative drug trial within four weeks of Screening (Visit 0);
9. Be pregnant or breastfeeding, or plan to become pregnant whilst in the trial;
10. For females of childbearing potential (at the discretion of the investigator), be using an unreliable form of contraception;
11. Have a “failed” or “incomplete” mannitol tolerance test; or
12. Have any concomitant medical, psychiatric, or social condition that, in the Investigator’s opinion, would put the subject at significant risk, may confound the results or may significantly interfere with the subject’s participation in the trial.

E.5 End points

E.5.1

Primary end point(s)

The absolute change from each baseline to week 8 of each treatment period in percentage of predicted FEV1.

E.5.1.1

Timepoint(s) of evaluation of this end point

Endpoint will be evaluated at the end of the trial.

E.5.2

Secondary end point(s)

• Change in percentage of predicted FVC between placebo and mannitol treatment
• Change in percentage of predicted FEF25-75 between placebo and mannitol treatment (exploratory endpoint)
• Adverse events, vital signs and physical examination
• Treatment induced sputum weight

E.5.2.1

Timepoint(s) of evaluation of this end point

Endpoints will be evaluated at the end of the trial.

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

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)

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

E.8.1.6

Cross over

Yes

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

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

Argentina

Austria

Belgium

Canada

France

Germany

Netherlands

Spain

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

Trial is ended approximately one week after LVLS, after the last subject receives telephone contact to follow up on any adverse events following the last dose of study drug.

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

Yes

F.1.1