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Safety/Tolerability Study of Arikayce™ in Cystic Fibrosis Patients With Chronic Infection Due to Pseudomonas Aeruginosa

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: NCT00558844
Recruitment Status : Completed
First Posted : November 15, 2007
Results First Posted : June 4, 2019
Last Update Posted : June 4, 2019
Sponsor:
Information provided by (Responsible Party):
Insmed Incorporated

Brief Summary:
This is a study to determine the safety and tolerability of 28 days of daily dosing of 560 mg of Arikayce™ versus placebo and daily dosing of 70 mg and 140 mg of Arikayce™ versus placebo in patients who have Cystic fibrosis (CF) and chronic infection due to pseudomonas aeruginosa.

Condition or disease Intervention/treatment Phase
Cystic Fibrosis Drug: Arikayce™ 560 mg Drug: Placebo for 560 mg Drug: Arikayce™ 70 mg Drug: Arikayce™ 140 mg Drug: Placebo for 70 mg / 140 mg Phase 1 Phase 2

Detailed Description:

CF is a gentic disease resulting from mutations in a 230 kb gene on chromosome 7 known as the cystic fibrosis transmembrane conductance regulator (CFTR). Study subjects with CF manifest pathological changes in a variety or organs that express CFTR. The lungs are frequently affected, the sequelae being chronic infections and airway inflammation. The principal goal of both treatment of subjects with CF is to slow the chronic deterioration of lung function.

Study subjects will be randomized to receive either study drug or placebo (1.5% NaCl) by inhalation via a PARI eFlow nebulizer. Each subject will complete 28 days of daily dosing. All study patients will be followed for safety, pharmacokinetics, clinical and microbiologic activity for 56 days post completion of study treatment. For the two lower doses (70 mg and 140 mg): patients received drug for 28 days, followed by a 28 day safety evaluation. For 560 mg: patients received drug for 28 days, followed by a 56 day safety evaluation. The total study period will be up to 84 days, with screening visit occurring within the preceding 14 days prior to study day 1. Patients will be clinically evaluated during the first 48 hours post first study dose and weekly for the 28 day treatment period and during the follow up visits at study days 35, 42, 49, 56, 70 and 85 days to determine safety and tolerability, pharmacokinetics (PK) and clinical and microbiologic activity.

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 Arikayce™ compared to placebo. Serum, urine and sputum specimens will be collected at periodic intervals to assess PK. Additionally, sputum samples will be collected to determine changes in bacterial density. Pulmonary function testing and CFQ-R measurements will be assessed at selected time points throughout the study. An exploratory evaluation of a Cystic Fibrosis Symptom Diary (CFSD) will also be implemented. Arikace™,Arikayce™, Liposomal Amikacin for Inhalation (LAI), and Amikacin Liposome Inhalation Suspension (ALIS) may be used interchangeably throughout this study and other studies evaluating amikacin liposomal inhalation suspension.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 41 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase 1b/2a Multidose Safety and Tolerability Study of Liposomal Amikacin for Inhalation (Arikayce™) in Cystic Fibrosis Patient With Chronic Infections Due to Pseudomonas Aeruginosa.
Study Start Date : January 2008
Actual Primary Completion Date : June 2009
Actual Study Completion Date : June 2009

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cystic Fibrosis

Arm Intervention/treatment
Active Comparator: A
Arikayce™ at 560 mg Subjects randomized 2:1 to receive Arikayce 560 mg or Placebo.
Drug: Arikayce™ 560 mg

Arikayce™ at 560 mg

Subjects will be randomly assigned to study drug dose of of Arikayce™ or placebo in accordance with a code provided by the Sponsor/CRO. Randomization will be made in a 2:1 allocation between Arikayce™ and placebo. They will be blinded whether they receive Arikayce™ or Placebo Study subjects will receive Arikayce™ or placebo on Days 1 through Day 28. Drug is administered once a day via a nebulizer.


Placebo Comparator: B
Matching placebo for 560 mg Subjects randomized 2:1 to receive Arikayce 560 mg or Placebo.
Drug: Placebo for 560 mg

Matching placebo

Subjects will be randomly assigned to study drug dose of of Arikayce™ or placebo in accordance with a code provided by the Sponsor/CRO. Randomization will be made in a 2:1 allocation between Arikayce™ and placebo. They will be blinded whether they receive Arikayce™ or Placebo Study subjects will receive Arikayce™ or placebo on Days 1 through Day 28. Drug is administered once a day via a nebulizer.


Active Comparator: C
Arikayce™ at 70 mg Subjects randomized 1:1:1 to receive Arikayce 70 mg, Arikayce 140 mg or Placebo.
Drug: Arikayce™ 70 mg
Subjects will be randomly assigned to study drug dose of of Arikayce™ or placebo in accordance with a code provided by the Sponsor/CRO. Randomization will be made in a 1:1:1 allocation between Arikayce™ and placebo. They will be blinded whether they receive Arikayce™ or Placebo Study subjects will receive Arikayce™ or placebo on Days 1 through Day 28. Drug is administered once a day via a nebulizer.

Active Comparator: D
Arikayce™ at 140 mg Subjects randomized 1:1:1 to receive Arikayce 70 mg, Arikayce 140 mg or Placebo.
Drug: Arikayce™ 140 mg
Subjects will be randomly assigned to study drug dose of of Arikayce™ or placebo in accordance with a code provided by the Sponsor/CRO. Randomization will be made in a 1:1:1 allocation between Arikayce™ and placebo. They will be blinded whether they receive Arikayce™ or Placebo Study subjects will receive Arikayce™ or placebo on Days 1 through Day 28. Drug is administered once a day via a nebulizer.

Placebo Comparator: E
Matching placebo for 70 mg/140 mg Subjects randomized 1:1:1 to receive Arikayce 70 mg, Arikayce 140 mg or Placebo.
Drug: Placebo for 70 mg / 140 mg

Matching placebo

Subjects will be randomly assigned to study drug dose of of Arikayce™ or placebo in accordance with a code provided by the Sponsor/CRO. Randomization will be made in a 1:1:1 allocation between Arikayce™ and placebo. They will be blinded whether they receive Arikayce™ or Placebo Study subjects will receive Arikayce™ or placebo on Days 1 through Day 28. Drug is administered once a day via a nebulizer.





Primary Outcome Measures :
  1. Number of Participants With Treatment-Emergent Adverse Events [ Time Frame: 56 days ]
    To evaluate the safety and tolerability of 28 days of daily dosing of nebulized Arikayce™, liposomal amikacin for inhalation.


Secondary Outcome Measures :
  1. Pharmacokinetics of Arikayce™ in Serum [ Time Frame: Day 1, Day 14 and Day 28 ]
    Measure PK parameter (Cmax) of Arikayce in serum

  2. Pharmacokinetics (PK) of Arikayce™ in Sputum [ Time Frame: Day 1 post-dose, Day 14 pre- and post-dose, Day 28 pre- and post-dose ]
    Measure PK parameters (sputum concentration) of Arikayce in sputum, pre- and post-dose

  3. Pharmacokinetics (PK) of Arikayce™ in Urine [ Time Frame: Day 1, Day 14 and Day 28 ]
    Measure PK parameter (Ae0-24) of Arikayce in urine

  4. Pharmacokinetics (PK) of Arikayce™ in Serum [ Time Frame: Day 1, Day 14 and Day 28 ]
    Measure PK parameter (AUC) of Arikayce in Serum

  5. Pulmonary Function: Pre-Dose FEV1 (%-Predicted) [ Time Frame: Baseline, Day 28, Day 56, Day 70 and Day 84 ]
    Relative Change (%) from Baseline to Day 28, Day 56, Day 70, and Day 84 in Pulmonary Function

  6. Density of Pseudomonas Aeruginosa in Sputum [ Time Frame: Day 7, Day 14, Day 21, Day 28 and Day 35 ]
    Change (log10 CFU) from Baseline by Study Day and Treatment Arm

  7. Duration of Systemic Anti-Pseudomonal Rescue Therapy [ Time Frame: Through study duration, approximately 84 days ]
  8. CFQ-R Respiratory Scale (Relative Change % From Baseline) [ Time Frame: Day 15, Day 28 and Day 42 ]
    Quality of Life was measured by the absolute change from baseline in the Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory scale. Disease specific instrument designed to measure impact on overall health, daily life, perceived well-being and symptoms in patients with a diagnosis of cystic fibrosis. Scores range from 0 to 100, with higher scores indicating better health. Scores for each Health Related Quality of Life (HRQoL) domain; after recoding, each item is summed to generate a domain score and standardized.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   6 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Male or female study subjects must be adults (≥ 6 years of age)
  • Confirmed diagnosis of CF
  • History of chronic infection with P.aeruginosa
  • FEV1 ≥40% of predicted at Screening
  • Ability to comply with study medication use, study visits and procedures
  • Ability to produce 0.5 grams of sputum

Key Exclusion Criteria:

  • Administration of any investigational drug within 8 weeks to Study Day 1
  • Emergency room visit or hospitalization for CF or respiratory-related illness within 4 weeks prior to screening
  • History of alcohol, medication or illicit drug abuse within 1 yr. to screening
  • History of lung transplantation
  • Female of childbearing potential who are not practicing an acceptable method of birth control or who are lactating
  • Positive Pregnancy test
  • Use of any anti-pseudomonal antibiotics within 28 days prior to Study Day 1
  • Initiation of chronic therapy within 28 days prior to Study Day 1
  • History of sputum or throat swab culture yielding Burkholderia cepacia within 2 years prior to screening
  • History of mycobacterial and/or Aspergillus infection requiring treatment within 2 years prior to screening
  • History of biliary cirrhosis with portal hypertension, or splenomegaly

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): NCT00558844


Locations
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United States, Alabama
Birmingham, Alabama, United States
United States, California
Los Angeles, California, United States
United States, Florida
Miami, Florida, United States
Orlando, Florida, United States
United States, Indiana
Indianapolis, Indiana, United States
United States, Iowa
Iowa City, Iowa, United States
United States, Maryland
Baltimore, Maryland, United States
United States, Massachusetts
Boston, Massachusetts, United States
United States, Michigan
Ann Arbor, Michigan, United States
United States, Minnesota
Minneapolis, Minnesota, United States
United States, Mississippi
Jackson, Mississippi, United States
United States, Missouri
Saint Louis, Missouri, United States
United States, New Jersey
Morristown, New Jersey, United States
New Brunswick, New Jersey, United States
United States, New Mexico
Albuquerque, New Mexico, United States
United States, New York
Rochester, New York, United States
United States, Pennsylvania
Philadelphia, Pennsylvania, United States
United States, South Dakota
Sioux Falls, South Dakota, United States
United States, Washington
Seattle, Washington, United States
Sponsors and Collaborators
Insmed Incorporated
Investigators
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Study Director: Gina Eagle, MD Insmed Incorporated
Additional Information:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Insmed Incorporated
ClinicalTrials.gov Identifier: NCT00558844    
Other Study ID Numbers: TR02-106
First Posted: November 15, 2007    Key Record Dates
Results First Posted: June 4, 2019
Last Update Posted: June 4, 2019
Last Verified: May 2019
Keywords provided by Insmed Incorporated:
Cystic Fibrosis
Respiratory Infections
Pulmonary Cystic Fibrosis
CFTR
Additional relevant MeSH terms:
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Infection
Cystic Fibrosis
Fibrosis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases