Bronchiectasis
Conditions
Keywords
Bronchiectasis, Respiratory Infections, Amikacin, Respiratory Tract Diseases, Respiratory Tract Infections, Lung Diseases, Pseudomonas aeruginosa, Amikacin liposome inhalation suspension (ALIS)
Brief summary
This is a study to determine the safety and tolerability of 28 days of daily dosing of two doses (280 mg and 560 mg) of Arikayce™ versus placebo in patients who have bronchiectasis and chronic infection due to Pseudomonas infection.
Detailed description
Bronchiectasis is a chronic disorder of the major bronchi and bronchioles characterized by permanent dilation, microbial infection, a persistent inflammatory response with the release of immune mediators and microbial toxins leading to destruction. The origin of bronchiectasis varies, but the presence of microbial infection and a persistent inflammatory response is typical of the disease. The chronic nature of the infection and the associated considerable morbidity provides the rationale for using aerosolized antibiotics for the treatment of bronchiectasis patients. This is a multi-national Phase 2 study of safety and tolerability of 28 days of daily dosing with two dose levels (280 mg and 560 mg) of Arikayce™ versus placebo in subjects with bronchiectasis and chronic Pseudomonas infection. Study subjects will be randomized to receive either study drug or placebo by inhalation via a PARI eFlow® nebulizer. Each subject will complete 28 days of daily dosing. All study subjects will be followed for microbiologic activity for 14 days after completion of treatment and for safety for 28 days post completion of study treatment. The total study duration will be 56 days, with the screening visit occurring within the preceding 14 days prior to study day 1. At Day 1 (baseline), subjects will be evaluated at pre-dose and during the first 4-5 hours post-dose. Subjects will return at Week 2 (day 14) after start of treatment and at the end of Week 4 (Day 28) treatment period to determine safety and efficacy of Arikayce™. Subjects will be followed up on study Days 42 and 56 (about 2 and 4 weeks after end of treatment) for safety determination. After completion of this study, subjects will be followed up for an additional 6 months via phone contacts and records review, if hospitalized or treated for pulmonary exacerbation (under the extension protocol). 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 pharmacokinetics (PK) in subjects who consent for the PK portion of the study. Additionally, sputum samples will be collected to determine changes in bacterial density. Total Pulmonary Symptom Severity Score (PSSS) will be assessed, and respiratory quality of life will be evaluated by using the St. George's Respiratory Questionnaire (SGRQ). Arikace™,Arikayce™, Liposomal Amikacin for Inhalation (LAI), and Amikacin Liposome Inhalation Suspension (ALIS) may be used interchangeably throughout this study and the other studies evaluating amikacin liposome inhalation suspension.
Interventions
DRUG280 mg Arikayce™
Study subjects will receive Arikace™ 280 mg on Days 1 through Day 28. Drug is administered once a day via a nebulizer.
DRUGMatching Placebo for Cohort 1
Study subjects will receive placebo on Days 1 through Day 28. Drug is administered once a day via a nebulizer.
DRUG560 mg Arikayce™
Study subjects will receive Arikace™ 560 mg on Days 1 through Day 28. Drug is administered once a day via a nebulizer.
DRUGMatching Placebo for Cohort 2
Study subjects will receive 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
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female study subjects≥ 18 years of age * Confirmed diagnosis of multi-focal bronchiectasis in two or more lung segments by HRCT of the chest * History of chronic infection with P. aeruginosa * Confirmation of infection with P. aeruginosa at screening * SaO2 ≥ 90% at Screening while breathing room air * Ability to comply with study medication use, study visits, and study procedures as judged by the investigator * Ability to produce at least 0.5 grams sputum or be willing to undergo an induction to produce sputum for clinical evaluation Key
Exclusion criteria
* Forced Expiratory Volume in 1 second (FEV1) \< 50% of predicted at Screening * Patients with hemoptysis of ≥60 mL within 4 weeks prior to screening * Bronchiectasis due to cystic fibrosis (CF), bronchopulmonary Aspergillus, aspiration of foreign body, or secondary to lung compression from tumors * History of non-tuberculous mycobacterial and/or Aspergillus infection requiring treatment or treated within 2 years prior to screening * Pulmonary tuberculosis requiring treatment or treated within two years prior to screening * History of Lung transplantation * Use of any inhalation or systemic antibiotics (IV antibiotics, or oral antibiotics) within 4 weeks prior to Study Day 1 * Evidence of biliary cirrhosis with portal hypertension * Smoking tobacco or any substance within 6 months prior to screening, and throughout the study * History of alcohol, medication, or illicit drug abuse within the 1 year prior to screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serious Adverse Events up to 28 Days After Study Medication Discontinuation | Screening to Day 56 | Number of subjects with a SAE in the Arikace™ groups and the placebo group up to 28 days after study medication discontinuation. See SAE table in the safety section for details. |
| Treatment-emergent Marked Laboratory Abnormalities up to 28 Days After Study Medication Discontinuation | Day 1 through 56. | Number of subjects reporting Incidence of clinically significant abnormalities in clinical values (Common Terminology Criteria for Adverse Events \[CTCAE\] grade \>= 3) in Arikayce™ and placebo groups. |
| Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Pre-dose, 0-1 hour post-dose and 2-4 hours post-dose on day 1, 0-1 hour post-dose and 2-4 hours post-dose on day 14, and 0-1 hour post-dose and 2-4 hours post-dose on day 28 | Changes in PFT from pre-dose during the study were measured on Days 1, 14, and 28. Acute tolerability of the study treatment was assessed by examining the relative (rel.) changes in FEV1 from pre-dose assessments to 0-1 hour post-dose and 2-4 hours post-dose for each time point at which post-dose spirometry was conducted. |
| Treatment-emergent PFT Abnormalities up to the End of Study | Day 1, Day 14 and Day 28 | Number of Subjects with Decrease of \>= 15% in FEV1 (L) from Pre- to Post-dose by Study Day |
| Number of Subjects With an Adverse Event Leading to Permanent Discontinuation of Study Medication | Screening to Day 56 | — |
| Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Day 1 through 56. | Number of Subjects reporting TEAE in the Arikayce™ groups and the placebo groups during the study. The table shows the events incidents, not the number of participants. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Pulmonary Symptom Severity Score (PSSS) | Baseline to Day 14, Day 28, Day 42 and Day 56. | Changes in the severity and intensity (frequency x severity) of individual symptoms and change in composite PSSS from baseline to Days 14, 28, 42 and 56. The Pulmonary Symptom Severity Score (PSSS) was assessed on patient's responses to the Patients Symptoms Questionnaire, which employs symptom frequency and severity scales described for the validated Memorial Symptoms Assessment Scale. Symptom severity was scored on a scale of 0 (not applicable or symptom not present) to 4 (very severe) for each of the 5 symptoms (cough, shortness of breath, sputum production \[frequency and severity\], fatigue, and wheezing), and a composite score (range, 0 to 20 \[low score represents better outcome\]) was obtained as the sum of the severity scores for each symptom. |
| To Evaluate Change in St. George's Respiratory Questionnaire Measurements | Day 1 to Day 14, Day 28, Day 42 and Day 56. | A composite total score is derived as the sum of domain scores for symptoms, activity, and impact, with 0 as the best possible score and 100 as the worst possible score. A reduction in score of 4 points is generally recognized as a clinically meaningful improvement in quality of life. This analysis compared the changes from Day 1 (prior to first dosing) to Days 14, 28, 42, and 56. |
| To Evaluate the Use of Systemic Antipseudomonal Rescue Therapy | Screening to Day 56. | — |
| Change From Baseline in Log10CFU Per Gram (Density) of Pseudomonas Aeruginosa in Sputum. | Baseline to Day 14, Day 28 and Day 42. | The change in Pseudomonas aeruginosa density from from baseline to Day 14, 28, and 42 were evaluated.Treatment differences with respect to the changes from baseline to each measured study day, defined as the log10 of the sum of all morphotypes (colony-forming units \[CFU\]) per gram of sputum in (log10CFU/gram \[g\]), was estimated for each treatment group; standard deviations accompanied the treatment differences. |
Countries
Bulgaria, Greece, Hungary, India, Poland, Serbia, Ukraine, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arikayce™ at 280 mg Study subjects will receive Arikayce™ 280 mg on Days 1-28. | 24 |
| Matching Placebo (280 mg) Study subjects will receive matching placebo on Days 1-28. | 10 |
| Arikayce™ at 560 mg Study subjects will receive Arikayce™ 560 mg on Days 1-28. | 19 |
| Matching Placebo (560 mg) Study subjects will receive matching placebo on Days 1-28. | 9 |
| Total | 62 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 2 | 2 |
Baseline characteristics
| Characteristic | Arikayce™ at 280 mg | Matching Placebo (280 mg) | Arikayce™ at 560 mg | Matching Placebo (560 mg) | Total |
|---|---|---|---|---|---|
| Age, Continuous | 49.9 years STANDARD_DEVIATION 21.1 | 46.8 years STANDARD_DEVIATION 15 | 58.5 years STANDARD_DEVIATION 16 | 52.3 years STANDARD_DEVIATION 11.1 | 52.4 years STANDARD_DEVIATION 17.7 |
| Sex: Female, Male Female | 10 Participants | 4 Participants | 11 Participants | 5 Participants | 30 Participants |
| Sex: Female, Male Male | 14 Participants | 6 Participants | 8 Participants | 4 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 10 | 0 / 19 | 0 / 9 |
| other Total, other adverse events | 11 / 24 | 5 / 10 | 11 / 19 | 6 / 9 |
| serious Total, serious adverse events | 1 / 24 | 0 / 10 | 1 / 19 | 1 / 9 |
Outcome results
Primary
Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment
Number of Subjects reporting TEAE in the Arikayce™ groups and the placebo groups during the study. The table shows the events incidents, not the number of participants.
Time frame: Day 1 through 56.
Population: Safety population, the same as the mITT population, defined as all randomized patients who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arikace™ 280 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Pruritus | 0 Participants |
| Arikace™ 280 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Pharyngolaryngeal pain | 1 Participants |
| Arikace™ 280 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Agitation | 1 Participants |
| Arikace™ 280 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Blood creatinine increased | 0 Participants |
| Arikace™ 280 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Forced expiratory volume decreased | 1 Participants |
| Arikace™ 280 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Dysphonia | 1 Participants |
| Arikace™ 280 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Aphthous stomatitis | 0 Participants |
| Arikace™ 280 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Haemoptysis | 2 Participants |
| Arikace™ 280 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Dysgeusia | 1 Participants |
| Arikace™ 280 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Dizziness | 0 Participants |
| Arikace™ 280 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Arthralgia | 1 Participants |
| Arikace™ 280 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Bronchial disorder | 3 Participants |
| Arikace™ 280 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Chronic obstructive pulmonary disease | 1 Participants |
| Arikace™ 280 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Cervicobrachial syndrome | 0 Participants |
| Arikace™ 280 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Abortion incomplete | 0 Participants |
| Arikace™ 280 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Insomnia | 0 Participants |
| Arikace™ 280 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Pyrexia | 2 Participants |
| Arikace™ 280 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Palpitations | 0 Participants |
| Arikace™ 280 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Fatigue | 0 Participants |
| Arikace™ 280 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Productive Cough | 2 Participants |
| Arikace™ 280 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Wheezing | 1 Participants |
| Arikace™ 280 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Lung abscess | 0 Participants |
| Arikace™ 280 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Bronchiectasis | 0 Participants |
| Arikace™ 280 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Anorexia | 0 Participants |
| Arikace™ 280 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Dyspnoea | 0 Participants |
| Arikace™ 280 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Laryngitis | 0 Participants |
| Arikace™ 280 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Upper respiratory tract infection | 1 Participants |
| Arikace™ 280 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Toothache | 1 Participants |
| Arikace™ 280 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Headache | 1 Participants |
| Arikace™ 280 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Cough | 1 Participants |
| Arikace™ 280 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Tinnitus | 1 Participants |
| Arikace™ 280 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Sinus bradycardia | 0 Participants |
| Arikace™ 280 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Nasopharyngitis | 1 Participants |
| Arikace™ 280 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Nausea | 0 Participants |
| Arikace™ 280 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Rhinorrhoea | 0 Participants |
| Arikace™ 280 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Rash | 0 Participants |
| Arikace™ 280 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Sneezing | 0 Participants |
| Arikace™ 280 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Constipation | 0 Participants |
| Matching Placebo (280 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Bronchiectasis | 0 Participants |
| Matching Placebo (280 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Productive Cough | 3 Participants |
| Matching Placebo (280 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Bronchial disorder | 0 Participants |
| Matching Placebo (280 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Cough | 2 Participants |
| Matching Placebo (280 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Haemoptysis | 1 Participants |
| Matching Placebo (280 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Pyrexia | 1 Participants |
| Matching Placebo (280 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Wheezing | 2 Participants |
| Matching Placebo (280 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Dyspnoea | 2 Participants |
| Matching Placebo (280 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Headache | 1 Participants |
| Matching Placebo (280 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Nasopharyngitis | 1 Participants |
| Matching Placebo (280 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Sneezing | 2 Participants |
| Matching Placebo (280 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Agitation | 0 Participants |
| Matching Placebo (280 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Aphthous stomatitis | 1 Participants |
| Matching Placebo (280 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Arthralgia | 0 Participants |
| Matching Placebo (280 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Cervicobrachial syndrome | 1 Participants |
| Matching Placebo (280 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Chronic obstructive pulmonary disease | 0 Participants |
| Matching Placebo (280 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Dizziness | 1 Participants |
| Matching Placebo (280 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Dysgeusia | 0 Participants |
| Matching Placebo (280 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Dysphonia | 0 Participants |
| Matching Placebo (280 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Forced expiratory volume decreased | 0 Participants |
| Matching Placebo (280 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Pharyngolaryngeal pain | 0 Participants |
| Matching Placebo (280 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Pruritus | 1 Participants |
| Matching Placebo (280 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Rash | 1 Participants |
| Matching Placebo (280 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Rhinorrhoea | 1 Participants |
| Matching Placebo (280 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Sinus bradycardia | 1 Participants |
| Matching Placebo (280 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Tinnitus | 0 Participants |
| Matching Placebo (280 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Toothache | 0 Participants |
| Matching Placebo (280 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Upper respiratory tract infection | 0 Participants |
| Matching Placebo (280 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Anorexia | 0 Participants |
| Matching Placebo (280 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Fatigue | 0 Participants |
| Matching Placebo (280 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Insomnia | 0 Participants |
| Matching Placebo (280 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Abortion incomplete | 0 Participants |
| Matching Placebo (280 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Blood creatinine increased | 0 Participants |
| Matching Placebo (280 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Constipation | 0 Participants |
| Matching Placebo (280 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Laryngitis | 0 Participants |
| Matching Placebo (280 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Lung abscess | 0 Participants |
| Matching Placebo (280 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Nausea | 0 Participants |
| Matching Placebo (280 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Palpitations | 0 Participants |
| Arikace™ 560 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Bronchiectasis | 1 Participants |
| Arikace™ 560 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Pharyngolaryngeal pain | 0 Participants |
| Arikace™ 560 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Pyrexia | 1 Participants |
| Arikace™ 560 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Headache | 4 Participants |
| Arikace™ 560 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Fatigue | 1 Participants |
| Arikace™ 560 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Rash | 0 Participants |
| Arikace™ 560 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Tinnitus | 0 Participants |
| Arikace™ 560 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Pruritus | 0 Participants |
| Arikace™ 560 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Insomnia | 1 Participants |
| Arikace™ 560 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Nasopharyngitis | 1 Participants |
| Arikace™ 560 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Haemoptysis | 1 Participants |
| Arikace™ 560 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Palpitations | 1 Participants |
| Arikace™ 560 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Abortion incomplete | 1 Participants |
| Arikace™ 560 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Bronchial disorder | 1 Participants |
| Arikace™ 560 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Toothache | 0 Participants |
| Arikace™ 560 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Productive Cough | 2 Participants |
| Arikace™ 560 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Cervicobrachial syndrome | 0 Participants |
| Arikace™ 560 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Dyspnoea | 3 Participants |
| Arikace™ 560 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Arthralgia | 0 Participants |
| Arikace™ 560 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Nausea | 1 Participants |
| Arikace™ 560 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Chronic obstructive pulmonary disease | 0 Participants |
| Arikace™ 560 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Rhinorrhoea | 0 Participants |
| Arikace™ 560 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Upper respiratory tract infection | 1 Participants |
| Arikace™ 560 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Blood creatinine increased | 1 Participants |
| Arikace™ 560 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Dizziness | 1 Participants |
| Arikace™ 560 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Constipation | 0 Participants |
| Arikace™ 560 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Aphthous stomatitis | 0 Participants |
| Arikace™ 560 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Sneezing | 0 Participants |
| Arikace™ 560 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Dysgeusia | 0 Participants |
| Arikace™ 560 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Lung abscess | 0 Participants |
| Arikace™ 560 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Anorexia | 1 Participants |
| Arikace™ 560 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Cough | 5 Participants |
| Arikace™ 560 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Dysphonia | 2 Participants |
| Arikace™ 560 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Laryngitis | 1 Participants |
| Arikace™ 560 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Agitation | 0 Participants |
| Arikace™ 560 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Wheezing | 1 Participants |
| Arikace™ 560 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Forced expiratory volume decreased | 0 Participants |
| Arikace™ 560 mg | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Sinus bradycardia | 0 Participants |
| Matching Placebo (560 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Insomnia | 1 Participants |
| Matching Placebo (560 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Pharyngolaryngeal pain | 0 Participants |
| Matching Placebo (560 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Constipation | 1 Participants |
| Matching Placebo (560 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Pruritus | 0 Participants |
| Matching Placebo (560 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Nasopharyngitis | 0 Participants |
| Matching Placebo (560 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Bronchial disorder | 0 Participants |
| Matching Placebo (560 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Rash | 0 Participants |
| Matching Placebo (560 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Rhinorrhoea | 1 Participants |
| Matching Placebo (560 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Headache | 1 Participants |
| Matching Placebo (560 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Sinus bradycardia | 0 Participants |
| Matching Placebo (560 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Laryngitis | 0 Participants |
| Matching Placebo (560 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Tinnitus | 0 Participants |
| Matching Placebo (560 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Dyspnoea | 1 Participants |
| Matching Placebo (560 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Toothache | 0 Participants |
| Matching Placebo (560 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Palpitations | 0 Participants |
| Matching Placebo (560 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Upper respiratory tract infection | 0 Participants |
| Matching Placebo (560 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Wheezing | 0 Participants |
| Matching Placebo (560 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Anorexia | 1 Participants |
| Matching Placebo (560 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Pyrexia | 2 Participants |
| Matching Placebo (560 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Bronchiectasis | 1 Participants |
| Matching Placebo (560 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Lung abscess | 1 Participants |
| Matching Placebo (560 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Fatigue | 1 Participants |
| Matching Placebo (560 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Haemoptysis | 0 Participants |
| Matching Placebo (560 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Productive Cough | 3 Participants |
| Matching Placebo (560 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Sneezing | 0 Participants |
| Matching Placebo (560 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Abortion incomplete | 0 Participants |
| Matching Placebo (560 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Arthralgia | 0 Participants |
| Matching Placebo (560 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Cough | 0 Participants |
| Matching Placebo (560 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Cervicobrachial syndrome | 0 Participants |
| Matching Placebo (560 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Chronic obstructive pulmonary disease | 0 Participants |
| Matching Placebo (560 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Aphthous stomatitis | 0 Participants |
| Matching Placebo (560 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Dizziness | 0 Participants |
| Matching Placebo (560 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Blood creatinine increased | 0 Participants |
| Matching Placebo (560 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Dysgeusia | 0 Participants |
| Matching Placebo (560 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Agitation | 0 Participants |
| Matching Placebo (560 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Dysphonia | 0 Participants |
| Matching Placebo (560 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Nausea | 0 Participants |
| Matching Placebo (560 mg) | Number of Participants Reporting Treatment-emergent AEs (TEAEs) up to End of Treatment | Forced expiratory volume decreased | 0 Participants |
Primary
Number of Subjects With an Adverse Event Leading to Permanent Discontinuation of Study Medication
Time frame: Screening to Day 56
Population: The analysis population is the safety population, the same as the mITT population, defined as all randomized patients who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arikace™ 280 mg | Number of Subjects With an Adverse Event Leading to Permanent Discontinuation of Study Medication | 0 Participants |
| Matching Placebo (280 mg) | Number of Subjects With an Adverse Event Leading to Permanent Discontinuation of Study Medication | 0 Participants |
| Arikace™ 560 mg | Number of Subjects With an Adverse Event Leading to Permanent Discontinuation of Study Medication | 1 Participants |
| Matching Placebo (560 mg) | Number of Subjects With an Adverse Event Leading to Permanent Discontinuation of Study Medication | 0 Participants |
Primary
Serious Adverse Events up to 28 Days After Study Medication Discontinuation
Number of subjects with a SAE in the Arikace™ groups and the placebo group up to 28 days after study medication discontinuation. See SAE table in the safety section for details.
Time frame: Screening to Day 56
Population: The safety population is the modified intent-to-treat (mITT) population, defined as all randomized patients who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arikace™ 280 mg | Serious Adverse Events up to 28 Days After Study Medication Discontinuation | 1 Participants |
| Matching Placebo (280 mg) | Serious Adverse Events up to 28 Days After Study Medication Discontinuation | 0 Participants |
| Arikace™ 560 mg | Serious Adverse Events up to 28 Days After Study Medication Discontinuation | 1 Participants |
| Matching Placebo (560 mg) | Serious Adverse Events up to 28 Days After Study Medication Discontinuation | 1 Participants |
Primary
Treatment-emergent Marked Laboratory Abnormalities up to 28 Days After Study Medication Discontinuation
Number of subjects reporting Incidence of clinically significant abnormalities in clinical values (Common Terminology Criteria for Adverse Events \[CTCAE\] grade \>= 3) in Arikayce™ and placebo groups.
Time frame: Day 1 through 56.
Population: The safety population is the mITT population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arikace™ 280 mg | Treatment-emergent Marked Laboratory Abnormalities up to 28 Days After Study Medication Discontinuation | Leukocytes | 1 Participants |
| Arikace™ 280 mg | Treatment-emergent Marked Laboratory Abnormalities up to 28 Days After Study Medication Discontinuation | Neutrophils Abs | 4 Participants |
| Arikace™ 280 mg | Treatment-emergent Marked Laboratory Abnormalities up to 28 Days After Study Medication Discontinuation | Sodium | 1 Participants |
| Arikace™ 280 mg | Treatment-emergent Marked Laboratory Abnormalities up to 28 Days After Study Medication Discontinuation | Uric acid | 0 Participants |
| Matching Placebo (280 mg) | Treatment-emergent Marked Laboratory Abnormalities up to 28 Days After Study Medication Discontinuation | Neutrophils Abs | 0 Participants |
| Matching Placebo (280 mg) | Treatment-emergent Marked Laboratory Abnormalities up to 28 Days After Study Medication Discontinuation | Sodium | 0 Participants |
| Matching Placebo (280 mg) | Treatment-emergent Marked Laboratory Abnormalities up to 28 Days After Study Medication Discontinuation | Uric acid | 1 Participants |
| Matching Placebo (280 mg) | Treatment-emergent Marked Laboratory Abnormalities up to 28 Days After Study Medication Discontinuation | Leukocytes | 0 Participants |
| Arikace™ 560 mg | Treatment-emergent Marked Laboratory Abnormalities up to 28 Days After Study Medication Discontinuation | Sodium | 0 Participants |
| Arikace™ 560 mg | Treatment-emergent Marked Laboratory Abnormalities up to 28 Days After Study Medication Discontinuation | Neutrophils Abs | 1 Participants |
| Arikace™ 560 mg | Treatment-emergent Marked Laboratory Abnormalities up to 28 Days After Study Medication Discontinuation | Uric acid | 1 Participants |
| Arikace™ 560 mg | Treatment-emergent Marked Laboratory Abnormalities up to 28 Days After Study Medication Discontinuation | Leukocytes | 0 Participants |
| Matching Placebo (560 mg) | Treatment-emergent Marked Laboratory Abnormalities up to 28 Days After Study Medication Discontinuation | Uric acid | 1 Participants |
| Matching Placebo (560 mg) | Treatment-emergent Marked Laboratory Abnormalities up to 28 Days After Study Medication Discontinuation | Neutrophils Abs | 0 Participants |
| Matching Placebo (560 mg) | Treatment-emergent Marked Laboratory Abnormalities up to 28 Days After Study Medication Discontinuation | Leukocytes | 0 Participants |
| Matching Placebo (560 mg) | Treatment-emergent Marked Laboratory Abnormalities up to 28 Days After Study Medication Discontinuation | Sodium | 0 Participants |
Primary
Treatment-emergent PFT Abnormalities up to the End of Study
Number of Subjects with Decrease of \>= 15% in FEV1 (L) from Pre- to Post-dose by Study Day
Time frame: Day 1, Day 14 and Day 28
Population: The analysis population is the safety population, the same as the mITT population, defined as all randomized patients who received at least 1 dose of study drug.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Arikace™ 280 mg | Treatment-emergent PFT Abnormalities up to the End of Study | Day 1 | No | 22 Participants |
| Arikace™ 280 mg | Treatment-emergent PFT Abnormalities up to the End of Study | Day 1 | Yes | 2 Participants |
| Arikace™ 280 mg | Treatment-emergent PFT Abnormalities up to the End of Study | Day 14 | No | 23 Participants |
| Arikace™ 280 mg | Treatment-emergent PFT Abnormalities up to the End of Study | Day 14 | Yes | 1 Participants |
| Arikace™ 280 mg | Treatment-emergent PFT Abnormalities up to the End of Study | Day 28 | No | 23 Participants |
| Arikace™ 280 mg | Treatment-emergent PFT Abnormalities up to the End of Study | Day 28 | Yes | 1 Participants |
| Matching Placebo (280 mg) | Treatment-emergent PFT Abnormalities up to the End of Study | Day 28 | Yes | 0 Participants |
| Matching Placebo (280 mg) | Treatment-emergent PFT Abnormalities up to the End of Study | Day 14 | Yes | 0 Participants |
| Matching Placebo (280 mg) | Treatment-emergent PFT Abnormalities up to the End of Study | Day 1 | No | 10 Participants |
| Matching Placebo (280 mg) | Treatment-emergent PFT Abnormalities up to the End of Study | Day 14 | No | 10 Participants |
| Matching Placebo (280 mg) | Treatment-emergent PFT Abnormalities up to the End of Study | Day 1 | Yes | 0 Participants |
| Matching Placebo (280 mg) | Treatment-emergent PFT Abnormalities up to the End of Study | Day 28 | No | 10 Participants |
| Arikace™ 560 mg | Treatment-emergent PFT Abnormalities up to the End of Study | Day 1 | Yes | 2 Participants |
| Arikace™ 560 mg | Treatment-emergent PFT Abnormalities up to the End of Study | Day 14 | No | 18 Participants |
| Arikace™ 560 mg | Treatment-emergent PFT Abnormalities up to the End of Study | Day 14 | Yes | 1 Participants |
| Arikace™ 560 mg | Treatment-emergent PFT Abnormalities up to the End of Study | Day 28 | Yes | 0 Participants |
| Arikace™ 560 mg | Treatment-emergent PFT Abnormalities up to the End of Study | Day 28 | No | 19 Participants |
| Arikace™ 560 mg | Treatment-emergent PFT Abnormalities up to the End of Study | Day 1 | No | 17 Participants |
| Matching Placebo (560 mg) | Treatment-emergent PFT Abnormalities up to the End of Study | Day 28 | No | 9 Participants |
| Matching Placebo (560 mg) | Treatment-emergent PFT Abnormalities up to the End of Study | Day 28 | Yes | 0 Participants |
| Matching Placebo (560 mg) | Treatment-emergent PFT Abnormalities up to the End of Study | Day 1 | Yes | 0 Participants |
| Matching Placebo (560 mg) | Treatment-emergent PFT Abnormalities up to the End of Study | Day 14 | Yes | 0 Participants |
| Matching Placebo (560 mg) | Treatment-emergent PFT Abnormalities up to the End of Study | Day 1 | No | 9 Participants |
| Matching Placebo (560 mg) | Treatment-emergent PFT Abnormalities up to the End of Study | Day 14 | No | 9 Participants |
Primary
Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment
Changes in PFT from pre-dose during the study were measured on Days 1, 14, and 28. Acute tolerability of the study treatment was assessed by examining the relative (rel.) changes in FEV1 from pre-dose assessments to 0-1 hour post-dose and 2-4 hours post-dose for each time point at which post-dose spirometry was conducted.
Time frame: Pre-dose, 0-1 hour post-dose and 2-4 hours post-dose on day 1, 0-1 hour post-dose and 2-4 hours post-dose on day 14, and 0-1 hour post-dose and 2-4 hours post-dose on day 28
Population: The analysis population is the safety population, the same as the mITT population, defined as all randomized patients who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arikace™ 280 mg | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day 1: Pre-Dose | 1.917 L | Standard Deviation 0.793 |
| Arikace™ 280 mg | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day 28: 0 - 1 Hr Post-Dose | 1.928 L | Standard Deviation 0.751 |
| Arikace™ 280 mg | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day14:0-1 Hr Post-Dose Rel. Change from Pre-dose | 0.800 L | Standard Deviation 8.818 |
| Arikace™ 280 mg | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day 1: 2 - 4 Hrs Post-Dose | 1.955 L | Standard Deviation 0.766 |
| Arikace™ 280 mg | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day14:2-4 Hr Post-Dose Rel. Change from Pre-dose | 2.388 L | Standard Deviation 9.02 |
| Arikace™ 280 mg | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day 28: Pre-Dose | 1.919 L | Standard Deviation 0.761 |
| Arikace™ 280 mg | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day1:0-1 Hr Post-Dose Rel. Change from Pre-dose | 0.816 L | Standard Deviation 9.317 |
| Arikace™ 280 mg | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day 1: 0 - 1 Hr Post-Dose | 1.922 L | Standard Deviation 0.78 |
| Arikace™ 280 mg | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day 28:0-1 Hr Post-Dose Rel. Change from Pre-dose | 0.635 L | Standard Deviation 7.647 |
| Arikace™ 280 mg | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day1:2-4 Hrs Post-Dose Rel. Change from Pre-dose | 3.323 L | Standard Deviation 11.181 |
| Arikace™ 280 mg | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day 14: Pre-Dose | 1.892 L | Standard Deviation 0.759 |
| Arikace™ 280 mg | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day 28: 2 - 4 Hrs Post-Dose | 1.908 L | Standard Deviation 0.754 |
| Arikace™ 280 mg | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day 14: 0 - 1 Hr Post-Dose | 1.907 L | Standard Deviation 0.776 |
| Arikace™ 280 mg | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day 28:2-4 Hrs Post-Dose Rel. Change from Pre-dose | -0.356 L | Standard Deviation 8.858 |
| Arikace™ 280 mg | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day 14: 2 - 4 Hr Post-Dose | 1.931 L | Standard Deviation 0.771 |
| Matching Placebo (280 mg) | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day 14: 2 - 4 Hr Post-Dose | 1.797 L | Standard Deviation 0.52 |
| Matching Placebo (280 mg) | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day 28: 0 - 1 Hr Post-Dose | 1.803 L | Standard Deviation 0.502 |
| Matching Placebo (280 mg) | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day1:2-4 Hrs Post-Dose Rel. Change from Pre-dose | 1.484 L | Standard Deviation 3.507 |
| Matching Placebo (280 mg) | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day14:0-1 Hr Post-Dose Rel. Change from Pre-dose | 2.061 L | Standard Deviation 4.509 |
| Matching Placebo (280 mg) | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day 1: 0 - 1 Hr Post-Dose | 1.820 L | Standard Deviation 0.546 |
| Matching Placebo (280 mg) | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day 28: Pre-Dose | 1.794 L | Standard Deviation 0.507 |
| Matching Placebo (280 mg) | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day 28: 2 - 4 Hrs Post-Dose | 1.809 L | Standard Deviation 0.527 |
| Matching Placebo (280 mg) | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day14:2-4 Hr Post-Dose Rel. Change from Pre-dose | 2.711 L | Standard Deviation 6.62 |
| Matching Placebo (280 mg) | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day 1: 2 - 4 Hrs Post-Dose | 1.864 L | Standard Deviation 0.52 |
| Matching Placebo (280 mg) | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day 14: 0 - 1 Hr Post-Dose | 1.794 L | Standard Deviation 0.556 |
| Matching Placebo (280 mg) | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day 28:2-4 Hrs Post-Dose Rel. Change from Pre-dose | 0.601 L | Standard Deviation 3.184 |
| Matching Placebo (280 mg) | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day 28:0-1 Hr Post-Dose Rel. Change from Pre-dose | 0.654 L | Standard Deviation 3.675 |
| Matching Placebo (280 mg) | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day 14: Pre-Dose | 1.761 L | Standard Deviation 0.55 |
| Matching Placebo (280 mg) | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day1:0-1 Hr Post-Dose Rel. Change from Pre-dose | -1.186 L | Standard Deviation 3.028 |
| Matching Placebo (280 mg) | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day 1: Pre-Dose | 1.841 L | Standard Deviation 0.536 |
| Arikace™ 560 mg | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day 14: 2 - 4 Hr Post-Dose | 1.843 L | Standard Deviation 0.567 |
| Arikace™ 560 mg | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day 1: Pre-Dose | 1.939 L | Standard Deviation 0.515 |
| Arikace™ 560 mg | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day 1: 0 - 1 Hr Post-Dose | 1.907 L | Standard Deviation 0.475 |
| Arikace™ 560 mg | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day 1: 2 - 4 Hrs Post-Dose | 1.912 L | Standard Deviation 0.477 |
| Arikace™ 560 mg | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day1:0-1 Hr Post-Dose Rel. Change from Pre-dose | -0.873 L | Standard Deviation 9.64 |
| Arikace™ 560 mg | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day1:2-4 Hrs Post-Dose Rel. Change from Pre-dose | -0.661 L | Standard Deviation 8.374 |
| Arikace™ 560 mg | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day 14: Pre-Dose | 1.864 L | Standard Deviation 0.607 |
| Arikace™ 560 mg | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day 14: 0 - 1 Hr Post-Dose | 1.856 L | Standard Deviation 0.555 |
| Arikace™ 560 mg | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day14:0-1 Hr Post-Dose Rel. Change from Pre-dose | -1.629 L | Standard Deviation 9.961 |
| Arikace™ 560 mg | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day14:2-4 Hr Post-Dose Rel. Change from Pre-dose | -3.114 L | Standard Deviation 8.506 |
| Arikace™ 560 mg | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day 28: Pre-Dose | 1.846 L | Standard Deviation 0.532 |
| Arikace™ 560 mg | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day 28: 0 - 1 Hr Post-Dose | 1.797 L | Standard Deviation 0.541 |
| Arikace™ 560 mg | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day 28: 2 - 4 Hrs Post-Dose | 1.799 L | Standard Deviation 0.578 |
| Arikace™ 560 mg | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day 28:0-1 Hr Post-Dose Rel. Change from Pre-dose | 0.607 L | Standard Deviation 4.185 |
| Arikace™ 560 mg | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day 28:2-4 Hrs Post-Dose Rel. Change from Pre-dose | -0.006 L | Standard Deviation 6.156 |
| Matching Placebo (560 mg) | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day 14: 0 - 1 Hr Post-Dose | 1.908 L | Standard Deviation 0.611 |
| Matching Placebo (560 mg) | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day 1: 0 - 1 Hr Post-Dose | 1.807 L | Standard Deviation 0.666 |
| Matching Placebo (560 mg) | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day 28: 0 - 1 Hr Post-Dose | 1.901 L | Standard Deviation 0.55 |
| Matching Placebo (560 mg) | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day 14: Pre-Dose | 1.895 L | Standard Deviation 0.592 |
| Matching Placebo (560 mg) | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day1:2-4 Hrs Post-Dose Rel. Change from Pre-dose | 3.082 L | Standard Deviation 11.671 |
| Matching Placebo (560 mg) | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day 1: Pre-Dose | 1.758 L | Standard Deviation 0.654 |
| Matching Placebo (560 mg) | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day 28: 2 - 4 Hrs Post-Dose | 1.940 L | Standard Deviation 0.641 |
| Matching Placebo (560 mg) | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day1:0-1 Hr Post-Dose Rel. Change from Pre-dose | 3.128 L | Standard Deviation 12.088 |
| Matching Placebo (560 mg) | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day 1: 2 - 4 Hrs Post-Dose | 1.812 L | Standard Deviation 0.675 |
| Matching Placebo (560 mg) | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day 28:2-4 Hrs Post-Dose Rel. Change from Pre-dose | -0.542 L | Standard Deviation 7.69 |
| Matching Placebo (560 mg) | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day14:2-4 Hr Post-Dose Rel. Change from Pre-dose | 1.228 L | Standard Deviation 9.617 |
| Matching Placebo (560 mg) | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day14:0-1 Hr Post-Dose Rel. Change from Pre-dose | 0.589 L | Standard Deviation 4.558 |
| Matching Placebo (560 mg) | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day 28:0-1 Hr Post-Dose Rel. Change from Pre-dose | -1.437 L | Standard Deviation 6.454 |
| Matching Placebo (560 mg) | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day 28: Pre-Dose | 1.934 L | Standard Deviation 0.56 |
| Matching Placebo (560 mg) | Treatment-emergent Pulmonary Function Test (PFT) for Acute Tolerability Assessment | Day 14: 2 - 4 Hr Post-Dose | 1.901 L | Standard Deviation 0.542 |
Secondary
Change From Baseline in Log10CFU Per Gram (Density) of Pseudomonas Aeruginosa in Sputum.
The change in Pseudomonas aeruginosa density from from baseline to Day 14, 28, and 42 were evaluated.Treatment differences with respect to the changes from baseline to each measured study day, defined as the log10 of the sum of all morphotypes (colony-forming units \[CFU\]) per gram of sputum in (log10CFU/gram \[g\]), was estimated for each treatment group; standard deviations accompanied the treatment differences.
Time frame: Baseline to Day 14, Day 28 and Day 42.
Population: Per source, this is the Pa population, which includes patients who grew Pa on day 1, analyzed as treated.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arikace™ 280 mg | Change From Baseline in Log10CFU Per Gram (Density) of Pseudomonas Aeruginosa in Sputum. | Day 14 Change from Baseline | -0.227 log10CFU per gram | Standard Deviation 0.805 |
| Arikace™ 280 mg | Change From Baseline in Log10CFU Per Gram (Density) of Pseudomonas Aeruginosa in Sputum. | Day 42 Change from Baseline | 0.101 log10CFU per gram | Standard Deviation 0.788 |
| Arikace™ 280 mg | Change From Baseline in Log10CFU Per Gram (Density) of Pseudomonas Aeruginosa in Sputum. | Day 28 Change from Baseline | -0.094 log10CFU per gram | Standard Deviation 0.975 |
| Matching Placebo (280 mg) | Change From Baseline in Log10CFU Per Gram (Density) of Pseudomonas Aeruginosa in Sputum. | Day 14 Change from Baseline | -0.333 log10CFU per gram | Standard Deviation 0.515 |
| Matching Placebo (280 mg) | Change From Baseline in Log10CFU Per Gram (Density) of Pseudomonas Aeruginosa in Sputum. | Day 42 Change from Baseline | -0.057 log10CFU per gram | Standard Deviation 0.627 |
| Matching Placebo (280 mg) | Change From Baseline in Log10CFU Per Gram (Density) of Pseudomonas Aeruginosa in Sputum. | Day 28 Change from Baseline | 0.315 log10CFU per gram | Standard Deviation 0.732 |
| Arikace™ 560 mg | Change From Baseline in Log10CFU Per Gram (Density) of Pseudomonas Aeruginosa in Sputum. | Day 28 Change from Baseline | -1.013 log10CFU per gram | Standard Deviation 1.099 |
| Arikace™ 560 mg | Change From Baseline in Log10CFU Per Gram (Density) of Pseudomonas Aeruginosa in Sputum. | Day 14 Change from Baseline | -2.016 log10CFU per gram | Standard Deviation 1.942 |
| Arikace™ 560 mg | Change From Baseline in Log10CFU Per Gram (Density) of Pseudomonas Aeruginosa in Sputum. | Day 42 Change from Baseline | 0.046 log10CFU per gram | Standard Deviation 0.705 |
| Matching Placebo (560 mg) | Change From Baseline in Log10CFU Per Gram (Density) of Pseudomonas Aeruginosa in Sputum. | Day 14 Change from Baseline | -0.474 log10CFU per gram | Standard Deviation 1.942 |
| Matching Placebo (560 mg) | Change From Baseline in Log10CFU Per Gram (Density) of Pseudomonas Aeruginosa in Sputum. | Day 42 Change from Baseline | -0.641 log10CFU per gram | Standard Deviation 1.095 |
| Matching Placebo (560 mg) | Change From Baseline in Log10CFU Per Gram (Density) of Pseudomonas Aeruginosa in Sputum. | Day 28 Change from Baseline | -0.302 log10CFU per gram | Standard Deviation 0.443 |
Secondary
To Evaluate Change in St. George's Respiratory Questionnaire Measurements
A composite total score is derived as the sum of domain scores for symptoms, activity, and impact, with 0 as the best possible score and 100 as the worst possible score. A reduction in score of 4 points is generally recognized as a clinically meaningful improvement in quality of life. This analysis compared the changes from Day 1 (prior to first dosing) to Days 14, 28, 42, and 56.
Time frame: Day 1 to Day 14, Day 28, Day 42 and Day 56.
Population: The analysis population is the mITT population, defined as all randomized patients who received at least one dose of study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arikace™ 280 mg | To Evaluate Change in St. George's Respiratory Questionnaire Measurements | Day 14 change from Day 1 | -4.024 score on a scale | Standard Deviation 8.558 |
| Arikace™ 280 mg | To Evaluate Change in St. George's Respiratory Questionnaire Measurements | Day 28 change from Day 1 | -6.205 score on a scale | Standard Deviation 13.661 |
| Arikace™ 280 mg | To Evaluate Change in St. George's Respiratory Questionnaire Measurements | Day 42 change from Day 1 | -7.611 score on a scale | Standard Deviation 13.274 |
| Arikace™ 280 mg | To Evaluate Change in St. George's Respiratory Questionnaire Measurements | Day 56 change from Day 1 | -7.937 score on a scale | Standard Deviation 16.281 |
| Matching Placebo (280 mg) | To Evaluate Change in St. George's Respiratory Questionnaire Measurements | Day 28 change from Day 1 | -5.812 score on a scale | Standard Deviation 12.039 |
| Matching Placebo (280 mg) | To Evaluate Change in St. George's Respiratory Questionnaire Measurements | Day 42 change from Day 1 | -6.130 score on a scale | Standard Deviation 14.271 |
| Matching Placebo (280 mg) | To Evaluate Change in St. George's Respiratory Questionnaire Measurements | Day 56 change from Day 1 | -7.371 score on a scale | Standard Deviation 11.27 |
| Matching Placebo (280 mg) | To Evaluate Change in St. George's Respiratory Questionnaire Measurements | Day 14 change from Day 1 | -6.350 score on a scale | Standard Deviation 8.756 |
| Arikace™ 560 mg | To Evaluate Change in St. George's Respiratory Questionnaire Measurements | Day 42 change from Day 1 | -8.196 score on a scale | Standard Deviation 12.332 |
| Arikace™ 560 mg | To Evaluate Change in St. George's Respiratory Questionnaire Measurements | Day 28 change from Day 1 | -6.200 score on a scale | Standard Deviation 11.855 |
| Arikace™ 560 mg | To Evaluate Change in St. George's Respiratory Questionnaire Measurements | Day 56 change from Day 1 | -9.282 score on a scale | Standard Deviation 10.302 |
| Arikace™ 560 mg | To Evaluate Change in St. George's Respiratory Questionnaire Measurements | Day 14 change from Day 1 | -6.101 score on a scale | Standard Deviation 12.164 |
| Matching Placebo (560 mg) | To Evaluate Change in St. George's Respiratory Questionnaire Measurements | Day 56 change from Day 1 | -1.637 score on a scale | Standard Deviation 15.161 |
| Matching Placebo (560 mg) | To Evaluate Change in St. George's Respiratory Questionnaire Measurements | Day 28 change from Day 1 | -8.304 score on a scale | Standard Deviation 12.993 |
| Matching Placebo (560 mg) | To Evaluate Change in St. George's Respiratory Questionnaire Measurements | Day 14 change from Day 1 | -2.807 score on a scale | Standard Deviation 7.256 |
| Matching Placebo (560 mg) | To Evaluate Change in St. George's Respiratory Questionnaire Measurements | Day 42 change from Day 1 | 0.242 score on a scale | Standard Deviation 5.818 |
Secondary
To Evaluate the Use of Systemic Antipseudomonal Rescue Therapy
Time frame: Screening to Day 56.
Population: The analysis population is the mITT population, defined as all randomized patients who received at least one dose of study medication
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arikace™ 280 mg | To Evaluate the Use of Systemic Antipseudomonal Rescue Therapy | Rescue Medication Initiation by Day 56 | 0 Participants |
| Arikace™ 280 mg | To Evaluate the Use of Systemic Antipseudomonal Rescue Therapy | Rescue Medication Initiation by Day 28 | 0 Participants |
| Arikace™ 280 mg | To Evaluate the Use of Systemic Antipseudomonal Rescue Therapy | No Rescue Medication Initiation | 24 Participants |
| Matching Placebo (280 mg) | To Evaluate the Use of Systemic Antipseudomonal Rescue Therapy | Rescue Medication Initiation by Day 28 | 0 Participants |
| Matching Placebo (280 mg) | To Evaluate the Use of Systemic Antipseudomonal Rescue Therapy | Rescue Medication Initiation by Day 56 | 0 Participants |
| Matching Placebo (280 mg) | To Evaluate the Use of Systemic Antipseudomonal Rescue Therapy | No Rescue Medication Initiation | 10 Participants |
| Arikace™ 560 mg | To Evaluate the Use of Systemic Antipseudomonal Rescue Therapy | Rescue Medication Initiation by Day 28 | 0 Participants |
| Arikace™ 560 mg | To Evaluate the Use of Systemic Antipseudomonal Rescue Therapy | No Rescue Medication Initiation | 19 Participants |
| Arikace™ 560 mg | To Evaluate the Use of Systemic Antipseudomonal Rescue Therapy | Rescue Medication Initiation by Day 56 | 0 Participants |
| Matching Placebo (560 mg) | To Evaluate the Use of Systemic Antipseudomonal Rescue Therapy | Rescue Medication Initiation by Day 56 | 1 Participants |
| Matching Placebo (560 mg) | To Evaluate the Use of Systemic Antipseudomonal Rescue Therapy | Rescue Medication Initiation by Day 28 | 1 Participants |
| Matching Placebo (560 mg) | To Evaluate the Use of Systemic Antipseudomonal Rescue Therapy | No Rescue Medication Initiation | 7 Participants |
Secondary
Total Pulmonary Symptom Severity Score (PSSS)
Changes in the severity and intensity (frequency x severity) of individual symptoms and change in composite PSSS from baseline to Days 14, 28, 42 and 56. The Pulmonary Symptom Severity Score (PSSS) was assessed on patient's responses to the Patients Symptoms Questionnaire, which employs symptom frequency and severity scales described for the validated Memorial Symptoms Assessment Scale. Symptom severity was scored on a scale of 0 (not applicable or symptom not present) to 4 (very severe) for each of the 5 symptoms (cough, shortness of breath, sputum production \[frequency and severity\], fatigue, and wheezing), and a composite score (range, 0 to 20 \[low score represents better outcome\]) was obtained as the sum of the severity scores for each symptom.
Time frame: Baseline to Day 14, Day 28, Day 42 and Day 56.
Population: The safety population is used for this analysis. It is the same as the mITT population, defined as all randomized patients who received at least one dose of study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arikace™ 280 mg | Total Pulmonary Symptom Severity Score (PSSS) | Day 14 change from Day 1 | -1.125 score on a scale | Standard Deviation 2.213 |
| Arikace™ 280 mg | Total Pulmonary Symptom Severity Score (PSSS) | Day 28 change from Day 1 | -2.167 score on a scale | Standard Deviation 2.988 |
| Arikace™ 280 mg | Total Pulmonary Symptom Severity Score (PSSS) | Day 42 change from Day 1 | -2.458 score on a scale | Standard Deviation 3.476 |
| Arikace™ 280 mg | Total Pulmonary Symptom Severity Score (PSSS) | Day 56 change from Day 1 | -2.458 score on a scale | Standard Deviation 2.874 |
| Matching Placebo (280 mg) | Total Pulmonary Symptom Severity Score (PSSS) | Day 28 change from Day 1 | 0.000 score on a scale | Standard Deviation 2.357 |
| Matching Placebo (280 mg) | Total Pulmonary Symptom Severity Score (PSSS) | Day 42 change from Day 1 | -1.000 score on a scale | Standard Deviation 1.491 |
| Matching Placebo (280 mg) | Total Pulmonary Symptom Severity Score (PSSS) | Day 56 change from Day 1 | -1.500 score on a scale | Standard Deviation 2.121 |
| Matching Placebo (280 mg) | Total Pulmonary Symptom Severity Score (PSSS) | Day 14 change from Day 1 | -0.200 score on a scale | Standard Deviation 0.789 |
| Arikace™ 560 mg | Total Pulmonary Symptom Severity Score (PSSS) | Day 42 change from Day 1 | -1.882 score on a scale | Standard Deviation 4.285 |
| Arikace™ 560 mg | Total Pulmonary Symptom Severity Score (PSSS) | Day 28 change from Day 1 | -1.000 score on a scale | Standard Deviation 4.087 |
| Arikace™ 560 mg | Total Pulmonary Symptom Severity Score (PSSS) | Day 56 change from Day 1 | -2.167 score on a scale | Standard Deviation 3.053 |
| Arikace™ 560 mg | Total Pulmonary Symptom Severity Score (PSSS) | Day 14 change from Day 1 | -0.471 score on a scale | Standard Deviation 2.035 |
| Matching Placebo (560 mg) | Total Pulmonary Symptom Severity Score (PSSS) | Day 56 change from Day 1 | -2.000 score on a scale | Standard Deviation 1.69 |
| Matching Placebo (560 mg) | Total Pulmonary Symptom Severity Score (PSSS) | Day 28 change from Day 1 | -0.125 score on a scale | Standard Deviation 4.257 |
| Matching Placebo (560 mg) | Total Pulmonary Symptom Severity Score (PSSS) | Day 14 change from Day 1 | -0.250 score on a scale | Standard Deviation 2.053 |
| Matching Placebo (560 mg) | Total Pulmonary Symptom Severity Score (PSSS) | Day 42 change from Day 1 | 1.125 score on a scale | Standard Deviation 3.137 |