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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01883531
Recruitment Status : Completed
First Posted : June 21, 2013
Last Update Posted : October 14, 2015
Sponsor:
Information provided by (Responsible Party):
Pharmaxis

Brief 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.

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.


Condition or disease Intervention/treatment Phase
Cystic Fibrosis Drug: Inhaled Mannitol Drug: Inhaled Placebo Phase 2

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).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 95 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
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
Study Start Date : June 2013
Actual Primary Completion Date : October 2015
Actual Study Completion Date : October 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cystic Fibrosis
Drug Information available for: Mannitol

Arm Intervention/treatment
Placebo Comparator: Inhaled Placebo
Eight-week treatment period with inhaled placebo b.d.
Drug: Inhaled Placebo
The PLacebo is non respirable mannitol due to the big size particle
Other Name: Control

Active Comparator: Inhaled Mannitol
Eight-week treatment period Inhaled Mannitol 400 mg b.d.
Drug: Inhaled Mannitol
Active treatment is inhaled mannitol with a particle size of 3-4 microns
Other Names:
  • Mannitol
  • IDPM
  • Dry Powder Mannitol for Inhalation
  • Bronchitol




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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. ]
    To determine the effect of inhaled mannitol on FVC

  2. 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. ]
    To determine the effect of inhaled mannitol on FEF25-75 (exploratory endpoint)

  3. Assess safety [ Time Frame: From each treatment period baseline to week 8 of each treatment period. ]
    Assessment of safety will be made on the basis of reviewing changes in physical examination and using adverse event data.

  4. Sputum weight [ Time Frame: The absolute change from each treatment period baseline to week 8 of each treatment period in sputum weight. ]
    To evaluate the difference in treatment induced sputum weight in subjects treated with inhaled mannitol compared with placebo



Information from the National Library of Medicine

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Ages Eligible for Study:   6 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria: The subject must:

  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 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;
  3. 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);
  4. Be aged greater than or equal to 6 years and < 18 years;
  5. 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
  6. Be able to perform all the techniques necessary to measure lung function.

Exclusion Criteria: The subject must NOT:

  1. Be using maintenance nebulised hypertonic saline;
  2. Be considered "terminally ill"; eligible for lung transplantation, or have received a lung transplant previously;
  3. Require home oxygen or assisted ventilation;
  4. 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);
  5. Have a known intolerance to mannitol;
  6. Be taking non-selective beta-blockers;
  7. 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;
  8. Have a known cerebral, aortic or abdominal aneurysm;
  9. Be currently participating in, or have participated in another investigative drug trial within four weeks of Screening (Visit 0);
  10. Be pregnant or breastfeeding, or plan to become pregnant whilst in the trial;
  11. For females of childbearing potential, be using an unreliable form of contraception, (at the discretion of the investigator);
  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; or
  13. Have a "failed" or "incomplete" mannitol tolerance test (as described in Section 8.3.1.1).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01883531


Locations
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United Kingdom
John Radcliffe Hospital
Oxford, United Kingdom, OX3 9DU
Sponsors and Collaborators
Pharmaxis
Investigators
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Principal Investigator: Christiane De Boeck UZ Leuven, Belgium
Principal Investigator: Jeremy Hull, Dr John Radcliffe Hospital, Oxford, UK
Principal Investigator: Anne Munck, Dr Hôpital Robert Debré, France
Principal Investigator: Joachim Riethmuller, Dr Universitats Kinderklinik Tubingen, Germany
Principal Investigator: Larry Lands, MD 'Montreal Children's Hospital, Montreal, Canada
Principal Investigator: Alexander Möller, MD University Childrens Hospital Zurich
Principal Investigator: Sonia Volpi, MD Azienda Ospedaliera Universitaria Integrata Verona Italy
Principal Investigator: Harm Tiddens, MD Erasmus MC-Sophia Children's Hospital, Rotterdam, Netherlands
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Responsible Party: Pharmaxis
ClinicalTrials.gov Identifier: NCT01883531    
Other Study ID Numbers: DPM-CF-204
2012-002699-14 ( EudraCT Number )
First Posted: June 21, 2013    Key Record Dates
Last Update Posted: October 14, 2015
Last Verified: October 2015
Keywords provided by Pharmaxis:
improving lung function
paediatric and adolescent
FEV1
Additional relevant MeSH terms:
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Cystic Fibrosis
Fibrosis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Mannitol
Diuretics, Osmotic
Diuretics
Natriuretic Agents
Physiological Effects of Drugs