Multidose Safety and Tolerability Study of (Arikace™) for Inhalation In Cystic Fibrosis Patients - Full Text View

Sponsored by:	Transave
Information provided by:	Transave
ClinicalTrials.gov Identifier:	NCT00558844

Purpose

This is a study to determine the safety and tolerability of 28 days of daily dosing of 560 mg of Arikace™ versus placebo in patients who have Cystic fibrosis.

Condition	Intervention	Phase
Cystic Fibrosis	Drug: Arikace™	Phase I Phase II

Genetics Home Reference related topics: cystic fibrosis

MedlinePlus related topics: Cystic Fibrosis

Drug Information available for: Amikacin Amikacin sulfate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Parallel Assignment, Safety/Efficacy Study
Official Title:	Phase 1b/2a Multidose Safety and Tolerability Study of Liposomal Amikacin for Inhalation (Arikace™) in Cystic Fibrosis Patient With Chronic Infections Due to Pseudomonas Aeruginosa.

Further study details as provided by Transave:

Primary Outcome Measures:

To evaluate the safety and tolerability of 28 days of daily dosing of nebulized Arikace™, liposomal amikacin for inhalation. [ Time Frame: 28 Days of daily dosing ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

To access pharmacokinetics (PK) of Arikace™ in serum and urine, and evaluate sputum amikacin levels [ Time Frame: 28 Days of daily dosing ] [ Designated as safety issue: Yes ]
To evaluate change in Pulmonary function [ Time Frame: 28 Days of daily dosing ] [ Designated as safety issue: Yes ]
To evaluate change in density of Pseudomonas aeruginosa in sputum [ Time Frame: 28 Days of daily dosing ] [ Designated as safety issue: Yes ]
To evaluate time to and duration of systemic anti-Pseudomonal rescue therapy [ Time Frame: 28 Days of daily dosing ] [ Designated as safety issue: No ]
To evaluate change in CFQ-R measurements [ Time Frame: 28 Days of daily dosing ] [ Designated as safety issue: Yes ]
Exploratory evaluation of a Cystic Fibrosis Symptom Diary (CFSD) [ Time Frame: 28 Days of daily dosing ] [ Designated as safety issue: No ]
Exploratory evaluation of durability of clinical benefit [ Time Frame: 28 days of daily dosing ] [ Designated as safety issue: No ]

Estimated Enrollment:	40
Study Start Date:	June 2007
Estimated Study Completion Date:	April 2009
Estimated Primary Completion Date:	February 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Active Comparator Arikace at 560 mg	Drug: Arikace™ Subjects will be randomly assigned to study drug dose of of Arikace™ or placebo in accordance with a code provided by the Sponsor/CRO. Randomization will be made in a 2:1 allocation between Arikace™ and placebo. They will be blinded whether they 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.
B: Placebo Comparator Matching placebo	Drug: Arikace™ Subjects will be randomly assigned to study drug dose of of Arikace™ or placebo in accordance with a code provided by the Sponsor/CRO. Randomization will be made in a 2:1 allocation between Arikace™ and placebo. They will be blinded whether they 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.

Arms

Assigned Interventions

A: Active Comparator

Arikace at 560 mg

Drug: Arikace™

Subjects will be randomly assigned to study drug dose of of Arikace™ or placebo in accordance with a code provided by the Sponsor/CRO. Randomization will be made in a 2:1 allocation between Arikace™ and placebo. They will be blinded whether they 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.

B: Placebo Comparator

Matching placebo

Drug: Arikace™

Subjects will be randomly assigned to study drug dose of of Arikace™ or placebo in accordance with a code provided by the Sponsor/CRO. Randomization will be made in a 2:1 allocation between Arikace™ and placebo. They will be blinded whether they 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.

Detailed Description:

Cystic fibrosis (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. 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 Arikace™ 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.

Eligibility

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

Criteria

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

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00558844

Contacts

Contact: J. P. Clancy, M.D.

205-939-5479

jclancy@peds.uab.edu

Locations

United States, Alabama
University of Alabama	Recruiting
Birmingham, Alabama, United States, 35233
Contact: J.P. Clancy, M.D. 205-939-5479 jclancy@peds.uab.edu
Contact: Heather Young 205-939-9568 hyoung@peds.uab.edu

Sponsors and Collaborators

Transave

Investigators

Principal Investigator:

J. P. Clancy, M.D.

University of Alabama, 620 ACC, 1600 7th Avenue, South Birmingham, AL 35233

More Information

Responsible Party:	Transave ( Scott Rauscher, Clinical Project Manager )
Study ID Numbers:	TR02-106
Study First Received:	November 13, 2007
Last Updated:	October 14, 2008
ClinicalTrials.gov Identifier:	NCT00558844
Health Authority:	United States: Food and Drug Administration

Keywords provided by Transave:

Cystic Fibrosis
Respiratory Infections
Pulmonary Cystic Fibrosis
CFTR

Study placed in the following topic categories:

Digestive System Diseases
Amikacin
Genetic Diseases, Inborn
Respiratory Tract Diseases
Cystic Fibrosis
Respiratory Tract Infections

Fibrosis
Lung Diseases
Infant, Newborn, Diseases
Pancreatic Diseases
Cystic fibrosis

Additional relevant MeSH terms:

Pathologic Processes

ClinicalTrials.gov processed this record on January 16, 2009