A Study to Determine the Safety and Tolerability of Arikace™ Versus Placebo in Patients Who Have Bronchiectasis.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Insmed
ClinicalTrials.gov Identifier:
NCT00775138
First received: October 15, 2008
Last updated: May 31, 2012
Last verified: May 2012
  Purpose

This is a study to determine the safety and tolerability of 28 days of daily dosing of two doses (280mg and 560mg) of Arikace™ versus placebo in patients who have Bronchiectasis.


Condition Intervention Phase
Bronchiectasis
Drug: Arikace 280 mg
Drug: Arikace 560 mg
Drug: Matching Placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Placebo Controlled, Randomized, Parallel Cohort, Safety And Tolerability Study Of 2 Dose Levels Of Liposomal Amikacin For Inhalation (Arikace™) In Patients With Bronchiectasis Complicated By Chronic Infection Due To Pseudomonas Aeruginosa

Resource links provided by NLM:


Further study details as provided by Insmed:

Primary Outcome Measures:
  • Treatment emergent adverse events up to end of treatment [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
  • Treatment emergent marked laboratory abnormalities up to 28 days after study medication discontinuation [ Time Frame: 56 days ] [ Designated as safety issue: Yes ]
  • Treatment emergent pulmonary function test (PFT) abnormalities post-dose for acute tolerability assessment [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
  • Treatment emergent pulmonary function test (PFT) abnormalities up to end of treatment [ Time Frame: 56 days ] [ Designated as safety issue: Yes ]
  • Adverse events leading to permanent discontinuation of study medication [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
  • Serious adverse events up to 28 days after study medication discontinuation [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To access pharmacokinetics (PK) of Arikace™ in serum and urine, and evaluate sputum amikacin levels [ Time Frame: 28 days dosing ] [ Designated as safety issue: Yes ]
  • To evaluate change in Pulmonary function [ Time Frame: 28 days dosing ] [ Designated as safety issue: Yes ]
  • To evaluate change in density of Pseudomonas aeruginosa in sputum [ Time Frame: 28 days dosing ] [ Designated as safety issue: Yes ]
  • To evaluate time to and duration of systemic anti-Pseudomonal rescue therapy [ Time Frame: 28 days dosing ] [ Designated as safety issue: Yes ]
  • To evaluate change in St. George's Respiratory Questionnaire measurements [ Time Frame: 28 days dosing ] [ Designated as safety issue: No ]

Enrollment: 64
Study Start Date: June 2008
Study Completion Date: May 2009
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arikace at 280 mg
Subjects will be randomly assigned to study drug dose of 280mg or 560mg and then within dose group to either Arikace™ or placebo in accordance with a code provided by the Sponsor/CRO. At each dose of study drug, randomization will be made in a 2:1 allocation between Arikace™ and placebo. Thus, the final allocation among study drug levels and placebo will be 1:1:1 (Arikace™ 280mg: Arikace™ 560mg: placebo, both doses). Because of the mode of study drug delivery, study subjects will not be blinded to whether they have been assigned to the 280mg concentration or the 560mg concentration, however, they will be blinded to whether they will receive Arikace™ or placebo. Study subjects will receive Arikace™ or placebo on Days 1 through Day 28. Drug is administered once a day via a nebulizer.
Drug: Arikace 280 mg
Study subjects will receive Arikace™ 280 mg on Days 1 through Day 28. Drug is administered once a day via a nebulizer.
Experimental: Arikace at 560 mg
Subjects will be randomly assigned to study drug dose of 280mg or 560mg and then within dose group to either Arikace™ or placebo in accordance with a code provided by the Sponsor/CRO. At each dose of study drug, randomization will be made in a 2:1 allocation between Arikace™ and placebo. Thus, the final allocation among study drug levels and placebo will be 1:1:1 (Arikace™ 280mg: Arikace™ 560mg: placebo, both doses). Because of the mode of study drug delivery, study subjects will not be blinded to whether they have been assigned to the 280mg concentration or the 560mg concentration, however, they will be blinded to whether they will receive Arikace™ or placebo. Study subjects will receive Arikace™ or placebo on Days 1 through Day 28. Drug is administered once a day via a nebulizer.
Drug: Arikace 560 mg
Study subjects will receive Arikace™ 560 mg on Days 1 through Day 28. Drug is administered once a day via a nebulizer.
Placebo Comparator: Matching placebo (280mg or 560mg)
Subjects will be randomly assigned to study drug dose of 280mg or 560mg and then within dose group to either Arikace™ or placebo in accordance with a code provided by the Sponsor/CRO. At each dose of study drug, randomization will be made in a 2:1 allocation between Arikace™ and placebo. Thus, the final allocation among study drug levels and placebo will be 1:1:1 (Arikace™ 280mg: Arikace™ 560mg: placebo, both doses). Because of the mode of study drug delivery, study subjects will not be blinded to whether they have been assigned to the 280mg concentration or the 560mg concentration, however, they will be blinded to whether they will receive Arikace™ or placebo. Study subjects will receive Arikace™ or placebo on Days 1 through Day 28. Drug is administered once a day via a nebulizer.
Drug: Matching Placebo
Study subjects will receive placebo on Days 1 through Day 28. Drug is administered once a day via a nebulizer.

Detailed Description:

Bronchiectasis is a chronic disorder of the major bronchi and bronchioles characterized by permanent dilation, microbial infection, a persistent inflammatory response with the release of immune mediators and microbial toxins leading to destruction. The origin of bronchiectasis varies, but the presence of microbial infection and a persistent inflammatory response is typical of the disease. The chronic nature of the infection and the associated considerable morbidity provides the rationale for using aerosolized antibiotics for the treatment of bronchiectasis patients.

This is a multi-national Phase 2 study of safety and tolerability of 28 days of daily dosing with two dose levels (280 mg and 560 mg) of Arikace™ versus placebo in subjects with bronchiectasis (BR) and chronic pseudomonas infection. Study subjects will be randomized to receive either study drug or placebo by inhalation via a PARI eFlow nebulizer. Each subject will complete 28 days of daily dosing. All study subjects will be followed for microbiologic activity for 14 days after completion of treatment and for safety for 28 days post completion of study treatment.

The total study duration will be 56 days, with screening visit occurring within the preceding 14 days prior to study day 1. At Day 1 (baseline), subjects will be evaluated at pre-dose and during the first 4-5 hours post-dose. Subjects will return at 2 weeks (day 14) after start of treatment and at the end of 4 weeks (Day 28) treatment period to determine safety and, efficacy of Arikace™. Subjects will be followed up at study days 42 and 56 (about 2 and 4 weeks after end of treatment) for safety determination. After completion of this study, subjects will be, followed up for an additional 6 months via phone contacts and records review, if hospitalized or treated for pulmonary exacerbation (under the extension protocol).

Clinical laboratory parameters, audiology testing, clinical adverse events and pulmonary function will be evaluated for all study subjects in order to determine the qualitative and quantitative safety and tolerability of Arikace™ compared to placebo. Serum, urine and sputum specimens will be collected at periodic intervals to assess PK in subjectswho consent for the PK portion of the study. Additionally, sputum samples will be collected to determine changes in bacterial density. Total Pulmonary Symptom Severity Score will be assessed, and Respiratory quality of life will be evaluated by using the St. George's Respiratory Questionnaire (SGRQ).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female study subjects≥ 18 years of age
  • Confirmed diagnosis of multi-focal bronchiectasis in two or more lung segments by HRCT of the chest
  • History of chronic infection with P. aeruginosa
  • Confirmation of infection with P. aeruginosa at screening
  • SaO2 ≥ 90% at Screening while breathing room air
  • Ability to comply with study medication use, study visits, and study procedures as judged by the investigator
  • Ability to produce at least 0.5 grams sputum or be willing to undergo an induction to produce sputum for clinical evaluation

Exclusion Criteria:

  • Forced Expiratory Volume in 1 second (FEV1) < 50% of predicted at Screening
  • Bronchiectasis due to cystic fibrosis (CF), bronchopulmonary Aspergillus, aspiration of foreign body, or secondary to lung compression from tumors
  • History of non-tuberculous mycobacterial and/or Aspergillus infection requiring treatment or treated within 2 years prior to screening
  • Pulmonary tuberculosis requiring treatment or treated within two years prior to screening
  • History of Lung transplantation
  • Use of any inhalation or systemic antibiotics (IV antibiotics, or oral antibiotics) within 4 weeks prior to Study Day 1
  • Evidence of biliary cirrhosis with portal hypertension
  • Smoking tobacco or any substance within 6 months prior to screening, and throughout the study
  • History of alcohol, medication, or illicit drug abuse within the 1 year prior to screening
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00775138

Locations
United States, District of Columbia
Georgetown University
Washington, District of Columbia, United States, 20057
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States
Bulgaria
SHAT of Pulmonology Diseases "Sveta Sofia"
Sofia, Bulgaria
V-MHAT, Pulmonology Department
Sofia, Bulgaria
Tokuda Hospital Sofia, Internal Diseases, Sector Pulmonology
Sofia, Bulgaria
Greece
Chest Diseases Hospital of Athens "Soritia"
Athens, Greece
Hungary
Kaposi Mór Teaching Hospital
Mosdos, Hungary
India
Chest and Maternity Centre
Bangalore, India
M.S. Ramaiah Medical Hospital
Bangalore, India
Global Hospitals
Hyderabaad, India
Nizam's Institute of Medical Sciences
Hyderabaad, India
Kunal Institute of Medical Specialties
Hyderabaad, India
Kasturba Medical College
Manipal, India
Bhatia Hospital
Mumbai, India
Heart Care Center
Mumbai, India
Suchak Hospital
Mumbai, India
Center for Chest Diseases
New Delhi, India
ENGEE Health Care Pvt. Ltd.
New Delhi, India
Poland
Instytut Gruźlicy i Chorób Płuc Klinika Pulmonologii i Mukowiscydozy
Rabka Zdrój, Poland
Serbia
Clinical Center of Serbia - Institute of Lung Disease
Belgrade, Serbia
Clinical Centre Kragujevac, Department for Lung Diseases
Kragujevac, Serbia
Clinical Centre Nis, Clinic for lung diseases and tbc
Nis, Serbia
Ukraine
Institute of Phthisilogy and Pulmonology "F.G. Yanovsky"
Kiev, Ukraine
Tuberculosis City Hospital No1
Kiev, Ukraine
United Kingdom
Papworth Hospital
Cambridge, United Kingdom
Royal Brompton Hospital
London, United Kingdom
Sponsors and Collaborators
Insmed
  More Information

No publications provided

Responsible Party: Insmed
ClinicalTrials.gov Identifier: NCT00775138     History of Changes
Other Study ID Numbers: TR02-107
Study First Received: October 15, 2008
Last Updated: May 31, 2012
Health Authority: United States: Food and Drug Administration
Belgium: Federal Agency for Medicinal Products and Health Products
Bulgaria: Bulgarian Drug Agency
Hungary: National Institute of Pharmacy
United Kingdom: Medicines and Healthcare Products Regulatory Agency
India: Drugs Controller General of India
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products

Keywords provided by Insmed:
Bronchiectasis
Respiratory Infections
Amikacin
Genetic Diseases, Inborn
Respiratory Tract Diseases
Cystic Fibrosis
Respiratory Tract Infections
Lung Diseases
Infant, Newborn, Diseases
Pancreatic Diseases
Cystic fibrosis

Additional relevant MeSH terms:
Bronchiectasis
Bronchial Diseases
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on September 18, 2014