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

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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

Tracking Information
First Submitted Date  ICMJE June 17, 2013
First Posted Date  ICMJE June 21, 2013
Last Update Posted Date October 14, 2015
Study Start Date  ICMJE June 2013
Actual Primary Completion Date October 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 19, 2013)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 19, 2013)
  • 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
  • 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)
  • 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.
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Crossover Trial Determining the Efficacy of Dry Powder Mannitol to Improve Lung Function in Subjects Aged 6-17 Years
Official Title  ICMJE 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
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.

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).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Cystic Fibrosis
Intervention  ICMJE
  • 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
  • Drug: Inhaled Placebo
    The PLacebo is non respirable mannitol due to the big size particle
    Other Name: Control
Study Arms  ICMJE
  • Placebo Comparator: Inhaled Placebo
    Eight-week treatment period with inhaled placebo b.d.
    Intervention: Drug: Inhaled Placebo
  • Active Comparator: Inhaled Mannitol
    Eight-week treatment period Inhaled Mannitol 400 mg b.d.
    Intervention: Drug: Inhaled Mannitol
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 12, 2015)
95
Original Estimated Enrollment  ICMJE
 (submitted: June 19, 2013)
160
Actual Study Completion Date  ICMJE October 2015
Actual Primary Completion Date October 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Years to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01883531
Other Study ID Numbers  ICMJE DPM-CF-204
2012-002699-14 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Pharmaxis
Study Sponsor  ICMJE Pharmaxis
Collaborators  ICMJE Not Provided
Investigators  ICMJE
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
PRS Account Pharmaxis
Verification Date October 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP