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TerminatedNCT00865280CSSIUpdated Mar 12, 2021Results posted

Study the Safety and Efficacy of PTK 0796 in Patients With Complicated Skin and Skin Structure Infection (CSSSI)

A Phase 3 interventional study of PTK 0796 and linezolid in Skin Diseases, Infectious, sponsored by Paratek Pharmaceuticals Inc. Terminated at 7 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-03-12.

Sponsored by Paratek Pharmaceuticals Inc · Phase 3, Interventional, and Treatment

Why this study was terminated
Terminated
Phase
Phase 3
Study type
Interventional
Enrollment
143
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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).

Read the 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.

02

Conditions studied

  • Skin Diseases, Infectious

Keywords

  • CSSI
  • Abscess
  • Wound
  • Cellulitis
  • Complicated Skin and Skin Structure Infections (cSSSI)
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts 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

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
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
143 participants (actual)

Study arms

  • Experimental
    PTK 0796

    PTK 0796 100 mg for injection; PTK 0796 tablet, 300 mg (2 x 150 mg tablets)

    Drug: PTK 0796

  • 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 · Drug: moxifloxacin

Interventions

  • DrugPTK 0796

    PTK 0796 100 mg for injection; PTK 0796 tablet 150 mg

    Also known as: omadacycline

  • 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

    Also known as: Zyvox™; Avelox™

  • Drugmoxifloxacin

    moxifloxacin 400 mg tablet; moxifloxacin 400 mg IV infusion solution

05

What researchers measure

Primary outcomes

  1. 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

  2. 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)

  3. 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

  4. 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

  5. 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)

  6. 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)

Secondary outcomes

  1. 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)

06

Results

Posted Mar 12, 2021
Limitations and caveats
Changes in Food and Drug Administration (FDA) criteria for the identification and enrollment of participants with complicated skin and skin structure infections as well as the primary endpoint led to administrative termination of the study.

Participant flow

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).

Participant flow — Overall Study
MilestoneOmadacyclineLinezolid
Started7073
Completed6470
Not completed63
Withdrew: Withdrawal by subject41
Withdrew: End of treatment/lost to follow-up01
Withdrew: Adverse event/lost to follow-up10
Withdrew: Exclusion condition10
Withdrew: Adverse event01

Outcome measures

PrimaryNumber 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
Reported as:
Count of participants · Participants
Number of Participants Classified as a Sponsor-defined Clinical Success in the Intent-to-Treat (ITT) Population at End of Treatment
ParticipantsOmadacyclineLinezolid
Clinical success6166
Clinical failure13
Clinical non-evaluable63
Statistical analysis
  • Omadacycline vs Linezolid · Treatment difference: -2.0 · 95% CI -12.4 to 8.5The 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.
PrimaryNumber 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)
Reported as:
Count of participants · Participants
Number of Participants Classified as a Sponsor-defined Clinical Success in the ITT Population at Test of Cure
ParticipantsOmadacyclineLinezolid
Clinical success5864
Clinical failure23
Clinical non-evaluable85
Statistical analysis
  • Omadacycline vs Linezolid · Treatment difference: -3.6 · 95% CI -15.5 to 8.3The 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.
PrimaryNumber 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
Reported as:
Count of participants · Participants
Number of Participants With Wound Infections Classified as a Sponsor-defined Clinical Success in the Clinically Evaluable (CE) Population at End of Treatment
ParticipantsOmadacyclineLinezolid
Clinical success1312
Cinical failure01
Statistical analysis
  • Omadacycline vs Linezolid · Treatment difference: 7.7 · 95% CI -11.2 to 26.6The 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.
PrimaryNumber 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
Reported as:
Count of participants · Participants
Number of Participants With Cellulitis Classified as a Sponsor-defined Clinical Success in the CE Population at End of Treatment
ParticipantsOmadacyclineLinezolid
Clinical success3844
Clinical failure11
Statistical analysis
  • Omadacycline vs Linezolid · Treatment difference: -0.3 · 95% CI -8.3 to 7.6The 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.
PrimaryNumber 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)
Reported as:
Count of participants · Participants
Number of Participants With Wound Infections Classified as a Sponsor-defined Clinical Success in the CE Population at Test of Cure
ParticipantsOmadacyclineLinezolid
Clinical success1312
Clinical failure01
Statistical analysis
  • Omadacycline vs Linezolid · Treatment difference: 7.7 · 95% CI -11.2 to 26.6The 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.
PrimaryNumber 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)
Reported as:
Count of participants · Participants
Number of Participants With Cellulitis Classified as a Sponsor-defined Clinical Success in the CE Population at Test of Cure
ParticipantsOmadacyclineLinezolid
Clinical success3844
Clinical failure11
Statistical analysis
  • Omadacycline vs Linezolid · Treatment difference: -0.3 · 95% CI -8.3 to 7.6The 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.
SecondaryNumber 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)
Reported as:
Count of participants · Participants
Number of Participants With the Indicated Type of Adverse Event (AE)
ParticipantsOmadacyclineLinezolid
Treatment-emergent adverse event (TEAE)5658
Study drug-related TEAE4141
AEs leading to study drug discontinuation20

Adverse events

Collected over 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]). Non-serious events are listed at a 2% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Omadacycline1/68 (1.5%)3/68 (4.4%)52/68 (76.5%)
Linezolid0/72 (0%)1/72 (1.4%)55/72 (76.4%)
Most frequent serious events
Most frequent serious events
EventOmadacyclineLinezolid
Small intestinal obstructionGastrointestinal disorders1/680/72
GastroenteritisInfections and infestations1/680/72
Lung cancer metastaticNeoplasms benign, malignant and unspecified (incl cysts and polyps)1/680/72
DepressionPsychiatric disorders1/680/72
CellulitisInfections and infestations0/681/72
Most frequent other events
Showing 10 of 42
Most frequent other events
EventOmadacyclineLinezolid
NauseaGastrointestinal disorders18/6819/72
HeadacheNervous system disorders16/685/72
DiarrhoeaGastrointestinal disorders3/6813/72
VomitingGastrointestinal disorders6/6811/72
DizzinessNervous system disorders7/686/72
ConstipationGastrointestinal disorders6/682/72
Blood creatine phosphokinase increasedInvestigations6/682/72
RashSkin and subcutaneous tissue disorders1/686/72
Infusion site painGeneral disorders5/682/72
InsomniaPsychiatric disorders2/685/72

Baseline characteristics

Intent-to-Treat Population: all enrolled participants who received at least one dose of study medication

Age, Customized
Age, Customized(Participants)OmadacyclineLinezolidTotal
>=18 to <=44 years385189
>44 to <=64262046
>64415
Sex: Female, Male
Sex: Female, Male(Participants)OmadacyclineLinezolidTotal
Female262147
Male425193
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)OmadacyclineLinezolidTotal
Caucasian5661117
Black7714
Asian101
Pacific Islander202
Other; Not Specified246
07

Study locations

7 sites
  • Paratek Recruiting Site
    Fountain Valley, California 92708, United States
  • Parateck Recruiting Site
    La Mesa, California 91942, United States
  • Paratek Recruiting Site
    Oceanside, California 92056, United States
  • Paratek Recruiting Site
    San Diego, California 92114, United States
  • Paratek Recruiting Site
    San Jose, California 95154, United States
  • Parateck Recruiting Site
    Columbus, Georgia 31904, United States
  • Paratek Recruiting Site
    Savannah, Georgia 31406, United States
08

Registry details

Key details

Study ID
NCT00865280
Lead sponsor
Paratek Pharmaceuticals Inc
Collaborators
Novartis Pharmaceuticals
Responsible party
Sponsor
First posted
Mar 19, 2009
Start date
Apr 4, 2009
Primary completion
Apr 15, 2010
Completion
Apr 15, 2010
Results posted
Mar 12, 2021
Last update
Mar 12, 2021

Study contacts

Mary West
study director · Paratek Pharmaceuticals

Oversight

Data monitoring committee
No
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