Bacterial Pneumonia, Community-Acquired Infections
Conditions
Brief summary
The purpose of this study is to evaluate the safety and efficacy of omadacycline as compared to moxifloxacin in the treatment of adults with community-acquired bacterial pneumonia.
Interventions
DRUGOmadacycline
Injection for IV; Oral tablets
DRUGMoxifloxacin
IV solution; Oral tablets
Sponsors
Paratek Pharmaceuticals Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients, ages 18 years or older who have signed the informed consent * Has qualifying bacterial pneumonia * Female patients must not be pregnant at the time of enrollment * Must agree to a reliable method of birth control during the study and for 30 days following the last dose of study drug
Exclusion criteria
* Known or suspected hospital-acquired pneumonia * Evidence of significant immunological disease * Has a history of hypersensitivity or allergic reaction to any tetracycline or to any fluoroquinolone antibiotic * Has received an investigational drug within past 30 days * Women who are pregnant or nursing
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Early Clinical Response | Screening; 72 to 120 hours after the first dose of test article | Early clinical response is defined as clinical success, categorized by survival with improvement of at least 1 level compared to Baseline in at least 2 CABP symptoms (cough, sputum production, pleuritic chest pain, and dyspnea) with no worsening in the other CABP symptoms. Response was determined programmatically using the investigator's assessment of the CABP symptoms. The severity of the participant's CABP symptoms was evaluated on a 4-point scale (absent, mild, moderate, or severe) based upon the CABP Subject Symptom Severity Guidance Framework for Investigator Assessment. An indeterminate response is defined as one that could not be adequately inferred because the participant was not assessed because they withdrew consent, were lost to follow-up, or other specified reason. Clinical failure is defined as no improvement by at least 1 level in CABP symptoms, worsening of any CABP symptom, alternative antibacterial treatment for CABP, discontinuation due to adverse event, or death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With the Indicated Investigator Assessment of Clinical Response in the ITT Population at the Post Therapy Evaluation (PTE) Visit | Screening; 5 to 10 days after the last day of therapy | At the PTE Visit the investigator indicated one of the following outcomes relating to the primary infection under study: Clinical Success: survival after completion of a test article regimen without receiving any systemic antibacterial therapy other than test article, resolution of signs/symptoms of the infection present at Screening with no new symptoms/complications attributable to CABP and no need for further antibacterial therapy. Clinical Failure: alternative antibacterial treatment for CABP was required prior to the PTE Visit related to either (a) progression/development of new CABP symptoms or (b) development of infectious complications of CABP. Other reasons for clinical failure: participant received antibiotics that may have been effective for the infection under study for a different infection from the one under study; death prior to the PTE Visit. Indeterminate: the clinical response to test article could not be adequately inferred. |
| Number of Participants With the Indicated Investigator Assessment of Clinical Response in the Clinically Evaluable-Post Therapy Evaluation (CT-PTE) Population | Screening; 5 to 10 days after the last day of therapy | At the PTE Visit the investigator indicated one of the following outcomes relating to the primary infection under study: Clinical Success: survival after completion of a test article regimen without receiving any systemic antibacterial therapy other than test article, resolution of signs/symptoms of the infection present at Screening with no new symptoms/complications attributable to CABP and no need for further antibacterial therapy. Clinical Failure: alternative antibacterial treatment for CABP was required prior to the PTE Visit related to either (a) progression/development of new CABP symptoms or (b) development of infectious complications of CABP. Other reasons for clinical failure: participant received antibiotics that may have been effective for the infection under study for a different infection from the one under study; death prior to the PTE Visit. |
Countries
Belgium, Brazil, Bulgaria, Croatia, Czechia, Georgia, Germany, Greece, Hungary, Israel, Latvia, Mexico, Peru, Philippines, Poland, Romania, Russia, Slovakia, South Africa, South Korea, Spain, Taiwan, Turkey (Türkiye), Ukraine, United States
Participant flow
Recruitment details
Participant randomization was stratified by Pneumonia Outcomes Research Team (PORT) Risk Class (II or III/IV), receipt of an allowed antibacterial therapy in the 72 hours prior to study treatment, and geographic region. All participants were expected to present with CABP severe enough to require at least 3 days of intravenous (IV) treatment.
Pre-assignment details
Participants who met inclusion criteria and did not meet exclusion criteria were randomly assigned to a treatment group, and received their first dose of test article within 4 hours after randomization. All participants were expected to present with CABP PORT Risk Class II, III, or IV to require a minimum of at least 3 days of IV treatment.
Participants by arm
| Arm | Count |
|---|---|
| Omadacycline Participants received omadacycline 100 milligrams (mg) intravenously (IV) every 12 hours (q12h) (first 2 doses), followed by 100 mg IV every 24 hours (q24h) (starting 24 hours after the first dose), with the option to switch to a 300 mg (two 150 mg omadacycline tablets and 1 over-encapsulated placebo tablet matching moxifloxacin) oral administration q24h after at least 3 days (4 doses) of IV treatment. The total duration of test article therapy (IV plus oral administration) for all participants was at least 7 days and no more than 14 days. | 386 |
| Moxifloxacin Participants received moxifloxacin 400 mg IV q24h (with a single placebo infusion to match the omadacycline dosing regimen 12 hours after the first dose on Day 1) with the option to switch to a 400 mg (one 400 mg moxifloxacin over-encapsulated tablet and 2 placebo tablets matching omadacycline tablets) oral administration q24h after at least 3 days (4 doses) of IV treatment. The total duration of test article therapy (IV plus oral administration) for all participants was at least 7 days and no more than 14 days. | 388 |
| Total | 774 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 7 | 9 |
| Overall Study | Death | 6 | 3 |
| Overall Study | Lost to Follow-up | 0 | 3 |
| Overall Study | Missed EOT/PTE Visit | 5 | 2 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Randomized, but Not Treated | 4 | 0 |
| Overall Study | Randomized with Exclusion Criteria | 1 | 0 |
| Overall Study | Withdrawal by Subject | 7 | 8 |
Baseline characteristics
| Characteristic | Omadacycline | Moxifloxacin | Total |
|---|---|---|---|
| Age, Customized 18 to 45 years old | 62 Participants | 61 Participants | 123 Participants |
| Age, Customized >45 to 65 years old | 172 Participants | 155 Participants | 327 Participants |
| Age, Customized >65 years old | 152 Participants | 172 Participants | 324 Participants |
| Age, Customized >75 years old | 75 Participants | 83 Participants | 158 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 17 Participants | 18 Participants | 35 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants | 7 Participants | 18 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 | 2 Participants | 6 Participants | 8 Participants |
| Race (NIH/OMB) White | 356 Participants | 355 Participants | 711 Participants |
| Sex: Female, Male Female | 178 Participants | 169 Participants | 347 Participants |
| Sex: Female, Male Male | 208 Participants | 219 Participants | 427 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 8 / 382 | 4 / 388 |
| other Total, other adverse events | 63 / 382 | 94 / 388 |
| serious Total, serious adverse events | 23 / 382 | 26 / 388 |
Outcome results
Primary
Number of Participants With Early Clinical Response
Early clinical response is defined as clinical success, categorized by survival with improvement of at least 1 level compared to Baseline in at least 2 CABP symptoms (cough, sputum production, pleuritic chest pain, and dyspnea) with no worsening in the other CABP symptoms. Response was determined programmatically using the investigator's assessment of the CABP symptoms. The severity of the participant's CABP symptoms was evaluated on a 4-point scale (absent, mild, moderate, or severe) based upon the CABP Subject Symptom Severity Guidance Framework for Investigator Assessment. An indeterminate response is defined as one that could not be adequately inferred because the participant was not assessed because they withdrew consent, were lost to follow-up, or other specified reason. Clinical failure is defined as no improvement by at least 1 level in CABP symptoms, worsening of any CABP symptom, alternative antibacterial treatment for CABP, discontinuation due to adverse event, or death.
Time frame: Screening; 72 to 120 hours after the first dose of test article
Population: Intent-to-Treat (ITT) Population: all randomized participants regardless of whether or not the participant received the test article
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Omadacycline | Number of Participants With Early Clinical Response | Clinical success | 313 Participants |
| Omadacycline | Number of Participants With Early Clinical Response | Clinical failure | 49 Participants |
| Omadacycline | Number of Participants With Early Clinical Response | Indeterminate | 24 Participants |
| Moxifloxacin | Number of Participants With Early Clinical Response | Clinical success | 321 Participants |
| Moxifloxacin | Number of Participants With Early Clinical Response | Clinical failure | 47 Participants |
| Moxifloxacin | Number of Participants With Early Clinical Response | Indeterminate | 20 Participants |
95% CI: [-7.1, 3.8]
Secondary
Number of Participants With the Indicated Investigator Assessment of Clinical Response in the Clinically Evaluable-Post Therapy Evaluation (CT-PTE) Population
At the PTE Visit the investigator indicated one of the following outcomes relating to the primary infection under study: Clinical Success: survival after completion of a test article regimen without receiving any systemic antibacterial therapy other than test article, resolution of signs/symptoms of the infection present at Screening with no new symptoms/complications attributable to CABP and no need for further antibacterial therapy. Clinical Failure: alternative antibacterial treatment for CABP was required prior to the PTE Visit related to either (a) progression/development of new CABP symptoms or (b) development of infectious complications of CABP. Other reasons for clinical failure: participant received antibiotics that may have been effective for the infection under study for a different infection from the one under study; death prior to the PTE Visit.
Time frame: Screening; 5 to 10 days after the last day of therapy
Population: CE-PTE Population: all participants in the ITT Population meeting additional pre-defined criteria
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Omadacycline | Number of Participants With the Indicated Investigator Assessment of Clinical Response in the Clinically Evaluable-Post Therapy Evaluation (CT-PTE) Population | Clinical success | 316 Participants |
| Omadacycline | Number of Participants With the Indicated Investigator Assessment of Clinical Response in the Clinically Evaluable-Post Therapy Evaluation (CT-PTE) Population | Clinical failure | 24 Participants |
| Moxifloxacin | Number of Participants With the Indicated Investigator Assessment of Clinical Response in the Clinically Evaluable-Post Therapy Evaluation (CT-PTE) Population | Clinical success | 312 Participants |
| Moxifloxacin | Number of Participants With the Indicated Investigator Assessment of Clinical Response in the Clinically Evaluable-Post Therapy Evaluation (CT-PTE) Population | Clinical failure | 33 Participants |
95% CI: [-1.7, 6.8]
Secondary
Number of Participants With the Indicated Investigator Assessment of Clinical Response in the ITT Population at the Post Therapy Evaluation (PTE) Visit
At the PTE Visit the investigator indicated one of the following outcomes relating to the primary infection under study: Clinical Success: survival after completion of a test article regimen without receiving any systemic antibacterial therapy other than test article, resolution of signs/symptoms of the infection present at Screening with no new symptoms/complications attributable to CABP and no need for further antibacterial therapy. Clinical Failure: alternative antibacterial treatment for CABP was required prior to the PTE Visit related to either (a) progression/development of new CABP symptoms or (b) development of infectious complications of CABP. Other reasons for clinical failure: participant received antibiotics that may have been effective for the infection under study for a different infection from the one under study; death prior to the PTE Visit. Indeterminate: the clinical response to test article could not be adequately inferred.
Time frame: Screening; 5 to 10 days after the last day of therapy
Population: ITT Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Omadacycline | Number of Participants With the Indicated Investigator Assessment of Clinical Response in the ITT Population at the Post Therapy Evaluation (PTE) Visit | Clinical failure | 32 Participants |
| Omadacycline | Number of Participants With the Indicated Investigator Assessment of Clinical Response in the ITT Population at the Post Therapy Evaluation (PTE) Visit | Clinical success | 338 Participants |
| Omadacycline | Number of Participants With the Indicated Investigator Assessment of Clinical Response in the ITT Population at the Post Therapy Evaluation (PTE) Visit | Indeterminate | 16 Participants |
| Moxifloxacin | Number of Participants With the Indicated Investigator Assessment of Clinical Response in the ITT Population at the Post Therapy Evaluation (PTE) Visit | Clinical success | 330 Participants |
| Moxifloxacin | Number of Participants With the Indicated Investigator Assessment of Clinical Response in the ITT Population at the Post Therapy Evaluation (PTE) Visit | Indeterminate | 16 Participants |
| Moxifloxacin | Number of Participants With the Indicated Investigator Assessment of Clinical Response in the ITT Population at the Post Therapy Evaluation (PTE) Visit | Clinical failure | 42 Participants |
95% CI: [-2.4, 7.4]