Bacterial Infections, Skin Structures and Soft Tissue Infections
Conditions
Brief summary
The purpose of this study is to evaluate the safety and efficacy of omadacycline as compared to linezolid in the treatment of adults with acute bacterial skin and skin structure infections.
Interventions
DRUGOmadacycline
po tablets
DRUGLinezolid
po 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 a qualifying skin and skin structure infection * 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
* Infections where the outcome is strongly influenced by factors other than protocol-defined treatments and procedures, or that require antibacterial treatment for greater than 14 days * Evidence of significant immunological disease * Severe renal disease or requirement for dialysis * Evidence of septic shock * Has a history of hypersensitivity or allergic reaction to any tetracycline or to linezolid * Has received an investigational drug within the past 30 days * Women who are pregnant or nursing
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Early Clinical Response | Screening; 48 to 72 hours after the first dose of test article | Early clinical response is defined as clinical success, which is categorized as survival with at least a 20% reduction of acute bacterial skin and skin structure infection (ABSSSI) primary lesion size compared to Screening measurements, without receiving any rescue antibacterial therapy. An indeterminate classification is used for a response 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With the Indicated Investigator Assessment of Clinical Response in the mITT Population at the Post Therapy Evaluation (PTE) Visit | Screening; 7 to 14 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: participant was alive; infection was sufficiently resolved such that further antibacterial therapy was not needed. Participants may have had some residual changes related to infection requiring ancillary treatment. Clinical Failure was defined as meeting any of the following criteria: infection required additional treatment with alternative antibacterial therapy; participant received antibacterial therapy between the End-of-Treatment (EOT) Visit and the PTE Visit that may have been effective for the infection under study for a different infection from the one under study; unplanned major surgical intervention for the infection under study between the EOT and PTE Visits; participant died before evaluation; other specified reason. 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 (CE-PTE) Population | Screening; 7 to 14 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: participant was alive; infection was sufficiently resolved such that further antibacterial therapy was not needed. Participants may have had some residual changes related to infection requiring ancillary treatment. Clinical Failure was defined as meeting any of the following criteria: infection required additional treatment with alternative antibacterial therapy; participant received antibacterial therapy between the EOT Visit and the PTE Visit that may have been effective for the infection under study for a different infection from the one under study; unplanned major surgical intervention for the infection under study between the EOT and PTE Visits; participant died before evaluation; other specified reason. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Omadacycline Participants received omadacycline 450 milligrams (mg) orally every 24 hours (q24h) for 2 doses, followed by 300 mg orally q24h. The total treatment duration was 7 to 14 days. Participants received active omadacycline tablets and over-encapsulated linezolid placebo tablets. | 368 |
| Linezolid Participants received linezolid 600 mg orally every 12 hours (q12h). The total treatment duration was 7 to 14 days. Participants received omadacycline placebo tablets and over-encapsulated active linezolid tablets. | 367 |
| Total | 735 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Lost to Follow-up | 37 | 38 |
| Overall Study | Missed EOT/PTE Visit | 5 | 6 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Withdrawal by Subject | 11 | 12 |
Baseline characteristics
| Characteristic | Linezolid | Total | Omadacycline |
|---|---|---|---|
| Age, Continuous | 44.5 years STANDARD_DEVIATION 13.11 | 43.7 years STANDARD_DEVIATION 12.94 | 42.8 years STANDARD_DEVIATION 12.72 |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 10 Participants | 7 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 8 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 13 Participants | 35 Participants | 22 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 | 3 Participants | 3 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 11 Participants | 6 Participants |
| Race (NIH/OMB) White | 341 Participants | 668 Participants | 327 Participants |
| Sex: Female, Male Female | 147 Participants | 273 Participants | 126 Participants |
| Sex: Female, Male Male | 220 Participants | 462 Participants | 242 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 368 | 1 / 367 |
| other Total, other adverse events | 166 / 368 | 83 / 367 |
| serious Total, serious adverse events | 5 / 368 | 5 / 367 |
Outcome results
Primary
Number of Participants With Early Clinical Response
Early clinical response is defined as clinical success, which is categorized as survival with at least a 20% reduction of acute bacterial skin and skin structure infection (ABSSSI) primary lesion size compared to Screening measurements, without receiving any rescue antibacterial therapy. An indeterminate classification is used for a response 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.
Time frame: Screening; 48 to 72 hours after the first dose of test article
Population: Modified Intent-to-Treat (mITT) Population: all randomized participants without a baseline sole Gram-negative ABSSSI pathogen
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Omadacycline | Number of Participants With Early Clinical Response | Clinical success | 315 Participants |
| Omadacycline | Number of Participants With Early Clinical Response | Clinical failure | 26 Participants |
| Omadacycline | Number of Participants With Early Clinical Response | Indeterminate | 19 Participants |
| Linezolid | Number of Participants With Early Clinical Response | Indeterminate | 31 Participants |
| Linezolid | Number of Participants With Early Clinical Response | Clinical success | 297 Participants |
| Linezolid | Number of Participants With Early Clinical Response | Clinical failure | 32 Participants |
95% CI: [-0.2, 10.3]
Secondary
Number of Participants With the Indicated Investigator Assessment of Clinical Response in the Clinically Evaluable-Post Therapy Evaluation (CE-PTE) Population
At the PTE Visit the investigator indicated one of the following outcomes relating to the primary infection under study: Clinical Success: participant was alive; infection was sufficiently resolved such that further antibacterial therapy was not needed. Participants may have had some residual changes related to infection requiring ancillary treatment. Clinical Failure was defined as meeting any of the following criteria: infection required additional treatment with alternative antibacterial therapy; participant received antibacterial therapy between the EOT Visit and the PTE Visit that may have been effective for the infection under study for a different infection from the one under study; unplanned major surgical intervention for the infection under study between the EOT and PTE Visits; participant died before evaluation; other specified reason.
Time frame: Screening; 7 to 14 days after the last day of therapy
Population: CE-PTE Population: all participants in the mITT 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 (CE-PTE) Population | Clinical success | 278 Participants |
| Omadacycline | Number of Participants With the Indicated Investigator Assessment of Clinical Response in the Clinically Evaluable-Post Therapy Evaluation (CE-PTE) Population | Clinical failure | 6 Participants |
| Linezolid | Number of Participants With the Indicated Investigator Assessment of Clinical Response in the Clinically Evaluable-Post Therapy Evaluation (CE-PTE) Population | Clinical success | 279 Participants |
| Linezolid | Number of Participants With the Indicated Investigator Assessment of Clinical Response in the Clinically Evaluable-Post Therapy Evaluation (CE-PTE) Population | Clinical failure | 13 Participants |
95% CI: [-0.6, 5.6]
Secondary
Number of Participants With the Indicated Investigator Assessment of Clinical Response in the mITT 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: participant was alive; infection was sufficiently resolved such that further antibacterial therapy was not needed. Participants may have had some residual changes related to infection requiring ancillary treatment. Clinical Failure was defined as meeting any of the following criteria: infection required additional treatment with alternative antibacterial therapy; participant received antibacterial therapy between the End-of-Treatment (EOT) Visit and the PTE Visit that may have been effective for the infection under study for a different infection from the one under study; unplanned major surgical intervention for the infection under study between the EOT and PTE Visits; participant died before evaluation; other specified reason. Indeterminate The clinical response to test article could not be adequately inferred.
Time frame: Screening; 7 to 14 days after the last day of therapy
Population: mITT Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Omadacycline | Number of Participants With the Indicated Investigator Assessment of Clinical Response in the mITT Population at the Post Therapy Evaluation (PTE) Visit | Clinical success | 303 Participants |
| Omadacycline | Number of Participants With the Indicated Investigator Assessment of Clinical Response in the mITT Population at the Post Therapy Evaluation (PTE) Visit | Clinical failure | 12 Participants |
| Omadacycline | Number of Participants With the Indicated Investigator Assessment of Clinical Response in the mITT Population at the Post Therapy Evaluation (PTE) Visit | Indeterminate | 45 Participants |
| Linezolid | Number of Participants With the Indicated Investigator Assessment of Clinical Response in the mITT Population at the Post Therapy Evaluation (PTE) Visit | Clinical success | 291 Participants |
| Linezolid | Number of Participants With the Indicated Investigator Assessment of Clinical Response in the mITT Population at the Post Therapy Evaluation (PTE) Visit | Clinical failure | 21 Participants |
| Linezolid | Number of Participants With the Indicated Investigator Assessment of Clinical Response in the mITT Population at the Post Therapy Evaluation (PTE) Visit | Indeterminate | 48 Participants |
95% CI: [-2.2, 8.9]