Long Term Administration of Inhaled Mannitol in Cystic Fibrosis

October 6, 2020 updated by: Pharmaxis

Long Term Administration of Inhaled Mannitol in Cystic Fibrosis- A Safety and Efficacy Study

The purpose of this study is to examine the efficacy and safety of 26 weeks treatment with inhaled mannitol in subjects with cystic fibrosis. Previous studies have demonstrated improvements in lung function, mucociliary clearance, changes in physical properties of mucus, 24 hour sputum weight and quality of life. The results of this study are to further investigate and confirm these findings in addition to examine the effect on antibiotic use and chest infections. It is hypothesised that inhaled mannitol will have beneficial effects compared to a control treatment. An open label phase of 26 weeks duration will follow the blinded 26 week phase. During the open label phase all subjects will receive active treatment.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

318

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Buenos Aires, Argentina, C1426AAL
        • Atencion Integral en Reumatologia (AIR)
      • Cordoba, Argentina, 5000
        • Clinica Universitaria Privada Reina Fabiola - Universidad Cotolica de Cordoba
      • Cordoba, Argentina, 5000
        • Hospital de Ninos del la Santisima Trinidad
    • Buenos Aires
      • Bahia Blanca, Buenos Aires, Argentina, 8000
        • Hospital Interzonal Dr Jose Penna Bahia Blanca
      • Caba, Buenos Aires, Argentina, C1425EFD
        • Hospital de Ninos Dr Ricardo Gutierrez, Pediatria
      • Ciudad Autonoma, Buenos Aires, Argentina, C1270AAN
        • Hospital Gral. de Ninos Pedro de Elizalde
      • La Plata, Buenos Aires, Argentina, 1900
        • Hospital de Ninos Superiora Sor Maria Ludovica de La Plata
    • Mendosa
      • Guaymallen, Mendosa, Argentina, 5519
        • Hospital Pediatrico Dr Humberto J Notti
  • Belgium
      • Brussel, Belgium, 1090
        • UZ Brussel Laarbeeklan 101
      • Leuven, Belgium, 3000
        • UZ Gasthuisberg
    • Antwerpen
      • Edegem, Antwerpen, Belgium, 2650
        • Pediatrics Respiratory Medicine
    • Brussel
      • Bruxelles, Brussel, Belgium, 1090
        • Hopital Universitaire Reine Fabiola
  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N4N1
        • Foothills Medical Center
    • Nova Scotia
      • Halifax, Nova Scotia, Canada, B3H3A7
        • QEII Health Sciences Center
    • Ontario
      • London, Ontario, Canada, N6A1V2
        • The Children's Asthma Clinic
  • France
      • Paris, France, 75019
        • Hopital Robert Debre
    • Cedex
      • Nantes, Cedex, France, 44093
        • Hôpital Mère-Enfant
    • Cedix
      • Le Chesnay, Cedix, France, 78157
        • Hôpital André Mignot
    • Lille
      • Lille CEDEX, Lille, France, 59037
        • Hopital Jeanne de Flandre
    • Lyon
      • Bron Cedex, Lyon, France, 69677
        • Hopital Femme-Mere-Enfents
    • Strasbourg
      • Strasbourg CEDEX, Strasbourg, France, 67098
        • Hopital de Hautepierre
  • Germany
      • Munchen, Germany, 80336
        • University of Munich Medizinischen Klinik Innenstadt
      • Tubingen, Germany, 72076
        • Universitats Kinderklinik Tubungen Wurzburg
      • Wurzburg, Germany, 97080
        • Universitats Kinderklinik Wurzburg
  • Netherlands
      • Amsterdam, Netherlands, 1100DD
        • Academic Medical Centre
  • United States
    • Arizona
      • Tucson, Arizona, United States, 85724
        • University of Arizona
    • Connecticut
      • Hartford, Connecticut, United States, 66106
        • Central Connecticut Cystic Fibrosis Center
    • Florida
      • Jacksonville, Florida, United States, 32207
        • Nemours Childrens Clinic
      • Miami, Florida, United States, 33136
        • Batchelor Children's Research Institute - University of Miami
      • Orlando, Florida, United States, 32801
        • Nemours Children's Clinic Orlando
    • Idaho
      • Idaho, Idaho, United States, 83712
        • St Lukes CF Center of Idaho
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern Memorial Hospital
    • Louisiana
      • Shreveport, Louisiana, United States, 71130-3932
        • Louisiana State University Health Sciences Center
    • Maine
      • Portland, Maine, United States, 4102
        • Maine Pediatric Specialty Group
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • John Hopkins
    • Massachusetts
      • Boston, Massachusetts, United States, 62114
        • Massachusetts General Hospital
    • Missouri
      • Columbia, Missouri, United States, 65212
        • University of Missouri
    • Nebraska
      • Omaha, Nebraska, United States, 68198-5300
        • Nebraska Medical Center - Nebraska Regional CF Center
    • New York
      • Buffalo, New York, United States, 14222
        • Women and Childrens Hospital of Buffalo
    • Ohio
      • Toledo, Ohio, United States, 43606
        • The Toledo Hospital and Toledo Childrens Hospital
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • University of Oklahoma Health Sciences Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19134
        • St Christopher's Hospital for Children
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of SC
    • South Dakota
      • Sioux Falls, South Dakota, United States, 57117
        • Sanford Children's Specialty Clinic
    • Tennessee
      • Memphis, Tennessee, United States, 38105
        • Le Bonheur Children's Medical Center
    • Texas
      • Austin, Texas, United States, 78723
        • Children's Chest Associates of Austin
      • Houston, Texas, United States, 77030
        • Baylor College of Medicine
      • San Antonio, Texas, United States, 78212
        • Alamo Clinical Research Associates
      • San Antonio, Texas, United States, 78229-3900
        • Christus Santa Rosa Children's Hospital Cystic Fibrosis Center
    • Virginia
      • Richmond, Virginia, United States, 23298
        • Virginia Commonwealth University
      • Richmond, Virginia, United States, 23298
        • Pediatric Research, VCU Medical Centre
    • Washington
      • Seattle, Washington, United States, 58103
        • University of Washington Medical Centre
    • Wisconsin
      • Madison, Wisconsin, United States, 53972
        • University of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 years and older (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Have given written informed consent to participate in this study in accordance with local regulations
  2. Have a confirmed diagnosis of cystic fibrosis (positive sweat chloride value ≥ 60 mEq/L) and/or genotype with two identifiable mutations consistent with CF, accompanied by one or more clinical features consistent with the CF phenotype)
  3. Be aged > 6 years old
  4. Have FEV1 >40 % and < 90% predicted
  5. Be able to perform all the techniques necessary to measure lung function

Exclusion Criteria:

  1. Investigators, site personnel directly affiliated with this study, or their immediate families. Immediate family is defined as a spouse, parent, child or sibling, whether biologically or legally adopted.
  2. Be considered "terminally ill" or eligible for lung transplantation
  3. Have had a lung transplant
  4. Be using nebulized hypertonic saline in the 4 weeks prior to visit 1
  5. Have had a significant episode of hemoptysis (>60 mL) in the three months prior to enrolment
  6. Have had a myocardial infarction in the three months prior to enrolment
  7. Have had a cerebral vascular accident in the three months prior to enrolment
  8. Have had major ocular surgery in the three months prior to enrolment
  9. Have had major abdominal, chest or brain surgery in the three months prior to enrolment
  10. Have a known cerebral, aortic or abdominal aneurysm
  11. Be breast feeding or pregnant, or plan to become pregnant while in the study
  12. Be using an unreliable form of contraception (female subjects at risk of pregnancy only)
  13. Be participating in another investigative drug study, parallel to, or within 4 weeks of visit 0
  14. Have a known allergy to mannitol
  15. Be using beta blockers
  16. Have uncontrolled hypertension - systolic BP > 190 and / or diastolic BP > 100
  17. Have a condition or be in a situation which in the Investigator's opinion may put the subject at significant risk, may confound results or may interfere significantly with the patient's participation in the study

  18. Be 'Mannitol Tolerance Test positive'

    -

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: A
active treatment
Drug: inhaled mannitol
400 mg BD for 26 + 26 weeks
PLACEBO_COMPARATOR: B
Drug: Placebo comparator
BD for 26 weeks followed by 26 weeks of inhaled mannitol in the open label phase

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Absolute FEV1 From Baseline Over 26 Weeks
Time Frame: 26 weeks
Change from baseline in forced expiratory volume at one second (FEV1) averaged over 26 weeks (measured at 6,14 and 26 weeks) The mean absolute change from baseline FEV1 (mL) over 26 weeks (measured at week 6, 14 and 26) will be compared between the two treatment groups with a REML (restricted maximum likelihood) based repeated measures approach.Least square means presented are for the average change over the 6, 14, and 26 week visits.
26 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in FEV1 From Baseline Over 26 Weeks - Dornase Users
Time Frame: 26 weeks

In the subset of dornase users, the mean absolute change from baseline FEV1 (mL) averaged over 26 weeks (measured at week 6, 14 and 26) will be compared between the two treatment groups with a REML (restricted maximum likelihood) based repeated measures approach. Least square means presented are for the average change over the 6, 14, and 26 week visits.

Change from baseline over 26 weeks (measured at 6,14, 26 weeks) in subset of dornase users
26 weeks
Rate of Protocol Defined Pulmonary Exacerbations (PDPE)
Time Frame: 26 weeks
Exacerbations treated with IV antibiotics and with at least 4 signs and symptoms according to Fuchs criteria (1994). Summary table presents the number with 0, 1,2 and 3 PDPEs during the 26 week treatment period.
26 weeks
Hospitalisations Associated With Protocol Defined Pulmonary Exacerbations (PDPEs)
Time Frame: 26 weeks
The number of hospitalisations is summarised and then the rate per person is analysed.
26 weeks
Antibiotic Use Associated With PDPEs
Time Frame: 26 weeks
Number of courses per person in the 26 week period is summarised and then the rate per person analysed.
26 weeks
Absolute Change in FEV1 Percent Predicted at 26 Weeks
Time Frame: 26 weeks
Change from baseline at 26 weeks in FEV1 percent predicted with BOCF for those with missing values at week 26
26 weeks
Change in FVC (mL) Across 26 Weeks
Time Frame: 26 weeks
Change from baseline in forced vital capacity (FVC) across 26 weeks (measured at 6,14 and 26 weeks)
26 weeks
Change From Baseline FEF25-75 (mL/s) Over 26 Weeks
Time Frame: 26 weeks
Change from baseline in forced expiratory flow at 25-75% of forced vital capacity (FEF25-75) (mL/s) averaged over 26 weeks (measured at 6,14 and 26 weeks) The mean absolute change from baseline over 26 weeks (measured at week 6, 14 and 26) was compared between the two treatment groups with a REML (restricted maximum likelihood) based repeated measures approach. Least square means presented are for the average change over the 6, 14, and 26 week visits.
26 weeks
Sputum Weight at Baseline in Response to First Dose of Treatment
Time Frame: up to 30 mins after first dose of trial treatment
Sputum was collected during and for 30 minutes following the administration of the first dose of study treatment.
up to 30 mins after first dose of trial treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Pharmaxis

Collaborators

ethica Clinical Research Inc.
Europe: KasaConsult bvba, Hoegaarden, Belgium
Argentina: Resolution Latin America; Buenos Aires, Argentina

Investigators

  • Principal Investigator: Moira L Aitken, MD, University of Washington Medical Centre, Seattle WA

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2008

Primary Completion (ACTUAL)

April 1, 2010

Study Completion (ACTUAL)

November 1, 2010

Study Registration Dates

First Submitted

February 27, 2008

First Submitted That Met QC Criteria

February 27, 2008

First Posted (ESTIMATE)

March 7, 2008

Study Record Updates

Last Update Posted (ACTUAL)

October 9, 2020

Last Update Submitted That Met QC Criteria

October 6, 2020

Last Verified

October 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DPM-CF-302

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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