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

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: 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



Information from the National Library of Medicine

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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


Locations
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United States, Alabama
Dr Lawrence Sinde
Mobile, Alabama, United States, 36608
United States, Arizona
University of Arizona
Tucson, Arizona, United States, 85724
United States, Arkansas
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States, 72205
United States, California
Pediatric Pulmonology
Long Beach, California, United States, 90806
University of CA, Davis
Sacramento, California, United States, 95817
United States, Connecticut
Hartford Hospital
Hartford, Connecticut, United States, 06102
United States, Florida
Dr Mitchell Rothstein
Jacksonville, Florida, United States, 32204
University of Miami
Miami, Florida, United States, 33136
Central Florida Pulmonary Group, P.A.
Orlando, Florida, United States, 32803
Tampa General Hospital
Tampa, Florida, United States, 33606
United States, Illinois
Cystic Fibrosis Center of Chicago
Glenview, Illinois, United States, 60025
Loyola University Medical Center
Maywood, Illinois, United States, 60153
Illinois Lung Institute
Peoria, Illinois, United States, 61537
United States, Kansas
University of Kansas Hospital
Kansas City, Kansas, United States, 64081
United States, Kentucky
Kosair Charities Pediatric Clinical Research Unit
Louisville, Kentucky, United States, 40202
United States, Maryland
John Hopkins
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 62114
United States, Michigan
Spectrum Health Offices of Research Administration
Grand Rapids, Michigan, United States, 49503
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, Mississippi
University of Mississippi Medical Center
Jackson, Mississippi, United States, 39216
United States, Missouri
Dr Joseph Ojile
Saint Louis, Missouri, United States, 63143
United States, New Hampshire
Dartmouth-Hitchcock Specialty Care
Bedford, New Hampshire, United States, 03110
United States, New York
Long Island Jewish Medical Center
New Hyde Park, New York, United States, 11040
The Cystic Fibrosis Center Beth Israel Medical Center
New York, New York, United States, 10003
Dr Allen Dozor
Valhalla, New York, United States, 10595
United States, Ohio
Akron Children's Hospital
Akron, Ohio, United States, 44308
University of Cincinnati
Cincinnati, Ohio, United States, 45267-0564
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
The Children's Medical Center of Dayton
Dayton, Ohio, United States, 45404
The Toledo Hospital and Toledo Childrens Hospital
Toledo, Ohio, United States, 43606
United States, Oklahoma
Pediatric Pulmonary & CF Center
Oklahoma City, Oklahoma, United States, 73104
Dr Santiago Reyes
Oklahoma City, Oklahoma, United States, 73112
United States, Oregon
Pediatric Clinic
Portland, Oregon, United States, 97227
United States, South Carolina
Medical University of SC
Charleston, South Carolina, United States, 29425
One Richland Medical Park
Columbia, South Carolina, United States, 29203
United States, Washington
University of Washington
Seattle, Washington, United States, 98195
Argentina
Insares
Mendoza, Provincia De Mendoza, Argentina, M5500CCG
Hospital Interzonal General de Agudos Dr. Jose Penna
Bahia Blanca, Argentina, 2401 (8001)
Hospital del Tórax Cetrángolo
Buenos Aires, Argentina, 1750
Hospital Regional Español de Bahía Blanca
Buenos Aires, Argentina, 8000
Hospital San Roque
Cordoba, Argentina, 1900 (5000)
Australia, Queensland
Mater Adult Hospital
Brisbane, Queensland, Australia, 4101
Belgium
UZ VUB
Brussels, Belgium, B-1090
UZ Leuven
Leuven, Belgium, B-3000
CHR Citadelle
Liege, Belgium, 4000
Canada
QEII Health Sciences Center
Halifax, Canada, B3H 3A7
Institut de recherches cliniques de Montréal
Montréal, Canada, H2X 2L0
The Ottawa Hospital, General Campus
Ottawa, Canada, K1H 8L6
Czechia
FN Brno
Brno, Czechia, 625 00
Hungary
Országos Korányi Tbc
Budapest, Hungary, H-1125
Klinikai Farmakológiai Központ
Debrecen, Hungary, H-1031
Mosdós Tüdőgyógyintézet
Mosdós, Hungary, H-7257
Törökbálint Tüdőgyógyintézet
Törökbálint, Hungary, H-2045
Israel
Pediatrics Pulmonary Department Rambam Healthcare Campus
Haifa, Israel, 31096
Schneider Children's Medical Center of Israel
Petah-Tikva, Israel, 49202
Italy
Spedali Civili Brescia
Brescia, Italy
IRCCS Ca' Granda Ospedale Maggiore Policlinico Mil
Milano, Italy
AOU San Luigi Gonzaga
Orbassano, Italy
Aziendao Spedaliera Universitaria
Parma, Italy
Cystic Fibrosis Center Hospital San Carlo
Potenza, Italy
Centro Fibrosi Cistica Policlinico Umberto I
Roma, Italy
Azienda Ospedaliera Universitaria Integratadi Verona
Verona, Italy
Mexico
Instituto Jaliscience de Investigacion Clinica
Guadalajara, Mexico, 44100
Unidad Médica de Occidente
Guadalajara, Mexico, 44220
Arke Estudios Clinicos S.A
Mexico City, Mexico, CP 6700
CEPREP- Hospital Universitario
Monterrey, Mexico, 64460
New Zealand
Greenlane Hospital
Auckland, New Zealand
Canterbury Respiratory Research Group
Christchurch, New Zealand, 8011
Otago Respiratory Research Unit, Dunedin Hospital
Dunedin, New Zealand
Poland
Szpital Dziecięcy Polanki im. M. Płażyńskiego w Gdańsku sp.
Gdańsk, Poland, 80-308
Centrum Medyczne Karpacz SA
Karpacz, Poland, 58-540
Wojewodzki Specjalistyczny Szpital Dzieciecy im. W. Buszkowskiego
Kielce, Poland, 25-381
Wojewodzki Szpital Specjalistyczny im.
Lodz, Poland, 93-513
Uniwersytet Medyczny im. Karola Marcinkowskiego w Poznaniu
Poznan, Poland, 60-569
Sanatorium Cassia-Villa Medica S.C.
Rabka Zdroj, Poland, 34-700
Podkarpacki Osrodek Pulmonologii i Alergologii
Rzeszow, Poland, 35-612
Romania
Institutul pentru Ocrotirea Mamei si Copilului "Alfred Rusescu"
Bucuresti, Romania, 020395
Institutul de Pneumoftiziologie "Marius Nasta" Bucuresti, Sectia Clinica Pneumologie V
Bucuresti, Romania, 050159
Spitalul Clinic de Pneumoftiziologie "Leon Daniello" Cluj-Napoca
Cluj - Napoca, Romania, 400371
Spitalul Clinic de Pneumoftiziologie Lasi
Lasi, Romania, 700115
Russian Federation
Tatiana I. Martynenko
Barnaul, Russian Federation, 656045
Pulmonology Research Institute
Moscow, Russian Federation, 105077
Research and Clinical Center of interstitial and orphan lung diseases
Saint-Petersburg, Russian Federation
Mikhail Smirnov
Vladimir, Russian Federation, 600023
Clinical Hospital# 2
Yaroslavl, Russian Federation, 150010
Slovakia
Oddelenie pneumológie a ftizeológie
Banská Bystrica, Slovakia, 975 17
Imuno-alergologická ambulancia
Bratislava, Slovakia, 825 56
Detská fakultná nemocnica Košice
Košice, Slovakia, 040 11
South Africa
University of Cape Town Lung Institute
Cape Town, South Africa, 7700
St. Augustine's Medical Centre 2
Durban, South Africa, 4001
Spain
Hospital Universitario Virgen de la Arrixaca
El Palmar, Spain
Hospital Universitaro La Paz
Madrid, Spain, 28046
Hospital Universitario Central de Asturias
Oviedo, Spain, 33006
Hospital Virgen del Rocio Hospital Unidad de Fibrosis Quistica
Sevilla, Spain, 41013
Hospital Universitario La Fe Neumología
Valencia, Spain, 46026
Ukraine
Dnipropetrovsk State Medical Academy, Faculty Theraphy and Endocrinology Chair
Dnipropetrovsk, Ukraine, 49044
Municipal Institution "Kherson City Clinical Hospital n.a. Afanasiy and Olha Tropin
Kherson, Ukraine, 73000
Kremenchuk First City Hospital n.a. O.T.Bogaevskyy
Kremenchuk, Ukraine, 396170
Department of Pulmonology and Thoracic Surgery of Public Institution " Kryvyy Rig City Clinical Hospital # 8
Kryvyy Rig, Ukraine, 50047
Hospital Department of Municipal Institution "Zaporizhzhya Regional Clinical Hospital"
Zaporizhzhya, Ukraine, 69600
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    
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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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