Skin Diseases, Infectious
Conditions
Keywords
CSSI, Abscess, Wound, Cellulitis, Complicated Skin and Skin Structure Infections (cSSSI)
Brief summary
A Phase III 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-0804 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 tablet 150 mg
DRUGlinezolid
For gram positive treatment: Linezolid 600 mg tablets and pre-mixed 600 mg IV infusion solution; For gram negative treatment: Moxifloxacin 400 mg tablets and pre-mixed 400mg IV infusion solution
DRUGmoxifloxacin
moxifloxacin 400 mg tablet; moxifloxacin 400 mg IV infusion solution
Sponsors
Novartis Pharmaceuticals
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
* Patients, ages 18 years or older * Is expected to require ≥4 days of IV antibiotic therapy * Has an acute complicated skin and skin structure infection with findings of systemic inflammatory response * 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
* Has received an investigational drug within past 1 month * Has been previously enrolled in this protocol * Has received \>24 hr of a potentially effective systemic antibiotic immediately prior to study drug * Is nursing
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Wound Infections Classified as a Sponsor-defined Clinical Success in the Clinically Evaluable (CE) Population at End of Treatment | up to 14 days | Sponsor-defined clinical success is defined as at least 72 hours of study drug and antibiotics not needed/infection sufficiently resolved. If a participant received antibiotics for a different infection after the primary qualifying infection was considered cured/largely resolved as per the investigator on the CRF check box, the participant was also considered as a sponsor-defined clinical success. Sponsor-defined clinical failures must have at least 48 hours of study drug in order to be considered a failure. The sponsor classified participants as clinical failures based on the following: 1) minimum duration of treatment required for outcomes evaluation, 2) use of pre-study antibiotics, 3) use of potentially confounding systemic antibiotics during the study, and 4) timing of concomitant curative surgical procedures. |
| Number of Participants Classified as a Sponsor-defined Clinical Success in the Intent-to-Treat (ITT) Population at End of Treatment | up to 14 days | Sponsor-defined clinical success is defined as at least 72 hours of study drug and antibiotics not needed/infection sufficiently resolved. If a participant received antibiotics for a different infection after the primary qualifying infection was considered cured/largely resolved as per the investigator on the Case Report Form (CRF) check box, the participant was also considered as a sponsor-defined clinical success. Sponsor-defined clinical failures must have at least 48 hours of study drug in order to be considered a failure. The sponsor classified participants as clinical failures based on the following: 1) minimum duration of treatment required for outcomes evaluation, 2) use of pre-study antibiotics, 3) use of potentially confounding systemic antibiotics during the study, and 4) timing of concomitant curative surgical procedures. |
| Number of Participants Classified as a Sponsor-defined Clinical Success in the ITT Population at Test of Cure | 10 to 17 days after last dose of treatment (total treatment of up to 14 days) | Sponsor-defined clinical success is defined as at least 72 hours of study drug and antibiotics not needed/infection sufficiently resolved. If a participant received antibiotics for a different infection after the primary qualifying infection was considered cured/largely resolved as per the investigator on the CRF check box, the participant was also considered as a sponsor-defined clinical success. Sponsor-defined clinical failures must have at least 48 hours of study drug in order to be considered a failure. The sponsor classified participants as clinical failures based on the following: 1) minimum duration of treatment required for outcomes evaluation, 2) use of pre-study antibiotics, 3) use of potentially confounding systemic antibiotics during the study, and 4) timing of concomitant curative surgical procedures. |
| Number of Participants With Cellulitis Classified as a Sponsor-defined Clinical Success in the CE Population at Test of Cure | 10 to 17 days after last dose of treatment (total treatment of up to 14 days) | Sponsor-defined clinical success is defined as at least 72 hours of study drug and antibiotics not needed/infection sufficiently resolved. If a participant received antibiotics for a different infection after the primary qualifying infection was considered cured/largely resolved as per the investigator on the CRF check box, the participant was also considered as a sponsor-defined clinical success. Sponsor-defined clinical failures must have at least 48 hours of study drug in order to be considered a failure. The sponsor classified participants as clinical failures based on the following: 1) minimum duration of treatment required for outcomes evaluation, 2) use of pre-study antibiotics, 3) use of potentially confounding systemic antibiotics during the study, and 4) timing of concomitant curative surgical procedures. |
| Number of Participants With Cellulitis Classified as a Sponsor-defined Clinical Success in the CE Population at End of Treatment | up to 14 days | Sponsor-defined clinical success is defined as at least 72 hours of study drug and antibiotics not needed/infection sufficiently resolved. If a participant received antibiotics for a different infection after the primary qualifying infection was considered cured/largely resolved as per the investigator on the CRF check box, the participant was also considered as a sponsor-defined clinical success. Sponsor-defined clinical failures must have at least 48 hours of study drug in order to be considered a failure. The sponsor classified participants as clinical failures based on the following: 1) minimum duration of treatment required for outcomes evaluation, 2) use of pre-study antibiotics, 3) use of potentially confounding systemic antibiotics during the study, and 4) timing of concomitant curative surgical procedures. |
| Number of Participants With Wound Infections Classified as a Sponsor-defined Clinical Success in the CE Population at Test of Cure | 10 to 17 days after last dose of treatment (total treatment of up to 14 days) | Sponsor-defined clinical success is defined as at least 72 hours of study drug and antibiotics not needed/infection sufficiently resolved. If a participant received antibiotics for a different infection after the primary qualifying infection was considered cured/largely resolved as per the investigator on the CRF check box, the participant was also considered as a sponsor-defined clinical success. Sponsor-defined clinical failures must have at least 48 hours of study drug in order to be considered a failure. The sponsor classified participants as clinical failures based on the following: 1) minimum duration of treatment required for outcomes evaluation, 2) use of pre-study antibiotics, 3) use of potentially confounding systemic antibiotics during the study, and 4) timing of concomitant curative surgical procedures. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With the Indicated Type of Adverse Event (AE) | from the time of informed consent to Test of Cure (10 to 17 days after end of treatment [total treatment of up to 14 days) | The assessment of safety was based mainly on the frequency of AEs, and summaries of vital signs and laboratory values (values classified as AE are captured in the AE module). An AE is defined as the appearance or worsening of any undesirable sign, symptom, or medical condition occurring after starting the study drug, whether or not the event was considered causally related to the medical product. An AE could have been a new occurrence or an existing process that increased in intensity or frequency. AEs were deemed treatment-emergent if the start date was on or after the date of the first dose but was not present before that date or if the AE started before the date of the first dose and increased in severity on or after that date. |
Countries
United States
Participant flow
Recruitment details
The study was designed to enroll adult participants with Complicated Skin and Skin Structure Infection (CSSI). Participants were stratified at study entry by type of infection (i.e., wound infection, cellulitis, major abscess).
Pre-assignment details
Participants who met inclusion criteria and did not meet exclusion criteria were randomly assigned to a treatment group.
Participants by arm
| Arm | Count |
|---|---|
| Omadacycline Participants received intravenous (IV) omadacycline 100 milligrams (mg) every 24 hours (q24h) for up to 4 to 7 days, then received a 300 mg oral administration q24h. The total treatment duration was up to 14 days. To maintain the blind, participants received an omadacycline infusion alternating with a placebo infusion q12h. | 68 |
| Linezolid Participants received IV linezolid 600 mg every 12 hours (q12h) for up to 4 to 7 days, then received a 600 mg oral administration q12h. The total treatment duration was up to 14 days. Participants received moxifloxacin 400 mg q24, IV or oral administration, as appropriate to accompany linezolid for suspected or confirmed gram-negative infections. | 72 |
| Total | 140 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Adverse Event/Lost to Follow-up | 1 | 0 |
| Overall Study | End of Treatment/Lost to Follow-up | 0 | 1 |
| Overall Study | Exclusion Condition | 1 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 1 |
Baseline characteristics
| Characteristic | Total | Omadacycline | Linezolid |
|---|---|---|---|
| Age, Customized >=18 to <=44 years | 89 Participants | 38 Participants | 51 Participants |
| Age, Customized >44 to <=64 | 46 Participants | 26 Participants | 20 Participants |
| Age, Customized >64 | 5 Participants | 4 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Black | 14 Participants | 7 Participants | 7 Participants |
| Race/Ethnicity, Customized Caucasian | 117 Participants | 56 Participants | 61 Participants |
| Race/Ethnicity, Customized Other; Not Specified | 6 Participants | 2 Participants | 4 Participants |
| Race/Ethnicity, Customized Pacific Islander | 2 Participants | 2 Participants | 0 Participants |
| Sex: Female, Male Female | 47 Participants | 26 Participants | 21 Participants |
| Sex: Female, Male Male | 93 Participants | 42 Participants | 51 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 68 | 0 / 72 |
| other Total, other adverse events | 52 / 68 | 55 / 72 |
| serious Total, serious adverse events | 3 / 68 | 1 / 72 |
Outcome results
Primary
Number of Participants Classified as a Sponsor-defined Clinical Success in the Intent-to-Treat (ITT) Population at End of Treatment
Sponsor-defined clinical success is defined as at least 72 hours of study drug and antibiotics not needed/infection sufficiently resolved. If a participant received antibiotics for a different infection after the primary qualifying infection was considered cured/largely resolved as per the investigator on the Case Report Form (CRF) check box, the participant was also considered as a sponsor-defined clinical success. Sponsor-defined clinical failures must have at least 48 hours of study drug in order to be considered a failure. The sponsor classified participants as clinical failures based on the following: 1) minimum duration of treatment required for outcomes evaluation, 2) use of pre-study antibiotics, 3) use of potentially confounding systemic antibiotics during the study, and 4) timing of concomitant curative surgical procedures.
Time frame: up to 14 days
Population: Intent-to-Treat (ITT) Population: all enrolled participants who received at least one dose of study medication. Participants were analyzed for efficacy according to randomization, regardless of treatment administered.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Omadacycline | Number of Participants Classified as a Sponsor-defined Clinical Success in the Intent-to-Treat (ITT) Population at End of Treatment | Clinical failure | 1 Participants |
| Omadacycline | Number of Participants Classified as a Sponsor-defined Clinical Success in the Intent-to-Treat (ITT) Population at End of Treatment | Clinical non-evaluable | 6 Participants |
| Omadacycline | Number of Participants Classified as a Sponsor-defined Clinical Success in the Intent-to-Treat (ITT) Population at End of Treatment | Clinical success | 61 Participants |
| Linezolid | Number of Participants Classified as a Sponsor-defined Clinical Success in the Intent-to-Treat (ITT) Population at End of Treatment | Clinical non-evaluable | 3 Participants |
| Linezolid | Number of Participants Classified as a Sponsor-defined Clinical Success in the Intent-to-Treat (ITT) Population at End of Treatment | Clinical success | 66 Participants |
| Linezolid | Number of Participants Classified as a Sponsor-defined Clinical Success in the Intent-to-Treat (ITT) Population at End of Treatment | Clinical failure | 3 Participants |
95% CI: [-12.4, 8.5]
Primary
Number of Participants Classified as a Sponsor-defined Clinical Success in the ITT Population at Test of Cure
Sponsor-defined clinical success is defined as at least 72 hours of study drug and antibiotics not needed/infection sufficiently resolved. If a participant received antibiotics for a different infection after the primary qualifying infection was considered cured/largely resolved as per the investigator on the CRF check box, the participant was also considered as a sponsor-defined clinical success. Sponsor-defined clinical failures must have at least 48 hours of study drug in order to be considered a failure. The sponsor classified participants as clinical failures based on the following: 1) minimum duration of treatment required for outcomes evaluation, 2) use of pre-study antibiotics, 3) use of potentially confounding systemic antibiotics during the study, and 4) timing of concomitant curative surgical procedures.
Time frame: 10 to 17 days after last dose of treatment (total treatment of up to 14 days)
Population: ITT Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Omadacycline | Number of Participants Classified as a Sponsor-defined Clinical Success in the ITT Population at Test of Cure | Clinical success | 58 Participants |
| Omadacycline | Number of Participants Classified as a Sponsor-defined Clinical Success in the ITT Population at Test of Cure | Clinical failure | 2 Participants |
| Omadacycline | Number of Participants Classified as a Sponsor-defined Clinical Success in the ITT Population at Test of Cure | Clinical non-evaluable | 8 Participants |
| Linezolid | Number of Participants Classified as a Sponsor-defined Clinical Success in the ITT Population at Test of Cure | Clinical success | 64 Participants |
| Linezolid | Number of Participants Classified as a Sponsor-defined Clinical Success in the ITT Population at Test of Cure | Clinical failure | 3 Participants |
| Linezolid | Number of Participants Classified as a Sponsor-defined Clinical Success in the ITT Population at Test of Cure | Clinical non-evaluable | 5 Participants |
95% CI: [-15.5, 8.3]
Primary
Number of Participants With Cellulitis Classified as a Sponsor-defined Clinical Success in the CE Population at End of Treatment
Sponsor-defined clinical success is defined as at least 72 hours of study drug and antibiotics not needed/infection sufficiently resolved. If a participant received antibiotics for a different infection after the primary qualifying infection was considered cured/largely resolved as per the investigator on the CRF check box, the participant was also considered as a sponsor-defined clinical success. Sponsor-defined clinical failures must have at least 48 hours of study drug in order to be considered a failure. The sponsor classified participants as clinical failures based on the following: 1) minimum duration of treatment required for outcomes evaluation, 2) use of pre-study antibiotics, 3) use of potentially confounding systemic antibiotics during the study, and 4) timing of concomitant curative surgical procedures.
Time frame: up to 14 days
Population: CE Population: all participants in the ITT Population who met specific criteria such that the clinical outcome of their infection could be inferred to reflect the effect of the study drug. Only those participants stratified with cellulitis at study entry were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Omadacycline | Number of Participants With Cellulitis Classified as a Sponsor-defined Clinical Success in the CE Population at End of Treatment | Clinical success | 38 Participants |
| Omadacycline | Number of Participants With Cellulitis Classified as a Sponsor-defined Clinical Success in the CE Population at End of Treatment | Clinical failure | 1 Participants |
| Linezolid | Number of Participants With Cellulitis Classified as a Sponsor-defined Clinical Success in the CE Population at End of Treatment | Clinical success | 44 Participants |
| Linezolid | Number of Participants With Cellulitis Classified as a Sponsor-defined Clinical Success in the CE Population at End of Treatment | Clinical failure | 1 Participants |
95% CI: [-8.3, 7.6]
Primary
Number of Participants With Cellulitis Classified as a Sponsor-defined Clinical Success in the CE Population at Test of Cure
Sponsor-defined clinical success is defined as at least 72 hours of study drug and antibiotics not needed/infection sufficiently resolved. If a participant received antibiotics for a different infection after the primary qualifying infection was considered cured/largely resolved as per the investigator on the CRF check box, the participant was also considered as a sponsor-defined clinical success. Sponsor-defined clinical failures must have at least 48 hours of study drug in order to be considered a failure. The sponsor classified participants as clinical failures based on the following: 1) minimum duration of treatment required for outcomes evaluation, 2) use of pre-study antibiotics, 3) use of potentially confounding systemic antibiotics during the study, and 4) timing of concomitant curative surgical procedures.
Time frame: 10 to 17 days after last dose of treatment (total treatment of up to 14 days)
Population: CE Population: all participants in the ITT Population who met specific criteria such that the clinical outcome of their infection could be inferred to reflect the effect of the study drug. Only those participants stratified with cellulitis at study entry were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Omadacycline | Number of Participants With Cellulitis Classified as a Sponsor-defined Clinical Success in the CE Population at Test of Cure | Clinical failure | 1 Participants |
| Omadacycline | Number of Participants With Cellulitis Classified as a Sponsor-defined Clinical Success in the CE Population at Test of Cure | Clinical success | 38 Participants |
| Linezolid | Number of Participants With Cellulitis Classified as a Sponsor-defined Clinical Success in the CE Population at Test of Cure | Clinical failure | 1 Participants |
| Linezolid | Number of Participants With Cellulitis Classified as a Sponsor-defined Clinical Success in the CE Population at Test of Cure | Clinical success | 44 Participants |
95% CI: [-8.3, 7.6]
Primary
Number of Participants With Wound Infections Classified as a Sponsor-defined Clinical Success in the CE Population at Test of Cure
Sponsor-defined clinical success is defined as at least 72 hours of study drug and antibiotics not needed/infection sufficiently resolved. If a participant received antibiotics for a different infection after the primary qualifying infection was considered cured/largely resolved as per the investigator on the CRF check box, the participant was also considered as a sponsor-defined clinical success. Sponsor-defined clinical failures must have at least 48 hours of study drug in order to be considered a failure. The sponsor classified participants as clinical failures based on the following: 1) minimum duration of treatment required for outcomes evaluation, 2) use of pre-study antibiotics, 3) use of potentially confounding systemic antibiotics during the study, and 4) timing of concomitant curative surgical procedures.
Time frame: 10 to 17 days after last dose of treatment (total treatment of up to 14 days)
Population: CE Population: all participants in the ITT Population who met specific criteria such that the clinical outcome of their infection could be inferred to reflect the effect of the study drug. Only those participants stratified with wound infection at study entry were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Omadacycline | Number of Participants With Wound Infections Classified as a Sponsor-defined Clinical Success in the CE Population at Test of Cure | Clinical success | 13 Participants |
| Omadacycline | Number of Participants With Wound Infections Classified as a Sponsor-defined Clinical Success in the CE Population at Test of Cure | Clinical failure | 0 Participants |
| Linezolid | Number of Participants With Wound Infections Classified as a Sponsor-defined Clinical Success in the CE Population at Test of Cure | Clinical success | 12 Participants |
| Linezolid | Number of Participants With Wound Infections Classified as a Sponsor-defined Clinical Success in the CE Population at Test of Cure | Clinical failure | 1 Participants |
95% CI: [-11.2, 26.6]
Primary
Number of Participants With Wound Infections Classified as a Sponsor-defined Clinical Success in the Clinically Evaluable (CE) Population at End of Treatment
Sponsor-defined clinical success is defined as at least 72 hours of study drug and antibiotics not needed/infection sufficiently resolved. If a participant received antibiotics for a different infection after the primary qualifying infection was considered cured/largely resolved as per the investigator on the CRF check box, the participant was also considered as a sponsor-defined clinical success. Sponsor-defined clinical failures must have at least 48 hours of study drug in order to be considered a failure. The sponsor classified participants as clinical failures based on the following: 1) minimum duration of treatment required for outcomes evaluation, 2) use of pre-study antibiotics, 3) use of potentially confounding systemic antibiotics during the study, and 4) timing of concomitant curative surgical procedures.
Time frame: up to 14 days
Population: CE Population: all participants in the ITT Population who met specific criteria such that the clinical outcome of their infection could be inferred to reflect the effect of the study drug. Only those participants stratified with wound infection at study entry were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Omadacycline | Number of Participants With Wound Infections Classified as a Sponsor-defined Clinical Success in the Clinically Evaluable (CE) Population at End of Treatment | Clinical success | 13 Participants |
| Omadacycline | Number of Participants With Wound Infections Classified as a Sponsor-defined Clinical Success in the Clinically Evaluable (CE) Population at End of Treatment | Cinical failure | 0 Participants |
| Linezolid | Number of Participants With Wound Infections Classified as a Sponsor-defined Clinical Success in the Clinically Evaluable (CE) Population at End of Treatment | Cinical failure | 1 Participants |
| Linezolid | Number of Participants With Wound Infections Classified as a Sponsor-defined Clinical Success in the Clinically Evaluable (CE) Population at End of Treatment | Clinical success | 12 Participants |
95% CI: [-11.2, 26.6]
Secondary
Number of Participants With the Indicated Type of Adverse Event (AE)
The assessment of safety was based mainly on the frequency of AEs, and summaries of vital signs and laboratory values (values classified as AE are captured in the AE module). An AE is defined as the appearance or worsening of any undesirable sign, symptom, or medical condition occurring after starting the study drug, whether or not the event was considered causally related to the medical product. An AE could have been a new occurrence or an existing process that increased in intensity or frequency. AEs were deemed treatment-emergent if the start date was on or after the date of the first dose but was not present before that date or if the AE started before the date of the first dose and increased in severity on or after that date.
Time frame: from the time of informed consent to Test of Cure (10 to 17 days after end of treatment [total treatment of up to 14 days)
Population: Safety Population: all enrolled participants who received at least one dose of study medication
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Omadacycline | Number of Participants With the Indicated Type of Adverse Event (AE) | Treatment-emergent adverse event (TEAE) | 56 Participants |
| Omadacycline | Number of Participants With the Indicated Type of Adverse Event (AE) | Study drug-related TEAE | 41 Participants |
| Omadacycline | Number of Participants With the Indicated Type of Adverse Event (AE) | AEs leading to study drug discontinuation | 2 Participants |
| Linezolid | Number of Participants With the Indicated Type of Adverse Event (AE) | AEs leading to study drug discontinuation | 0 Participants |
| Linezolid | Number of Participants With the Indicated Type of Adverse Event (AE) | Treatment-emergent adverse event (TEAE) | 58 Participants |
| Linezolid | Number of Participants With the Indicated Type of Adverse Event (AE) | Study drug-related TEAE | 41 Participants |