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An Open-Label Safety Extension Study to a Multicenter Study of Liposomal Amikacin for Inhalation (LAI) in Adult Patients with Nontuberculous Mycobacterial (NTM) Lung Infections caused by Mycobacterium avium complex (MAC) That are Refractory to Treatment

Phase 3
Completed
Conditions
Lung infection
Mycobacterial Lung lnfection
10028440
10024970
Registration Number
NL-OMON43501
Lead Sponsor
lnsmed lncorporated
Brief Summary

Trial is onging in other countries

Detailed Description

Not available

Recruitment & Eligibility

Status
Completed
Sex
Not specified
Target Recruitment
1
Inclusion Criteria

Subjects are eligible to participate in the study if they meet all the following inclusion criteria:
1. have successfully completed the Month 6 and EOT visits in INS-212
2. have not achieved the INS-212 protocol definition of culture conversion (3 consecutive monthly negative sputum cultures) by Month 6 in INS-212
OR
have experienced a relapse or recurrence (agar positive or more than 2 consecutive broth positive results after culture conversion has occurred) by Month 6 in INS-212
3. have demonstrated compliance with treatment regimen in INS-212, including LAI, if applicable
4. willing to adhere to multi-drug treatment regimen during the course of the study
5. female of child bearing potential agrees to practice an acceptable method of birth control (e.g., true abstinence [refraining from heterosexual intercourse during the study], hormonal or barrier
methods, partner sterilization, or intrauterine device [IUD]) while participating in the trial. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of the study, and withdrawal are not acceptable methods of contraception.
6. the subject will provide written informed consent
7. willing to have serum and sputum specimens stored
8. able to comply with study drug use, study visits, and study procedures as determined by the Investigator

Exclusion Criteria

Subjects are not eligible to participate in the study if they meet any of the following criteria:
1. achieved culture conversion without relapse or recurrence in the INS212study by Month 6
2. early discontinuation (prior to Month 6 study visit) from INS-212
3. met any of the exclusion criteria of the INS-212 study, with the exception of the following:
a. unable to perform the 6MWT
b. prior exposure to LAI (including clinical study)
c. in the opinion of the Investigator, patients who are not expected to survive the duration of the study
d. active allergic bronchopulmonary mycosis or any other condition requiring chronic systemic corticosteroids at a dose greater than the equivalent of 10 mg/day of prednisone within 3 months before Baseline (Day 1)
e. initiation of chronic therapy (e.g., high dose ibuprofen, inhaled anti-inflammatory agents including steroids, low dose maintenance steroids, rhDNase) at Baseline (Day 1)
4. positive pregnancy test or lactation. All women of child bearing potential will be tested. Women not of child bearing potential are defined as postmenopausal (i.e., amenorrheic for at least 1 year), or surgically or naturally sterile.
5. significant (as determined by the Investigator) hearing loss, vestibular dysfunction, or neuromuscular weakness where the potential risk of aminoglycoside toxicity outweighs the potential benefit
6. aspartate aminotransferase or alanine aminotransferase * 3 times the upper limit of normal (ULN) and/or total bilirubin * 2 times the ULN at their Month 6 study visit in INS-212
7. absolute neutrophil count *500/*L at their Month 6 study visit in INS2128. serum creatinine >2 times ULN at their Month 6 study visit in INS-212
9. current alcohol, medication abuse, or illicit drug abuse
10. any condition that, in the opinion of the Investigator, interferes with ability to safely complete the study or adhere to study requirements
11. diagnosis of myasthenia gravis

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
<p>PRIMARY ENDPOINT - SAFETY<br /><br>The primary endpoint is the frequency of treatment-emergent adverse events<br /><br>(TEAEs), TEAEs leading to withdrawal from study, treatment-emergent serious<br /><br>adverse events (SAEs), AEs of special interest, clinically significant abnormal<br /><br>laboratory test results, and vital signs measurements. The primary endpoint<br /><br>will evaluate the overall population and describe the subjects by treatment arm<br /><br>assigned in the INS-212 study (LAI added to a multi-drug regimen arm and a<br /><br>multi-drug regimen alone).</p><br>
Secondary Outcome Measures
NameTimeMethod
<p>SECONDARY ENDPOINTS - EFFICACY<br /><br>The secondary endpoints will evaluate the overall population and describe the<br /><br>subjects by treatment arm assigned in the INS-212 study (LAI added to a<br /><br>multi-drug regimen arm and a multi-drug regimen alone).<br /><br>1. Proportion of subjects achieving culture conversion (3 consecutive monthly<br /><br>negative sputum cultures without relapse or recurrence) by Month 12/EOT.<br /><br>2. Proportion of subjects achieving culture conversion by Month 6.<br /><br>3. Time to culture conversion. The date of conversion is defined by the date of<br /><br>the first of at least 3 consecutive monthly culture specimens that are MAC<br /><br>negative.<br /><br>4. The mean change from Baseline in 6MWT distance at Month 6 and Month 12/EOT</p><br>
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