Clinical trial NCT00558844: Safety/Tolerability Study of Arikayce™ in Cystic Fibrosis Patients With Chronic Infection Due to Pseudomonas Aeruginosa
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Cystic Fibrosis
Keywords: Cystic Fibrosis
Respiratory Infections
Pulmonary Cystic Fibrosis
CFTR
Lead sponsor: Insmed Incorporated
Sponsor class: INDUSTRY
First posted: 2007-11-15
Enrollment: 41
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events
timeFrame: 56 days
Secondary outcomes:
measure: Pharmacokinetics of Arikayce™ in Serum
timeFrame: Day 1, Day 14 and Day 28
measure: Pharmacokinetics (PK) of Arikayce™ in Sputum
timeFrame: Day 1 post-dose, Day 14 pre- and post-dose, Day 28 pre- and post-dose
measure: Pharmacokinetics (PK) of Arikayce™ in Urine
timeFrame: Day 1, Day 14 and Day 28
measure: Pharmacokinetics (PK) of Arikayce™ in Serum
timeFrame: Day 1, Day 14 and Day 28
measure: Pulmonary Function: Pre-Dose FEV1 (%-Predicted)
timeFrame: Baseline, Day 28, Day 56, Day 70 and Day 84
measure: Density of Pseudomonas Aeruginosa in Sputum
timeFrame: Day 7, Day 14, Day 21, Day 28 and Day 35
measure: Duration of Systemic Anti-Pseudomonal Rescue Therapy
timeFrame: Through study duration, approximately 84 days
measure: CFQ-R Respiratory Scale (Relative Change % From Baseline)
timeFrame: Day 15, Day 28 and Day 42
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Los Angeles
country: United States
state: California
city: Miami
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Indianapolis
country: United States
state: Indiana
city: Iowa City
country: United States
state: Iowa
city: Baltimore
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Ann Arbor
country: United States
state: Michigan
city: Minneapolis
country: United States
state: Minnesota
city: Jackson
country: United States
state: Mississippi
city: Saint Louis
country: United States
state: Missouri
city: Morristown
country: United States
state: New Jersey
city: New Brunswick
country: United States
state: New Jersey
city: Albuquerque
country: United States
state: New Mexico
city: Rochester
country: United States
state: New York
city: Philadelphia
country: United States
state: Pennsylvania
city: Sioux Falls
country: United States
state: South Dakota
city: Seattle
country: United States
state: Washington
Study officials:
affiliation: Insmed Incorporated
name: Gina Eagle, MD
role: STUDY_DIRECTOR
References:
citation: Okusanya OO, Bhavnani SM, Hammel JP, Forrest A, Bulik CC, Ambrose PG, Gupta R. Evaluation of the pharmacokinetics and pharmacodynamics of liposomal amikacin for inhalation in cystic fibrosis patients with chronic pseudomonal infections using data from two phase 2 clinical studies. Antimicrob Agents Chemother. 2014 Sep;58(9):5005-15. doi: 10.1128/AAC.02421-13. Epub 2014 Mar 31.
citation: Clancy JP, Dupont L, Konstan MW, Billings J, Fustik S, Goss CH, Lymp J, Minic P, Quittner AL, Rubenstein RC, Young KR, Saiman L, Burns JL, Govan JR, Ramsey B, Gupta R; Arikace Study Group. Phase II studies of nebulised Arikace in CF patients with Pseudomonas aeruginosa infection. Thorax. 2013 Sep;68(9):818-25. doi: 10.1136/thoraxjnl-2012-202230. Epub 2013 Jun 8.