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| ID | Type | Description | Link |
|---|---|---|---|
| 2015-003170-33 | EudraCT Number |
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This is an open-label safety extension study to assess the safety and tolerability of once daily dosing of 590 mg Liposomal Amikacin for Inhalation (LAI) added to a multi-drug regimen in participants with nontuberculous mycobacterial (NTM) lung infections due to Mycobacterium avium complex (MAC) who were refractory to therapy and failed to convert in Study INS-212 (NCT02344004).
Safety and tolerability of once daily dosing of 590 mg Liposomal Amikacin for Inhalation (LAI) added to a multi-drug regimen in participants with non-tuberculous mycobacterium (NTM) lung infections due to Mycobacterium avium complex (MAC) who are refractory to therapy and failed to convert in Study INS-212.
Participants participating in Study INS-212 who had not achieved the INS-212 protocol definition of culture conversion (3 consecutive monthly negative sputum cultures) or who had experienced a relapse or recurrence (agar positive or more than 2 consecutive broth positive results after culture conversion had occurred) by Month 6, as determined by their sputum culture results from Day 1 through Month 6 and confirmed at their scheduled Month 8 visit, were eligible to participate in Study INS-312. For participants who chose to participate in Study INS-312, the Month 8 visit of Study INS-212 became their end of treatment (EOT) visit; these participants were then asked to provide written informed consent for Study INS-312 and were enrolled directly into Study INS-312 after having met all eligibility criteria.
Participants in Study INS-212 had either received 590 mg LAI plus an MDR (LAI + MDR arm) or a multidrug regimen alone (MDR alone arm). All participants in this safety extension study were to continue the multidrug antimycobacterial regimen that they were receiving during Study INS-212 and will receive LAI 590 mg administered daily (QD) for up to 12 months. The participants will remain in the study for up to a total of 13 months (up to 12 months on-treatment plus 1 month off LAI treatment for safety follow up).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Prior LAI + Multidrug Regimen | Experimental | Participants in the prior Study INS-212 who received LAI+MDR. All participants in this safety extension study received LAI+MDR. |
|
| Prior Multidrug Regimen Alone | Experimental | Participants in the prior Study INS-212 who received MDR alone. All participants in this safety extension study received LAI+MDR. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LAI 590 mg | Drug | LAI 590 mg QD: administered by inhaling drug product that had been aerosolized in an investigational eFlow nebulizer over approximately 14 minutes |
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| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAEs are defined as those AEs that occurred on or after the date of first dose of study medication in INS-312 and within 28 days after the last dose. If it couldn't be determined whether the AE is treatment emergent due to a partial onset date, then it was classified as treatment emergent. | From baseline to 28 days after end of treatment, up to 13 months |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Achieving Culture Conversion by Month 6 and Month 12 | 6 months: Converters are defined as participants who had 3 consecutive monthly MAC-negative sputum cultures by Month 6 (last opportunity to convert was at Month 4). 12 months: Converters are defined as participants who had 3 consecutive monthly MAC-negative sputum cultures by Month 12 (last opportunity to convert was at Month 10). |
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Key Inclusion Criteria:
Key Exclusion Criteria:
1. achieved culture conversion without relapse or recurrence in the Study INS-212 study by Month 6
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| Name | Affiliation | Role |
|---|---|---|
| Kevin Mange, MD | Insmed Incorporated | Study Director |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41186908 | Derived | Yamazaki Y, Nakagawa T, Jumadilova Z, Yuen D, Villa R, Hasegawa N. Management and Resolution of Hypersensitivity Pneumonitis-Related Events in Japanese Patients Treated with Amikacin Liposome Inhalation Suspension in the CONVERT and INS-312 Clinical Trials. Infect Dis Ther. 2026 Jan;15(1):365-379. doi: 10.1007/s40121-025-01247-7. Epub 2025 Nov 4. | |
| 33326356 |
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Participants in Study INS-212 had either received 590 mg LAI plus an MDR (LAI + MDR arm) or a multidrug regimen alone (MDR alone arm). All participants in this safety extension study, INS-312, were to continue the multidrug antimycobacterial regimen that they were receiving during Study INS-212 and received LAI 590 mg QD for up to 12 months.
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| ID | Title | Description |
|---|---|---|
| FG000 | Prior LAI + Multidrug Regimen | Participants in the prior Study INS-212 who received LAI+MDR. All participants in this safety extension study received LAI+MDR. |
| FG001 | Prior Multidrug Regimen Alone | Participants in the prior Study INS-212 who received MDR alone. All participants in this safety extension study received LAI+MDR. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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Safety population, defined as participants who received at least 1 dose of LAI.
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| ID | Title | Description |
|---|---|---|
| BG000 | Prior LAI + Multidrug Regimen | Participants in the prior Study INS-212 who received LAI+MDR. All participants in this safety extension study received LAI+MDR. |
| BG001 | Prior Multidrug Regimen Alone |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAEs are defined as those AEs that occurred on or after the date of first dose of study medication in INS-312 and within 28 days after the last dose. If it couldn't be determined whether the AE is treatment emergent due to a partial onset date, then it was classified as treatment emergent. | Safety population | Posted | Number | participants | From baseline to 28 days after end of treatment, up to 13 months |
|
From baseline up to 28 days after end of treatment, up to 13 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Prior LAI + Multidrug Regimen | Participants in the prior Study INS-212 who received LAI+MDR. All participants in this safety extension study received LAI+MDR. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Atrial fibrillation | Cardiac disorders | MedDRA version 17.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA version 17.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Kevin Mange (Senior Vice President, Clinical Development & Medical Affairs, ALIS) | Insmed Inc | 908-947-2651 | kevin.mange@insmed.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 13, 2018 | Oct 12, 2019 | SAP_000.pdf |
| Prot | Yes | No | No | Study Protocol | May 25, 2017 | Oct 12, 2019 | Prot_001.pdf |
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| Multi-drug regimen | Drug | Multidrug antimycobacterial regimen from study INS-212 |
|
| by Month 6 and Month 12 |
| Time to Culture Conversion | The time to culture conversion is defined as the date of conversion for participants achieving culture conversion is defined as the date of the first of 3-consecutive monthly negative sputum cultures. Then, the number of days to culture conversion is defined as the difference between the date of conversion and the date of first dose of LAI. | by Month 12 |
| Change From Baseline (Day 1) to Month 6 and Month 12 in the 6MWT Distance | A 6-minute walk assessment of exertional capability was performed at Baseline (Day 1) and Month 6 and Month 12/EOT. The standardized protocol based on the American Thoracic Society (ATS) guidelines (http://doi.org/10.1164/ajrccm.166.1.at1102) was used. After assessments were performed for heart rate, blood pressure, pulse oximetry (SpO2), dyspnea, and overall fatigue using the Borg scale, participants were instructed to walk on a prescribed course as far as they could in 6 minutes. Pre-test assessment parameters were repeated after exertion. The maximum distance achieved and post exertion heart rate and SpO2 were compared to pre-test values. The maximum distance achieved was recorded in the electronic case report form. | From baseline to Month 12 or end of treatment |
| Winthrop KL, Flume PA, Thomson R, Mange KC, Yuen DW, Ciesielska M, Morimoto K, Ruoss SJ, Codecasa LR, Yim JJ, Marras TK, van Ingen J, Wallace RJ Jr, Brown-Elliott BA, Coulter C, Griffith DE. Amikacin Liposome Inhalation Suspension for Mycobacterium avium Complex Lung Disease: A 12-Month Open-Label Extension Clinical Trial. Ann Am Thorac Soc. 2021 Jul;18(7):1147-1157. doi: 10.1513/AnnalsATS.202008-925OC. |
| Protocol Violation |
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| Lack of Efficacy |
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| Withdrawal by Subject |
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| Lost to Follow-up |
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| Physician Decision |
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| Other not specified |
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Participants in the prior Study INS-212 who received MDR alone. All participants in this safety extension study received LAI+MDR.
| BG002 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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Participants in the prior Study INS-212 who received MDR alone. All participants in this safety extension study received LAI+MDR. |
|
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| Secondary | Number of Participants Achieving Culture Conversion by Month 6 and Month 12 | 6 months: Converters are defined as participants who had 3 consecutive monthly MAC-negative sputum cultures by Month 6 (last opportunity to convert was at Month 4). 12 months: Converters are defined as participants who had 3 consecutive monthly MAC-negative sputum cultures by Month 12 (last opportunity to convert was at Month 10). | Safety population | Posted | Count of Participants | Participants | by Month 6 and Month 12 |
|
|
|
| Secondary | Time to Culture Conversion | The time to culture conversion is defined as the date of conversion for participants achieving culture conversion is defined as the date of the first of 3-consecutive monthly negative sputum cultures. Then, the number of days to culture conversion is defined as the difference between the date of conversion and the date of first dose of LAI. | The Safety population was the set of all enrolled participants who received at least 1 dose of LAI. | Posted | Median | Full Range | months | by Month 12 |
|
|
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| Secondary | Change From Baseline (Day 1) to Month 6 and Month 12 in the 6MWT Distance | A 6-minute walk assessment of exertional capability was performed at Baseline (Day 1) and Month 6 and Month 12/EOT. The standardized protocol based on the American Thoracic Society (ATS) guidelines (http://doi.org/10.1164/ajrccm.166.1.at1102) was used. After assessments were performed for heart rate, blood pressure, pulse oximetry (SpO2), dyspnea, and overall fatigue using the Borg scale, participants were instructed to walk on a prescribed course as far as they could in 6 minutes. Pre-test assessment parameters were repeated after exertion. The maximum distance achieved and post exertion heart rate and SpO2 were compared to pre-test values. The maximum distance achieved was recorded in the electronic case report form. | Baseline: number of participants with data at this visit. Change from baseline: number of participants with both baseline and 6 month scores. | Posted | Mean | Standard Deviation | meters | From baseline to Month 12 or end of treatment |
|
|
|
| 2 |
| 73 |
| 20 |
| 73 |
| 45 |
| 73 |
| EG001 | Prior Multidrug Regimen Alone | Participants in the prior Study INS-212 who received MDR alone. All participants in this safety extension study received LAI+MDR. | 4 | 90 | 32 | 90 | 75 | 90 |
| Cataract | Eye disorders | MedDRA version 17.1 | Systematic Assessment |
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| Vision blurred | Eye disorders | MedDRA version 17.1 | Systematic Assessment |
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| Ascites | Gastrointestinal disorders | MedDRA version 17.1 | Systematic Assessment |
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| Gastritis | Gastrointestinal disorders | MedDRA version 17.1 | Systematic Assessment |
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| Asthenia | General disorders | MedDRA version 17.1 | Systematic Assessment |
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| Chest pain | General disorders | MedDRA version 17.1 | Systematic Assessment |
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| Performance status decreased | General disorders | MedDRA version 17.1 | Systematic Assessment |
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| Bronchopulmonary aspergillosis allergic | Infections and infestations | MedDRA version 17.1 | Systematic Assessment |
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| Gastroenteritis viral | Infections and infestations | MedDRA version 17.1 | Systematic Assessment |
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| Infective exacerbation of bronchiectasis | Infections and infestations | MedDRA version 17.1 | Systematic Assessment |
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| Laryngitis | Infections and infestations | MedDRA version 17.1 | Systematic Assessment |
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| Lower respiratory tract infection | Infections and infestations | MedDRA version 17.1 | Systematic Assessment |
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| Mycobacterium abscessus infection | Infections and infestations | MedDRA version 17.1 | Systematic Assessment |
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| Mycobacterium avium complex infection | Infections and infestations | MedDRA version 17.1 | Systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA version 17.1 | Systematic Assessment |
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| Pneumonia fungal | Infections and infestations | MedDRA version 17.1 | Systematic Assessment |
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| Post procedural pneumonia | Infections and infestations | MedDRA version 17.1 | Systematic Assessment |
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| Respiratory tract infection | Infections and infestations | MedDRA version 17.1 | Systematic Assessment |
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| Sinobronchitis | Infections and infestations | MedDRA version 17.1 | Systematic Assessment |
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| Hip fracture | Injury, poisoning and procedural complications | MedDRA version 17.1 | Systematic Assessment |
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| Pelvic fracture | Injury, poisoning and procedural complications | MedDRA version 17.1 | Systematic Assessment |
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| Radius fracture | Injury, poisoning and procedural complications | MedDRA version 17.1 | Systematic Assessment |
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| Dehydration | Metabolism and nutrition disorders | MedDRA version 17.1 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA version 17.1 | Systematic Assessment |
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| Breast cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 17.1 | Systematic Assessment |
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| Cerebral infarction | Nervous system disorders | MedDRA version 17.1 | Systematic Assessment |
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| Neuropathy peripheral | Nervous system disorders | MedDRA version 17.1 | Systematic Assessment |
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| Transient ischaemic attack | Nervous system disorders | MedDRA version 17.1 | Systematic Assessment |
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| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA version 17.1 | Systematic Assessment |
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| Alveolitis allergic | Respiratory, thoracic and mediastinal disorders | MedDRA version 17.1 | Systematic Assessment |
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| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA version 17.1 | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA version 17.1 | Systematic Assessment |
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| Dyspnoea at rest | Respiratory, thoracic and mediastinal disorders | MedDRA version 17.1 | Systematic Assessment |
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| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA version 17.1 | Systematic Assessment |
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| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA version 17.1 | Systematic Assessment |
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| Interstitial lung disease | Respiratory, thoracic and mediastinal disorders | MedDRA version 17.1 | Systematic Assessment |
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| Lung infiltration | Respiratory, thoracic and mediastinal disorders | MedDRA version 17.1 | Systematic Assessment |
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| Pneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA version 17.1 | Systematic Assessment |
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| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA version 17.1 | Systematic Assessment |
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| Pulmonary fibrosis | Respiratory, thoracic and mediastinal disorders | MedDRA version 17.1 | Systematic Assessment |
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| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA version 17.1 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA version 17.1 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA version 17.1 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA version 17.1 | Systematic Assessment |
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| Infective exacerbation of bronchiectasis | Infections and infestations | MedDRA version 17.1 | Systematic Assessment |
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| Weight decreased | Investigations | MedDRA version 17.1 | Systematic Assessment |
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| Haematuria | Renal and urinary disorders | MedDRA version 17.1 | Systematic Assessment |
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| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA version 17.1 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA version 17.1 | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA version 17.1 | Systematic Assessment |
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| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA version 17.1 | Systematic Assessment |
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| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA version 17.1 | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA version 17.1 | Systematic Assessment |
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The PI agrees not to originate or use the name of Insmed Incorporated, or study drug code in any publicity, news release, or other public announcement, written or oral, whether to the public, press, or otherwise, relating to this protocol, to any amendment to the protocol, or to the performance of this protocol, without the prior written consent of Insmed Incorporated.
| Change from Baseline to Month 6 |
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| Change from Baseline to Month 12 |
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