Trial Outcomes & Findings for Study the Safety and Efficacy of PTK 0796 in Patients With Complicated Skin and Skin Structure Infection (CSSSI) (NCT NCT00865280)

Last Updated: 2021-03-12

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

143 participants

Primary outcome timeframe

up to 14 days

Results posted on

2021-03-12

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).

Participants who met inclusion criteria and did not meet exclusion criteria were randomly assigned to a treatment group.

Participant milestones

Participant milestones
Measure	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.	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.
Overall Study STARTED	70	73
Overall Study COMPLETED	64	70
Overall Study NOT COMPLETED	6	3

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.
Overall Study Withdrawal by Subject	4	1
Overall Study End of Treatment/Lost to Follow-up	0	1
Overall Study Adverse Event/Lost to Follow-up	1	0
Overall Study Exclusion Condition	1	0
Overall Study Adverse Event	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Omadacycline n=68 Participants 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.	Linezolid n=72 Participants 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 n=140 Participants Total of all reporting groups
Age, Customized >=18 to <=44 years	38 Participants n=5 Participants	51 Participants n=7 Participants	89 Participants n=5 Participants
Age, Customized >44 to <=64	26 Participants n=5 Participants	20 Participants n=7 Participants	46 Participants n=5 Participants
Age, Customized >64	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants
Sex: Female, Male Female	26 Participants n=5 Participants	21 Participants n=7 Participants	47 Participants n=5 Participants
Sex: Female, Male Male	42 Participants n=5 Participants	51 Participants n=7 Participants	93 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	56 Participants n=5 Participants	61 Participants n=7 Participants	117 Participants n=5 Participants
Race/Ethnicity, Customized Black	7 Participants n=5 Participants	7 Participants n=7 Participants	14 Participants n=5 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Pacific Islander	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Other; Not Specified	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Omadacycline n=68 Participants 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.	Linezolid n=72 Participants 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.
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	66 Participants
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	3 Participants
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	3 Participants

PRIMARY outcome

Timeframe: 10 to 17 days after last dose of treatment (total treatment of up to 14 days)

Population: ITT Population

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.

Outcome measures

Outcome measures
Measure	Omadacycline n=68 Participants 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.	Linezolid n=72 Participants 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.
Number of Participants Classified as a Sponsor-defined Clinical Success in the ITT Population at Test of Cure Clinical success	58 Participants	64 Participants
Number of Participants Classified as a Sponsor-defined Clinical Success in the ITT Population at Test of Cure Clinical failure	2 Participants	3 Participants
Number of Participants Classified as a Sponsor-defined Clinical Success in the ITT Population at Test of Cure Clinical non-evaluable	8 Participants	5 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Omadacycline n=13 Participants 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.	Linezolid n=13 Participants 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.
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	12 Participants
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	1 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Omadacycline n=39 Participants 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.	Linezolid n=45 Participants 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.
Number of Participants With Cellulitis Classified as a Sponsor-defined Clinical Success in the CE Population at End of Treatment Clinical success	38 Participants	44 Participants
Number of Participants With Cellulitis Classified as a Sponsor-defined Clinical Success in the CE Population at End of Treatment Clinical failure	1 Participants	1 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Omadacycline n=13 Participants 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.	Linezolid n=13 Participants 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.
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	1 Participants
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	12 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Omadacycline n=39 Participants 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.	Linezolid n=45 Participants 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.
Number of Participants With Cellulitis Classified as a Sponsor-defined Clinical Success in the CE Population at Test of Cure Clinical success	38 Participants	44 Participants
Number of Participants With Cellulitis Classified as a Sponsor-defined Clinical Success in the CE Population at Test of Cure Clinical failure	1 Participants	1 Participants

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure	Omadacycline n=68 Participants 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.	Linezolid n=72 Participants 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.
Number of Participants With the Indicated Type of Adverse Event (AE) Treatment-emergent adverse event (TEAE)	56 Participants	58 Participants
Number of Participants With the Indicated Type of Adverse Event (AE) Study drug-related TEAE	41 Participants	41 Participants
Number of Participants With the Indicated Type of Adverse Event (AE) AEs leading to study drug discontinuation	2 Participants	0 Participants

Adverse Events

Omadacycline

Serious events: 3 serious events

Other events: 52 other events

Deaths: 1 deaths

Linezolid

Serious events: 1 serious events

Other events: 55 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Omadacycline n=68 participants at risk 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.	Linezolid n=72 participants at risk 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.
Gastrointestinal disorders Small intestinal obstruction	1.5% 1/68 • 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 events are reported for members of the Safety Population, comprised of all enrolled participants who received at least one dose of study medication	0.00% 0/72 • 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 events are reported for members of the Safety Population, comprised of all enrolled participants who received at least one dose of study medication
Infections and infestations Gastroenteritis	1.5% 1/68 • 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 events are reported for members of the Safety Population, comprised of all enrolled participants who received at least one dose of study medication	0.00% 0/72 • 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 events are reported for members of the Safety Population, comprised of all enrolled participants who received at least one dose of study medication
Infections and infestations Cellulitis	0.00% 0/68 • 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 events are reported for members of the Safety Population, comprised of all enrolled participants who received at least one dose of study medication	1.4% 1/72 • 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 events are reported for members of the Safety Population, comprised of all enrolled participants who received at least one dose of study medication
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung cancer metastatic	1.5% 1/68 • 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 events are reported for members of the Safety Population, comprised of all enrolled participants who received at least one dose of study medication	0.00% 0/72 • 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 events are reported for members of the Safety Population, comprised of all enrolled participants who received at least one dose of study medication
Psychiatric disorders Depression	1.5% 1/68 • 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 events are reported for members of the Safety Population, comprised of all enrolled participants who received at least one dose of study medication	0.00% 0/72 • 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 events are reported for members of the Safety Population, comprised of all enrolled participants who received at least one dose of study medication

Other adverse events

Additional Information

Paratek Medical Information

Paratek Pharmaceuticals, Inc.

Phone: 1-833-727-2835

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60