Study to Evaluate Efficacy of LAI When Added to Multi-drug Regimen Compared to Multi-drug Regimen Alone
Study to Evaluate Efficacy of LAI When Added to Multi-drug Regimen Compared to Multi-drug Regimen Alone
A study to evaluate the effectiveness of Liposomal Amikacin for Inhalation (LAI) 590 mg
 administered once daily (QD) when added to multi-drug regimen (MDR) in participants with
 Nontuberculous Mycobacterial (NTM) lung infection caused by Mycobacterium Avium Complex (MAC)
 that were refractory to treatment.

 Participants were randomized 2:1 to LAI 590 mg administered QD + MDR or MDR alone.
This is a randomized, open-label, multicenter study of LAI in adult participants with NTM
 lung infections caused by MAC that were refractory to treatment. Participants received either
 LAI 590 mg administered QD by inhalation plus a multidrug regimen, hereafter referred to as
 LAI + MDR or a multidrug regimen alone, hereafter referred to as MDR alone for a minimum of 8
 months. Participants who demonstrated culture conversion by Month 6 went on to complete a
 treatment course of 12 months, starting from the first of 3 negative cultures that defined
 culture conversion.

 Sputum culture results were made available to the site after the Month 6 sputum result was
 known, in time for the Month 8 visit. Prior to the Month 8 visit, the culture results from
 Baseline to Month 6 inclusively were blinded to the site and Sponsor. The results were
 blinded to reduce the potential for bias in an open-label study. At Month 8 (-28 to +7 days),
 after all sputum culture results were made available to the site only, up to and including
 Month 6, participants were assessed as converters or non-converters.

 A converter was defined as a participant who had 3 consecutive monthly MAC-negative sputum
 cultures at any time within the first 6 months of the study.

 "Relapse or recurrence" was defined as having MAC-positive sputum cultures in liquid broth
 media (agar negative) for 3 or more consecutive months, or having at least 1 MAC-positive
 sputum culture on solid media (agar positive) after achieving culture conversion.

 A non-converter was defined as a participant who did not have 3 consecutive monthly
 MAC-negative sputum cultures at any time within the first 6 months of the study.

 All converters remained in the study. Converters who, after culture conversion, subsequently
 had MAC-positive sputum cultures in liquid broth media (agar negative) for 1 or 2 consecutive
 months only by Month 6 also remained in the study. Participants who remained in the study
 continued their randomized treatment regimen until they completed a total of 12 months of
 treatment (EOT), starting from the first of 3 negative cultures that defined culture
 conversion. These participants returned after the EOT visit for 28 days, 3, 6, and 12 months
 off-treatment follow-up visits. The 12 months off-treatment follow-up visit was the end of
 study (EOS) visit. No NTM treatment was administered during the off-treatment phase.

 At Month 8, all non-converters as assessed at the Month 6 visit were discontinued from Study
 INS-212. Participants who experienced a relapse or recurrence by Month 6 also discontinued
 from Study INS-212 at their Month 8 visit. These participants were potentially eligible to
 enter a separate open-label study of LAI (Study INS-312), provided all entry criteria were
 met for that study.
Inclusion Criteria:

 1. Be continually positive for MAC on sputum culture while adhering to a multi-drug
 treatment regimen for a minimum duration of 6 months which is either ongoing or was
 completed no more than 12 months before screening

 2. Be diagnosed with MAC NTM lung infection with evidence of nodular bronchiectasis
 and/or fibrocavitary disease by chest CT

 3. Be willing to adhere to multi-drug treatment regimen during the course of the study

 Exclusion Criteria:

 1. Patients with cystic fibrosis

 2. Positive pregnancy test or lactation at screening. All women of child bearing
 potential will be tested. Women not of childbearing potential are defined as
 postmenopausal (i.e., amenorrheic for at least 1 year), or surgically or naturally
 sterile.

 3. Active pulmonary tuberculosis requiring treatment at screening

 4. History of lung transplantation

 5. Prior exposure to LAI (including clinical study).