Trial Outcomes & Findings for Oral Omadacycline vs. Placebo in Adults With NTM Pulmonary Disease Caused by Mycobacterium Abscessus Complex (MABc) (NCT NCT04922554)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

66 participants

Primary outcome timeframe

Day 1 to Day 84

Results posted on

2025-07-30

Participant Flow

This is a randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of omadacycline in adult participants with nontuberculous mycobacterial pulmonary disease caused by Mycobacterium abscessus complex.

A total of 66 participants were enrolled at 17 sites in the US.

Participant milestones

Participant milestones
Measure	Omadacycline 300 mg Participants received omadacycline 300 mg orally (PO) (administered as two 150 mg tablets) every 24 hours (q24h).	Placebo Participants received matching placebo PO (administered as two tablets) q24h.
Overall Study STARTED	41	25
Overall Study COMPLETED	36	25
Overall Study NOT COMPLETED	5	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Omadacycline 300 mg Participants received omadacycline 300 mg orally (PO) (administered as two 150 mg tablets) every 24 hours (q24h).	Placebo Participants received matching placebo PO (administered as two tablets) q24h.
Overall Study Adverse Event	4	0
Overall Study Withdrawal by Subject	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Omadacycline 300 mg n=41 Participants Participants received omadacycline 300 mg PO (administered as two 150 mg tablets) q24h.	Placebo n=25 Participants Participants received matching placebo PO (administered as two tablets) q24h.	Total n=66 Participants Total of all reporting groups
Age, Continuous	69.3 Years STANDARD_DEVIATION 9.61 • n=5 Participants	72.8 Years STANDARD_DEVIATION 7.64 • n=7 Participants	70.6 Years STANDARD_DEVIATION 9.02 • n=5 Participants
Sex: Female, Male Female	30 Participants n=5 Participants	15 Participants n=7 Participants	45 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	10 Participants n=7 Participants	21 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	36 Participants n=5 Participants	23 Participants n=7 Participants	59 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 1 to Day 84

Population: Intent-to-treat (ITT) analysis set included all randomized participants.

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.

Outcome measures

Outcome measures
Measure	Omadacycline 300 mg n=41 Participants Participants received omadacycline 300 mg PO (administered as two 150 mg tablets) q24h.	Placebo n=25 Participants Participants received matching placebo PO (administered as two tablets) q24h.
Percentage of Participants With Clinical Response on NTM Symptom Assessment Scale at Day 84	34.1 Percentage of participants	20.0 Percentage of participants

PRIMARY outcome

Timeframe: Day 1 to Day 84

Population: ITT Analysis Set

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.

Outcome measures

Outcome measures
Measure	Omadacycline 300 mg n=41 Participants Participants received omadacycline 300 mg PO (administered as two 150 mg tablets) q24h.	Placebo n=25 Participants Participants received matching placebo PO (administered as two tablets) q24h.
Percentage of Participants With Clinical Response on NTM Symptom Assessment Scale at Day 84 With no Deterioration in Severity of Symptoms That Were Present at Baseline.	34.1 percentage of participants	12.0 percentage of participants

PRIMARY outcome

Timeframe: From screening period (up to 8 weeks prior to randomization) through Day 114 (at any study timepoint)

Population: Safety Analysis Set included all participants who received at least 1 dose of test article.

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.

Outcome measures

Outcome measures
Measure	Omadacycline 300 mg n=41 Participants Participants received omadacycline 300 mg PO (administered as two 150 mg tablets) q24h.	Placebo n=25 Participants Participants received matching placebo PO (administered as two tablets) q24h.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) TEAEs	35 Participants	21 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) SAEs	0 Participants	2 Participants

PRIMARY outcome

Timeframe: Day 1 (Baseline) to Day 84/EOT

Population: Safety Analysis Set

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

Outcome measures

Outcome measures
Measure	Omadacycline 300 mg n=41 Participants Participants received omadacycline 300 mg PO (administered as two 150 mg tablets) q24h.	Placebo n=25 Participants Participants received matching placebo PO (administered as two tablets) q24h.
Change From Baseline in Laboratory Test Parameters - Hepatic and Enzymatic Biomarkers Alkaline Phosphatase	-3.3 Units per litre Standard Deviation 14.46	-3.0 Units per litre Standard Deviation 11.22
Change From Baseline in Laboratory Test Parameters - Hepatic and Enzymatic Biomarkers Alanine Aminotransferase	10.4 Units per litre Standard Deviation 17.19	-1.4 Units per litre Standard Deviation 9.74
Change From Baseline in Laboratory Test Parameters - Hepatic and Enzymatic Biomarkers Aspartate Aminotransferase	3.9 Units per litre Standard Deviation 8.72	-3.0 Units per litre Standard Deviation 11.88
Change From Baseline in Laboratory Test Parameters - Hepatic and Enzymatic Biomarkers Creatine Kinase	2.5 Units per litre Standard Deviation 28.76	-26.6 Units per litre Standard Deviation 116.68
Change From Baseline in Laboratory Test Parameters - Hepatic and Enzymatic Biomarkers Gamma Glutamyl Transferase	1.7 Units per litre Standard Deviation 14.35	-0.6 Units per litre Standard Deviation 12.83
Change From Baseline in Laboratory Test Parameters - Hepatic and Enzymatic Biomarkers Lipase	3.5 Units per litre Standard Deviation 16.50	-2.2 Units per litre Standard Deviation 8.39

PRIMARY outcome

Timeframe: Day 1 through Day 84 (at any study timepoint)

Population: Safety Analysis Set

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.

Outcome measures

Outcome measures
Measure	Omadacycline 300 mg n=41 Participants Participants received omadacycline 300 mg PO (administered as two 150 mg tablets) q24h.	Placebo n=25 Participants Participants received matching placebo PO (administered as two tablets) q24h.
Number of Participants With Potentially Clinically Significant (PCS) Laboratory Parameter Alkaline Phosphatase	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant (PCS) Laboratory Parameter Alanine Aminotransferase	2 Participants	0 Participants
Number of Participants With Potentially Clinically Significant (PCS) Laboratory Parameter Aspartate Aminotransferase	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant (PCS) Laboratory Parameter Calcium	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant (PCS) Laboratory Parameter Creatinine	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant (PCS) Laboratory Parameter Gamma Glutamyl Transferase	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant (PCS) Laboratory Parameter Lipase	3 Participants	0 Participants
Number of Participants With Potentially Clinically Significant (PCS) Laboratory Parameter Magnesium	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant (PCS) Laboratory Parameter Phosphate	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant (PCS) Laboratory Parameter Potassium	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant (PCS) Laboratory Parameter Sodium	1 Participants	0 Participants
Number of Participants With Potentially Clinically Significant (PCS) Laboratory Parameter Bilirubin	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant (PCS) Laboratory Parameter Neutrophils	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant (PCS) Laboratory Parameter Hemoglobin	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant (PCS) Laboratory Parameter Platelets	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant (PCS) Laboratory Parameter Leukocytes	0 Participants	1 Participants

PRIMARY outcome

Timeframe: Day 1 (Baseline) to Day 84/EOT

Population: Safety Analysis Set

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

Outcome measures

Outcome measures
Measure	Omadacycline 300 mg n=41 Participants Participants received omadacycline 300 mg PO (administered as two 150 mg tablets) q24h.	Placebo n=25 Participants Participants received matching placebo PO (administered as two tablets) q24h.
Change From Baseline in Systolic and Diastolic Blood Pressure Systolic Blood Pressure	4.3 Millimeter of mercury Standard Deviation 12.53	2.4 Millimeter of mercury Standard Deviation 12.62
Change From Baseline in Systolic and Diastolic Blood Pressure Diastolic Blood Pressure	-0.5 Millimeter of mercury Standard Deviation 8.63	0.7 Millimeter of mercury Standard Deviation 10.45

PRIMARY outcome

Timeframe: Day 1 (Baseline) to Day 84/EOT

Population: Safety Analysis Set

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

Outcome measures

Outcome measures
Measure	Omadacycline 300 mg n=41 Participants Participants received omadacycline 300 mg PO (administered as two 150 mg tablets) q24h.	Placebo n=25 Participants Participants received matching placebo PO (administered as two tablets) q24h.
Change From Baseline in Heart Rate	1.1 Beats per minute Standard Deviation 8.66	0.2 Beats per minute Standard Deviation 10.09

PRIMARY outcome

Timeframe: Day 1 through Day 84 (at any study timepoint)

Population: Safety Analysis Set

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

Outcome measures

Outcome measures
Measure	Omadacycline 300 mg n=41 Participants Participants received omadacycline 300 mg PO (administered as two 150 mg tablets) q24h.	Placebo n=25 Participants Participants received matching placebo PO (administered as two tablets) q24h.
Number of Participants With PCS Threshold Vital Signs Measurement Heart rate: >120 and increase of >=15 bpm	0 Participants	0 Participants
Number of Participants With PCS Threshold Vital Signs Measurement Heart rate: <=50 and decrease of >=15 bpm	0 Participants	0 Participants
Number of Participants With PCS Threshold Vital Signs Measurement Systolic blood pressure: >=180 and increase of >=20 mmHg	0 Participants	0 Participants
Number of Participants With PCS Threshold Vital Signs Measurement Systolic blood pressure: <=90 and decrease of >=20 mmHg	0 Participants	0 Participants
Number of Participants With PCS Threshold Vital Signs Measurement Diastolic blood pressure: >=105 and increase of >=15 mmHg	0 Participants	0 Participants
Number of Participants With PCS Threshold Vital Signs Measurement Diastolic blood pressure: <=50 and decrease of >=15 mmHg	2 Participants	0 Participants
Number of Participants With PCS Threshold Vital Signs Measurement Temperature: >38.0	0 Participants	0 Participants
Number of Participants With PCS Threshold Vital Signs Measurement Temperature: <36.0	4 Participants	0 Participants

PRIMARY outcome

Timeframe: Day 1 (Baseline) to Day 84/EOT

Population: Safety Analysis Set

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

Outcome measures

Outcome measures
Measure	Omadacycline 300 mg n=41 Participants Participants received omadacycline 300 mg PO (administered as two 150 mg tablets) q24h.	Placebo n=25 Participants Participants received matching placebo PO (administered as two tablets) q24h.
Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, and QTcF Interval PR Interval	9.7 milliseconds Standard Deviation 57.23	5.8 milliseconds Standard Deviation 40.93
Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, and QTcF Interval QRS Duration	-0.5 milliseconds Standard Deviation 9.23	-2.3 milliseconds Standard Deviation 5.11
Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, and QTcF Interval QT Interval	-11.7 milliseconds Standard Deviation 18.66	-2.0 milliseconds Standard Deviation 29.63
Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, and QTcF Interval QTcF Interval	-8.5 milliseconds Standard Deviation 34.04	-7.3 milliseconds Standard Deviation 68.65

PRIMARY outcome

Timeframe: Day 1 through Day 84/EOT (at any study timepoint)

Population: Safety Analysis Set. Only those participants with data available at specified timepoints has been presented.

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

Outcome measures

Outcome measures
Measure	Omadacycline 300 mg n=40 Participants Participants received omadacycline 300 mg PO (administered as two 150 mg tablets) q24h.	Placebo n=25 Participants Participants received matching placebo PO (administered as two tablets) q24h.
Number of Participants With PCS QTcF Value > 480 msec	1 Participants	2 Participants
Number of Participants With PCS QTcF Value > 450 msec	3 Participants	5 Participants
Number of Participants With PCS QTcF Value > 500 msec	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 1 (Baseline) to Day 84/EOT

Population: ITT analysis set. Only those participants with data available at specified timepoints has been presented.

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.

Outcome measures

Outcome measures
Measure	Omadacycline 300 mg n=41 Participants Participants received omadacycline 300 mg PO (administered as two 150 mg tablets) q24h.	Placebo n=24 Participants Participants received matching placebo PO (administered as two tablets) q24h.
Change From Baseline in the Total Score of the Quality of Life - Bronchiectasis (QOL-B) Questionnaire - Emotional Functioning Domain	3.5 Score on a scale Standard Error 2.05	2.7 Score on a scale Standard Error 2.69

SECONDARY outcome

Timeframe: Day 1 (Baseline) to Day 84/EOT

Population: ITT analysis set. Only those participants with data available at specified timepoints has been presented.

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.

Outcome measures

Outcome measures
Measure	Omadacycline 300 mg n=41 Participants Participants received omadacycline 300 mg PO (administered as two 150 mg tablets) q24h.	Placebo n=23 Participants Participants received matching placebo PO (administered as two tablets) q24h.
Change From Baseline in the Total Score of the QOL-B Questionnaire - Health Perceptions Domain	4.2 Score on a scale Standard Error 2.43	-0.9 Score on a scale Standard Error 3.25

SECONDARY outcome

Timeframe: Day 1 (Baseline) to Day 84/EOT

Population: ITT analysis set. Only those participants with data available at specified timepoints has been presented.

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.

Outcome measures

Outcome measures
Measure	Omadacycline 300 mg n=41 Participants Participants received omadacycline 300 mg PO (administered as two 150 mg tablets) q24h.	Placebo n=24 Participants Participants received matching placebo PO (administered as two tablets) q24h.
Change From Baseline in the Total Score of the QOL-B Questionnaire - Physical Functioning Domain	5.6 Score on a scale Standard Error 3.21	-2.7 Score on a scale Standard Error 4.20

SECONDARY outcome

Timeframe: Day 1 (Baseline) to Day 84/EOT

Population: ITT analysis set. Only those participants with data available at specified timepoints has been presented.

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.

Outcome measures

Outcome measures
Measure	Omadacycline 300 mg n=41 Participants Participants received omadacycline 300 mg PO (administered as two 150 mg tablets) q24h.	Placebo n=24 Participants Participants received matching placebo PO (administered as two tablets) q24h.
Change From Baseline in the Total Score of the QOL-B Questionnaire - Respiratory Symptoms Domain	7.5 Score on a scale Standard Error 2.10	2.0 Score on a scale Standard Error 2.75

SECONDARY outcome

Timeframe: Day 1 (Baseline) to Day 84/EOT

Population: ITT analysis set. Only those participants with data available at specified timepoints has been presented.

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.

Outcome measures

Outcome measures
Measure	Omadacycline 300 mg n=41 Participants Participants received omadacycline 300 mg PO (administered as two 150 mg tablets) q24h.	Placebo n=23 Participants Participants received matching placebo PO (administered as two tablets) q24h.
Change From Baseline in the Total Score of the QOL-B Questionnaire - Role Functioning Domain	7.4 Score on a scale Standard Error 2.14	0.9 Score on a scale Standard Error 2.86

SECONDARY outcome

Timeframe: Day 1 (Baseline) to Day 84/EOT

Population: ITT analysis set. Only those participants with data available at specified timepoints has been presented.

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.

Outcome measures

Outcome measures
Measure	Omadacycline 300 mg n=41 Participants Participants received omadacycline 300 mg PO (administered as two 150 mg tablets) q24h.	Placebo n=23 Participants Participants received matching placebo PO (administered as two tablets) q24h.
Change From Baseline in the Total Score of the QOL-B Questionnaire - Social Functioning Domain	9.6 Score on a scale Standard Error 2.45	2.6 Score on a scale Standard Error 3.27

SECONDARY outcome

Timeframe: Day 1 (Baseline) to Day 84/EOT

Population: ITT analysis set. Only those participants with data available at specified timepoints has been presented.

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.

Outcome measures

Outcome measures
Measure	Omadacycline 300 mg n=27 Participants Participants received omadacycline 300 mg PO (administered as two 150 mg tablets) q24h.	Placebo n=15 Participants Participants received matching placebo PO (administered as two tablets) q24h.
Change From Baseline in the Total Score of the QOL-B Questionnaire - Treatment Burden Domain	2.8 Score on a scale Standard Error 2.38	2.3 Score on a scale Standard Error 3.20

SECONDARY outcome

Timeframe: Day 1 (Baseline) to Day 84/EOT

Population: ITT analysis set. Only those participants with data available at specified timepoints has been presented.

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.

Outcome measures

Outcome measures
Measure	Omadacycline 300 mg n=41 Participants Participants received omadacycline 300 mg PO (administered as two 150 mg tablets) q24h.	Placebo n=24 Participants Participants received matching placebo PO (administered as two tablets) q24h.
Change From Baseline in the Total Score of the QOL-B Questionnaire - Vitality Domain	9.3 Score on a scale Standard Error 2.50	-4.3 Score on a scale Standard Error 3.27

SECONDARY outcome

Timeframe: Day 1 (Baseline) to Day 84/EOT

Population: ITT Analysis Set. Only those participants with data available at specified timepoints has been presented.

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

Outcome measures

Outcome measures
Measure	Omadacycline 300 mg n=41 Participants Participants received omadacycline 300 mg PO (administered as two 150 mg tablets) q24h.	Placebo n=25 Participants Participants received matching placebo PO (administered as two tablets) q24h.
Change From Baseline in Global Score and Individual Domain Scores of the SGRQ - Total Score Activity score	-2.7 Score on a scale Standard Error 2.50	-3.6 Score on a scale Standard Error 3.17
Change From Baseline in Global Score and Individual Domain Scores of the SGRQ - Total Score Impact score	-3.7 Score on a scale Standard Error 2.29	-3.5 Score on a scale Standard Error 2.99
Change From Baseline in Global Score and Individual Domain Scores of the SGRQ - Total Score Symptom score	-5.6 Score on a scale Standard Error 2.43	-0.6 Score on a scale Standard Error 3.11
Change From Baseline in Global Score and Individual Domain Scores of the SGRQ - Total Score Total score	-3.7 Score on a scale Standard Error 2.06	-3.0 Score on a scale Standard Error 2.67

SECONDARY outcome

Timeframe: Day 1 (Baseline) to Day 84/EOT

Population: ITT Analysis Set. Only those participants with data available at specified timepoints has been presented.

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.

Outcome measures

Outcome measures
Measure	Omadacycline 300 mg n=40 Participants Participants received omadacycline 300 mg PO (administered as two 150 mg tablets) q24h.	Placebo n=24 Participants Participants received matching placebo PO (administered as two tablets) q24h.
Change From Baseline in Patient-Reported Outcomes Measurement Information System Short Form v1.0 - Fatigue 7a Daily (PROMIS-7a) Score	-4.3 score on a scale Standard Error 1.01	1.3 score on a scale Standard Error 1.30

SECONDARY outcome

Timeframe: Day 1 to Day 84/EOT

Population: ITT Analysis Set

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.

Outcome measures

Outcome measures
Measure	Omadacycline 300 mg n=41 Participants Participants received omadacycline 300 mg PO (administered as two 150 mg tablets) q24h.	Placebo n=25 Participants Participants received matching placebo PO (administered as two tablets) q24h.
Number of Participants With Improvement in Patient Clinical Impression of Change (PGI-C)	31 Participants	9 Participants

SECONDARY outcome

Timeframe: Day 84/EOT

Population: ITT Analysis Set

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.

Outcome measures

Outcome measures
Measure	Omadacycline 300 mg n=41 Participants Participants received omadacycline 300 mg PO (administered as two 150 mg tablets) q24h.	Placebo n=25 Participants Participants received matching placebo PO (administered as two tablets) q24h.
Number of Participants Reporting "Not Present or Mild Severity" in Patient Clinical Impression of Severity (PGI-S)	26 Participants	12 Participants

SECONDARY outcome

Timeframe: Day 84/EOT

Population: ITT Analysis Set

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.

Outcome measures

Outcome measures
Measure	Omadacycline 300 mg n=41 Participants Participants received omadacycline 300 mg PO (administered as two 150 mg tablets) q24h.	Placebo n=25 Participants Participants received matching placebo PO (administered as two tablets) q24h.
Number of Participants With Clinical Global Impression - Severity of Illness (CGI-S) Normal, not at all ill	14 Participants	4 Participants
Number of Participants With Clinical Global Impression - Severity of Illness (CGI-S) Borderline ill	9 Participants	8 Participants
Number of Participants With Clinical Global Impression - Severity of Illness (CGI-S) Mildly ill	11 Participants	9 Participants
Number of Participants With Clinical Global Impression - Severity of Illness (CGI-S) Moderately ill	6 Participants	4 Participants
Number of Participants With Clinical Global Impression - Severity of Illness (CGI-S) Markedly ill	0 Participants	0 Participants
Number of Participants With Clinical Global Impression - Severity of Illness (CGI-S) Severely ill	1 Participants	0 Participants
Number of Participants With Clinical Global Impression - Severity of Illness (CGI-S) Among the most extremely ill participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 1 to Day 84/EOT

Population: ITT Analysis Set

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.

Outcome measures

Outcome measures
Measure	Omadacycline 300 mg n=41 Participants Participants received omadacycline 300 mg PO (administered as two 150 mg tablets) q24h.	Placebo n=25 Participants Participants received matching placebo PO (administered as two tablets) q24h.
Number of Participants With Clinical Global Impression - Improvement (CGI-I)	29 Participants	11 Participants

SECONDARY outcome

Timeframe: Day 1 through Day 84 (at any study timepoint)

Population: ITT Analysis Set

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.

Outcome measures

Outcome measures
Measure	Omadacycline 300 mg n=41 Participants Participants received omadacycline 300 mg PO (administered as two 150 mg tablets) q24h.	Placebo n=25 Participants Participants received matching placebo PO (administered as two tablets) q24h.
Number of Participants With New Symptoms With a Severity Worse Than Mild on the NTM Symptom Assessment Questionnaire at Any Time Post-baseline	4 Participants	6 Participants

SECONDARY outcome

Timeframe: Day 1 to Day 84

Population: ITT Analysis Set. Only those participants with data available at specified timepoints has been presented.

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.

Outcome measures

Outcome measures
Measure	Omadacycline 300 mg n=34 Participants Participants received omadacycline 300 mg PO (administered as two 150 mg tablets) q24h.	Placebo n=24 Participants Participants received matching placebo PO (administered as two tablets) q24h.
Number of Participants With Decreased Semi-Quantitative Score of Mycobacterial Sputum Culture From Day 1 to Day 84	26 Participants	11 Participants

SECONDARY outcome

Timeframe: Day 1 through Day 84 (at any study timepoint)

Population: ITT Analysis Set. Only those participants with data available at specified timepoints has been presented.

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.

Outcome measures

Outcome measures
Measure	Omadacycline 300 mg n=37 Participants Participants received omadacycline 300 mg PO (administered as two 150 mg tablets) q24h.	Placebo n=23 Participants Participants received matching placebo PO (administered as two tablets) q24h.
Time to Growth in Liquid Medium Only	34 Days Interval 28.0 to 83.0	NA Days Interval 28.0 to Not Applicable (NA) indicates median and upper limit of CI was not calculated due to less than 50% of participants had growth in liquid medium only.

SECONDARY outcome

Timeframe: Day 1 through Day 84 (at any study timepoint)

Population: ITT Analysis Set

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).

Outcome measures

Outcome measures
Measure	Omadacycline 300 mg n=41 Participants Participants received omadacycline 300 mg PO (administered as two 150 mg tablets) q24h.	Placebo n=25 Participants Participants received matching placebo PO (administered as two tablets) q24h.
Time to First Negative Sputum Culture	30 Days Interval 28.0 to 84.0	NA Days Interval 30.0 to NA indicates median and upper limit of CI was not calculated due to less than 50% of participants had growth in liquid medium only.

Adverse Events

Omadacycline 300 mg

Serious events: 0 serious events

Other events: 35 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Omadacycline 300 mg n=41 participants at risk Participants received omadacycline 300 mg PO (administered as two 150 mg tablets) q24h.	Placebo n=25 participants at risk Participants received matching placebo PO (administered as two tablets) q24h.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/41 • Adverse events were monitored from screening period (up to 8 weeks prior to randomization) through the final Follow-up assessment, which occurred up to 30 days after the last dose of study treatment, with the treatment period lasting for 84 days.	4.0% 1/25 • Number of events 1 • Adverse events were monitored from screening period (up to 8 weeks prior to randomization) through the final Follow-up assessment, which occurred up to 30 days after the last dose of study treatment, with the treatment period lasting for 84 days.
Infections and infestations COVID-19	0.00% 0/41 • Adverse events were monitored from screening period (up to 8 weeks prior to randomization) through the final Follow-up assessment, which occurred up to 30 days after the last dose of study treatment, with the treatment period lasting for 84 days.	4.0% 1/25 • Number of events 1 • Adverse events were monitored from screening period (up to 8 weeks prior to randomization) through the final Follow-up assessment, which occurred up to 30 days after the last dose of study treatment, with the treatment period lasting for 84 days.

Other adverse events

Additional Information

Paratek Medical Information

Paratek Pharmaceuticals Inc

Phone: 1-833-727-2835

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER

Measure	Omadacycline 300 mg n=41 participants at risk Participants received omadacycline 300 mg PO (administered as two 150 mg tablets) q24h.	Placebo n=25 participants at risk Participants received matching placebo PO (administered as two tablets) q24h.
Gastrointestinal disorders Nausea	53.7% 22/41 • Number of events 37 • Adverse events were monitored from screening period (up to 8 weeks prior to randomization) through the final Follow-up assessment, which occurred up to 30 days after the last dose of study treatment, with the treatment period lasting for 84 days.	8.0% 2/25 • Number of events 3 • Adverse events were monitored from screening period (up to 8 weeks prior to randomization) through the final Follow-up assessment, which occurred up to 30 days after the last dose of study treatment, with the treatment period lasting for 84 days.
Gastrointestinal disorders Abdominal pain	14.6% 6/41 • Number of events 8 • Adverse events were monitored from screening period (up to 8 weeks prior to randomization) through the final Follow-up assessment, which occurred up to 30 days after the last dose of study treatment, with the treatment period lasting for 84 days.	4.0% 1/25 • Number of events 1 • Adverse events were monitored from screening period (up to 8 weeks prior to randomization) through the final Follow-up assessment, which occurred up to 30 days after the last dose of study treatment, with the treatment period lasting for 84 days.
Gastrointestinal disorders Vomiting	14.6% 6/41 • Number of events 15 • Adverse events were monitored from screening period (up to 8 weeks prior to randomization) through the final Follow-up assessment, which occurred up to 30 days after the last dose of study treatment, with the treatment period lasting for 84 days.	0.00% 0/25 • Adverse events were monitored from screening period (up to 8 weeks prior to randomization) through the final Follow-up assessment, which occurred up to 30 days after the last dose of study treatment, with the treatment period lasting for 84 days.
Gastrointestinal disorders Diarrhoea	12.2% 5/41 • Number of events 5 • Adverse events were monitored from screening period (up to 8 weeks prior to randomization) through the final Follow-up assessment, which occurred up to 30 days after the last dose of study treatment, with the treatment period lasting for 84 days.	4.0% 1/25 • Number of events 1 • Adverse events were monitored from screening period (up to 8 weeks prior to randomization) through the final Follow-up assessment, which occurred up to 30 days after the last dose of study treatment, with the treatment period lasting for 84 days.
Gastrointestinal disorders Gastrooesophageal reflux disease	2.4% 1/41 • Number of events 1 • Adverse events were monitored from screening period (up to 8 weeks prior to randomization) through the final Follow-up assessment, which occurred up to 30 days after the last dose of study treatment, with the treatment period lasting for 84 days.	8.0% 2/25 • Number of events 2 • Adverse events were monitored from screening period (up to 8 weeks prior to randomization) through the final Follow-up assessment, which occurred up to 30 days after the last dose of study treatment, with the treatment period lasting for 84 days.
Infections and infestations COVID-19	4.9% 2/41 • Number of events 2 • Adverse events were monitored from screening period (up to 8 weeks prior to randomization) through the final Follow-up assessment, which occurred up to 30 days after the last dose of study treatment, with the treatment period lasting for 84 days.	12.0% 3/25 • Number of events 3 • Adverse events were monitored from screening period (up to 8 weeks prior to randomization) through the final Follow-up assessment, which occurred up to 30 days after the last dose of study treatment, with the treatment period lasting for 84 days.
Nervous system disorders Headache	17.1% 7/41 • Number of events 8 • Adverse events were monitored from screening period (up to 8 weeks prior to randomization) through the final Follow-up assessment, which occurred up to 30 days after the last dose of study treatment, with the treatment period lasting for 84 days.	16.0% 4/25 • Number of events 5 • Adverse events were monitored from screening period (up to 8 weeks prior to randomization) through the final Follow-up assessment, which occurred up to 30 days after the last dose of study treatment, with the treatment period lasting for 84 days.
General disorders Fatigue	17.1% 7/41 • Number of events 8 • Adverse events were monitored from screening period (up to 8 weeks prior to randomization) through the final Follow-up assessment, which occurred up to 30 days after the last dose of study treatment, with the treatment period lasting for 84 days.	4.0% 1/25 • Number of events 1 • Adverse events were monitored from screening period (up to 8 weeks prior to randomization) through the final Follow-up assessment, which occurred up to 30 days after the last dose of study treatment, with the treatment period lasting for 84 days.
General disorders Vessel puncture site reaction	0.00% 0/41 • Adverse events were monitored from screening period (up to 8 weeks prior to randomization) through the final Follow-up assessment, which occurred up to 30 days after the last dose of study treatment, with the treatment period lasting for 84 days.	8.0% 2/25 • Number of events 2 • Adverse events were monitored from screening period (up to 8 weeks prior to randomization) through the final Follow-up assessment, which occurred up to 30 days after the last dose of study treatment, with the treatment period lasting for 84 days.
Investigations Alanine aminotransferase increased	9.8% 4/41 • Number of events 4 • Adverse events were monitored from screening period (up to 8 weeks prior to randomization) through the final Follow-up assessment, which occurred up to 30 days after the last dose of study treatment, with the treatment period lasting for 84 days.	0.00% 0/25 • Adverse events were monitored from screening period (up to 8 weeks prior to randomization) through the final Follow-up assessment, which occurred up to 30 days after the last dose of study treatment, with the treatment period lasting for 84 days.
Investigations Aspartate aminotransferase increased	7.3% 3/41 • Number of events 3 • Adverse events were monitored from screening period (up to 8 weeks prior to randomization) through the final Follow-up assessment, which occurred up to 30 days after the last dose of study treatment, with the treatment period lasting for 84 days.	0.00% 0/25 • Adverse events were monitored from screening period (up to 8 weeks prior to randomization) through the final Follow-up assessment, which occurred up to 30 days after the last dose of study treatment, with the treatment period lasting for 84 days.
Respiratory, thoracic and mediastinal disorders Haemoptysis	7.3% 3/41 • Number of events 3 • Adverse events were monitored from screening period (up to 8 weeks prior to randomization) through the final Follow-up assessment, which occurred up to 30 days after the last dose of study treatment, with the treatment period lasting for 84 days.	12.0% 3/25 • Number of events 4 • Adverse events were monitored from screening period (up to 8 weeks prior to randomization) through the final Follow-up assessment, which occurred up to 30 days after the last dose of study treatment, with the treatment period lasting for 84 days.
Respiratory, thoracic and mediastinal disorders Cough	4.9% 2/41 • Number of events 2 • Adverse events were monitored from screening period (up to 8 weeks prior to randomization) through the final Follow-up assessment, which occurred up to 30 days after the last dose of study treatment, with the treatment period lasting for 84 days.	12.0% 3/25 • Number of events 3 • Adverse events were monitored from screening period (up to 8 weeks prior to randomization) through the final Follow-up assessment, which occurred up to 30 days after the last dose of study treatment, with the treatment period lasting for 84 days.
Skin and subcutaneous tissue disorders Night sweats	9.8% 4/41 • Number of events 4 • Adverse events were monitored from screening period (up to 8 weeks prior to randomization) through the final Follow-up assessment, which occurred up to 30 days after the last dose of study treatment, with the treatment period lasting for 84 days.	0.00% 0/25 • Adverse events were monitored from screening period (up to 8 weeks prior to randomization) through the final Follow-up assessment, which occurred up to 30 days after the last dose of study treatment, with the treatment period lasting for 84 days.
Metabolism and nutrition disorders Decreased appetite	2.4% 1/41 • Number of events 1 • Adverse events were monitored from screening period (up to 8 weeks prior to randomization) through the final Follow-up assessment, which occurred up to 30 days after the last dose of study treatment, with the treatment period lasting for 84 days.	8.0% 2/25 • Number of events 2 • Adverse events were monitored from screening period (up to 8 weeks prior to randomization) through the final Follow-up assessment, which occurred up to 30 days after the last dose of study treatment, with the treatment period lasting for 84 days.