Liposomal Amikacin for Inhalation (LAI) for Nontuberculous Mycobacteria

Key Inclusion Criteria

• Diagnosis of pulmonary nontuberculous mycobacterial lung disease in accordance with the 2007 ATS/IDSA criteria with evidence of nodular bronchiectasis and/or cavitary disease by chest computed tomography (CT).
• History of chronic infection with either Mycobacterium avium complex or Mycobacterium abscessus or mixed infection with both species (defined as at least 2 documented positive cultures in the prior 2 years, of which at least one was obtained in the 6 months prior to screening).
• Positive sputum culture obtained at screening visit with either Mycobacterium avium complex or Mycobacterium abscessus or mixed infection with one dominant species.
• Receiving ATS/IDSA guidelines-based treatment regimen defined as: adherent to a multi-drug regimen for at least 6 months prior to screening with persistently positive mycobacterial cultures.
• Ability to produce at least 3 mL of sputum or be willing to undergo an induction that produces at least 3 mL of sputum for clinical evaluation.
• Female of childbearing potential agrees to practice an acceptable method of birth control (e.g., abstinence, hormonal or barrier methods, partner sterilization, or IUD).

Key Exclusion Criteria

• Forced Expiratory Volume in 1 second (FEV1) 450 msec for males or QTc> 470 msec for females.
• Subjects with hemoptysis of ≥60 mL in a 24 hour period within 4 weeks prior to screening.
• Active pulmonary malignancy (primary or metastatic) or any malignancy requiring chemotherapy or radiation therapy within one year prior to screening or anticipated during the study period.
• Active allergic bronchopulmonary mycosis or any other condition requiring systemic steroids at a dose > equivalent of 10 mg/day of prednisone within 3 months prior to screening or anticipated during the study period.
• Pulmonary tuberculosis requiring treatment or treated within 2 years prior to screening.
• History of lung transplantation.
• Hypersensitivity to aminoglycosides.
• Any change in chronic NTM multi-drug regimen within 28 days prior to Study Day 1.
• Evidence of biliary cirrhosis with portal hypertension.
• History of daily, continuous oxygen supplementation.
• Smoking tobacco or any substance within 6 months prior to screening or anticipated inability to refrain from smoking throughout the study.

Subjects with CF or primary ciliary dyskinesia were eligible to participate in the study if all eligibility criteria defined above were met. Subjects with CF were required to have documented confirmation of CF to be eligible for the study. The CF diagnosis had to be documented by a positive sweat test ≥ 60 mmol/L or by DNA analysis revealing both mutated alleles consistent with CF disease.