Phase 3 Study With Ciprofloxacin Dispersion for Inhalation in Non-CF Bronchiectasis (ORBIT-4)

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Pulmaquin® in the Management of Chronic Lung Infections With Pseudomonas Aeruginosa in Patients With Non-Cystic Fibrosis Bronchiectasis, Including 28 Day Open-Label Extension

This study (ARD-3150-1202, ORBIT-4) will evaluate the safety and efficacy of inhaled Pulmaquin (ciprofloxacin dispersion for inhalation) compared to inhaled placebo in subjects who have a confirmed diagnosis of non-cystic fibrosis (non-CF) bronchiectasis with a history of pulmonary exacerbations and chronic P. aeruginosa infections.

Study Overview

• Status: Completed
• Conditions: Non Cystic Fibrosis Bronchiectasis
• Intervention / Treatment: Drug: Placebo; Drug: Ciprofloxacin dispersion for inhalation

• Study Type: Interventional
• Enrollment (Actual): 304
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Greenslopes, Queensland, Australia
  • South Australia
    • Adelaide, South Australia, Australia
  • Western Australia
    • Nedlands, Western Australia, Australia
    • Perth, Western Australia, Australia
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada
  • Ontario
    • Toronto, Ontario, Canada
    • Windsor, Ontario, Canada
  • Quebec
    • St-Jerome, Quebec, Canada
• Former Serbia and Montenegro
  • Belgrade, Former Serbia and Montenegro
  • Knez Selo, Former Serbia and Montenegro
  • Kragujevac, Former Serbia and Montenegro
  • Sremska Kamenica, Former Serbia and Montenegro
• France
  • Créteil Cedex 01, France
  • Grenoble cedex, France
  • Nice Cedex 1, France
  • Pessac Cedex, France
  • Rouen Cedex, France
  • Toulouse cedex 9, France
• Georgia
  • Kutaisi, Georgia
  • Tbilisi, Georgia
• Hungary
  • Budapest, Hungary
  • Nyiregyhaza, Hungary
  • Szekesfehervar, Hungary
  • Torokbalint, Hungary
• Israel
  • Jerusalem, Israel
  • Petach Tikva, Israel
  • Ramat Gan, Israel
  • Tel-Aviv, Israel
• Italy
  • Avellino, Italy
  • Napoli, Italy
  • Parma, Italy
  • Pisa, Italy
  • San Gerardo, Italy
  • Terni, Italy
  • Trieste, Italy
• Korea, Republic of
  • Daegu, Korea, Republic of
  • Seoul, Korea, Republic of
  • Gyeonggi-do
    • Suwon, Gyeonggi-do, Korea, Republic of
• New Zealand
  • Tauranga, New Zealand
  • Auckland
    • Otahuhu, Auckland, New Zealand
  • Waikato
    • Hamilton, Waikato, New Zealand
• Peru
  • Lima
    • Jesus Maria, Lima, Peru
    • La Victoria, Lima, Peru
    • Pueblo Libre, Lima, Peru
    • San Juan de Miraflores, Lima, Peru
• Poland
  • Bialystok, Poland
  • Krakow, Poland
  • Ruda Slaska, Poland
  • Warsaw, Poland
• Romania
  • Arad, Romania
  • Bucuresti, Romania
  • Cluj-Napoca, Romania
  • Craiova, Romania
  • Iasi, Romania
• Spain
  • Barcelona, Spain
  • La Coruna, Spain
  • Lleida, Spain
  • Valencia, Spain
• United Kingdom
  • Cambridge, United Kingdom
  • Colchester, United Kingdom
  • Cottingham, United Kingdom
  • Lancaster, United Kingdom
  • Leeds, United Kingdom
  • London, United Kingdom
  • Manchester, United Kingdom
  • North Sheilds, United Kingdom
  • Southampton, United Kingdom
  • Telford, United Kingdom
  • Cleveland
    • Stockton-on-Trees, Cleveland, United Kingdom
  • Greater Manchester
    • Wigan, Greater Manchester, United Kingdom
• United States
  • Arizona
    • Phoenix, Arizona, United States
    • Scottsdale, Arizona, United States
  • California
    • Sacramento, California, United States
    • San Diego, California, United States
    • Torrance, California, United States
  • Connecticut
    • Danbury, Connecticut, United States
  • Florida
    • Miami, Florida, United States
    • Orlando, Florida, United States
    • Winter Park, Florida, United States
  • Georgia
    • Decatur, Georgia, United States
    • Duluth, Georgia, United States
  • Michigan
    • Port Huron, Michigan, United States
  • Nebraska
    • Omaha, Nebraska, United States
  • New Hampshire
    • Lebanon, New Hampshire, United States
  • New Jersey
    • Summit, New Jersey, United States
  • New Mexico
    • Albuquerque, New Mexico, United States
  • New York
    • New York, New York, United States
  • North Carolina
    • Chapel Hill, North Carolina, United States
  • Ohio
    • Columbus, Ohio, United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States
  • South Carolina
    • Rock Hill, South Carolina, United States
    • Spartanburg, South Carolina, United States
  • Texas
    • Tyler, Texas, United States
  • Washington
    • Seattle, Washington, United States
  • Wisconsin
    • Milwaukee, Wisconsin, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Confirmed diagnosis of non-CF bronchiectasis
• History of P. aeruginosa respiratory infections
• At least two pulmonary exacerbations treated with antibiotics in the previous year

Exclusion Criteria:

• Have a clinical diagnosis of CF
• Are pregnant

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Ciprofloxacin dispersion for inhalation; Liquid mixture of liposomally encapsulated and unencapsulated ciprofloxacin	Drug: Ciprofloxacin dispersion for inhalation
PLACEBO_COMPARATOR: Placebo; Liquid formulation of empty liposomes	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time to first pulmonary exacerbation (from baseline)	48 weeks

Collaborators and Investigators

• Sponsor: Aradigm Corporation
• Collaborators: Grifols Therapeutics LLC

Publications and helpful links

General Publications

• Chalmers JD, Cipolla D, Thompson B, Davis AM, O'Donnell A, Tino G, Gonda I, Haworth C, Froehlich J. Changes in respiratory symptoms during 48-week treatment with ARD-3150 (inhaled liposomal ciprofloxacin) in bronchiectasis: results from the ORBIT-3 and -4 studies. Eur Respir J. 2020 Oct 22;56(4):2000110. doi: 10.1183/13993003.00110-2020. Print 2020 Oct.
• Haworth CS, Bilton D, Chalmers JD, Davis AM, Froehlich J, Gonda I, Thompson B, Wanner A, O'Donnell AE. Inhaled liposomal ciprofloxacin in patients with non-cystic fibrosis bronchiectasis and chronic lung infection with Pseudomonas aeruginosa (ORBIT-3 and ORBIT-4): two phase 3, randomised controlled trials. Lancet Respir Med. 2019 Mar;7(3):213-226. doi: 10.1016/S2213-2600(18)30427-2. Epub 2019 Jan 15. Erratum In: Lancet Respir Med. 2019 Jan 25;:

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 28, 2014
• Primary Completion (ACTUAL): August 11, 2016
• Study Completion (ACTUAL): October 1, 2016

Study Registration Dates

• First Submitted: March 28, 2014
• First Submitted That Met QC Criteria: April 2, 2014
• First Posted (ESTIMATE): April 4, 2014

Study Record Updates

• Last Update Posted (ACTUAL): March 26, 2021
• Last Update Submitted That Met QC Criteria: March 23, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Non Cystic Fibrosis Bronchiectasis, Pulmaquin, Ciprofloxacin, Pseudomonas aeruginosa
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Bronchial Diseases; Fibrosis; Bronchiectasis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 CYP1A2 Inhibitors; Ciprofloxacin
• Other Study ID Numbers: ARD-3150-1202