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Oral Omadacycline vs. Oral Linezolid for the Treatment of ABSSSI

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ClinicalTrials.gov Identifier: NCT02877927
Recruitment Status : Completed
First Posted : August 24, 2016
Results First Posted : November 30, 2018
Last Update Posted : November 30, 2018
Sponsor:
Information provided by (Responsible Party):
Paratek Pharmaceuticals Inc

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Bacterial Infections
Skin Structures and Soft Tissue Infections
Interventions Drug: Omadacycline
Drug: Linezolid
Enrollment 735
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Omadacycline Linezolid
Hide Arm/Group Description Participants received omadacycline 450 milligrams (mg) orally every 24 hours (q24h) for 2 doses, followed by 300 mg orally q24h. The total treatment duration was 7 to 14 days. Participants received active omadacycline tablets and over-encapsulated linezolid placebo tablets. Participants received linezolid 600 mg orally every 12 hours (q12h). The total treatment duration was 7 to 14 days. Participants received omadacycline placebo tablets and over-encapsulated active linezolid tablets.
Period Title: Overall Study
Started 368 367
Completed 314 310
Not Completed 54 57
Reason Not Completed
Adverse Event             1             0
Lost to Follow-up             37             38
Withdrawal by Subject             11             12
Physician Decision             0             1
Missed EOT/PTE Visit             5             6
Arm/Group Title Omadacycline Linezolid Total
Hide Arm/Group Description Participants received omadacycline 450 milligrams (mg) orally every 24 hours (q24h) for 2 doses, followed by 300 mg orally q24h. The total treatment duration was 7 to 14 days. Participants received active omadacycline tablets and over-encapsulated linezolid placebo tablets. Participants received linezolid 600 mg orally every 12 hours (q12h). The total treatment duration was 7 to 14 days. Participants received omadacycline placebo tablets and over-encapsulated active linezolid tablets. Total of all reporting groups
Overall Number of Baseline Participants 368 367 735
Hide Baseline Analysis Population Description
Safety Population: all randomized participants who received test article
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 368 participants 367 participants 735 participants
42.8  (12.72) 44.5  (13.11) 43.7  (12.94)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 368 participants 367 participants 735 participants
Female
126
  34.2%
147
  40.1%
273
  37.1%
Male
242
  65.8%
220
  59.9%
462
  62.9%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 368 participants 367 participants 735 participants
American Indian or Alaska Native
7
   1.9%
3
   0.8%
10
   1.4%
Asian
3
   0.8%
5
   1.4%
8
   1.1%
Native Hawaiian or Other Pacific Islander
3
   0.8%
0
   0.0%
3
   0.4%
Black or African American
22
   6.0%
13
   3.5%
35
   4.8%
White
327
  88.9%
341
  92.9%
668
  90.9%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
6
   1.6%
5
   1.4%
11
   1.5%
1.Primary Outcome
Title Number of Participants With Early Clinical Response
Hide Description Early clinical response is defined as clinical success, which is categorized as survival with at least a 20% reduction of acute bacterial skin and skin structure infection (ABSSSI) primary lesion size compared to Screening measurements, without receiving any rescue antibacterial therapy. An indeterminate classification is used for a response that could not be adequately inferred because the participant was not assessed because they withdrew consent, were lost to follow-up, or other specified reason.
Time Frame Screening; 48 to 72 hours after the first dose of test article
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Intent-to-Treat (mITT) Population: all randomized participants without a baseline sole Gram-negative ABSSSI pathogen
Arm/Group Title Omadacycline Linezolid
Hide Arm/Group Description:
Participants received omadacycline 450 milligrams (mg) orally every 24 hours (q24h) for 2 doses, followed by 300 mg orally q24h. The total treatment duration was 7 to 14 days. Participants received active omadacycline tablets and over-encapsulated linezolid placebo tablets.
Participants received linezolid 600 mg orally every 12 hours (q12h). The total treatment duration was 7 to 14 days. Participants received omadacycline placebo tablets and over-encapsulated active linezolid tablets.
Overall Number of Participants Analyzed 360 360
Measure Type: Count of Participants
Unit of Measure: Participants
Clinical success
315
  87.5%
297
  82.5%
Clinical failure
26
   7.2%
32
   8.9%
Indeterminate
19
   5.3%
31
   8.6%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Omadacycline, Linezolid
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments A non-inferiority margin of 10% was used for the analysis.
Method of Estimation Estimation Parameter treatment difference
Estimated Value 5.0
Confidence Interval (2-Sided) 95%
-0.2 to 10.3
Estimation Comments The 95% confidence interval was constructed based on the Miettinen and Nurminen method without stratification. Treatment difference for a response of clinical success was calculated as omadacycline minus linezolid.
2.Secondary Outcome
Title Number of Participants With the Indicated Investigator Assessment of Clinical Response in the mITT Population at the Post Therapy Evaluation (PTE) Visit
Hide Description At the PTE Visit the investigator indicated one of the following outcomes relating to the primary infection under study: Clinical Success: participant was alive; infection was sufficiently resolved such that further antibacterial therapy was not needed. Participants may have had some residual changes related to infection requiring ancillary treatment. Clinical Failure was defined as meeting any of the following criteria: infection required additional treatment with alternative antibacterial therapy; participant received antibacterial therapy between the End-of-Treatment (EOT) Visit and the PTE Visit that may have been effective for the infection under study for a different infection from the one under study; unplanned major surgical intervention for the infection under study between the EOT and PTE Visits; participant died before evaluation; other specified reason. Indeterminate The clinical response to test article could not be adequately inferred.
Time Frame Screening; 7 to 14 days after the last day of therapy
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population
Arm/Group Title Omadacycline Linezolid
Hide Arm/Group Description:
Participants received omadacycline 450 milligrams (mg) orally every 24 hours (q24h) for 2 doses, followed by 300 mg orally q24h. The total treatment duration was 7 to 14 days. Participants received active omadacycline tablets and over-encapsulated linezolid placebo tablets.
Participants received linezolid 600 mg orally every 12 hours (q12h). The total treatment duration was 7 to 14 days. Participants received omadacycline placebo tablets and over-encapsulated active linezolid tablets.
Overall Number of Participants Analyzed 360 360
Measure Type: Count of Participants
Unit of Measure: Participants
Clinical success
303
  84.2%
291
  80.8%
Clinical failure
12
   3.3%
21
   5.8%
Indeterminate
45
  12.5%
48
  13.3%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Omadacycline, Linezolid
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments A non-inferiority margin of 10% was used for the analysis.
Method of Estimation Estimation Parameter treatment difference
Estimated Value 3.3
Confidence Interval (2-Sided) 95%
-2.2 to 8.9
Estimation Comments The 95% confidence interval was constructed based on the Miettinen and Nurminen method without stratification. Treatment difference for a response of clinical success was calculated as omadacycline minus linezolid.
3.Secondary Outcome
Title Number of Participants With the Indicated Investigator Assessment of Clinical Response in the Clinically Evaluable-Post Therapy Evaluation (CE-PTE) Population
Hide Description At the PTE Visit the investigator indicated one of the following outcomes relating to the primary infection under study: Clinical Success: participant was alive; infection was sufficiently resolved such that further antibacterial therapy was not needed. Participants may have had some residual changes related to infection requiring ancillary treatment. Clinical Failure was defined as meeting any of the following criteria: infection required additional treatment with alternative antibacterial therapy; participant received antibacterial therapy between the EOT Visit and the PTE Visit that may have been effective for the infection under study for a different infection from the one under study; unplanned major surgical intervention for the infection under study between the EOT and PTE Visits; participant died before evaluation; other specified reason.
Time Frame Screening; 7 to 14 days after the last day of therapy
Hide Outcome Measure Data
Hide Analysis Population Description
CE-PTE Population: all participants in the mITT Population meeting additional pre-defined criteria
Arm/Group Title Omadacycline Linezolid
Hide Arm/Group Description:
Participants received omadacycline 450 milligrams (mg) orally every 24 hours (q24h) for 2 doses, followed by 300 mg orally q24h. The total treatment duration was 7 to 14 days. Participants received active omadacycline tablets and over-encapsulated linezolid placebo tablets.
Participants received linezolid 600 mg orally every 12 hours (q12h). The total treatment duration was 7 to 14 days. Participants received omadacycline placebo tablets and over-encapsulated active linezolid tablets.
Overall Number of Participants Analyzed 284 292
Measure Type: Count of Participants
Unit of Measure: Participants
Clinical success
278
  97.9%
279
  95.5%
Clinical failure
6
   2.1%
13
   4.5%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Omadacycline, Linezolid
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments A non-inferiority margin of 10% was used for the analysis.
Method of Estimation Estimation Parameter treatment difference
Estimated Value 2.3
Confidence Interval (2-Sided) 95%
-0.6 to 5.6
Estimation Comments The 95% confidence interval was constructed based on the Miettinen and Nurminen method without stratification. Treatment difference for a response of clinical success was calculated as omadacycline minus linezolid.
Time Frame Adverse events were assessed from the signing of Informed Consent Form to the time of the Final Follow-up assessment (up to 30 to 37 days after the first dose of test article).
Adverse Event Reporting Description Adverse events are reported for members of the Safety Population, comprised of all randomized participants who received test article (either active or placebo). Treatment-emergent adverse events, defined as events occurring after the first dose of active test article, are reported.
 
Arm/Group Title Omadacycline Linezolid
Hide Arm/Group Description Participants received omadacycline 450 milligrams (mg) orally every 24 hours (q24h) for 2 doses, followed by 300 mg orally q24h. The total treatment duration was 7 to 14 days. Participants received active omadacycline tablets and over-encapsulated linezolid placebo tablets. Participants received linezolid 600 mg orally every 12 hours (q12h). The total treatment duration was 7 to 14 days. Participants received omadacycline placebo tablets and over-encapsulated active linezolid tablets.
All-Cause Mortality
Omadacycline Linezolid
Affected / at Risk (%) Affected / at Risk (%)
Total   0/368 (0.00%)   1/367 (0.27%) 
Show Serious Adverse Events Hide Serious Adverse Events
Omadacycline Linezolid
Affected / at Risk (%) Affected / at Risk (%)
Total   5/368 (1.36%)   5/367 (1.36%) 
General disorders     
Drug Withdrawal Syndrome * 1  1/368 (0.27%)  0/367 (0.00%) 
Death * 1  0/368 (0.00%)  1/367 (0.27%) 
Hepatobiliary disorders     
Cholecystitis Acute * 1  1/368 (0.27%)  0/367 (0.00%) 
Infections and infestations     
Wound Infection * 1  1/368 (0.27%)  1/367 (0.27%) 
Hepatitis C * 1  1/368 (0.27%)  0/367 (0.00%) 
Staphylococcal Bacteraemia * 1  1/368 (0.27%)  0/367 (0.00%) 
Subcutaneous Abscess * 1  1/368 (0.27%)  0/367 (0.00%) 
Sepsis * 1  0/368 (0.00%)  2/367 (0.54%) 
Cellulitis * 1  0/368 (0.00%)  1/367 (0.27%) 
Injury, poisoning and procedural complications     
Overdose * 1  1/368 (0.27%)  0/367 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Acute Respiratory Failure * 1  1/368 (0.27%)  0/367 (0.00%) 
Skin and subcutaneous tissue disorders     
Angioedema * 1  0/368 (0.00%)  1/367 (0.27%) 
1
Term from vocabulary, MedDRA 17.1
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Omadacycline Linezolid
Affected / at Risk (%) Affected / at Risk (%)
Total   166/368 (45.11%)   83/367 (22.62%) 
Gastrointestinal disorders     
Nausea * 1  111/368 (30.16%)  28/367 (7.63%) 
Vomiting * 1  62/368 (16.85%)  11/367 (3.00%) 
Diarrhea * 1  15/368 (4.08%)  10/367 (2.72%) 
Abdominal pain upper * 1  10/368 (2.72%)  4/367 (1.09%) 
Infections and infestations     
Wound infection * 1  21/368 (5.71%)  16/367 (4.36%) 
Cellulitis * 1  12/368 (3.26%)  8/367 (2.18%) 
Subcutaneous abscess * 1  5/368 (1.36%)  8/367 (2.18%) 
Investigations     
Alanine aminotransferase increased * 1  19/368 (5.16%)  11/367 (3.00%) 
Aspartate aminotransferase increased * 1  17/368 (4.62%)  12/367 (3.27%) 
Nervous system disorders     
Headache * 1  13/368 (3.53%)  8/367 (2.18%) 
1
Term from vocabulary, MedDRA 17.1
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The only disclosure restriction on the Principal Investigator 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 from the time submitted to the sponsor for review. The sponsor can request changes to the communication and require the removal of confidential information.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Paul McGovern; Vice President, Clinical Affairs
Organization: Paratek Pharmaceuticals, Inc.
Phone: 484-751-4935
EMail: Paul.Mcgovern@paratekpharma.com
Layout table for additonal information
Responsible Party: Paratek Pharmaceuticals Inc
ClinicalTrials.gov Identifier: NCT02877927     History of Changes
Other Study ID Numbers: PTK0796-ABSI-16301
First Submitted: August 15, 2016
First Posted: August 24, 2016
Results First Submitted: November 2, 2018
Results First Posted: November 30, 2018
Last Update Posted: November 30, 2018