Oral Omadacycline vs. Placebo in Adults With NTM Pulmonary Disease Caused by Mycobacterium Abscessus Complex (MABc)

A clinical responder is defined as a participant who shows improvement in at least 50% of baseline symptoms on the NTM Symptom Assessment Questionnaire at the Day 84 Visit. This self-administered tool assesses 12 common NTM symptoms, each rated on a 4-point scale (absent, mild, moderate, severe), reflecting the participant's overall impression over the past week. The questionnaire is completed solely by the participant, without any interpretation from clinicians or site staff.

A clinical responder is defined as a participant who shows improvement in at least 50% of baseline symptoms with no deterioration of symptoms present at baseline on the NTM Symptom Assessment Questionnaire at the Day 84 Visit. This self-administered tool assesses 12 common NTM symptoms, each rated on a 4-point scale (absent, mild, moderate, severe), reflecting the participant's overall impression over the past week. The questionnaire is completed solely by the participant, without any interpretation from clinicians or site staff.

A TEAE is an adverse event that occurred on or after first dose of test article and those existing AEs that worsened on or after first dose of test article. An SAE is an adverse event that results in death, is life-threatening, requires hospitalization or extends an existing one, causes significant or lasting disability/incapacity, or leads to a congenital anomaly or birth defect. Additionally, events that may not meet these criteria but are medically significant can also be classified as SAEs.

To assess the incidents of abnormal hepatic and enzymatic biomarkers following 84 days of IP administration

Laboratory PCS event is defined as at least a 2 grade increase from baseline based on the Division of Microbiology and Infectious Diseases (DMID) v5.0.

To assess the incidents of abnormal blood pressure assessments following 84 days of IP administration

To assess the incidents of abnormal heart rate following 84 days of IP administration

To assess the incidents of PCS heart rate and blood pressure following 84 days of IP administration

To assess the incidents of cardiac rhythm, PR interval, QRS interval, QT interval and QTc interval assessments following 84 days of IP administration

To assess the incidents of PCS and QTc interval assessments following 84 days of IP administration

The QOL-B is a self-administered, patient-reported outcome measure assessing symptoms, functioning and health-related quality of life for participants with non-cystic fibrosis bronchiectasis using a series of 37 questions. The QOL-B includes domains for physical functioning, role functioning, vitality, emotional functioning, social functioning, treatment burden, health perceptions and respiratory symptoms. For each domain, scores will be standardized on a 0 to 100 scale and higher scores represent better outcomes.

The QOL-B is a self-administered, patient-reported outcome measure assessing symptoms, functioning and health-related quality of life for participants with non-cystic fibrosis bronchiectasis using a series of 37 questions. The QOL-B includes domains for physical functioning, role functioning, vitality, emotional functioning, social functioning, treatment burden, health perceptions and respiratory symptoms. For each domain, scores will be standardized on a 0 to 100 scale and higher scores represent better outcomes.

The QOL-B is a self-administered, patient-reported outcome measure assessing symptoms, functioning and health-related quality of life for participants with non-cystic fibrosis bronchiectasis using a series of 37 questions. The QOL-B includes domains for physical functioning, role functioning, vitality, emotional functioning, social functioning, treatment burden, health perceptions and respiratory symptoms. For each domain, scores will be standardized on a 0 to 100 scale and higher scores represent better outcomes.

The QOL-B is a self-administered, patient-reported outcome measure assessing symptoms, functioning and health-related quality of life for participants with non-cystic fibrosis bronchiectasis using a series of 37 questions. The QOL-B includes domains for physical functioning, role functioning, vitality, emotional functioning, social functioning, treatment burden, health perceptions and respiratory symptoms. For each domain, scores will be standardized on a 0 to 100 scale and higher scores represent better outcomes.

The QOL-B is a self-administered, patient-reported outcome measure assessing symptoms, functioning and health-related quality of life for participants with non-cystic fibrosis bronchiectasis using a series of 37 questions. The QOL-B includes domains for physical functioning, role functioning, vitality, emotional functioning, social functioning, treatment burden, health perceptions and respiratory symptoms. For each domain, scores will be standardized on a 0 to 100 scale and higher scores represent better outcomes.

The QOL-B is a self-administered, patient-reported outcome measure assessing symptoms, functioning and health-related quality of life for participants with non-cystic fibrosis bronchiectasis using a series of 37 questions. The QOL-B includes domains for physical functioning, role functioning, vitality, emotional functioning, social functioning, treatment burden, health perceptions and respiratory symptoms. For each domain, scores will be standardized on a 0 to 100 scale and higher scores represent better outcomes.

The QOL-B is a self-administered, patient-reported outcome measure assessing symptoms, functioning and health-related quality of life for participants with non-cystic fibrosis bronchiectasis using a series of 37 questions. The QOL-B includes domains for physical functioning, role functioning, vitality, emotional functioning, social functioning, treatment burden, health perceptions and respiratory symptoms. For each domain, scores will be standardized on a 0 to 100 scale and higher scores represent better outcomes.

The QOL-B is a self-administered, patient-reported outcome measure assessing symptoms, functioning and health-related quality of life for participants with non-cystic fibrosis bronchiectasis using a series of 37 questions. The QOL-B includes domains for physical functioning, role functioning, vitality, emotional functioning, social functioning, treatment burden, health perceptions and respiratory symptoms. For each domain, scores will be standardized on a 0 to 100 scale and higher scores represent better outcomes.

The SGRQ is a disease-specific, 50-item instrument designed to measure the impact of obstructive airways disease on overall health, daily life, and perceived well-being in participants. It consists of three domains: Symptoms (distress from respiratory symptoms), Activity (limitations in mobility and physical activity), and Impacts (effects on employment, self-management, and medication needs). Scores range from 0 (no impairment) to 100 (maximum impairment) for each domain. The SGRQ Total Score is calculated by dividing the total score values of all positive responses across all domains in the questionnaire by the maximum possible total score that a participant could have achieved, and then multiplying the result by 100. Higher scores indicate worse health status

The PROMIS Fatigue is a self-administered questionnaire that assesses fatigue and its impact on physical, mental, and social activities. The fatigue short form is universal rather than disease-specific and assesses fatigue over the past 7 days. Participants respond to each of the 7 items using a 5-point Likert scale (e.g., "Not at all" to "Very much") and item responses are summed to produce a raw total score. Raw scores are converted to T-scores using standardized PROMIS scoring tables. The average change in PROMIS Fatigue T-scores was calculated for each study arm. The PROMIS Fatigue T-score is a standardized score (mean = 50, SD = 10) where higher scores indicate greater fatigue severity. A negative change from baseline (i.e., lower T-scores over time) indicates improvement in fatigue symptoms, whereas a positive change (i.e., higher T-scores) indicates worsening of fatigue.

The PGI-C is a self-administered, single question assessed using a 7-point scale that measures a participant's perceived change in clinical status and overall improvement. Participants with improvement includes: Very much improved, much improved, minimally improved; participants without improvement include: no change, minimally worse, much worse, very much worse.

The PGI-S is a self-administered, single question assessed using a 7-point scale that measures a participant's perception of disease severity. Participants with severity Not present or Mild include: not present, very mild, mild; Participants with severity Moderate or Severe include: moderate, moderately severe, severe, extremely severe.

The CGI-S is administered by an experienced clinician who is familiar with the disease under study. The CGI-S is a 1-item observer-rated scale that rates illness severity based upon observed and reported symptoms, behavior, and function over the past seven days.

The CGI-I is a single-item, observer-rated measure using a 7-point scale to assess overall improvement in a participant's condition due to drug treatment. Participants with improvement includes: very much improved, much improved, minimally improved; participants without improvement include: no change, minimally worse, much worse, very much worse.

The NTM symptom assessment questionnaire is a self-administered tool which assesses 12 common NTM symptoms on a 4-point scale (absent, mild, moderate, severe), reflecting the participant's overall impression over the past week. The questionnaire is completed solely by the participant, without any interpretation from clinicians or site staff.

Semi-quantitative score is derived based on growth in liquid medium, growth on agar plate, and colony count on agar plate; the score ranges from 0 to 6. A reduction in the semi-quantitative score reflects a decrease in the quantitative mycobacterial load.

Time to growth in liquid medium only is defined as the number of days from the date of study drug administration to the date of the first assessment where growth is detected in liquid medium only. The analysis was based on Kaplan Meier Estimation for Growth in Liquid Medium Only (Day). If there is no culture result indicating growth in liquid medium only and the culture plates are negative, the date of the first negative culture is used for determination of time to growth in liquid medium only.

Time to first negative sputum culture is defined as the number of days from the date of study drug administration to the date of the first negative sputum culture. The analysis was based on Kaplan Meier Estimation for Negative Sputum Culture (Day).