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Study to Evaluate Arikayce™ in CF Patients With Chronic Pseudomonas Aeruginosa Infections

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. Identifier: NCT01315678
Recruitment Status : Completed
First Posted : March 15, 2011
Last Update Posted : April 17, 2015
Information provided by (Responsible Party):
Insmed Incorporated

Brief Summary:

A major factor in the respiratory health of Cystic Fibrosis (CF) subjects is the prevalence of chronic Pseudomonas aeruginosa infections. The Pseudomonas aeruginosa infection rate in CF patients increases with age and by age 18 years approximately 85% of CF patients in the US are infected. Liposomal amikacin for inhalation (Arikayce™) was developed as a possible treatment for chronic infection due to Pseudomonas aeruginosa in CF patients.

The purpose of this European Registration study is to determine whether Arikayce™ is effective in treating chronic lung infections caused by Pseudomonas aeruginosa in Cystic Fibrosis subjects. The effectiveness, safety and tolerability of Arikayce™ will be compared to TOBI, an inhalation antibiotic already available for use. The study will enroll approximately 300 subjects in clinics in Europe and Canada. Subjects will be required to visit the clinic 9 times (including the Screening visit) over a period of approximately 6 months. No overnight stays at the clinic will be required.

Condition or disease Intervention/treatment Phase
Pseudomonas Aeruginosa Infection Drug: Liposomal amikacin for inhalation (Arikayce) using the PARI Investigational eFlow® Nebulizer. Drug: Tobramycin inhalation solution using a PARI LC® Plus nebulizer. Phase 3

Detailed Description:

Cystic Fibrosis (CF) is a genetic disease resulting from mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Patients with CF manifest pathological changes in a variety of organs that express CFTR. The lungs are frequently affected often resulting in chronic infections by bacteria such as Pseudomonas aeruginosa and airway inflammation. Treatment of chronic lung infections is one of the principal goals of CF therapy. Arikayce™ (liposomal amikacin for inhalation) is a sustained-release formulation of amikacin encapsulated inside nanoscale liposomal carriers designed for administration via inhalation. It is hypothesized that the sustained-release pulmonary targeting and biofilm penetration properties of this formulation will have several advantages over current therapies in treating CF patients with chronic lung infection caused by Pseudomonas aeruginosa.

This Phase 3 European Registration study has been designed to evaluate the efficacy, safety and tolerability of Arikayce™ in treating CF patients with chronic bronchopulmonary infection compared to a currently available antibiotic, TOBI® (tobramycin) Inhalation Solution. Eligible subjects will be randomized 1:1 to receive 590 mg of Arikayce™ once daily via a PARI Investigational eFlow® Nebulizer or 300 mg TOBI® BID via a PARI LC® PLUS nebulizer. Subjects will receive 3 cycles of treatment with each cycle being comprised of 28 days on treatment followed by 28 days off-treatment. Total study duration is up to 186 days (~6 months) including an up to 18 day Screening period. Subjects will be evaluated for safety, tolerability and efficacy bi-weekly during the first 4 weeks of treatment, and thereafter every 4 weeks for the duration of the study. Pharmacokinetics (PK) of Arikayce™ in blood, sputum and 24-hour urine will be determined in a subgroup of study subjects who consent to PK evaluation.

At the completion of the TR02-108 protocol, subjects who have consented and meet study safety criteria may enroll in the long-term, open-label, multi-cycle extension study of 590 mg of Arikayce™ (under a separate protocol TR02-110).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 302 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomized, Open-Label, Active-Controlled, Multicenter Study to Assess the Efficacy, Safety and Tolerability of Arikayce™ in Cystic Fibrosis Patients With Chronic Infection Due to Pseudomonas Aeruginosa
Study Start Date : March 2012
Actual Primary Completion Date : June 2013
Actual Study Completion Date : August 2013

Arm Intervention/treatment
Experimental: Arikayce™
Arikayce™ is liposomal amikacin for inhalation
Drug: Liposomal amikacin for inhalation (Arikayce) using the PARI Investigational eFlow® Nebulizer.

Liposomal amikacin for inhalation is provided as a sterile aqueous liposomal dispersion for inhalation via nebulization.

  • 590 mg of liposomal amikacin for inhalation is administered once daily using the PARI Investigational eFlow® Nebulizer.
  • Administration time is approximately 13 minutes.
  • Liposomal amikacin for inhalation will be administered for 3 cycles where each cycle consists of 28 days on-treatment followed by 28 days off-treatment.

Active Comparator: TOBI®
TOBI® is tobramycin inhalation solution
Drug: Tobramycin inhalation solution using a PARI LC® Plus nebulizer.

300 mg tobramycin inhalation solution is administered twice a day using a PARI LC® Plus nebulizer.

  • Nebulization time is approximately 20 minutes for each administration.
  • Tobramycin inhalation solution will be administered for 3 cycles where each cycle consists of 28 days on-treatment followed by 28 days off-treatment

Primary Outcome Measures :
  1. Relative change in Forced Expiratory Volume in 1 second (FEV1) from baseline to end of study (Day 168) [ Time Frame: 168 days ]

Secondary Outcome Measures :
  1. Changes in pulmonary function throughout the study [ Time Frame: 168 days ]
  2. Time to and proportion of subjects experiencing a pulmonary exacerbation [ Time Frame: 168 days ]
  3. Time to first antipseudomonal antibiotic treatment for pulmonary exacerbation [ Time Frame: 168 days ]
  4. Time to and number of hospitalizations [ Time Frame: 168 days ]
  5. Change in density in Pseudomonas aeruginosa in sputum [ Time Frame: 168 days ]
  6. Change in patient reported outcomes/symptoms [ Time Frame: 168 days ]
  7. Evaluation of safety and tolerability [ Time Frame: 168 days ]

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

Key Inclusion Criteria:

  • Written informed consent or assent
  • Confirmed diagnosis of CF
  • History of chronic infection with Pseudomonas aeruginosa
  • Sputum culture positive for Pseudomonas aeruginosa at Screening
  • FEV1 ≥ 25% of predicted value at Screening

Key Exclusion Criteria:

  • FEV1 <25% of predicted at Screening
  • History of major complications of lung disease within 8 weeks prior to Screening
  • Hemoptysis of ≥60 mL in a 24-hour period within 4 weeks prior to Screening
  • History of positive culture for Burkholderia cepacia within 2 years prior to Screening
  • History of pulmonary tuberculosis or non-tuberculous mycobacterial lung disease treated within 2 years prior to Screening or requiring treatment at the time of screening
  • History of Allergic Broncho-Pulmonary Aspergillosis or any other condition requiring systemic steroids at a dose ≥ equivalent of 10 mg/day of prednisone within 3 months prior to Screening
  • Presence of any clinically significant cardiac disease
  • History of lung transplantation
  • Daily, continuous oxygen supplementation or nighttime supplemental oxygen requirement of greater than 2 L/min
  • Administration of any investigational products within 8 weeks prior to study Day 1
  • Smoking tobacco or any substance within 6 months prior to screening or anticipated inability to refrain from smoking throughout the study

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 identifier (NCT number): NCT01315678

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Sponsors and Collaborators
Insmed Incorporated
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Study Director: Gina Eagle, MD Insmed Incorporated

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Responsible Party: Insmed Incorporated Identifier: NCT01315678     History of Changes
Other Study ID Numbers: TR02-108
First Posted: March 15, 2011    Key Record Dates
Last Update Posted: April 17, 2015
Last Verified: March 2015

Keywords provided by Insmed Incorporated:
Cystic Fibrosis
Respiratory Infections
Pulmonary Cystic Fibrosis
Anti-bacterial Agents

Additional relevant MeSH terms:
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Communicable Diseases
Cystic Fibrosis
Pseudomonas Infections
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Gram-Negative Bacterial Infections
Bacterial Infections
Pharmaceutical Solutions
Anti-Bacterial Agents
Anti-Infective Agents