Comment Period Extended to 3/23/2015 for Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Study to Evaluate Arikace™ in CF Patients With Chronic Infection Due to Pseudomonas Aeruginosa

This study has been withdrawn prior to enrollment.
Information provided by (Responsible Party):
Insmed Incorporated Identifier:
First received: March 14, 2011
Last updated: January 9, 2015
Last verified: January 2015

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 (Arikace™) was developed as a possible treatment for chronic infection due to Pseudomonas aeruginosa in CF patients.

The purpose of this double-blind, placebo controlled study is to determine whether Arikace™ is effective in treating chronic lung infections caused by Pseudomonas aeruginosa in Cystic Fibrosis subjects. The study will enroll approximately 300 subjects in clinics in the US, Canada, Europe, Australia and New Zealand. Subjects will be randomized to 590 mg Arikace™ or placebo and will receive treatment for 28 days followed by a 56 day safety follow-up period. The subjects will be required to visit the clinic 8 times (including the Screening visit) over a period of approximately 3 months. No overnight stays at the clinic will be required. At the completion of the TR02-109 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 Arikace™ (under a separate protocol TR02-110).

Condition Intervention Phase
Cystic Fibrosis
Drug: Liposomal amikacin for inhalation
Drug: Placebo for liposomal amikacin for inhalation
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomized, Placebo-Controlled, Double-Blind, Multicenter Study to Assess the Efficacy, Safety and Tolerability of Arikace™ in Cystic Fibrosis Patients With Chronic Infection Due to Pseudomonas Aeruginosa

Resource links provided by NLM:

Further study details as provided by Insmed Incorporated:

Primary Outcome Measures:
  • Time to first protocol defined pulmonary exacerbation [ Time Frame: 84 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Relative change in FEV1 (liters) and FEV1 (% predicted) [ Time Frame: 84 days ] [ Designated as safety issue: Yes ]
  • Proportion of subjects experiencing protocol defined exacerbations [ Time Frame: 84 days ] [ Designated as safety issue: Yes ]
  • Time to first antipseudomonal antibiotic treatment for pulmonary exacerbation [ Time Frame: 84 days ] [ Designated as safety issue: Yes ]
  • Change in Pseudomonas aeruginosa and Burkholderia sp. density in sputum [ Time Frame: 84 days ] [ Designated as safety issue: Yes ]
  • Change in patient reported outcomes/symptoms [ Time Frame: 84 days ] [ Designated as safety issue: Yes ]
  • Evaluation of safety and tolerability [ Time Frame: 84 days ] [ Designated as safety issue: Yes ]

Enrollment: 0
Arms Assigned Interventions
Experimental: Arikace™
Liposomal amikacin for inhalation
Drug: Liposomal amikacin for inhalation
  • 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 28 days followed by 56 days off treatment.
Placebo Comparator: Placebo
Placebo for liposomal amikacin for inhalation
Drug: Placebo for liposomal amikacin for inhalation
  • Placebo is provided as a sterile aqueous lipid dispersion for inhalation via nebulization.
  • Administration procedures, volume and administration time are the same as for Arikace™.
  • Placebo will be administered for 28 days.

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. Arikace™ (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 double blind, placebo controlled Phase 3 study has been designed to evaluate the efficacy, safety and tolerability of Arikace™ in treating CF patients with chronic bronchopulmonary infection. Eligible subjects will be randomized 1:1 to receive 590 mg of Arikace™ or placebo once daily using a PARI Investigational eFlow® Nebulizer. Subjects will receive 28 days of treatment and will then be followed for safety for 56 days. Total study duration is up to 102 days (~3 months) including an up to 18 day Screening period. Subjects will be evaluated for safety, tolerability and efficacy bi-weekly throughout the study. Pharmacokinetics (PK) of Arikace™ 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 TR02-109 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 Arikace™ (under a separate protocol TR02-110).


Ages Eligible for Study:   6 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Key Inclusion Criteria:

  • Written informed consent or assent
  • Confirmed diagnosis of CF
  • History of chronic infection with Pseudomonas aeruginosa
  • History of documented pulmonary exacerbation requiring treatment with antibiotics in the 12 months prior to Screening
  • Sputum culture positive for Pseudomonas aeruginosa at Screening
  • FEV1 ≥ 25% of predicted value at Screening

Key Exclusion Criteria:

  • FEV1 <25% of predicted value at Screening
  • History of hypersensitivity to aminoglycosides
  • History of major complications of lung disease (including atelectasis, pneumothorax, major pleural effusion) within 8 weeks prior to Screening
  • Hemoptysis of ≥60 mL in a 24-hour period within 4 weeks 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 requiring systemic steroid treatment 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
  • Active pulmonary malignancy (primary or metastatic) or any malignancy requiring chemotherapy or radiation therapy within one year prior to Screening or anticipated during the study period
  • 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
  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 identifier: NCT01315691

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

No publications provided

Responsible Party: Insmed Incorporated Identifier: NCT01315691     History of Changes
Other Study ID Numbers: TR02-109
Study First Received: March 14, 2011
Last Updated: January 9, 2015
Health Authority: United States: Food and Drug Administration
European Union: European Medicines Agency

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

Additional relevant MeSH terms:
Cystic Fibrosis
Digestive System Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Lung Diseases
Pancreatic Diseases
Pathologic Processes
Respiratory Tract Diseases
Anti-Bacterial Agents
Anti-Infective Agents
Pharmacologic Actions
Therapeutic Uses processed this record on February 27, 2015