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A Safety and Efficacy Trial of Inhaled Mannitol in Adult Cystic Fibrosis Subjects

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ClinicalTrials.gov Identifier: NCT02134353
Recruitment Status : Completed
First Posted : May 9, 2014
Last Update Posted : March 9, 2018
Sponsor:
Information provided by (Responsible Party):
Pharmaxis

Brief Summary:

This trial aims to provide prospective evidence of the safety and efficacy of mannitol 400 mg b.i.d. in subjects aged 18 years and above.

We hypothesize that inhaled mannitol 400 mg b.i.d. will increase the mean change from baseline FEV1 (mL) compared to control over the 26-week treatment period in adult subjects with cystic fibrosis. Any improvement in FEV1 is considered clinically meaningful, however, this trial has set a threshold of 80 mL for the purposes of determining an appropriate sample size for statistical power while retaining trial feasibility in an orphan disease population


Condition or disease Intervention/treatment Phase
Cystic Fibrosis Drug: Inhaled mannitol Drug: Placebo Comparator: Arm B - Control Phase 3

Detailed Description:
This is a double-blind, randomized, parallel arm, controlled, multicenter, and interventional clinical trial. Potential subjects will sign the informed consent form (ICF) and be assessed for eligibility. After satisfying all inclusion & exclusion criteria, subjects will be given a mannitol tolerance test (MTT). Those subjects that pass the MTT will be randomized to receive inhaled mannitol (400 mg b.i.d.) or control b.i.d. for a period of 26-weeks.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 423 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Long Term Administration of Inhaled Mannitol in Cystic Fibrosis - A Safety and Efficacy Trial in Adult Cystic Fibrosis Subjects
Study Start Date : October 2014
Actual Primary Completion Date : February 2017
Actual Study Completion Date : February 2017

Resource links provided by the National Library of Medicine

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

Arm Intervention/treatment
Experimental: Experimental arm A
Active treatment. Inhaled Mannitol
Drug: Inhaled mannitol
Inhaled mannitol 400 mg BD for 26 weeks

Placebo Comparator: Arm B - Control
Arm B
Drug: Placebo Comparator: Arm B - Control
Placebo Comparator: Arm B - Control BD for 26 weeks




Primary Outcome Measures :
  1. Mean change in FEV1 (mL) from baseline (Visit 1) over the 26-week treatment period (to Visit 4). [ Time Frame: 26 weeks ]
    The mean absolute change from baseline FEV1 (mL) over weeks 6, 14 and 26 will be compared between the two treatment groups with a REML based repeated measures approach


Secondary Outcome Measures :
  1. Mean change from baseline FVC (mL) over the 26-week treatment period [ Time Frame: 26 weeks ]
    To determine whether inhaled mannitol (400 mg b.i.d.) is superior to control for improving lung function as measured by mean change from baseline FVC (mL) over the 26-week treatment period in adult subjects with CF.


Other Outcome Measures:
  1. Time to first pulmonary exacerbation over the 26-week treatment period [ Time Frame: 26 weeks ]
    To determine whether inhaled mannitol (400 mg b.i.d.) is superior to control in increasing the time to first pulmonary exacerbation over the 26-week treatment period in adult subjects with CF

  2. Rate of pulmonary exacerbations over the 26-week treatment period [ Time Frame: 26 weeks ]
    To determine whether inhaled mannitol (400 mg b.i.d.) decreases the rate of pulmonary exacerbations over the 26-week treatment period compared to control in adult subjects with CF

  3. Number of days in hospital due to pulmonary exacerbation [ Time Frame: 26 weeks ]
    To determine whether in adult subjects with CF, inhaled mannitol (400 mg b.i.d.) is superior to control for decreasing the number of days in hospital due to pulmonary exacerbation.

  4. The incidence of pulmonary exacerbations [ Time Frame: 26 weeks ]
    To determine whether in adult subjects with CF, inhaled mannitol (400 mg b.i.d.) is superior to control for decreasing incidence of pulmonary exacerbations

  5. Number of days on antibiotics (oral, inhaled or IV) due to pulmonary exacerbation [ Time Frame: 26 weeks ]
    To determine whether in adult subjects with CF, inhaled mannitol (400 mg b.i.d.) is superior to control for decreasing the number of days in hospital due to pulmonary exacerbation.

  6. Ease of expectoration measured using a visual analogue scale [ Time Frame: 26 weeks ]
    To determine whether in adult subjects with CF, inhaled mannitol (400 mg b.i.d.) is superior to control for improving ease of expectoration

  7. CFQ-R respiratory domain score [ Time Frame: 26 weeks ]
    To determine whether in adult subjects with CF, inhaled mannitol (400 mg b.i.d.) is superior to control for improving respiratory symptoms measured by CFQ-R respiratory domain



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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Have given written informed consent to participate in this trial 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 at least 18 years old;
  4. Have FEV1 > 40 % and < 90% predicted (using NHanes III [1]);
  5. Be able to perform all the techniques necessary to measure lung function;
  6. Be adherent with maintenance therapies (antibiotics and or rhDNase), if used, for at least 80% of the time in the two weeks prior to visit 1 and
  7. If rhDNase and/or maintenance antibiotic are being used treatment must have been established at least 1 month prior to screening (Visit 0). The subject should remain on the rhDNase and / or maintenance antibiotics for the duration of the trial. The subject should not commence treatment with rhDNase or maintenance antibiotics during the trial

Exclusion Criteria:

  1. Be investigators, site personnel directly affiliated with this trial, 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 maintenance nebulized hypertonic saline in the 2 weeks prior to visit 1;
  5. Have had a significant episode of hemoptysis (> 60 mL) in the three months prior to Visit 0;
  6. Have had a myocardial infarction in the three months prior to Visit 0;
  7. Have had a cerebral vascular accident in the three months prior to Visit 0;
  8. Have had major ocular surgery in the three months prior to Visit 0;
  9. Have had major abdominal, chest or brain surgery in the three months prior to Visit 0;
  10. Have a known cerebral, aortic or abdominal aneurysm;
  11. Be breast feeding or pregnant, or plan to become pregnant while in the trial;
  12. Be using an unreliable form of contraception (female subjects at risk of pregnancy only);
  13. Be participating in another investigative drug trial, parallel to, or within 4 weeks of screening (Visit 0);
  14. Have a known allergy to mannitol;
  15. Be using non-selective oral beta blockers;
  16. Have uncontrolled hypertension -i.e. 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 subject's participation in the trial;or
  18. Have a failed or incomplete MTT at trial entry (as evaluated in Section 8.1.1.1).
  19. The subject must not commence treatment with rhDNase or maintenance antibiotics during the trial.

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): NCT02134353


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Sponsors and Collaborators
Pharmaxis
Investigators
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Principal Investigator: Moira Aitken, MD
Study Director: Brett Charlton, MD Medical Director

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Responsible Party: Pharmaxis
ClinicalTrials.gov Identifier: NCT02134353     History of Changes
Other Study ID Numbers: DPM-CF-303
First Posted: May 9, 2014    Key Record Dates
Last Update Posted: March 9, 2018
Last Verified: March 2018

Additional relevant MeSH terms:
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Fibrosis
Cystic 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