Cystic Fibrosis
Conditions
Keywords
Cystic Fibrosis, Respiratory Infections, Pulmonary Cystic Fibrosis, CFTR
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.
Interventions
DRUGArikayce™ 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.
DRUGPlacebo 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.
DRUGArikayce™ 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.
DRUGArikayce™ 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.
DRUGPlacebo 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.
Sponsors
Insmed Incorporated
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events | 56 days | To evaluate the safety and tolerability of 28 days of daily dosing of nebulized Arikayce™, liposomal amikacin for inhalation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK) of Arikayce™ in Sputum | 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 | Day 1, Day 14 and Day 28 | Measure PK parameter (Ae0-24) of Arikayce in urine |
| Pharmacokinetics (PK) of Arikayce™ in Serum | Day 1, Day 14 and Day 28 | Measure PK parameter (AUC) of Arikayce in Serum |
| Pharmacokinetics of Arikayce™ in Serum | Day 1, Day 14 and Day 28 | Measure PK parameter (Cmax) of Arikayce in serum |
| Density of Pseudomonas Aeruginosa in Sputum | 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 | Through study duration, approximately 84 days | — |
| CFQ-R Respiratory Scale (Relative Change % From Baseline) | 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. |
| Pulmonary Function: Pre-Dose FEV1 (%-Predicted) | 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arikayce™ at 560 mg Subjects randomized 2:1 to receive Arikayce 560 mg or Placebo. | 15 |
| Placebo at 560 mg Subjects randomized 2:1 to receive Arikayce 560 mg or Placebo. | 7 |
| Arikayce™ at 70 mg Subjects randomized 1:1:1 to receive Arikayce 70 mg, Arikayce 140 mg or Placebo. | 7 |
| Arikayce™ at 140 mg Subjects randomized 1:1:1 to receive Arikayce 70 mg, Arikayce 140 mg or Placebo. | 5 |
| Placebo at 70 mg/140 mg Subjects randomized 1:1:1 to receive Arikayce 70 mg, Arikayce 140 mg or Placebo. | 7 |
| Total | 41 |
Baseline characteristics
| Characteristic | Arikayce™ at 560 mg | Placebo at 560 mg | Arikayce™ at 70 mg | Arikayce™ at 140 mg | Placebo at 70 mg/140 mg | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 31.5 years STANDARD_DEVIATION 14.5 | 26.3 years STANDARD_DEVIATION 6.7 | 33.1 years STANDARD_DEVIATION 9.7 | 35.4 years STANDARD_DEVIATION 6 | 24.4 years STANDARD_DEVIATION 6.3 | 29.9 years STANDARD_DEVIATION 12.6 |
| Race/Ethnicity, Customized Black | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 14 Participants | 6 Participants | 7 Participants | 5 Participants | 6 Participants | 38 Participants |
| Region of Enrollment United States | 15 Participants | 7 Participants | 7 Participants | 5 Participants | 7 Participants | 41 Participants |
| Sex: Female, Male Female | 5 Participants | 3 Participants | 6 Participants | 1 Participants | 5 Participants | 20 Participants |
| Sex: Female, Male Male | 10 Participants | 4 Participants | 1 Participants | 4 Participants | 2 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 7 | 0 / 7 | 0 / 5 | 0 / 7 |
| other Total, other adverse events | 14 / 15 | 7 / 7 | 7 / 7 | 4 / 5 | 6 / 7 |
| serious Total, serious adverse events | 5 / 15 | 2 / 7 | 0 / 7 | 1 / 5 | 1 / 7 |
Outcome results
Primary
Number of Participants With Treatment-Emergent Adverse Events
To evaluate the safety and tolerability of 28 days of daily dosing of nebulized Arikayce™, liposomal amikacin for inhalation.
Time frame: 56 days
Population: Analyses were performed using the modified intent-to-treat (mITT) population, defined as all randomized subjects who received at least one dose of study drug
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arikayce™ at 560 mg | Number of Participants With Treatment-Emergent Adverse Events | Patients with Serious AEs | 5 Participants |
| Arikayce™ at 560 mg | Number of Participants With Treatment-Emergent Adverse Events | Patients with AEs | 14 Participants |
| Arikayce™ at 560 mg | Number of Participants With Treatment-Emergent Adverse Events | Patients Permanently Discontinuing due to AEs | 4 Participants |
| Arikayce™ at 560 mg | Number of Participants With Treatment-Emergent Adverse Events | Patients with Treatment Related AEs | 7 Participants |
| Arikayce™ at 560 mg | Number of Participants With Treatment-Emergent Adverse Events | Deaths | 0 Participants |
| Placebo at 560 mg | Number of Participants With Treatment-Emergent Adverse Events | Patients with Serious AEs | 2 Participants |
| Placebo at 560 mg | Number of Participants With Treatment-Emergent Adverse Events | Deaths | 0 Participants |
| Placebo at 560 mg | Number of Participants With Treatment-Emergent Adverse Events | Patients with Treatment Related AEs | 2 Participants |
| Placebo at 560 mg | Number of Participants With Treatment-Emergent Adverse Events | Patients Permanently Discontinuing due to AEs | 0 Participants |
| Placebo at 560 mg | Number of Participants With Treatment-Emergent Adverse Events | Patients with AEs | 7 Participants |
| Arikayce™ at 70 mg | Number of Participants With Treatment-Emergent Adverse Events | Deaths | 0 Participants |
| Arikayce™ at 70 mg | Number of Participants With Treatment-Emergent Adverse Events | Patients with AEs | 7 Participants |
| Arikayce™ at 70 mg | Number of Participants With Treatment-Emergent Adverse Events | Patients with Treatment Related AEs | 2 Participants |
| Arikayce™ at 70 mg | Number of Participants With Treatment-Emergent Adverse Events | Patients with Serious AEs | 0 Participants |
| Arikayce™ at 70 mg | Number of Participants With Treatment-Emergent Adverse Events | Patients Permanently Discontinuing due to AEs | 0 Participants |
| Arikayce™ at 140 mg | Number of Participants With Treatment-Emergent Adverse Events | Patients Permanently Discontinuing due to AEs | 0 Participants |
| Arikayce™ at 140 mg | Number of Participants With Treatment-Emergent Adverse Events | Patients with AEs | 4 Participants |
| Arikayce™ at 140 mg | Number of Participants With Treatment-Emergent Adverse Events | Patients with Serious AEs | 1 Participants |
| Arikayce™ at 140 mg | Number of Participants With Treatment-Emergent Adverse Events | Deaths | 0 Participants |
| Arikayce™ at 140 mg | Number of Participants With Treatment-Emergent Adverse Events | Patients with Treatment Related AEs | 2 Participants |
| Placebo at 70mg/140 mg | Number of Participants With Treatment-Emergent Adverse Events | Deaths | 0 Participants |
| Placebo at 70mg/140 mg | Number of Participants With Treatment-Emergent Adverse Events | Patients with Serious AEs | 1 Participants |
| Placebo at 70mg/140 mg | Number of Participants With Treatment-Emergent Adverse Events | Patients with AEs | 6 Participants |
| Placebo at 70mg/140 mg | Number of Participants With Treatment-Emergent Adverse Events | Patients Permanently Discontinuing due to AEs | 0 Participants |
| Placebo at 70mg/140 mg | Number of Participants With Treatment-Emergent Adverse Events | Patients with Treatment Related AEs | 2 Participants |
Secondary
CFQ-R Respiratory Scale (Relative Change % From Baseline)
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.
Time frame: Day 15, Day 28 and Day 42
Population: Analyses were performed using the modified intent-to-treat (mITT) population, defined as all randomized subjects who received at least one dose of study drug
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arikayce™ at 560 mg | CFQ-R Respiratory Scale (Relative Change % From Baseline) | Day 15 | 0.385 Percent (%) | Standard Deviation 0.638 |
| Arikayce™ at 560 mg | CFQ-R Respiratory Scale (Relative Change % From Baseline) | Day 42 | 0.094 Percent (%) | Standard Deviation 0.826 |
| Arikayce™ at 560 mg | CFQ-R Respiratory Scale (Relative Change % From Baseline) | Day 28 | 0.387 Percent (%) | Standard Deviation 0.683 |
| Placebo at 560 mg | CFQ-R Respiratory Scale (Relative Change % From Baseline) | Day 28 | -0.054 Percent (%) | Standard Deviation 0.229 |
| Placebo at 560 mg | CFQ-R Respiratory Scale (Relative Change % From Baseline) | Day 15 | -0.063 Percent (%) | Standard Deviation 0.135 |
| Placebo at 560 mg | CFQ-R Respiratory Scale (Relative Change % From Baseline) | Day 42 | -0.084 Percent (%) | Standard Deviation 0.258 |
| Arikayce™ at 70 mg | CFQ-R Respiratory Scale (Relative Change % From Baseline) | Day 28 | 0.126 Percent (%) | Standard Deviation 0.255 |
| Arikayce™ at 70 mg | CFQ-R Respiratory Scale (Relative Change % From Baseline) | Day 15 | 0.075 Percent (%) | Standard Deviation 0.273 |
| Arikayce™ at 70 mg | CFQ-R Respiratory Scale (Relative Change % From Baseline) | Day 42 | -0.012 Percent (%) | Standard Deviation 0.305 |
| Arikayce™ at 140 mg | CFQ-R Respiratory Scale (Relative Change % From Baseline) | Day 15 | 0.100 Percent (%) | Standard Deviation 0.173 |
| Arikayce™ at 140 mg | CFQ-R Respiratory Scale (Relative Change % From Baseline) | Day 42 | 0.225 Percent (%) | Standard Deviation 0.215 |
| Arikayce™ at 140 mg | CFQ-R Respiratory Scale (Relative Change % From Baseline) | Day 28 | 0.228 Percent (%) | Standard Deviation 0.304 |
| Placebo at 70mg/140 mg | CFQ-R Respiratory Scale (Relative Change % From Baseline) | Day 28 | -0.029 Percent (%) | Standard Deviation 0.233 |
| Placebo at 70mg/140 mg | CFQ-R Respiratory Scale (Relative Change % From Baseline) | Day 15 | 0.042 Percent (%) | Standard Deviation 0.104 |
| Placebo at 70mg/140 mg | CFQ-R Respiratory Scale (Relative Change % From Baseline) | Day 42 | 0.006 Percent (%) | Standard Deviation 0.173 |
Secondary
Density of Pseudomonas Aeruginosa in Sputum
Change (log10 CFU) from Baseline by Study Day and Treatment Arm
Time frame: Day 7, Day 14, Day 21, Day 28 and Day 35
Population: Analyses were performed using the modified intent-to-treat (mITT) population, defined as all randomized subjects who received at least one dose of study drug
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arikayce™ at 560 mg | Density of Pseudomonas Aeruginosa in Sputum | Day 21 | -0.750 Log 10 CFU/g | Standard Deviation 1.466 |
| Arikayce™ at 560 mg | Density of Pseudomonas Aeruginosa in Sputum | Day 7 | -1.605 Log 10 CFU/g | Standard Deviation 1.308 |
| Arikayce™ at 560 mg | Density of Pseudomonas Aeruginosa in Sputum | Day 35 | -1.963 Log 10 CFU/g | Standard Deviation 2.456 |
| Arikayce™ at 560 mg | Density of Pseudomonas Aeruginosa in Sputum | Day 14 | -1.082 Log 10 CFU/g | Standard Deviation 1.354 |
| Arikayce™ at 560 mg | Density of Pseudomonas Aeruginosa in Sputum | Day 28 | -1.576 Log 10 CFU/g | Standard Deviation 1.979 |
| Placebo at 560 mg | Density of Pseudomonas Aeruginosa in Sputum | Day 35 | 0.578 Log 10 CFU/g | Standard Deviation 0.539 |
| Placebo at 560 mg | Density of Pseudomonas Aeruginosa in Sputum | Day 21 | -0.057 Log 10 CFU/g | Standard Deviation 0.6 |
| Placebo at 560 mg | Density of Pseudomonas Aeruginosa in Sputum | Day 14 | 1.098 Log 10 CFU/g | Standard Deviation 2.477 |
| Placebo at 560 mg | Density of Pseudomonas Aeruginosa in Sputum | Day 7 | 1.118 Log 10 CFU/g | Standard Deviation 2.214 |
| Placebo at 560 mg | Density of Pseudomonas Aeruginosa in Sputum | Day 28 | 0.836 Log 10 CFU/g | Standard Deviation 1.544 |
| Arikayce™ at 70 mg | Density of Pseudomonas Aeruginosa in Sputum | Day 21 | -1.560 Log 10 CFU/g | Standard Deviation 2.845 |
| Arikayce™ at 70 mg | Density of Pseudomonas Aeruginosa in Sputum | Day 14 | -1.121 Log 10 CFU/g | Standard Deviation 1.404 |
| Arikayce™ at 70 mg | Density of Pseudomonas Aeruginosa in Sputum | Day 7 | -1.093 Log 10 CFU/g | Standard Deviation 0.616 |
| Arikayce™ at 70 mg | Density of Pseudomonas Aeruginosa in Sputum | Day 28 | -1.771 Log 10 CFU/g | Standard Deviation 1.741 |
| Arikayce™ at 70 mg | Density of Pseudomonas Aeruginosa in Sputum | Day 35 | -0.675 Log 10 CFU/g | Standard Deviation 0.452 |
| Arikayce™ at 140 mg | Density of Pseudomonas Aeruginosa in Sputum | Day 35 | 0.256 Log 10 CFU/g | Standard Deviation 1.058 |
| Arikayce™ at 140 mg | Density of Pseudomonas Aeruginosa in Sputum | Day 7 | -0.637 Log 10 CFU/g | Standard Deviation 0.711 |
| Arikayce™ at 140 mg | Density of Pseudomonas Aeruginosa in Sputum | Day 28 | -0.381 Log 10 CFU/g | Standard Deviation 0.66 |
| Arikayce™ at 140 mg | Density of Pseudomonas Aeruginosa in Sputum | Day 21 | -0.255 Log 10 CFU/g | Standard Deviation 1.977 |
| Arikayce™ at 140 mg | Density of Pseudomonas Aeruginosa in Sputum | Day 14 | -0.175 Log 10 CFU/g | Standard Deviation 1.014 |
| Placebo at 70mg/140 mg | Density of Pseudomonas Aeruginosa in Sputum | Day 21 | -0.337 Log 10 CFU/g | Standard Deviation 1.384 |
| Placebo at 70mg/140 mg | Density of Pseudomonas Aeruginosa in Sputum | Day 28 | -0.426 Log 10 CFU/g | Standard Deviation 0.435 |
| Placebo at 70mg/140 mg | Density of Pseudomonas Aeruginosa in Sputum | Day 7 | -0.254 Log 10 CFU/g | Standard Deviation 0.991 |
| Placebo at 70mg/140 mg | Density of Pseudomonas Aeruginosa in Sputum | Day 35 | 0.028 Log 10 CFU/g | Standard Deviation 0.243 |
| Placebo at 70mg/140 mg | Density of Pseudomonas Aeruginosa in Sputum | Day 14 | -0.159 Log 10 CFU/g | Standard Deviation 0.499 |
Secondary
Duration of Systemic Anti-Pseudomonal Rescue Therapy
Time frame: Through study duration, approximately 84 days
Population: Analyses were performed using the modified intent-to-treat (mITT) population, defined as all randomized subjects who received at least one dose of study drug
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arikayce™ at 560 mg | Duration of Systemic Anti-Pseudomonal Rescue Therapy | 22.800 days | Standard Deviation 12.778 |
| Placebo at 560 mg | Duration of Systemic Anti-Pseudomonal Rescue Therapy | 30.333 days | Standard Deviation 15.044 |
| Arikayce™ at 70 mg | Duration of Systemic Anti-Pseudomonal Rescue Therapy | 17.500 days | Standard Deviation 4.95 |
| Arikayce™ at 140 mg | Duration of Systemic Anti-Pseudomonal Rescue Therapy | 18.000 days | Standard Deviation 0 |
| Placebo at 70mg/140 mg | Duration of Systemic Anti-Pseudomonal Rescue Therapy | 30.500 days | Standard Deviation 10.607 |
Secondary
Pharmacokinetics of Arikayce™ in Serum
Measure PK parameter (Cmax) of Arikayce in serum
Time frame: Day 1, Day 14 and Day 28
Population: Analyses were performed using the modified intent-to-treat (mITT) population, defined as all randomized subjects who received at least one dose of study drug
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arikayce™ at 560 mg | Pharmacokinetics of Arikayce™ in Serum | Day 28 | 2.71 mg/L | Standard Deviation 1.75 |
| Arikayce™ at 560 mg | Pharmacokinetics of Arikayce™ in Serum | Day 14 | 2.17 mg/L | Standard Deviation 1.48 |
| Arikayce™ at 560 mg | Pharmacokinetics of Arikayce™ in Serum | Day 1 | 1.59 mg/L | Standard Deviation 0.973 |
| Arikayce™ at 70 mg | Pharmacokinetics of Arikayce™ in Serum | Day 28 | 0.293 mg/L | Standard Deviation 0.026 |
| Arikayce™ at 70 mg | Pharmacokinetics of Arikayce™ in Serum | Day 1 | 0.216 mg/L | Standard Deviation 0.054 |
| Arikayce™ at 70 mg | Pharmacokinetics of Arikayce™ in Serum | Day 14 | 0.265 mg/L | Standard Deviation 0.06 |
| Arikayce™ at 140 mg | Pharmacokinetics of Arikayce™ in Serum | Day 14 | 0.447 mg/L | Standard Deviation 0.157 |
| Arikayce™ at 140 mg | Pharmacokinetics of Arikayce™ in Serum | Day 1 | 0.375 mg/L | Standard Deviation 0.167 |
| Arikayce™ at 140 mg | Pharmacokinetics of Arikayce™ in Serum | Day 28 | 0.481 mg/L | Standard Deviation 0.213 |
Secondary
Pharmacokinetics (PK) of Arikayce™ in Serum
Measure PK parameter (AUC) of Arikayce in Serum
Time frame: Day 1, Day 14 and Day 28
Population: Analyses were performed using the modified intent-to-treat (mITT) population, defined as all randomized subjects who received at least one dose of study drug
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arikayce™ at 560 mg | Pharmacokinetics (PK) of Arikayce™ in Serum | Day 14 | 15.0 mg*hr/L | Standard Deviation 7.96 |
| Arikayce™ at 560 mg | Pharmacokinetics (PK) of Arikayce™ in Serum | Day 1 | 11.3 mg*hr/L | Standard Deviation 5.81 |
| Arikayce™ at 560 mg | Pharmacokinetics (PK) of Arikayce™ in Serum | Day 28 | 17.1 mg*hr/L | Standard Deviation 7.58 |
| Arikayce™ at 70 mg | Pharmacokinetics (PK) of Arikayce™ in Serum | Day 14 | 1.56 mg*hr/L | Standard Deviation 0.553 |
| Arikayce™ at 70 mg | Pharmacokinetics (PK) of Arikayce™ in Serum | Day 1 | 1.06 mg*hr/L | Standard Deviation 0.243 |
| Arikayce™ at 70 mg | Pharmacokinetics (PK) of Arikayce™ in Serum | Day 28 | 1.59 mg*hr/L | Standard Deviation 0.531 |
| Arikayce™ at 140 mg | Pharmacokinetics (PK) of Arikayce™ in Serum | Day 1 | 2.90 mg*hr/L | Standard Deviation 1.08 |
| Arikayce™ at 140 mg | Pharmacokinetics (PK) of Arikayce™ in Serum | Day 28 | 4.16 mg*hr/L | Standard Deviation 1.56 |
| Arikayce™ at 140 mg | Pharmacokinetics (PK) of Arikayce™ in Serum | Day 14 | 4.32 mg*hr/L | Standard Deviation 1.96 |
Secondary
Pharmacokinetics (PK) of Arikayce™ in Sputum
Measure PK parameters (sputum concentration) of Arikayce in sputum, pre- and post-dose
Time frame: Day 1 post-dose, Day 14 pre- and post-dose, Day 28 pre- and post-dose
Population: Analyses were performed using the modified intent-to-treat (mITT) population, defined as all randomized subjects who received at least one dose of study drug
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arikayce™ at 560 mg | Pharmacokinetics (PK) of Arikayce™ in Sputum | Day 28 pre-dose | 124 mcg/g | Standard Deviation 114 |
| Arikayce™ at 560 mg | Pharmacokinetics (PK) of Arikayce™ in Sputum | Day 14 1 hour post-dose | 2643 mcg/g | Standard Deviation 101 |
| Arikayce™ at 560 mg | Pharmacokinetics (PK) of Arikayce™ in Sputum | Day 1 1 hour post-dose | 4417 mcg/g | Standard Deviation 74.5 |
| Arikayce™ at 560 mg | Pharmacokinetics (PK) of Arikayce™ in Sputum | Day 14 pre-dose | 132 mcg/g | Standard Deviation 205 |
| Arikayce™ at 560 mg | Pharmacokinetics (PK) of Arikayce™ in Sputum | Day 28 1 hour post-dose | 2670 mcg/g | Standard Deviation 66.2 |
| Arikayce™ at 70 mg | Pharmacokinetics (PK) of Arikayce™ in Sputum | Day 14 1 hour post-dose | 1012 mcg/g | Standard Deviation 119 |
| Arikayce™ at 70 mg | Pharmacokinetics (PK) of Arikayce™ in Sputum | Day 1 1 hour post-dose | 1119 mcg/g | Standard Deviation 64.5 |
| Arikayce™ at 70 mg | Pharmacokinetics (PK) of Arikayce™ in Sputum | Day 14 pre-dose | 150 mcg/g | Standard Deviation 221 |
| Arikayce™ at 70 mg | Pharmacokinetics (PK) of Arikayce™ in Sputum | Day 28 pre-dose | 49.7 mcg/g | Standard Deviation 189 |
| Arikayce™ at 70 mg | Pharmacokinetics (PK) of Arikayce™ in Sputum | Day 28 1 hour post-dose | 753 mcg/g | Standard Deviation 82.2 |
| Arikayce™ at 140 mg | Pharmacokinetics (PK) of Arikayce™ in Sputum | Day 28 1 hour post-dose | 1468 mcg/g | Standard Deviation 90.9 |
| Arikayce™ at 140 mg | Pharmacokinetics (PK) of Arikayce™ in Sputum | Day 28 pre-dose | 20.5 mcg/g | Standard Deviation 57 |
| Arikayce™ at 140 mg | Pharmacokinetics (PK) of Arikayce™ in Sputum | Day 1 1 hour post-dose | 1632 mcg/g | Standard Deviation 36.9 |
| Arikayce™ at 140 mg | Pharmacokinetics (PK) of Arikayce™ in Sputum | Day 14 1 hour post-dose | 1534 mcg/g | Standard Deviation 63.3 |
| Arikayce™ at 140 mg | Pharmacokinetics (PK) of Arikayce™ in Sputum | Day 14 pre-dose | 20.1 mcg/g | Standard Deviation 43.8 |
Secondary
Pharmacokinetics (PK) of Arikayce™ in Urine
Measure PK parameter (Ae0-24) of Arikayce in urine
Time frame: Day 1, Day 14 and Day 28
Population: Analyses were performed using the modified intent-to-treat (mITT) population, defined as all randomized subjects who received at least one dose of study drug
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arikayce™ at 560 mg | Pharmacokinetics (PK) of Arikayce™ in Urine | Day 28 | 62.9 mg | Standard Deviation 38 |
| Arikayce™ at 560 mg | Pharmacokinetics (PK) of Arikayce™ in Urine | Day 1 | 25.9 mg | Standard Deviation 27.1 |
| Arikayce™ at 560 mg | Pharmacokinetics (PK) of Arikayce™ in Urine | Day 14 | 63.6 mg | Standard Deviation 29.1 |
| Arikayce™ at 70 mg | Pharmacokinetics (PK) of Arikayce™ in Urine | Day 14 | 7.76 mg | Standard Deviation 3.19 |
| Arikayce™ at 70 mg | Pharmacokinetics (PK) of Arikayce™ in Urine | Day 28 | 7.13 mg | Standard Deviation 4.31 |
| Arikayce™ at 70 mg | Pharmacokinetics (PK) of Arikayce™ in Urine | Day 1 | 4.80 mg | Standard Deviation 1.43 |
| Arikayce™ at 140 mg | Pharmacokinetics (PK) of Arikayce™ in Urine | Day 1 | 15.2 mg | Standard Deviation 8.74 |
| Arikayce™ at 140 mg | Pharmacokinetics (PK) of Arikayce™ in Urine | Day 28 | 17.7 mg | Standard Deviation 8.33 |
| Arikayce™ at 140 mg | Pharmacokinetics (PK) of Arikayce™ in Urine | Day 14 | 21.7 mg | Standard Deviation 12.4 |
Secondary
Pulmonary Function: Pre-Dose FEV1 (%-Predicted)
Relative Change (%) from Baseline to Day 28, Day 56, Day 70, and Day 84 in Pulmonary Function
Time frame: Baseline, Day 28, Day 56, Day 70 and Day 84
Population: Analyses were performed using the modified intent-to-treat (mITT) population, defined as all randomized subjects who received at least one dose of study drug
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arikayce™ at 560 mg | Pulmonary Function: Pre-Dose FEV1 (%-Predicted) | Day 28 | -0.003 Percent (%) | Standard Deviation 0.124 |
| Arikayce™ at 560 mg | Pulmonary Function: Pre-Dose FEV1 (%-Predicted) | Baseline | 68.800 Percent (%) | Standard Deviation 17.026 |
| Arikayce™ at 560 mg | Pulmonary Function: Pre-Dose FEV1 (%-Predicted) | Day 56 | 0.029 Percent (%) | Standard Deviation 0.092 |
| Arikayce™ at 560 mg | Pulmonary Function: Pre-Dose FEV1 (%-Predicted) | Day 84 | 0.000 Percent (%) | Standard Deviation 0.078 |
| Arikayce™ at 560 mg | Pulmonary Function: Pre-Dose FEV1 (%-Predicted) | Day 70 | 0.026 Percent (%) | Standard Deviation 0.107 |
| Placebo at 560 mg | Pulmonary Function: Pre-Dose FEV1 (%-Predicted) | Day 84 | -0.067 Percent (%) | Standard Deviation 0.145 |
| Placebo at 560 mg | Pulmonary Function: Pre-Dose FEV1 (%-Predicted) | Baseline | 66.143 Percent (%) | Standard Deviation 12.02 |
| Placebo at 560 mg | Pulmonary Function: Pre-Dose FEV1 (%-Predicted) | Day 28 | -0.001 Percent (%) | Standard Deviation 0.075 |
| Placebo at 560 mg | Pulmonary Function: Pre-Dose FEV1 (%-Predicted) | Day 56 | -0.028 Percent (%) | Standard Deviation 0.129 |
| Placebo at 560 mg | Pulmonary Function: Pre-Dose FEV1 (%-Predicted) | Day 70 | -0.043 Percent (%) | Standard Deviation 0.097 |
| Arikayce™ at 70 mg | Pulmonary Function: Pre-Dose FEV1 (%-Predicted) | Baseline | 59.286 Percent (%) | Standard Deviation 12.593 |
| Arikayce™ at 70 mg | Pulmonary Function: Pre-Dose FEV1 (%-Predicted) | Day 28 | 0.029 Percent (%) | Standard Deviation 0.124 |
| Arikayce™ at 70 mg | Pulmonary Function: Pre-Dose FEV1 (%-Predicted) | Day 56 | 0.024 Percent (%) | Standard Deviation 0.076 |
| Arikayce™ at 140 mg | Pulmonary Function: Pre-Dose FEV1 (%-Predicted) | Day 28 | -0.029 Percent (%) | Standard Deviation 0.089 |
| Arikayce™ at 140 mg | Pulmonary Function: Pre-Dose FEV1 (%-Predicted) | Day 56 | -0.020 Percent (%) | Standard Deviation 0.087 |
| Arikayce™ at 140 mg | Pulmonary Function: Pre-Dose FEV1 (%-Predicted) | Baseline | 70.400 Percent (%) | Standard Deviation 10.09 |
| Placebo at 70mg/140 mg | Pulmonary Function: Pre-Dose FEV1 (%-Predicted) | Day 28 | -0.010 Percent (%) | Standard Deviation 0.06 |
| Placebo at 70mg/140 mg | Pulmonary Function: Pre-Dose FEV1 (%-Predicted) | Day 56 | 0.011 Percent (%) | Standard Deviation 0.067 |
| Placebo at 70mg/140 mg | Pulmonary Function: Pre-Dose FEV1 (%-Predicted) | Baseline | 69.286 Percent (%) | Standard Deviation 16.55 |