Crossover Trial Determining the Efficacy of Dry Powder Mannitol to Improve Lung Function in Subjects Aged 6-17 Years

A Phase 2 study testing Inhaled Mannitol in people with Cystic Fibrosis, run by Syntara at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

It is hypothesised that inhaled mannitol 400 mg b.d. will lead to a significant improvement in the absolute change in percentage of predicted FEV1 from baseline following eight-weeks of trial treatment compared to treatment with inhaled placebo b.d. Read more about this study

Who is it for?: Ages 6 to 17 years
Conditions the study is for: Cystic Fibrosis
What is being tested?: Inhaled Mannitol
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 95 participants
Where: 1 siteUnited Kingdom
Study dates: Jun 2013to Oct 2015
Phase: Phase 2
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 6 to 17 years
All sexes
No healthy volunteers
Child

Who may be able to join

Personally provide, or have a legal guardian provide written informed consent to participate in the trial, according to local regulations;
rhDNase and maintenance antibiotic use is allowed but treatment must have been established at least 3 months 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;
Have a confirmed diagnosis of cystic fibrosis (sweat test result greater than or equal to 60 mEq/L chloride and/or genotyping showing two identifiable mutations consistent with a diagnosis of cystic fibrosis);
Be aged greater than or equal to 6 years and < 18 years;
Have a percentage of predicted FEV1 of greater than or equal to 30% and less than or equal to 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 greater than or equal to 8 years; and
Be able to perform all the techniques necessary to measure lung function.

Who cannot join

Be using maintenance nebulised hypertonic saline;
Be considered "terminally ill"; eligible for lung transplantation, or have received a lung transplant previously;
Require home oxygen or assisted ventilation;
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);
Have a known intolerance to mannitol;
Be taking non-selective beta-blockers;

Show all 13Show fewer

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;
Have a known cerebral, aortic or abdominal aneurysm;
Be currently participating in, or have participated in another investigative drug trial within four weeks of Screening (Visit 0);
Be pregnant or breastfeeding, or plan to become pregnant whilst in the trial;
For females of childbearing potential, be using an unreliable form of contraception, (at the discretion of the investigator);
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; or
Have a "failed" or "incomplete" mannitol tolerance test (as described in Section 8.3.1.1).

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

John Radcliffe Hospital
Oxford, Oxford, OX3 9DU

Other trials in United Kingdom

About this study

Official title: 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

Any improvement in FEV1 is considered clinically meaningful; however, this trial has set a threshold of 3% for the purposes of determining an appropriate sample size for statistical power whilst retaining trial feasibility in an orphan disease population.

Read the detailed description

Drug Name: Dry powder mannitol for inhalation Phase: 2 Indication: Paediatric and adolescent cystic fibrosis Trial Centres: Multicentre Sponsor: Pharmaxis Limited, 20 Rodborough Road, Frenchs Forest, NSW 2086 Australia Trial Duration: 27 weeks Number of Subjects: 160 Trial Design: Randomised, multicentre, double-blind, placebo-controlled, crossover Primary Objective: 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 Dosage and Administration: Trial drug is to be administered via a dry powder inhaler.

Mannitol 400 mg b.d. for 8 weeks followed by a 8-week washout followed by placebo b.d. for 8 weeks; or
Placebo b.d. for 8 weeks followed by a 8-week washout followed by mannitol 400 mg b.d. for 8 weeks.

Statistical Methods:

The primary and secondary efficacy analyses will be based upon a modified Grizzle model for crossover design. Absolute and relative changes from baseline in percentage of predicted FEV1 and FVC will be analysed. The absolute change in percentage of predicted lung function (FEV1 and FVC) will be the primary focus. Changes in FEF25-75 will also be analysed.
Safety data will be analysed descriptively (listings and summary tables).

Conditions: Cystic Fibrosis
Being tested: Inhaled Mannitol, Inhaled Placebo
Keywords: improving lung function, paediatric and adolescent, FEV1
Medical subject headings: Cystic Fibrosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Inhaled MannitolDrug
Also called Mannitol, IDPM, Dry Powder Mannitol for Inhalation, Bronchitol
Active treatment is inhaled mannitol with a particle size of 3-4 microns
Inhaled PlaceboDrug
Also called Control
The PLacebo is non respirable mannitol due to the big size particle

Study groups in NCT01883531
Study group	Role	What they receive
Inhaled Placebo	Placebo comparator	Eight-week treatment period with inhaled placebo b.d. Receives: Drug: Inhaled Placebo
Inhaled Mannitol	Active comparator	Eight-week treatment period Inhaled Mannitol 400 mg b.d. Receives: Drug: Inhaled Mannitol

What is being measured

The primary outcome is the main question the study is designed to answer.

Effect on lung function (FEV1)
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.
Measured: The absolute change from each treatment period baseline to week 8 of each treatment period in percentage of predicted FEV1.

Secondary outcomes (4)

Effect on FVC
To determine the effect of inhaled mannitol on FVC
Measured: The absolute change from each treatment period baseline to week 8 of each treatment period in percentage of predicted FVC.
Effect of inhaled mannitol on FEF25-75
To determine the effect of inhaled mannitol on FEF25-75 (exploratory endpoint)
Measured: The absolute change from each treatment period baseline to week 8 of each treatment period in percentage of predicted FEF25-75.
Assess safety
Assessment of safety will be made on the basis of reviewing changes in physical examination and using adverse event data.
Measured: From each treatment period baseline to week 8 of each treatment period.
Sputum weight
To evaluate the difference in treatment induced sputum weight in subjects treated with inhaled mannitol compared with placebo
Measured: The absolute change from each treatment period baseline to week 8 of each treatment period in sputum weight.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jun 2013Oct 2015

First posted21 Jun 2013 (estimated)
Study startJun 2013
Primary completionOct 2015
Study completionOct 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Cystic FibrosisStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 95 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01883531
Sponsor's protocol ID: DPM-CF-204
Other IDs: 2012-002699-14
Status last verified: Oct 2015
First submitted: 17 Jun 2013
Last updated: 14 Oct 2015
Results posted: No
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Cystic Fibrosis trials

Study at a glance

From the registry record, last updated by the sponsor on 14 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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
ClinicalTrials.gov ID: NCT01883531
Acronym / sponsor ID: DPM-CF-204
Conditions: Cystic Fibrosis
Keywords: improving lung function, paediatric and adolescent, FEV1
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 95 participants (actual)
Lead sponsor: SyntaraIndustry (pharma, biotech, devices)
Study start: Jun 2013
Primary completion: Oct 2015 (actual)
Study completion: Oct 2015 (actual)
First posted: 21 Jun 2013 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Mannitol 400 mg b.d. for 8 weeks followed by a 8-week washout followed by placebo b.d. for 8 weeks; or
Placebo b.d. for 8 weeks followed by a 8-week washout followed by mannitol 400 mg b.d. for 8 weeks.

Statistical Methods:

The primary and secondary efficacy analyses will be based upon a modified Grizzle model for crossover design. Absolute and relative changes from baseline in percentage of predicted FEV1 and FVC will be analysed. The absolute change in percentage of predicted lung function (FEV1 and FVC) will be the primary focus. Changes in FEF25-75 will also be analysed.
Safety data will be analysed descriptively (listings and summary tables).

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 2

Arm	Type	Receives
Inhaled Placebo	Placebo comparator	Drug: Inhaled PlaceboEight-week treatment period with inhaled placebo b.d.
Inhaled Mannitol	Active comparator	Drug: Inhaled MannitolEight-week treatment period Inhaled Mannitol 400 mg b.d.

Who may qualify

Ages: 6 to 17 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (6 listed)

Personally provide, or have a legal guardian provide written informed consent to participate in the trial, according to local regulations;
rhDNase and maintenance antibiotic use is allowed but treatment must have been established at least 3 months 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;
Have a confirmed diagnosis of cystic fibrosis (sweat test result greater than or equal to 60 mEq/L chloride and/or genotyping showing two identifiable mutations consistent with a diagnosis of cystic fibrosis);
Be aged greater than or equal to 6 years and < 18 years;
Have a percentage of predicted FEV1 of greater than or equal to 30% and less than or equal to 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 greater than or equal to 8 years; and

Key exclusion criteria (13 listed)

Be using maintenance nebulised hypertonic saline;
Be considered "terminally ill"; eligible for lung transplantation, or have received a lung transplant previously;
Require home oxygen or assisted ventilation;
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);
Have a known intolerance to mannitol;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Inhaled MannitolAlso: Mannitol, IDPM, Dry Powder Mannitol for Inhalation, BronchitolActive treatment is inhaled mannitol with a particle size of 3-4 microns	Drug	Inhaled Mannitol
Inhaled PlaceboAlso: ControlThe PLacebo is non respirable mannitol due to the big size particle	Drug	Inhaled Placebo

Primary outcome

Effect on lung function (FEV1)
Time frame: The absolute change from each treatment period baseline to week 8 of each treatment period in percentage of predicted FEV1.
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.

4 secondary outcomes

Effect on FVC
Time frame: The absolute change from each treatment period baseline to week 8 of each treatment period in percentage of predicted FVC.
Effect of inhaled mannitol on FEF25-75
Time frame: The absolute change from each treatment period baseline to week 8 of each treatment period in percentage of predicted FEF25-75.
Assess safety
Time frame: From each treatment period baseline to week 8 of each treatment period.
Sputum weight
Time frame: The absolute change from each treatment period baseline to week 8 of each treatment period in sputum weight.

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 14 Oct 2015.

Related trials for Cystic Fibrosis

RecruitingPhase 2
A Study of 24 to 52 Weeks Treatment to Evaluate The Efficacy And Safety of Galvokimig in Adult Study Participants With Non-Cystic Fibrosis Bronchiectasis
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Active, not recruitingObservational study
CFTR Modulator Effects on Bone and Muscle in Adults With Cystic Fibrosis
Cystic Fibrosis, Bone Loss
RecruitingObservational study
Natural History of Bronchiectasis
Bronchiectasis, Cystic Fibrosis
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Role of Genetic Factors in the Development of Lung Disease
Cystic Fibrosis, Pulmonary Fibrosis
RecruitingPhase 2
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Christiane De Boeck principal investigator

UZ Leuven, Belgium

Jeremy Hull, Dr principal investigator

John Radcliffe Hospital, Oxford, UK

Anne Munck, Dr principal investigator

Hôpital Robert Debré, France

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Inhaled Mannitol in people with Cystic Fibrosis, run by Syntara at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Effect on lung function (FEV1) (time frame: The absolute change from each treatment period baseline to week 8 of each treatment period in percentage of predicted FEV1.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01883531.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Oct 2015.