Bacterial Skin Disease, Infectious Skin Disease
Conditions
Keywords
CSSSI
Brief summary
A Phase II trial to demonstrate the safety and efficacy of PTK 0796 in the treatment of complicated skin and skin structure infections (cSSSI).
Detailed description
The pharmacologic profile of PTK 0796 in humans suggests that it has the potential to be used safely and effectively for this indication. Data from in vitro and animal studies support this hypothesis. In PTK 0796-CSSI-0702 the safety and efficacy of PTK 0796 in the treatment of cSSSI will be compared to an antibiotic approved for this indication by FDA. Initial treatment will be administered intravenously with the option for subsequent oral treatment.
Interventions
DRUGPTK 0796
PTK 0796 100 mg for injection; PTK 0796 capsule 100 mg
DRUGLinezolid
Pre-mixed 600 mg IV infusion solution; Linezolid 600 mg 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 80 Years
Healthy volunteers
No
Inclusion criteria
1. Patients, ages 18 years to 80 years 2. Has an acute complicated skin and skin structure infection 3. Female patients must not be pregnant at the time of enrollment and 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
1. Has received an investigational drug within past 1 month 2. Has been previously enrolled in this protocol 3. Has received \>48 hr of a potentially effective systemic antibiotic immediately prior to study drug 4. Is nursing
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinical Response in the Modified Intent-to-Treat (mITT) Population | 10 to 17 days after the last dose of test article (intravenous or oral) (total treatment of up to 14 days) | Clinical response is defined as clinical success (CS), which is categorized as a determination by a blinded evaluator (BE) that the infection had sufficiently resolved such that antibiotics were no longer needed, the participant (par.) received ≥1 dose of test article, the par. did not receive non-study antibiotics on \>2 calendar days from Day 1 to the Test of Cure assessment, and the par. did not meet any of the criteria for clinical failure. Clinical failure (CF) is categorized as a determination by a BE that the infection had responded inadequately such that alternative antibiotics were needed, the BE discontinued test article due to an adverse event that was possibly/probably related to test article, the primary site of infection was surgically removed, or the par. received potentially effective antibiotics for treatment of the primary infection site on \>2 days after study enrollment. A classification of indeterminate is used for any outcome that was not classified as CS or CF. |
| Number of Participants With Clinical Response in the Clinically Evaluable (CE) Population | 10 to 17 days after the last dose of test article (intravenous or oral) (total treatment of up to 14 days) | Clinical response is defined as CS, which was categorized as a determination by a BE that the infection had sufficiently resolved such that antibiotics were no longer needed, the participant received ≥1 dose of test article, the participant did not receive non-study antibiotics on \>2 calendar days from Day 1 to the Test of Cure assessment, and the participant did not meet any of the criteria for clinical failure. CF was categorized as a determination by a BE that the infection had responded inadequately such that alternative antibiotics were needed, the BE discontinued test article due to an adverse event that was possibly/probably related to test article, the primary site of infection was surgically removed, or the participant received potentially effective antibiotics for treatment of the primary infection site on \>2 days after study enrollment. A classification of indeterminate is used for any outcome that was not classified as CS or CF. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Microbiologic Response in the mITT Population | 10 to 17 days after the last dose of test article (intravenous or oral) (total treatment of up to 14 days) | Microbiological response to treatment was determined using the following classification: (a) microbiologic success: all infecting pathogens isolated at Baseline were eradicated or presumed eradicated at the Test of Cure evaluation and no superinfecting pathogen was isolated from the site of infection under study; (b) microbiological failure: persistence or presumed persistence of one or more infecting pathogens or isolation of a superinfecting pathogen from the site of infection under study. |
| Number of Participants With Microbiologic Response in the Microbiologically Evaluable (ME) Population | 10 to 17 days after the last dose of test article (intravenous or oral) (total treatment of up to 14 days) | Microbiological response to treatment was determined using the following classification: (a) microbiologic success: all infecting pathogens isolated at Baseline were eradicated or presumed eradicated at the Test of Cure evaluation and no superinfecting pathogen was isolated from the site of infection under study; (b) microbiological failure: persistence or presumed persistence of one or more infecting pathogens or isolation of a superinfecting pathogen from the site of infection under study. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Omadacycline Participants received intravenous (IV) omadacycline 100 milligrams (mg) infused over 30 minutes, every 24 hours (q24h), with the option to switch to two 100-mg capsules via oral administration q24h at the discretion of the investigator. All participants received up to 7 days of IV therapy and up to 14 days of IV and oral therapy combined. | 111 |
| Linezolid Participants received IV linezolid 600 mg infused over 30 minutes, every 12 hours (q12h), with the option to switch to one 600-mg tablet via oral administration q12h at the discretion of the investigator. All participants received up to 7 days of IV therapy and up to 14 days of IV and oral therapy combined. | 108 |
| Total | 219 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 |
| Overall Study | Lost to Follow-up | 2 | 6 |
| Overall Study | Missing Reason | 0 | 1 |
| Overall Study | Randomized, not Treated | 7 | 8 |
| Overall Study | Treatment Failure | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Omadacycline | Linezolid | Total |
|---|---|---|---|
| Age, Continuous | 44.4 years STANDARD_DEVIATION 14.06 | 45.4 years STANDARD_DEVIATION 13.34 | 44.9 years STANDARD_DEVIATION 13.69 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Asian Hawaiian or Other Pacific Islander | 5 participants | 1 participants | 6 participants |
| Race/Ethnicity, Customized Black or African American | 8 participants | 6 participants | 14 participants |
| Race/Ethnicity, Customized Caucasian | 97 participants | 99 participants | 196 participants |
| Race/Ethnicity, Customized Recorded as Other | 1 participants | 1 participants | 2 participants |
| Sex: Female, Male Female | 45 Participants | 51 Participants | 96 Participants |
| Sex: Female, Male Male | 66 Participants | 57 Participants | 123 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 111 | 0 / 108 |
| other Total, other adverse events | 44 / 111 | 54 / 108 |
| serious Total, serious adverse events | 1 / 111 | 2 / 108 |
Outcome results
Primary
Number of Participants With Clinical Response in the Clinically Evaluable (CE) Population
Clinical response is defined as CS, which was categorized as a determination by a BE that the infection had sufficiently resolved such that antibiotics were no longer needed, the participant received ≥1 dose of test article, the participant did not receive non-study antibiotics on \>2 calendar days from Day 1 to the Test of Cure assessment, and the participant did not meet any of the criteria for clinical failure. CF was categorized as a determination by a BE that the infection had responded inadequately such that alternative antibiotics were needed, the BE discontinued test article due to an adverse event that was possibly/probably related to test article, the primary site of infection was surgically removed, or the participant received potentially effective antibiotics for treatment of the primary infection site on \>2 days after study enrollment. A classification of indeterminate is used for any outcome that was not classified as CS or CF.
Time frame: 10 to 17 days after the last dose of test article (intravenous or oral) (total treatment of up to 14 days)
Population: CE Population: all enrolled participants who received at least 1 dose of test article and who had a qualifying skin and skin structure infection, received the correct test article for at least 5 calendar days, had the necessary clinical evaluations performed, and did not receive potentially confounding non-study antibiotics
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Omadacycline | Number of Participants With Clinical Response in the Clinically Evaluable (CE) Population | Clinical success | 98 participants |
| Omadacycline | Number of Participants With Clinical Response in the Clinically Evaluable (CE) Population | Clinical failure | 2 participants |
| Linezolid | Number of Participants With Clinical Response in the Clinically Evaluable (CE) Population | Clinical success | 82 participants |
| Linezolid | Number of Participants With Clinical Response in the Clinically Evaluable (CE) Population | Clinical failure | 6 participants |
95% CI: [-1.7, 11.4]
Primary
Number of Participants With Clinical Response in the Modified Intent-to-Treat (mITT) Population
Clinical response is defined as clinical success (CS), which is categorized as a determination by a blinded evaluator (BE) that the infection had sufficiently resolved such that antibiotics were no longer needed, the participant (par.) received ≥1 dose of test article, the par. did not receive non-study antibiotics on \>2 calendar days from Day 1 to the Test of Cure assessment, and the par. did not meet any of the criteria for clinical failure. Clinical failure (CF) is categorized as a determination by a BE that the infection had responded inadequately such that alternative antibiotics were needed, the BE discontinued test article due to an adverse event that was possibly/probably related to test article, the primary site of infection was surgically removed, or the par. received potentially effective antibiotics for treatment of the primary infection site on \>2 days after study enrollment. A classification of indeterminate is used for any outcome that was not classified as CS or CF.
Time frame: 10 to 17 days after the last dose of test article (intravenous or oral) (total treatment of up to 14 days)
Population: mITT Population: all enrolled participants who received at least 1 dose of test article and who had at least 1 infecting pathogen isolated at the Baseline evaluation. Non-evaluable participants are included as clinical failures.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Omadacycline | Number of Participants With Clinical Response in the Modified Intent-to-Treat (mITT) Population | Clinical success | 75 participants |
| Omadacycline | Number of Participants With Clinical Response in the Modified Intent-to-Treat (mITT) Population | Clinical failure | 9 participants |
| Omadacycline | Number of Participants With Clinical Response in the Modified Intent-to-Treat (mITT) Population | Clinical failure: failure | 2 participants |
| Omadacycline | Number of Participants With Clinical Response in the Modified Intent-to-Treat (mITT) Population | Clinical failure: non-evaluable | 7 participants |
| Linezolid | Number of Participants With Clinical Response in the Modified Intent-to-Treat (mITT) Population | Clinical failure: non-evaluable | 15 participants |
| Linezolid | Number of Participants With Clinical Response in the Modified Intent-to-Treat (mITT) Population | Clinical success | 59 participants |
| Linezolid | Number of Participants With Clinical Response in the Modified Intent-to-Treat (mITT) Population | Clinical failure: failure | 4 participants |
| Linezolid | Number of Participants With Clinical Response in the Modified Intent-to-Treat (mITT) Population | Clinical failure | 19 participants |
95% CI: [1.3, 26]
Secondary
Number of Participants With Microbiologic Response in the Microbiologically Evaluable (ME) Population
Microbiological response to treatment was determined using the following classification: (a) microbiologic success: all infecting pathogens isolated at Baseline were eradicated or presumed eradicated at the Test of Cure evaluation and no superinfecting pathogen was isolated from the site of infection under study; (b) microbiological failure: persistence or presumed persistence of one or more infecting pathogens or isolation of a superinfecting pathogen from the site of infection under study.
Time frame: 10 to 17 days after the last dose of test article (intravenous or oral) (total treatment of up to 14 days)
Population: ME Population: all participants in the CE cohort who had an infecting pathogen identified at Baseline
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Omadacycline | Number of Participants With Microbiologic Response in the Microbiologically Evaluable (ME) Population | Microbiological success | 73 participants |
| Omadacycline | Number of Participants With Microbiologic Response in the Microbiologically Evaluable (ME) Population | Microbiological failure | 4 participants |
| Linezolid | Number of Participants With Microbiologic Response in the Microbiologically Evaluable (ME) Population | Microbiological success | 57 participants |
| Linezolid | Number of Participants With Microbiologic Response in the Microbiologically Evaluable (ME) Population | Microbiological failure | 6 participants |
95% CI: [-5.3, 14]
Secondary
Number of Participants With Microbiologic Response in the mITT Population
Microbiological response to treatment was determined using the following classification: (a) microbiologic success: all infecting pathogens isolated at Baseline were eradicated or presumed eradicated at the Test of Cure evaluation and no superinfecting pathogen was isolated from the site of infection under study; (b) microbiological failure: persistence or presumed persistence of one or more infecting pathogens or isolation of a superinfecting pathogen from the site of infection under study.
Time frame: 10 to 17 days after the last dose of test article (intravenous or oral) (total treatment of up to 14 days)
Population: mITT Population. Non-evaluable participants are included as microbiological failures.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Omadacycline | Number of Participants With Microbiologic Response in the mITT Population | Microbiological success | 73 participants |
| Omadacycline | Number of Participants With Microbiologic Response in the mITT Population | Microbiological failure | 11 participants |
| Linezolid | Number of Participants With Microbiologic Response in the mITT Population | Microbiological success | 57 participants |
| Linezolid | Number of Participants With Microbiologic Response in the mITT Population | Microbiological failure | 21 participants |
95% CI: [0.9, 26.7]