CSSI: Study the Safety and Efficacy of PTK 0796 in Patients With Complicated Skin and Skin Structure Infection (CSSSI)
Study Details
Study Description
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: PTK 0796 PTK 0796 100 mg for injection; PTK 0796 tablet, 300 mg (2 x 150 mg tablets) |
Drug: PTK 0796
PTK 0796 100 mg for injection; PTK 0796 tablet 150 mg
Other Names:
|
| Active Comparator: Linezolid Gram positive treatment: Linezolid 600 mg tablets and pre-mixed 600 mg IV infusion solution; Gram negative treatment: moxifloxacin 400 mg tablet and moxifloxacin 400 mg IV infusion solution |
Drug: linezolid
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
Other Names:
Drug: moxifloxacin
moxifloxacin 400 mg tablet; moxifloxacin 400 mg IV infusion solution
|
Outcome Measures
Primary Outcome Measures
- 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 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 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.
- 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.
Secondary Outcome Measures
- 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.
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Paratek Recruiting Site | Fountain Valley | California | United States | 92708 |
| 2 | Parateck Recruiting Site | La Mesa | California | United States | 91942 |
| 3 | Paratek Recruiting Site | Oceanside | California | United States | 92056 |
| 4 | Paratek Recruiting Site | San Diego | California | United States | 92114 |
| 5 | Paratek Recruiting Site | San Jose | California | United States | 95154 |
| 6 | Parateck Recruiting Site | Columbus | Georgia | United States | 31904 |
| 7 | Paratek Recruiting Site | Savannah | Georgia | United States | 31406 |
Sponsors and Collaborators
- Paratek Pharmaceuticals Inc
- Novartis Pharmaceuticals
Investigators
- Study Director: Mary West, Paratek Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- PTK 0796 CSSI-0804
Study Results
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 Detail | Participants who met inclusion criteria and did not meet exclusion criteria were randomly assigned to a treatment group. |
| Arm/Group Title | Omadacycline | Linezolid |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Period Title: Overall Study | ||
| STARTED | 70 | 73 |
| COMPLETED | 64 | 70 |
| NOT COMPLETED | 6 | 3 |
Baseline Characteristics
| Arm/Group Title | Omadacycline | Linezolid | Total |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | Total of all reporting groups |
| Overall Participants | 68 | 72 | 140 |
| Age, Customized (Count of Participants) | |||
| >=18 to <=44 years |
38
55.9%
|
51
70.8%
|
89
63.6%
|
| >44 to <=64 |
26
38.2%
|
20
27.8%
|
46
32.9%
|
| >64 |
4
5.9%
|
1
1.4%
|
5
3.6%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
26
38.2%
|
21
29.2%
|
47
33.6%
|
| Male |
42
61.8%
|
51
70.8%
|
93
66.4%
|
| Race/Ethnicity, Customized (Count of Participants) | |||
| Caucasian |
56
82.4%
|
61
84.7%
|
117
83.6%
|
| Black |
7
10.3%
|
7
9.7%
|
14
10%
|
| Asian |
1
1.5%
|
0
0%
|
1
0.7%
|
| Pacific Islander |
2
2.9%
|
0
0%
|
2
1.4%
|
| Other; Not Specified |
2
2.9%
|
4
5.6%
|
6
4.3%
|
Outcome Measures
| Title | Number of Participants Classified as a Sponsor-defined Clinical Success in the Intent-to-Treat (ITT) Population at End of Treatment |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Omadacycline | Linezolid |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 68 | 72 |
| Clinical success |
61
89.7%
|
66
91.7%
|
| Clinical failure |
1
1.5%
|
3
4.2%
|
| Clinical non-evaluable |
6
8.8%
|
3
4.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Omadacycline, Linezolid |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority | |
| Comments | A non-inferiority margin of 10% was used for the analysis. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | treatment difference |
| Estimated Value | -2.0 | |
| Confidence Interval |
(2-Sided) 95% -12.4 to 8.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The 95% confidence interval (CI) was based on a normal approximation to the binomial distribution with continuity correction. Treatment difference for a response of clinical success was calculated as omadacycline minus linezolid. | |
| Title | Number of Participants Classified as a Sponsor-defined Clinical Success in the ITT Population at Test of Cure |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population |
| Arm/Group Title | Omadacycline | Linezolid |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 68 | 72 |
| Clinical success |
58
85.3%
|
64
88.9%
|
| Clinical failure |
2
2.9%
|
3
4.2%
|
| Clinical non-evaluable |
8
11.8%
|
5
6.9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Omadacycline, Linezolid |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority | |
| Comments | A non-inferiority margin of 10% was used for the analysis. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | treatment difference |
| Estimated Value | -3.6 | |
| Confidence Interval |
(2-Sided) 95% -15.5 to 8.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The 95% CI was based on a normal approximation to the binomial distribution with continuity correction. Treatment difference for a response of clinical success was calculated as omadacycline minus linezolid. | |
| Title | Number of Participants With Wound Infections Classified as a Sponsor-defined Clinical Success in the Clinically Evaluable (CE) Population at End of Treatment |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Omadacycline | Linezolid |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 13 | 13 |
| Clinical success |
13
19.1%
|
12
16.7%
|
| Cinical failure |
0
0%
|
1
1.4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Omadacycline, Linezolid |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority | |
| Comments | A non-inferiority margin of 10% was used for the analysis. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | treatment difference |
| Estimated Value | 7.7 | |
| Confidence Interval |
(2-Sided) 95% -11.2 to 26.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The 95% CI was based on a normal approximation to the binomial distribution with continuity correction. Treatment difference for a response of clinical success was calculated as omadacycline minus linezolid. | |
| Title | Number of Participants With Cellulitis Classified as a Sponsor-defined Clinical Success in the CE Population at End of Treatment |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Omadacycline | Linezolid |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 39 | 45 |
| Clinical success |
38
55.9%
|
44
61.1%
|
| Clinical failure |
1
1.5%
|
1
1.4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Omadacycline, Linezolid |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority | |
| Comments | A non-inferiority margin of 10% was used for the analysis. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | treatment difference |
| Estimated Value | -0.3 | |
| Confidence Interval |
(2-Sided) 95% -8.3 to 7.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The 95% CI was based on a normal approximation to the binomial distribution with continuity correction. Treatment difference for a response of clinical success was calculated as omadacycline minus linezolid. | |
| Title | Number of Participants With Wound Infections Classified as a Sponsor-defined Clinical Success in the CE Population at Test of Cure |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Omadacycline | Linezolid |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 13 | 13 |
| Clinical success |
13
19.1%
|
12
16.7%
|
| Clinical failure |
0
0%
|
1
1.4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Omadacycline, Linezolid |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority | |
| Comments | A non-inferiority margin of 10% was used for the analysis. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | treatment difference |
| Estimated Value | 7.7 | |
| Confidence Interval |
(2-Sided) 95% -11.2 to 26.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The 95% CI was based on a normal approximation to the binomial distribution with continuity correction. Treatment difference for a response of clinical success was calculated as omadacycline minus linezolid. | |
| Title | Number of Participants With Cellulitis Classified as a Sponsor-defined Clinical Success in the CE Population at Test of Cure |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Omadacycline | Linezolid |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 39 | 45 |
| Clinical success |
38
55.9%
|
44
61.1%
|
| Clinical failure |
1
1.5%
|
1
1.4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Omadacycline, Linezolid |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority | |
| Comments | A non-inferiority margin of 10% was used for the analysis. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | treatment difference |
| Estimated Value | -0.3 | |
| Confidence Interval |
(2-Sided) 95% -8.3 to 7.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The 95% CI was based on a normal approximation to the binomial distribution with continuity correction. Treatment difference for a response of clinical success was calculated as omadacycline minus linezolid. | |
| Title | Number of Participants With the Indicated Type of Adverse Event (AE) |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population: all enrolled participants who received at least one dose of study medication |
| Arm/Group Title | Omadacycline | Linezolid |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 68 | 72 |
| Treatment-emergent adverse event (TEAE) |
56
82.4%
|
58
80.6%
|
| Study drug-related TEAE |
41
60.3%
|
41
56.9%
|
| AEs leading to study drug discontinuation |
2
2.9%
|
0
0%
|
Adverse Events
| 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]) | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Adverse events are reported for members of the Safety Population, comprised of all enrolled participants who received at least one dose of study medication | |||
| Arm/Group Title | Omadacycline | Linezolid | ||
| Arm/Group Description | 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. | 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. | ||
All Cause Mortality |
||||
| Omadacycline | Linezolid | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/68 (1.5%) | 0/72 (0%) | ||
Serious Adverse Events |
||||
| Omadacycline | Linezolid | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/68 (4.4%) | 1/72 (1.4%) | ||
| Gastrointestinal disorders | ||||
| Small intestinal obstruction | 1/68 (1.5%) | 0/72 (0%) | ||
| Infections and infestations | ||||
| Gastroenteritis | 1/68 (1.5%) | 0/72 (0%) | ||
| Cellulitis | 0/68 (0%) | 1/72 (1.4%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Lung cancer metastatic | 1/68 (1.5%) | 0/72 (0%) | ||
| Psychiatric disorders | ||||
| Depression | 1/68 (1.5%) | 0/72 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Omadacycline | Linezolid | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 52/68 (76.5%) | 55/72 (76.4%) | ||
| Cardiac disorders | ||||
| Palpitations | 2/68 (2.9%) | 0/72 (0%) | ||
| Tachycardia | 2/68 (2.9%) | 4/72 (5.6%) | ||
| Gastrointestinal disorders | ||||
| Nausea | 18/68 (26.5%) | 19/72 (26.4%) | ||
| Constipation | 6/68 (8.8%) | 2/72 (2.8%) | ||
| Vomiting | 6/68 (8.8%) | 11/72 (15.3%) | ||
| Diarrhoea | 3/68 (4.4%) | 13/72 (18.1%) | ||
| Dry mouth | 3/68 (4.4%) | 1/72 (1.4%) | ||
| Toothache | 2/68 (2.9%) | 0/72 (0%) | ||
| Dyspepsia | 1/68 (1.5%) | 3/72 (4.2%) | ||
| General disorders | ||||
| Infusion site pain | 5/68 (7.4%) | 2/72 (2.8%) | ||
| Fatigue | 3/68 (4.4%) | 3/72 (4.2%) | ||
| Infusion site erythema | 2/68 (2.9%) | 1/72 (1.4%) | ||
| Oedema peripheral | 3/68 (4.4%) | 1/72 (1.4%) | ||
| Pain | 2/68 (2.9%) | 1/72 (1.4%) | ||
| Infections and infestations | ||||
| Cellulitis | 2/68 (2.9%) | 1/72 (1.4%) | ||
| Infection | 2/68 (2.9%) | 1/72 (1.4%) | ||
| Abscess | 1/68 (1.5%) | 2/72 (2.8%) | ||
| Oral candidiasis | 0/68 (0%) | 2/72 (2.8%) | ||
| Investigations | ||||
| Blood creatine phosphokinase increased | 6/68 (8.8%) | 2/72 (2.8%) | ||
| Alanine aminotransferase increased | 1/68 (1.5%) | 4/72 (5.6%) | ||
| Aspartate aminotransferase increased | 1/68 (1.5%) | 2/72 (2.8%) | ||
| Metabolism and nutrition disorders | ||||
| Increased appetite | 2/68 (2.9%) | 0/72 (0%) | ||
| Decreased appetite | 1/68 (1.5%) | 4/72 (5.6%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 2/68 (2.9%) | 2/72 (2.8%) | ||
| Back pain | 2/68 (2.9%) | 0/72 (0%) | ||
| Pain in extremity | 2/68 (2.9%) | 1/72 (1.4%) | ||
| Nervous system disorders | ||||
| Headache | 16/68 (23.5%) | 5/72 (6.9%) | ||
| Dizziness | 7/68 (10.3%) | 6/72 (8.3%) | ||
| Dysgeusia | 1/68 (1.5%) | 4/72 (5.6%) | ||
| Tremor | 0/68 (0%) | 2/72 (2.8%) | ||
| Psychiatric disorders | ||||
| Insomnia | 2/68 (2.9%) | 5/72 (6.9%) | ||
| Renal and urinary disorders | ||||
| Dysuria | 2/68 (2.9%) | 1/72 (1.4%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 2/68 (2.9%) | 0/72 (0%) | ||
| Oropharyngeal pain | 1/68 (1.5%) | 3/72 (4.2%) | ||
| Rhinorrhoea | 0/68 (0%) | 2/72 (2.8%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Pruritus | 2/68 (2.9%) | 1/72 (1.4%) | ||
| Night sweats | 2/68 (2.9%) | 0/72 (0%) | ||
| Hyperhidrosis | 1/68 (1.5%) | 2/72 (2.8%) | ||
| Rash | 1/68 (1.5%) | 6/72 (8.3%) | ||
| Dermatitis contact | 0/68 (0%) | 2/72 (2.8%) | ||
| Pruritus generalised | 2/68 (2.9%) | 1/72 (1.4%) | ||
| Vascular disorders | ||||
| Flushing | 2/68 (2.9%) | 0/72 (0%) | ||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Paratek Medical Information |
|---|---|
| Organization | Paratek Pharmaceuticals, Inc. |
| Phone | 1-833-727-2835 |
| medinfo@paratekpharma.com |
- PTK 0796 CSSI-0804