Community-Acquired Bacterial Pneumonia (CABP)
Conditions
Brief summary
Study to Determine the Safety, Tolerability, Pharmacokinetics and Efficacy of Oral Nafithromycin Versus Oral Moxifloxacin in the Treatment of Community-Acquired Bacterial Pneumonia (CABP) in Adults
Interventions
DRUGNafithromycin 800 mg 3 days
DRUGNafithromycin 800 mg 5 days
DRUGMoxifloxacin 400 mg
Sponsors
ACM
Wockhardt
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
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
Meet the clinical criteria for CABP based on following: 1. Clinical symptoms (new or worsening) 2. Vital sign abnormalities 3. Laboratory abnormalities 4. Radiographic evidence of CABP 5. PORT score
Exclusion criteria
1. Subjects with any of the following confirmed or suspected types of pneumonia: 1. Aspiration pneumonia 2. Hospital-acquired bacterial pneumonia (HABP) 3. Healthcare-associated bacterial pneumonia (HCAP) 4. Ventilator-associated bacterial pneumonia (VABP) 5. Pneumonia that may be caused by pathogen(s) resistant to either study drug 2. Receipt of 1 or more dose(s) of a potentially effective systemic antibacterial treatment for treatment of the current CABP 3. Suspected or confirmed non-infectious causes of pulmonary infiltrates 4. Subjects requiring concomitant adjunctive or additional potentially-effective systemic antibacterial treatment for management of CABP
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Response in the ITT Population | Day 4 from start of drug administration | The primary efficacy endpoint was clinical response (response, non-response, or indeterminate) at Day 4, tested in the ITT population. Clinical response was determined programmatically using the investigator's assessment of CABP symptoms entered into the eCRF. The severity of the subject CABP symptoms of dyspnea (shortness of breath), cough, production of purulent sputum, and pleuritic chest pain were evaluated on a 4-point scale (absent, mild, moderate, or severe) based upon the CABP Symptom Severity Guidance |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Response in the Micro-ITT Population | Day 4 from start of drug administration | Clinical response (response, non-response, or indeterminate) at Day 4 was also tested in the micro-ITT population as a secondary efficacy endpoint. Clinical response was determined programmatically using the investigator's assessment of CABP symptoms entered into the eCRF. The severity of the subject CABP symptoms of dyspnea (shortness of breath), cough, production of purulent sputum, and pleuritic chest pain were evaluated on a 4-point scale (absent, mild, moderate, or severe) based upon the CABP Symptom Severity Guidance |
Countries
United States
Participant flow
Recruitment details
2 subjects withdrew consent prior to receiving study drug and 7 subjects whose PK results showed no detectable level of either nafithromycin or moxifloxacin hence 9 subjects excluded from the Safety population.
Participants by arm
| Arm | Count |
|---|---|
| Nafithromycin 800 mg 3 Days PO q24h for 3 days; subjects will receive matching placebo , to maintain the blind
Nafithromycin 800 mg 3 days | 74 |
| Nafithromycin 800 mg 5 Days PO q24h for 5 days; subjects will receive matching placebo, to maintain the blind
Nafithromycin 800 mg 5 days | 73 |
| Moxifloxacin 400 mg 7 Days PO q24h for 7 days;subjects will also receive two nafithromycin placebo tablets PO q24h on Days 1 through Day 7 to maintain the blind
Moxifloxacin 400 mg 7 days | 77 |
| Total | 224 |
Baseline characteristics
| Characteristic | Nafithromycin 800 mg 3 Days | Total | Moxifloxacin 400 mg 7 Days | Nafithromycin 800 mg 5 Days |
|---|---|---|---|---|
| Age, Continuous | 57.00 Years STANDARD_DEVIATION 15.73 | 56.00 Years STANDARD_DEVIATION 15.89 | 56.10 Years STANDARD_DEVIATION 15.18 | 54.90 Years STANDARD_DEVIATION 16.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 13 Participants | 8 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 71 Participants | 209 Participants | 68 Participants | 70 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 6 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 15 Participants | 48 Participants | 15 Participants | 18 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 57 Participants | 168 Participants | 59 Participants | 52 Participants |
| Region of Enrollment Bulgaria | 14 Participants | 41 Participants | 11 Participants | 16 Participants |
| Region of Enrollment Georgia | 8 Participants | 25 Participants | 9 Participants | 8 Participants |
| Region of Enrollment Latvia | 4 Participants | 9 Participants | 4 Participants | 1 Participants |
| Region of Enrollment Romania | 7 Participants | 15 Participants | 4 Participants | 4 Participants |
| Region of Enrollment Serbia | 18 Participants | 58 Participants | 21 Participants | 19 Participants |
| Region of Enrollment South Africa | 19 Participants | 60 Participants | 20 Participants | 21 Participants |
| Region of Enrollment United States | 4 Participants | 16 Participants | 8 Participants | 4 Participants |
| Sex: Female, Male Female | 37 Participants | 104 Participants | 35 Participants | 32 Participants |
| Sex: Female, Male Male | 37 Participants | 120 Participants | 42 Participants | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 74 | 0 / 72 | 1 / 76 |
| other Total, other adverse events | 11 / 74 | 9 / 72 | 6 / 76 |
| serious Total, serious adverse events | 1 / 74 | 1 / 72 | 2 / 76 |
Outcome results
Primary
Clinical Response in the ITT Population
The primary efficacy endpoint was clinical response (response, non-response, or indeterminate) at Day 4, tested in the ITT population. Clinical response was determined programmatically using the investigator's assessment of CABP symptoms entered into the eCRF. The severity of the subject CABP symptoms of dyspnea (shortness of breath), cough, production of purulent sputum, and pleuritic chest pain were evaluated on a 4-point scale (absent, mild, moderate, or severe) based upon the CABP Symptom Severity Guidance
Time frame: Day 4 from start of drug administration
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nafithromycin 800 mg 3 Days | Clinical Response in the ITT Population | 68 Participants |
| Nafithromycin 800 mg 5 Days | Clinical Response in the ITT Population | 65 Participants |
| Moxifloxacin 400 mg | Clinical Response in the ITT Population | 67 Participants |
Secondary
Clinical Response in the Micro-ITT Population
Clinical response (response, non-response, or indeterminate) at Day 4 was also tested in the micro-ITT population as a secondary efficacy endpoint. Clinical response was determined programmatically using the investigator's assessment of CABP symptoms entered into the eCRF. The severity of the subject CABP symptoms of dyspnea (shortness of breath), cough, production of purulent sputum, and pleuritic chest pain were evaluated on a 4-point scale (absent, mild, moderate, or severe) based upon the CABP Symptom Severity Guidance
Time frame: Day 4 from start of drug administration
Population: The micro-ITT population included all ITT subjects who had at least one baseline Gram-positive or atypical bacterial pathogen known to cause CABP.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nafithromycin 800 mg 3 Days | Clinical Response in the Micro-ITT Population | 21 Participants |
| Nafithromycin 800 mg 5 Days | Clinical Response in the Micro-ITT Population | 26 Participants |
| Moxifloxacin 400 mg | Clinical Response in the Micro-ITT Population | 18 Participants |