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

October 15, 2008
May 31, 2012
June 2008
May 2009   (final data collection date for primary outcome measure)
  • 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 ]
Same as current
Complete list of historical versions of study NCT00775138 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
A Study to Determine the Safety and Tolerability of Arikace™ Versus Placebo in Patients Who Have Bronchiectasis.
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

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.

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).

Interventional
Phase 1
Phase 2
Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Bronchiectasis
  • 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.
  • 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.
  • Drug: Matching Placebo
    Study subjects will receive placebo on Days 1 through Day 28. Drug is administered once a day via a nebulizer.
  • 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.
    Intervention: Drug: Arikace 280 mg
  • 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.
    Intervention: Drug: Arikace 560 mg
  • 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.
    Intervention: Drug: Matching Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
64
May 2009
May 2009   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Bulgaria,   Greece,   Hungary,   India,   Poland,   Serbia,   Ukraine,   United Kingdom
 
NCT00775138
TR02-107
Yes
Insmed
Insmed
Not Provided
Not Provided
Insmed
May 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP