Safety/Tolerability Study of Arikayce™ in Cystic Fibrosis Patients With Chronic Infection Due to Pseudomonas Aeruginosa
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| ClinicalTrials.gov Identifier: NCT00558844 |
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Recruitment Status :
Completed
First Posted : November 15, 2007
Results First Posted : June 4, 2019
Last Update Posted : June 4, 2019
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| 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 |
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.
| 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 |
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: A
Arikayce™ at 560 mg Subjects randomized 2:1 to receive Arikayce 560 mg or Placebo.
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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. |
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Placebo Comparator: B
Matching placebo for 560 mg Subjects randomized 2:1 to receive Arikayce 560 mg or Placebo.
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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. |
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Active Comparator: C
Arikayce™ at 70 mg Subjects randomized 1:1:1 to receive Arikayce 70 mg, Arikayce 140 mg or Placebo.
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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. |
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Active Comparator: D
Arikayce™ at 140 mg Subjects randomized 1:1:1 to receive Arikayce 70 mg, Arikayce 140 mg or Placebo.
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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. |
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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.
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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. |
- 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.
- Pharmacokinetics of Arikayce™ in Serum [ Time Frame: Day 1, Day 14 and Day 28 ]Measure PK parameter (Cmax) of Arikayce in serum
- 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
- Pharmacokinetics (PK) of Arikayce™ in Urine [ Time Frame: Day 1, Day 14 and Day 28 ]Measure PK parameter (Ae0-24) of Arikayce in urine
- Pharmacokinetics (PK) of Arikayce™ in Serum [ Time Frame: Day 1, Day 14 and Day 28 ]Measure PK parameter (AUC) of Arikayce in Serum
- 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
- 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
- Duration of Systemic Anti-Pseudomonal Rescue Therapy [ Time Frame: Through study duration, approximately 84 days ]
- 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.
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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:
- 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
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
| 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 | |
| Study Director: | Gina Eagle, MD | Insmed Incorporated |
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| 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 |
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Cystic Fibrosis Respiratory Infections Pulmonary Cystic Fibrosis CFTR |
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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 |