Mycobacterium Abscessus Infection, Mycobacterium Infections, Nontuberculous, Nontuberculous Mycobacterial Lung Disease, Nontuberculous Mycobacterial Pulmonary Infection
Conditions
Keywords
Nontuberculous Mycobacteria (NTM), Mycobacterium abscessus complex (MABc), NTM pulmonary disease, NTM lung disease
Brief summary
The purpose of this study is to evaluate the efficacy, safety and tolerability of oral omadacycline as compared to placebo in the treatment of adults with Nontuberculous Mycobacterial (NTM) pulmonary disease caused by Mycobacterium abscessus complex (MABc)
Detailed description
The total duration of subject participation in the study is approximately 5 months which includes a total duration of study treatment for approximately 3 months (84 days). Eligible participants will be randomized 1.5:1 to receive 3 months of treatment with either omadacycline or placebo (monotherapy). The study will use a double-dummy design in order to maintain the study blinding.
Interventions
omadacycline 300 mg orally, once daily (150 mg tablets x 2)
DRUGPlacebo
placebo tablets resembling omadacycline orally, once daily (x 2 tablets)
Sponsors
Paratek Pharmaceuticals Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Has a diagnosis of Nontuberculous Mycobacterial pulmonary disease caused by MABc * Has at least 2 of the following NTM-infection symptoms present at Screening and Baseline: chronic cough, coughing up blood (hemoptysis), wheezing, chest pain, frequent throat clearing, phlegm or sputum production, shortness of breath, fatigue, fever, night sweats, poor appetite, and/or weight loss. * At least 1 positive pulmonary (sputum) culture for MABc in the 6 months prior to Screening and 1 positive culture at Screening * Radiographic evidence of MABc infection via computed tomography (CT) scan of the chest within 3 months prior to Screening * In the opinion of the investigator, guideline-directed antibiotic therapy for treatment of MABc will not be required within the next 3 months, and a delay, in order for the subject to participate in a placebo-controlled clinical trial, is considered reasonable and clinically acceptable * Additional inclusion criteria as per protocol Key
Exclusion criteria
* Has received antibiotic treatment within 6 months prior to Screening for MABc or MAC * Has received systemic or inhaled antibiotic therapy (other than chronic macrolide therapy) within 4 weeks prior to Screening * Has any of the following medical conditions: * Active pulmonary malignancy, or any type of malignancy requiring chemotherapy or radiation within 1 year prior to Screening * Active allergic bronchopulmonary mycosis, or any other condition requiring chronic treatment with systemic corticosteroids within 90 days prior to Screening * Radiologic evidence of cavitary disease * Known active pulmonary tuberculosis * Cystic fibrosis * History of lung transplantation * Another advanced lung disease with a known percent predicted forced expiratory volume in 1 second \< 30%. * Disseminated or extra-pulmonary NTM disease * Has been previously treated with omadacycline * Has a history of hypersensitivity or allergic reaction to tetracyclines * Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Clinical Response on NTM Symptom Assessment Scale at Day 84 | Day 1 to Day 84 | 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. |
| 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. | Day 1 to Day 84 | 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. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | From screening period (up to 8 weeks prior to randomization) through Day 114 (at any study timepoint) | 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. |
| Change From Baseline in Laboratory Test Parameters - Hepatic and Enzymatic Biomarkers | Day 1 (Baseline) to Day 84/EOT | To assess the incidents of abnormal hepatic and enzymatic biomarkers following 84 days of IP administration |
| Number of Participants With Potentially Clinically Significant (PCS) Laboratory Parameter | Day 1 through Day 84 (at any study timepoint) | 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. |
| Change From Baseline in Systolic and Diastolic Blood Pressure | Day 1 (Baseline) to Day 84/EOT | To assess the incidents of abnormal blood pressure assessments following 84 days of IP administration |
| Change From Baseline in Heart Rate | Day 1 (Baseline) to Day 84/EOT | To assess the incidents of abnormal heart rate following 84 days of IP administration |
| Number of Participants With PCS Threshold Vital Signs Measurement | Day 1 through Day 84 (at any study timepoint) | To assess the incidents of PCS heart rate and blood pressure following 84 days of IP administration |
| Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, and QTcF Interval | Day 1 (Baseline) to Day 84/EOT | To assess the incidents of cardiac rhythm, PR interval, QRS interval, QT interval and QTc interval assessments following 84 days of IP administration |
| Number of Participants With PCS QTcF Value | Day 1 through Day 84/EOT (at any study timepoint) | To assess the incidents of PCS and QTc interval assessments following 84 days of IP administration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Improvement in Patient Clinical Impression of Change (PGI-C) | Day 1 to Day 84/EOT | 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. |
| Number of Participants Reporting Not Present or Mild Severity in Patient Clinical Impression of Severity (PGI-S) | Day 84/EOT | 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. |
| Number of Participants With Clinical Global Impression - Severity of Illness (CGI-S) | Day 84/EOT | 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. |
| Number of Participants With Clinical Global Impression - Improvement (CGI-I) | Day 1 to Day 84/EOT | 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. |
| Change From Baseline in the Total Score of the Quality of Life - Bronchiectasis (QOL-B) Questionnaire - Emotional Functioning Domain | Day 1 (Baseline) to Day 84/EOT | 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. |
| Number of Participants With Decreased Semi-Quantitative Score of Mycobacterial Sputum Culture From Day 1 to Day 84 | Day 1 to Day 84 | 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 | Day 1 through Day 84 (at any study timepoint) | 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 | Day 1 through Day 84 (at any study timepoint) | 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). |
| Number of Participants With New Symptoms With a Severity Worse Than Mild on the NTM Symptom Assessment Questionnaire at Any Time Post-baseline | Day 1 through Day 84 (at any study timepoint) | 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. |
| Change From Baseline in the Total Score of the QOL-B Questionnaire - Health Perceptions Domain | Day 1 (Baseline) to Day 84/EOT | 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. |
| Change From Baseline in the Total Score of the QOL-B Questionnaire - Physical Functioning Domain | Day 1 (Baseline) to Day 84/EOT | 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. |
| Change From Baseline in the Total Score of the QOL-B Questionnaire - Respiratory Symptoms Domain | Day 1 (Baseline) to Day 84/EOT | 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. |
| Change From Baseline in the Total Score of the QOL-B Questionnaire - Role Functioning Domain | Day 1 (Baseline) to Day 84/EOT | 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. |
| Change From Baseline in the Total Score of the QOL-B Questionnaire - Social Functioning Domain | Day 1 (Baseline) to Day 84/EOT | 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. |
| Change From Baseline in the Total Score of the QOL-B Questionnaire - Treatment Burden Domain | Day 1 (Baseline) to Day 84/EOT | 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. |
| Change From Baseline in the Total Score of the QOL-B Questionnaire - Vitality Domain | Day 1 (Baseline) to Day 84/EOT | 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. |
| Change From Baseline in Global Score and Individual Domain Scores of the SGRQ - Total Score | Day 1 (Baseline) to Day 84/EOT | 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 |
| Change From Baseline in Patient-Reported Outcomes Measurement Information System Short Form v1.0 - Fatigue 7a Daily (PROMIS-7a) Score | Day 1 (Baseline) to Day 84/EOT | 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. |
Countries
United States
Participant flow
Recruitment details
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.
Pre-assignment details
A total of 66 participants were enrolled at 17 sites in the US.
Participants by arm
| Arm | Count |
|---|---|
| Omadacycline 300 mg Participants received omadacycline 300 mg PO (administered as two 150 mg tablets) q24h. | 41 |
| Placebo Participants received matching placebo PO (administered as two tablets) q24h. | 25 |
| Total | 66 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | Total | Omadacycline 300 mg |
|---|---|---|---|
| Age, Continuous | 72.8 Years STANDARD_DEVIATION 7.64 | 70.6 Years STANDARD_DEVIATION 9.02 | 69.3 Years STANDARD_DEVIATION 9.61 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 6 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 23 Participants | 59 Participants | 36 Participants |
| Sex: Female, Male Female | 15 Participants | 45 Participants | 30 Participants |
| Sex: Female, Male Male | 10 Participants | 21 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 41 | 0 / 25 |
| other Total, other adverse events | 35 / 41 | 21 / 25 |
| serious Total, serious adverse events | 0 / 41 | 2 / 25 |
Outcome results
Primary
Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, and QTcF Interval
To assess the incidents of cardiac rhythm, PR interval, QRS interval, QT interval and QTc interval assessments following 84 days of IP administration
Time frame: Day 1 (Baseline) to Day 84/EOT
Population: Safety Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Omadacycline 300 mg | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, and QTcF Interval | PR Interval | 9.7 milliseconds | Standard Deviation 57.23 |
| Omadacycline 300 mg | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, and QTcF Interval | QRS Duration | -0.5 milliseconds | Standard Deviation 9.23 |
| Omadacycline 300 mg | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, and QTcF Interval | QT Interval | -11.7 milliseconds | Standard Deviation 18.66 |
| Omadacycline 300 mg | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, and QTcF Interval | QTcF Interval | -8.5 milliseconds | Standard Deviation 34.04 |
| Placebo | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, and QTcF Interval | QTcF Interval | -7.3 milliseconds | Standard Deviation 68.65 |
| Placebo | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, and QTcF Interval | PR Interval | 5.8 milliseconds | Standard Deviation 40.93 |
| Placebo | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, and QTcF Interval | QT Interval | -2.0 milliseconds | Standard Deviation 29.63 |
| Placebo | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, and QTcF Interval | QRS Duration | -2.3 milliseconds | Standard Deviation 5.11 |
Primary
Change From Baseline in Heart Rate
To assess the incidents of abnormal heart rate following 84 days of IP administration
Time frame: Day 1 (Baseline) to Day 84/EOT
Population: Safety Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Omadacycline 300 mg | Change From Baseline in Heart Rate | 1.1 Beats per minute | Standard Deviation 8.66 |
| Placebo | Change From Baseline in Heart Rate | 0.2 Beats per minute | Standard Deviation 10.09 |
Primary
Change From Baseline in Laboratory Test Parameters - Hepatic and Enzymatic Biomarkers
To assess the incidents of abnormal hepatic and enzymatic biomarkers following 84 days of IP administration
Time frame: Day 1 (Baseline) to Day 84/EOT
Population: Safety Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Omadacycline 300 mg | Change From Baseline in Laboratory Test Parameters - Hepatic and Enzymatic Biomarkers | Alkaline Phosphatase | -3.3 Units per litre | Standard Deviation 14.46 |
| Omadacycline 300 mg | Change From Baseline in Laboratory Test Parameters - Hepatic and Enzymatic Biomarkers | Alanine Aminotransferase | 10.4 Units per litre | Standard Deviation 17.19 |
| Omadacycline 300 mg | Change From Baseline in Laboratory Test Parameters - Hepatic and Enzymatic Biomarkers | Aspartate Aminotransferase | 3.9 Units per litre | Standard Deviation 8.72 |
| Omadacycline 300 mg | Change From Baseline in Laboratory Test Parameters - Hepatic and Enzymatic Biomarkers | Creatine Kinase | 2.5 Units per litre | Standard Deviation 28.76 |
| Omadacycline 300 mg | Change From Baseline in Laboratory Test Parameters - Hepatic and Enzymatic Biomarkers | Gamma Glutamyl Transferase | 1.7 Units per litre | Standard Deviation 14.35 |
| Omadacycline 300 mg | Change From Baseline in Laboratory Test Parameters - Hepatic and Enzymatic Biomarkers | Lipase | 3.5 Units per litre | Standard Deviation 16.5 |
| Placebo | Change From Baseline in Laboratory Test Parameters - Hepatic and Enzymatic Biomarkers | Gamma Glutamyl Transferase | -0.6 Units per litre | Standard Deviation 12.83 |
| Placebo | Change From Baseline in Laboratory Test Parameters - Hepatic and Enzymatic Biomarkers | Alkaline Phosphatase | -3.0 Units per litre | Standard Deviation 11.22 |
| Placebo | Change From Baseline in Laboratory Test Parameters - Hepatic and Enzymatic Biomarkers | Creatine Kinase | -26.6 Units per litre | Standard Deviation 116.68 |
| Placebo | Change From Baseline in Laboratory Test Parameters - Hepatic and Enzymatic Biomarkers | Alanine Aminotransferase | -1.4 Units per litre | Standard Deviation 9.74 |
| Placebo | Change From Baseline in Laboratory Test Parameters - Hepatic and Enzymatic Biomarkers | Lipase | -2.2 Units per litre | Standard Deviation 8.39 |
| Placebo | Change From Baseline in Laboratory Test Parameters - Hepatic and Enzymatic Biomarkers | Aspartate Aminotransferase | -3.0 Units per litre | Standard Deviation 11.88 |
Primary
Change From Baseline in Systolic and Diastolic Blood Pressure
To assess the incidents of abnormal blood pressure assessments following 84 days of IP administration
Time frame: Day 1 (Baseline) to Day 84/EOT
Population: Safety Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Omadacycline 300 mg | Change From Baseline in Systolic and Diastolic Blood Pressure | Systolic Blood Pressure | 4.3 Millimeter of mercury | Standard Deviation 12.53 |
| Omadacycline 300 mg | Change From Baseline in Systolic and Diastolic Blood Pressure | Diastolic Blood Pressure | -0.5 Millimeter of mercury | Standard Deviation 8.63 |
| Placebo | Change From Baseline in Systolic and Diastolic Blood Pressure | Systolic Blood Pressure | 2.4 Millimeter of mercury | Standard Deviation 12.62 |
| Placebo | Change From Baseline in Systolic and Diastolic Blood Pressure | Diastolic Blood Pressure | 0.7 Millimeter of mercury | Standard Deviation 10.45 |
Primary
Number of Participants With PCS QTcF Value
To assess the incidents of PCS and QTc interval assessments following 84 days of IP administration
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Omadacycline 300 mg | Number of Participants With PCS QTcF Value | > 450 msec | 3 Participants |
| Omadacycline 300 mg | Number of Participants With PCS QTcF Value | > 480 msec | 1 Participants |
| Omadacycline 300 mg | Number of Participants With PCS QTcF Value | > 500 msec | 1 Participants |
| Placebo | Number of Participants With PCS QTcF Value | > 450 msec | 5 Participants |
| Placebo | Number of Participants With PCS QTcF Value | > 480 msec | 2 Participants |
| Placebo | Number of Participants With PCS QTcF Value | > 500 msec | 0 Participants |
Primary
Number of Participants With PCS Threshold Vital Signs Measurement
To assess the incidents of PCS heart rate and blood pressure following 84 days of IP administration
Time frame: Day 1 through Day 84 (at any study timepoint)
Population: Safety Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Omadacycline 300 mg | Number of Participants With PCS Threshold Vital Signs Measurement | Heart rate: >120 and increase of >=15 bpm | 0 Participants |
| Omadacycline 300 mg | Number of Participants With PCS Threshold Vital Signs Measurement | Heart rate: <=50 and decrease of >=15 bpm | 0 Participants |
| Omadacycline 300 mg | Number of Participants With PCS Threshold Vital Signs Measurement | Systolic blood pressure: >=180 and increase of >=20 mmHg | 0 Participants |
| Omadacycline 300 mg | Number of Participants With PCS Threshold Vital Signs Measurement | Systolic blood pressure: <=90 and decrease of >=20 mmHg | 0 Participants |
| Omadacycline 300 mg | Number of Participants With PCS Threshold Vital Signs Measurement | Diastolic blood pressure: >=105 and increase of >=15 mmHg | 0 Participants |
| Omadacycline 300 mg | Number of Participants With PCS Threshold Vital Signs Measurement | Diastolic blood pressure: <=50 and decrease of >=15 mmHg | 2 Participants |
| Omadacycline 300 mg | Number of Participants With PCS Threshold Vital Signs Measurement | Temperature: >38.0 | 0 Participants |
| Omadacycline 300 mg | Number of Participants With PCS Threshold Vital Signs Measurement | Temperature: <36.0 | 4 Participants |
| Placebo | Number of Participants With PCS Threshold Vital Signs Measurement | Temperature: <36.0 | 0 Participants |
| Placebo | Number of Participants With PCS Threshold Vital Signs Measurement | Heart rate: >120 and increase of >=15 bpm | 0 Participants |
| Placebo | Number of Participants With PCS Threshold Vital Signs Measurement | Diastolic blood pressure: >=105 and increase of >=15 mmHg | 0 Participants |
| Placebo | Number of Participants With PCS Threshold Vital Signs Measurement | Heart rate: <=50 and decrease of >=15 bpm | 0 Participants |
| Placebo | Number of Participants With PCS Threshold Vital Signs Measurement | Temperature: >38.0 | 0 Participants |
| Placebo | Number of Participants With PCS Threshold Vital Signs Measurement | Systolic blood pressure: >=180 and increase of >=20 mmHg | 0 Participants |
| Placebo | Number of Participants With PCS Threshold Vital Signs Measurement | Diastolic blood pressure: <=50 and decrease of >=15 mmHg | 0 Participants |
| Placebo | Number of Participants With PCS Threshold Vital Signs Measurement | Systolic blood pressure: <=90 and decrease of >=20 mmHg | 0 Participants |
Primary
Number of Participants With Potentially Clinically Significant (PCS) Laboratory Parameter
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.
Time frame: Day 1 through Day 84 (at any study timepoint)
Population: Safety Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Omadacycline 300 mg | Number of Participants With Potentially Clinically Significant (PCS) Laboratory Parameter | Alkaline Phosphatase | 0 Participants |
| Omadacycline 300 mg | Number of Participants With Potentially Clinically Significant (PCS) Laboratory Parameter | Alanine Aminotransferase | 2 Participants |
| Omadacycline 300 mg | Number of Participants With Potentially Clinically Significant (PCS) Laboratory Parameter | Aspartate Aminotransferase | 0 Participants |
| Omadacycline 300 mg | Number of Participants With Potentially Clinically Significant (PCS) Laboratory Parameter | Calcium | 0 Participants |
| Omadacycline 300 mg | Number of Participants With Potentially Clinically Significant (PCS) Laboratory Parameter | Creatinine | 0 Participants |
| Omadacycline 300 mg | Number of Participants With Potentially Clinically Significant (PCS) Laboratory Parameter | Gamma Glutamyl Transferase | 0 Participants |
| Omadacycline 300 mg | Number of Participants With Potentially Clinically Significant (PCS) Laboratory Parameter | Lipase | 3 Participants |
| Omadacycline 300 mg | Number of Participants With Potentially Clinically Significant (PCS) Laboratory Parameter | Magnesium | 0 Participants |
| Omadacycline 300 mg | Number of Participants With Potentially Clinically Significant (PCS) Laboratory Parameter | Phosphate | 0 Participants |
| Omadacycline 300 mg | Number of Participants With Potentially Clinically Significant (PCS) Laboratory Parameter | Potassium | 0 Participants |
| Omadacycline 300 mg | Number of Participants With Potentially Clinically Significant (PCS) Laboratory Parameter | Sodium | 1 Participants |
| Omadacycline 300 mg | Number of Participants With Potentially Clinically Significant (PCS) Laboratory Parameter | Bilirubin | 0 Participants |
| Omadacycline 300 mg | Number of Participants With Potentially Clinically Significant (PCS) Laboratory Parameter | Neutrophils | 0 Participants |
| Omadacycline 300 mg | Number of Participants With Potentially Clinically Significant (PCS) Laboratory Parameter | Hemoglobin | 0 Participants |
| Omadacycline 300 mg | Number of Participants With Potentially Clinically Significant (PCS) Laboratory Parameter | Platelets | 0 Participants |
| Omadacycline 300 mg | Number of Participants With Potentially Clinically Significant (PCS) Laboratory Parameter | Leukocytes | 0 Participants |
| Placebo | Number of Participants With Potentially Clinically Significant (PCS) Laboratory Parameter | Leukocytes | 1 Participants |
| Placebo | Number of Participants With Potentially Clinically Significant (PCS) Laboratory Parameter | Alkaline Phosphatase | 0 Participants |
| Placebo | Number of Participants With Potentially Clinically Significant (PCS) Laboratory Parameter | Phosphate | 0 Participants |
| Placebo | Number of Participants With Potentially Clinically Significant (PCS) Laboratory Parameter | Alanine Aminotransferase | 0 Participants |
| Placebo | Number of Participants With Potentially Clinically Significant (PCS) Laboratory Parameter | Neutrophils | 0 Participants |
| Placebo | Number of Participants With Potentially Clinically Significant (PCS) Laboratory Parameter | Aspartate Aminotransferase | 0 Participants |
| Placebo | Number of Participants With Potentially Clinically Significant (PCS) Laboratory Parameter | Potassium | 0 Participants |
| Placebo | Number of Participants With Potentially Clinically Significant (PCS) Laboratory Parameter | Calcium | 0 Participants |
| Placebo | Number of Participants With Potentially Clinically Significant (PCS) Laboratory Parameter | Platelets | 0 Participants |
| Placebo | Number of Participants With Potentially Clinically Significant (PCS) Laboratory Parameter | Creatinine | 0 Participants |
| Placebo | Number of Participants With Potentially Clinically Significant (PCS) Laboratory Parameter | Sodium | 0 Participants |
| Placebo | Number of Participants With Potentially Clinically Significant (PCS) Laboratory Parameter | Gamma Glutamyl Transferase | 0 Participants |
| Placebo | Number of Participants With Potentially Clinically Significant (PCS) Laboratory Parameter | Hemoglobin | 0 Participants |
| Placebo | Number of Participants With Potentially Clinically Significant (PCS) Laboratory Parameter | Lipase | 0 Participants |
| Placebo | Number of Participants With Potentially Clinically Significant (PCS) Laboratory Parameter | Bilirubin | 0 Participants |
| Placebo | Number of Participants With Potentially Clinically Significant (PCS) Laboratory Parameter | Magnesium | 0 Participants |
Primary
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Omadacycline 300 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 35 Participants |
| Omadacycline 300 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 21 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 2 Participants |
Primary
Percentage of Participants With Clinical Response on NTM Symptom Assessment Scale at Day 84
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.
Time frame: Day 1 to Day 84
Population: Intent-to-treat (ITT) analysis set included all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omadacycline 300 mg | Percentage of Participants With Clinical Response on NTM Symptom Assessment Scale at Day 84 | 34.1 Percentage of participants |
| Placebo | Percentage of Participants With Clinical Response on NTM Symptom Assessment Scale at Day 84 | 20.0 Percentage of participants |
p-value: 0.2182Chi-squared
Primary
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.
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.
Time frame: Day 1 to Day 84
Population: ITT Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omadacycline 300 mg | 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 |
| Placebo | 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. | 12.0 percentage of participants |
p-value: 0.046Chi-squared
Secondary
Change From Baseline in Global Score and Individual Domain Scores of the SGRQ - Total Score
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
Time frame: Day 1 (Baseline) to Day 84/EOT
Population: ITT Analysis Set. Only those participants with data available at specified timepoints has been presented.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Omadacycline 300 mg | 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 2.5 |
| Omadacycline 300 mg | 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 |
| Omadacycline 300 mg | 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 |
| Omadacycline 300 mg | 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 |
| Placebo | Change From Baseline in Global Score and Individual Domain Scores of the SGRQ - Total Score | Total score | -3.0 Score on a scale | Standard Error 2.67 |
| Placebo | Change From Baseline in Global Score and Individual Domain Scores of the SGRQ - Total Score | Activity score | -3.6 Score on a scale | Standard Error 3.17 |
| Placebo | Change From Baseline in Global Score and Individual Domain Scores of the SGRQ - Total Score | Symptom score | -0.6 Score on a scale | Standard Error 3.11 |
| Placebo | Change From Baseline in Global Score and Individual Domain Scores of the SGRQ - Total Score | Impact score | -3.5 Score on a scale | Standard Error 2.99 |
p-value: 0.826995% CI: [-7.26, 9.05]ANCOVA
p-value: 0.958495% CI: [-7.74, 7.35]ANCOVA
p-value: 0.212395% CI: [-12.88, 2.92]ANCOVA
p-value: 0.816195% CI: [-7.58, 5.99]ANCOVA
Secondary
Change From Baseline in Patient-Reported Outcomes Measurement Information System Short Form v1.0 - Fatigue 7a Daily (PROMIS-7a) Score
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.
Time frame: Day 1 (Baseline) to Day 84/EOT
Population: ITT Analysis Set. Only those participants with data available at specified timepoints has been presented.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Omadacycline 300 mg | 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 |
| Placebo | Change From Baseline in Patient-Reported Outcomes Measurement Information System Short Form v1.0 - Fatigue 7a Daily (PROMIS-7a) Score | 1.3 score on a scale | Standard Error 1.3 |
p-value: 0.00195% CI: [-8.95, -2.38]ANCOVA
Secondary
Change From Baseline in the Total Score of the QOL-B Questionnaire - Health Perceptions Domain
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.
Time frame: Day 1 (Baseline) to Day 84/EOT
Population: ITT analysis set. Only those participants with data available at specified timepoints has been presented.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Omadacycline 300 mg | 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 |
| Placebo | Change From Baseline in the Total Score of the QOL-B Questionnaire - Health Perceptions Domain | -0.9 Score on a scale | Standard Error 3.25 |
p-value: 0.214995% CI: [-3.03, 13.2]ANCOVA
Secondary
Change From Baseline in the Total Score of the QOL-B Questionnaire - Physical Functioning Domain
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.
Time frame: Day 1 (Baseline) to Day 84/EOT
Population: ITT analysis set. Only those participants with data available at specified timepoints has been presented.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Omadacycline 300 mg | 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 |
| Placebo | Change From Baseline in the Total Score of the QOL-B Questionnaire - Physical Functioning Domain | -2.7 Score on a scale | Standard Error 4.2 |
p-value: 0.12395% CI: [-2.31, 18.88]ANCOVA
Secondary
Change From Baseline in the Total Score of the QOL-B Questionnaire - Respiratory Symptoms Domain
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.
Time frame: Day 1 (Baseline) to Day 84/EOT
Population: ITT analysis set. Only those participants with data available at specified timepoints has been presented.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Omadacycline 300 mg | Change From Baseline in the Total Score of the QOL-B Questionnaire - Respiratory Symptoms Domain | 7.5 Score on a scale | Standard Error 2.1 |
| Placebo | Change From Baseline in the Total Score of the QOL-B Questionnaire - Respiratory Symptoms Domain | 2.0 Score on a scale | Standard Error 2.75 |
p-value: 0.116895% CI: [-1.41, 12.43]ANCOVA
Secondary
Change From Baseline in the Total Score of the QOL-B Questionnaire - Role Functioning Domain
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.
Time frame: Day 1 (Baseline) to Day 84/EOT
Population: ITT analysis set. Only those participants with data available at specified timepoints has been presented.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Omadacycline 300 mg | 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 |
| Placebo | Change From Baseline in the Total Score of the QOL-B Questionnaire - Role Functioning Domain | 0.9 Score on a scale | Standard Error 2.86 |
p-value: 0.074395% CI: [-0.66, 13.66]ANCOVA
Secondary
Change From Baseline in the Total Score of the QOL-B Questionnaire - Social Functioning Domain
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.
Time frame: Day 1 (Baseline) to Day 84/EOT
Population: ITT analysis set. Only those participants with data available at specified timepoints has been presented.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Omadacycline 300 mg | 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 |
| Placebo | Change From Baseline in the Total Score of the QOL-B Questionnaire - Social Functioning Domain | 2.6 Score on a scale | Standard Error 3.27 |
p-value: 0.089995% CI: [-1.13, 15.23]ANCOVA
Secondary
Change From Baseline in the Total Score of the QOL-B Questionnaire - Treatment Burden Domain
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.
Time frame: Day 1 (Baseline) to Day 84/EOT
Population: ITT analysis set. Only those participants with data available at specified timepoints has been presented.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Omadacycline 300 mg | 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 |
| Placebo | Change From Baseline in the Total Score of the QOL-B Questionnaire - Treatment Burden Domain | 2.3 Score on a scale | Standard Error 3.2 |
p-value: 0.901995% CI: [-7.6, 8.59]ANCOVA
Secondary
Change From Baseline in the Total Score of the QOL-B Questionnaire - Vitality Domain
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.
Time frame: Day 1 (Baseline) to Day 84/EOT
Population: ITT analysis set. Only those participants with data available at specified timepoints has been presented.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Omadacycline 300 mg | Change From Baseline in the Total Score of the QOL-B Questionnaire - Vitality Domain | 9.3 Score on a scale | Standard Error 2.5 |
| Placebo | Change From Baseline in the Total Score of the QOL-B Questionnaire - Vitality Domain | -4.3 Score on a scale | Standard Error 3.27 |
p-value: 0.001595% CI: [5.43, 21.89]ANCOVA
Secondary
Change From Baseline in the Total Score of the Quality of Life - Bronchiectasis (QOL-B) Questionnaire - Emotional Functioning Domain
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.
Time frame: Day 1 (Baseline) to Day 84/EOT
Population: ITT analysis set. Only those participants with data available at specified timepoints has been presented.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Omadacycline 300 mg | 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 |
| Placebo | Change From Baseline in the Total Score of the Quality of Life - Bronchiectasis (QOL-B) Questionnaire - Emotional Functioning Domain | 2.7 Score on a scale | Standard Error 2.69 |
p-value: 0.82495% CI: [-6.01, 7.52]ANCOVA
Secondary
Number of Participants Reporting Not Present or Mild Severity in Patient Clinical Impression of Severity (PGI-S)
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.
Time frame: Day 84/EOT
Population: ITT Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Omadacycline 300 mg | Number of Participants Reporting Not Present or Mild Severity in Patient Clinical Impression of Severity (PGI-S) | 26 Participants |
| Placebo | Number of Participants Reporting Not Present or Mild Severity in Patient Clinical Impression of Severity (PGI-S) | 12 Participants |
p-value: 0.305195% CI: [-9.1, 39.93]Fisher Exact
Secondary
Number of Participants With Clinical Global Impression - Improvement (CGI-I)
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.
Time frame: Day 1 to Day 84/EOT
Population: ITT Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Omadacycline 300 mg | Number of Participants With Clinical Global Impression - Improvement (CGI-I) | 29 Participants |
| Placebo | Number of Participants With Clinical Global Impression - Improvement (CGI-I) | 11 Participants |
p-value: 0.0753Wilcoxon rank sum test
Secondary
Number of Participants With Clinical Global Impression - Severity of Illness (CGI-S)
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.
Time frame: Day 84/EOT
Population: ITT Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Omadacycline 300 mg | Number of Participants With Clinical Global Impression - Severity of Illness (CGI-S) | Mildly ill | 11 Participants |
| Omadacycline 300 mg | Number of Participants With Clinical Global Impression - Severity of Illness (CGI-S) | Markedly ill | 0 Participants |
| Omadacycline 300 mg | Number of Participants With Clinical Global Impression - Severity of Illness (CGI-S) | Borderline ill | 9 Participants |
| Omadacycline 300 mg | Number of Participants With Clinical Global Impression - Severity of Illness (CGI-S) | Severely ill | 1 Participants |
| Omadacycline 300 mg | Number of Participants With Clinical Global Impression - Severity of Illness (CGI-S) | Moderately ill | 6 Participants |
| Omadacycline 300 mg | Number of Participants With Clinical Global Impression - Severity of Illness (CGI-S) | Among the most extremely ill participants | 0 Participants |
| Omadacycline 300 mg | Number of Participants With Clinical Global Impression - Severity of Illness (CGI-S) | Normal, not at all ill | 14 Participants |
| Placebo | Number of Participants With Clinical Global Impression - Severity of Illness (CGI-S) | Among the most extremely ill participants | 0 Participants |
| Placebo | Number of Participants With Clinical Global Impression - Severity of Illness (CGI-S) | Normal, not at all ill | 4 Participants |
| Placebo | Number of Participants With Clinical Global Impression - Severity of Illness (CGI-S) | Borderline ill | 8 Participants |
| Placebo | Number of Participants With Clinical Global Impression - Severity of Illness (CGI-S) | Mildly ill | 9 Participants |
| Placebo | Number of Participants With Clinical Global Impression - Severity of Illness (CGI-S) | Moderately ill | 4 Participants |
| Placebo | Number of Participants With Clinical Global Impression - Severity of Illness (CGI-S) | Markedly ill | 0 Participants |
| Placebo | Number of Participants With Clinical Global Impression - Severity of Illness (CGI-S) | Severely ill | 0 Participants |
p-value: 0.3552Wilcoxon rank sum test
Secondary
Number of Participants With Decreased Semi-Quantitative Score of Mycobacterial Sputum Culture From Day 1 to Day 84
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 frame: Day 1 to Day 84
Population: ITT Analysis Set. Only those participants with data available at specified timepoints has been presented.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Omadacycline 300 mg | Number of Participants With Decreased Semi-Quantitative Score of Mycobacterial Sputum Culture From Day 1 to Day 84 | 26 Participants |
| Placebo | Number of Participants With Decreased Semi-Quantitative Score of Mycobacterial Sputum Culture From Day 1 to Day 84 | 11 Participants |
p-value: 0.016895% CI: [1.24, 11.87]Chi-squared
Secondary
Number of Participants With Improvement in Patient Clinical Impression of Change (PGI-C)
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.
Time frame: Day 1 to Day 84/EOT
Population: ITT Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Omadacycline 300 mg | Number of Participants With Improvement in Patient Clinical Impression of Change (PGI-C) | 31 Participants |
| Placebo | Number of Participants With Improvement in Patient Clinical Impression of Change (PGI-C) | 9 Participants |
p-value: 0.00295% CI: [16.66, 62.56]Fisher Exact
Secondary
Number of Participants With New Symptoms With a Severity Worse Than Mild on the NTM Symptom Assessment Questionnaire at Any Time Post-baseline
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.
Time frame: Day 1 through Day 84 (at any study timepoint)
Population: ITT Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Omadacycline 300 mg | 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 |
| Placebo | Number of Participants With New Symptoms With a Severity Worse Than Mild on the NTM Symptom Assessment Questionnaire at Any Time Post-baseline | 6 Participants |
Secondary
Time to First Negative Sputum Culture
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).
Time frame: Day 1 through Day 84 (at any study timepoint)
Population: ITT Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Omadacycline 300 mg | Time to First Negative Sputum Culture | 30 Days |
| Placebo | Time to First Negative Sputum Culture | NA Days |
p-value: 0.0349Log Rank
Secondary
Time to Growth in Liquid Medium Only
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 frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Omadacycline 300 mg | Time to Growth in Liquid Medium Only | 34 Days |
| Placebo | Time to Growth in Liquid Medium Only | NA Days |
p-value: 0.0233Log Rank