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

NCT02134353 | Completed Phase 3 Results DMC

• 1 other identifier: DPM-CF-303
• Study Type: interventional
• Target: 423
• Locations: 18 countries
• Sites: 100

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

Conditions

Cystic Fibrosis

Outcome Measures

Primary Outcomes (1)

• Mean Change in FEV1 (mL) From Baseline (Visit 1) Over the 26-week Treatment Period (to Visit 4).

  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. Missing values due to withdrawal for reasons related to safety or efficacy were imputed using a baseline observation carried forward approach (BOCF).

  26 weeks

Secondary Outcomes (1)

• Mean Change From Baseline FVC (mL) Over the 26-week Treatment Period

  26 weeks

Other Outcomes (7)

• Time to First Pulmonary Exacerbation Over the 26-week Treatment Period

  26 weeks

• Number of Days on Antibiotics (Oral, Inhaled or IV) Due to Pulmonary Exacerbation

  26 weeks

• Number of Days in Hospital Due to Pulmonary Exacerbation

  26 weeks

Study Arms (2)

Experimental arm A

EXPERIMENTAL

Active treatment. Inhaled Mannitol

Drug: Inhaled mannitol

Arm B - Control

PLACEBO COMPARATOR

Arm B

Drug: Placebo Comparator: Arm B - Control

Interventions

Inhaled mannitol DRUG

Inhaled mannitol 400 mg BD for 26 weeks

Experimental arm A

Placebo Comparator: Arm B - Control DRUG

Placebo Comparator: Arm B - Control BD for 26 weeks

Arm B - Control

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have given written informed consent to participate in this trial in accordance with local regulations;
• 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);
• Be aged at least 18 years old;
• Have FEV1 \> 40 % and \< 90% predicted (using NHanes III \[1\]);
• Be able to perform all the techniques necessary to measure lung function;
• 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
• 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

You may not qualify if:

• 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;
• Be considered "terminally ill" or eligible for lung transplantation;
• Have had a lung transplant;
• Be using maintenance nebulized hypertonic saline in the 2 weeks prior to visit 1;
• Have had a significant episode of hemoptysis (\> 60 mL) in the three months prior to Visit 0;
• Have had a myocardial infarction in the three months prior to Visit 0;
• Have had a cerebral vascular accident in the three months prior to Visit 0;
• Have had major ocular surgery in the three months prior to Visit 0;
• Have had major abdominal, chest or brain surgery in the three months prior to Visit 0;
• Have a known cerebral, aortic or abdominal aneurysm;
• Be breast feeding or pregnant, or plan to become pregnant while in the trial;
• Be using an unreliable form of contraception (female subjects at risk of pregnancy only);
• Be participating in another investigative drug trial, parallel to, or within 4 weeks of screening (Visit 0);
• Have a known allergy to mannitol;
• Be using non-selective oral beta blockers;

Sponsors & Collaborators

• Syntara: lead

Study Sites (100)

Dr Lawrence Sinde

Mobile, Alabama, 36608, United States

Location

University of Arizona

Tucson, Arizona, 85724, United States

Location

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

Pediatric Pulmonology

Long Beach, California, 90806, United States

Location

University of CA, Davis

Sacramento, California, 95817, United States

Location

Hartford Hospital

Hartford, Connecticut, 06102, United States

Location

Dr Mitchell Rothstein

Jacksonville, Florida, 32204, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Central Florida Pulmonary Group, P.A.

Orlando, Florida, 32803, United States

Location

Tampa General Hospital

Tampa, Florida, 33606, United States

Location

Cystic Fibrosis Center of Chicago

Glenview, Illinois, 60025, United States

Location

Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

Illinois Lung Institute

Peoria, Illinois, 61537, United States

Location

University of Kansas Hospital

Kansas City, Kansas, 64081, United States

Location

Kosair Charities Pediatric Clinical Research Unit

Louisville, Kentucky, 40202, United States

Location

John Hopkins

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 62114, United States

Location

Spectrum Health Offices of Research Administration

Grand Rapids, Michigan, 49503, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

Dr Joseph Ojile

St Louis, Missouri, 63143, United States

Location

Dartmouth-Hitchcock Specialty Care

Bedford, New Hampshire, 03110, United States

Location

Long Island Jewish Medical Center

New Hyde Park, New York, 11040, United States

Location

The Cystic Fibrosis Center Beth Israel Medical Center

New York, New York, 10003, United States

Location

Dr Allen Dozor

Valhalla, New York, 10595, United States

Location

Akron Children's Hospital

Akron, Ohio, 44308, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267-0564, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

The Children's Medical Center of Dayton

Dayton, Ohio, 45404, United States

Location

The Toledo Hospital and Toledo Childrens Hospital

Toledo, Ohio, 43606, United States

Location

Pediatric Pulmonary & CF Center

Oklahoma City, Oklahoma, 73104, United States

Location

Dr Santiago Reyes

Oklahoma City, Oklahoma, 73112, United States

Location

Pediatric Clinic

Portland, Oregon, 97227, United States

Location

Medical University of SC

Charleston, South Carolina, 29425, United States

Location

One Richland Medical Park

Columbia, South Carolina, 29203, United States

Location

University of Washington

Seattle, Washington, 98195, United States

Location

Insares

Mendoza, Mendoza Province, M5500CCG, Argentina

Location

Hospital Interzonal General de Agudos Dr. Jose Penna

Bahía Blanca, 2401 (8001), Argentina

Location

Hospital del Tórax Cetrángolo

Buenos Aires, 1750, Argentina

Location

Hospital Regional Español de Bahía Blanca

Buenos Aires, 8000, Argentina

Location

Hospital San Roque

Córdoba, 1900 (5000), Argentina

Location

Mater Adult Hospital

Brisbane, Queensland, 4101, Australia

Location

UZ VUB

Brussels, B-1090, Belgium

Location

UZ Leuven

Leuven, B-3000, Belgium

Location

CHR Citadelle

Liège, 4000, Belgium

Location

QEII Health Sciences Center

Halifax, B3H 3A7, Canada

Location

Institut de recherches cliniques de Montréal

Montreal, H2X 2L0, Canada

Location

The Ottawa Hospital, General Campus

Ottawa, K1H 8L6, Canada

Location

FN Brno

Brno, 625 00, Czechia

Location

Országos Korányi Tbc

Budapest, H-1125, Hungary

Location

Klinikai Farmakológiai Központ

Debrecen, H-1031, Hungary

Location

Mosdós Tüdőgyógyintézet

Mosdós, H-7257, Hungary

Location

Törökbálint Tüdőgyógyintézet

Törökbálint, H-2045, Hungary

Location

Pediatrics Pulmonary Department Rambam Healthcare Campus

Haifa, 31096, Israel

Location

Schneider Children's Medical Center of Israel

Petah Tikva, 49202, Israel

Location

Spedali Civili Brescia

Brescia, Italy

Location

IRCCS Ca' Granda Ospedale Maggiore Policlinico Mil

Milan, Italy

Location

AOU San Luigi Gonzaga

Orbassano, Italy

Location

Aziendao Spedaliera Universitaria

Parma, Italy

Location

Cystic Fibrosis Center Hospital San Carlo

Potenza, Italy

Location

Centro Fibrosi Cistica Policlinico Umberto I

Roma, Italy

Location

Azienda Ospedaliera Universitaria Integratadi Verona

Verona, Italy

Location

Instituto Jaliscience de Investigacion Clinica

Guadalajara, 44100, Mexico

Location

Unidad Médica de Occidente

Guadalajara, 44220, Mexico

Location

Arke Estudios Clinicos S.A

Mexico City, CP 6700, Mexico

Location

CEPREP- Hospital Universitario

Monterrey, 64460, Mexico

Location

Greenlane Hospital

Auckland, New Zealand

Location

Canterbury Respiratory Research Group

Christchurch, 8011, New Zealand

Location

Otago Respiratory Research Unit, Dunedin Hospital

Dunedin, New Zealand

Location

Szpital Dziecięcy Polanki im. M. Płażyńskiego w Gdańsku sp.

Gdansk, 80-308, Poland

Location

Centrum Medyczne Karpacz SA

Karpacz, 58-540, Poland

Location

Wojewodzki Specjalistyczny Szpital Dzieciecy im. W. Buszkowskiego

Kielce, 25-381, Poland

Location

Wojewodzki Szpital Specjalistyczny im.

Lodz, 93-513, Poland

Location

Uniwersytet Medyczny im. Karola Marcinkowskiego w Poznaniu

Poznan, 60-569, Poland

Location

Sanatorium Cassia-Villa Medica S.C.

Rabka-Zdrój, 34-700, Poland

Location

Podkarpacki Osrodek Pulmonologii i Alergologii

Rzeszów, 35-612, Poland

Location

Institutul pentru Ocrotirea Mamei si Copilului "Alfred Rusescu"

Bucharest, 020395, Romania

Location

Institutul de Pneumoftiziologie "Marius Nasta" Bucuresti, Sectia Clinica Pneumologie V

Bucharest, 050159, Romania

Location

Spitalul Clinic de Pneumoftiziologie "Leon Daniello" Cluj-Napoca

Cluj-Napoca, 400371, Romania

Location

Spitalul Clinic de Pneumoftiziologie Lasi

Lasi, 700115, Romania

Location

Tatiana I. Martynenko

Barnaul, 656045, Russia

Location

Pulmonology Research Institute

Moscow, 105077, Russia

Location

Research and Clinical Center of interstitial and orphan lung diseases

Saint Petersburg, Russia

Location

Mikhail Smirnov

Vladimir, 600023, Russia

Location

Clinical Hospital# 2

Yaroslavl, 150010, Russia

Location

Oddelenie pneumológie a ftizeológie

Banská Bystrica, 975 17, Slovakia

Location

Imuno-alergologická ambulancia

Bratislava, 825 56, Slovakia

Location

Detská fakultná nemocnica Košice

Košice, 040 11, Slovakia

Location

University of Cape Town Lung Institute

Cape Town, 7700, South Africa

Location

St. Augustine's Medical Centre 2

Durban, 4001, South Africa

Location

Hospital Universitario Virgen de la Arrixaca

El Palmar, Spain

Location

Hospital Universitaro La Paz

Madrid, 28046, Spain

Location

Hospital Universitario Central de Asturias

Oviedo, 33006, Spain

Location

Hospital Virgen del Rocio Hospital Unidad de Fibrosis Quistica

Seville, 41013, Spain

Location

Hospital Universitario La Fe Neumología

Valencia, 46026, Spain

Location

Dnipropetrovsk State Medical Academy, Faculty Theraphy and Endocrinology Chair

Dnipropetrovsk, 49044, Ukraine

Location

Municipal Institution "Kherson City Clinical Hospital n.a. Afanasiy and Olha Tropin

Kherson, 73000, Ukraine

Location

Kremenchuk First City Hospital n.a. O.T.Bogaevskyy

Kremenchuk, 396170, Ukraine

Location

Department of Pulmonology and Thoracic Surgery of Public Institution " Kryvyy Rig City Clinical Hospital # 8

Kryvyy Rig, 50047, Ukraine

Location

Hospital Department of Municipal Institution "Zaporizhzhya Regional Clinical Hospital"

Zaporizhzhya, 69600, Ukraine

Location

Related Publications (1)

• Flume PA, Amelina E, Daines CL, Charlton B, Leadbetter J, Guasconi A, Aitken ML. Efficacy and safety of inhaled dry-powder mannitol in adults with cystic fibrosis: An international, randomized controlled study. J Cyst Fibros. 2021 Nov;20(6):1003-1009. doi: 10.1016/j.jcf.2021.02.011. Epub 2021 Mar 11.

  PMID: 33715994 DERIVED

MeSH Terms

Conditions

Cystic Fibrosis

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Results Point of Contact

• Title: Dr Brett Charlton
• Organization: Pharmaxis

Brett.Charlton@pharmaxis.com.au

+61 2 9454 7200

Study Officials

• Moira Aitken, MD

  PRINCIPAL INVESTIGATOR

• Brett Charlton, MD

  Medical Director

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 16, 2014
• First Posted: May 9, 2014
• Study Start: September 1, 2014
• Primary Completion: February 1, 2017
• Study Completion: February 1, 2017
• Last Updated: October 28, 2020
• Results First Posted: September 3, 2020

Record last verified: 2020-10

Locations

IT (7); ES (5); AU (1); CA (3); SL (3); AR (5); PL (7); NZ (3); ZA (2); RO (4); UA (5); IL (2); US (36); HU (4); BE (3); RU (5); CZ (1); ME (4)