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

• Sponsor: Paratek Pharmaceuticals Inc (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03716024
• Collaborator: (none)
• Enrollment: 234
• Locations: 11
• Arms: 2
• Actual Duration (Months): 5.7
• Patients Per Site: 21.3
• Patients Per Site Per Month: 3.7

Study Details

Study Description

Brief Summary

A Phase II 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
Infectious Skin Disease; Bacterial Skin Disease	Drug: PTK 0796; Drug: Linezolid	Phase 2

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-0702 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

• Study Type: Interventional
• Actual Enrollment: 234 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Evaluator-Blinded, Phase 2 Study to Compare the Safety and Efficacy of PTK 0796 With Linezolid (Zyvox®) in the Treatment of Adults With Complicated Skin and Skin Structure Infection (cSSSI)
• Actual Study Start Date: Jul 18, 2007
• Actual Primary Completion Date: Jan 7, 2008
• Actual Study Completion Date: Jan 7, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PTK 0796	Drug: PTK 0796; PTK 0796 100 mg for injection; PTK 0796 capsule 100 mg
Active Comparator: Linezolid	Drug: Linezolid; Pre-mixed 600 mg IV infusion solution; Linezolid 600 mg tablets

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Clinical Response in the Modified Intent-to-Treat (mITT) Population [10 to 17 days after the last dose of test article (intravenous or oral) (total treatment of up to 14 days)]

   Clinical response is defined as clinical success (CS), which is categorized as a determination by a blinded evaluator (BE) that the infection had sufficiently resolved such that antibiotics were no longer needed, the participant (par.) received ≥1 dose of test article, the par. did not receive non-study antibiotics on >2 calendar days from Day 1 to the Test of Cure assessment, and the par. did not meet any of the criteria for clinical failure. Clinical failure (CF) is categorized as a determination by a BE that the infection had responded inadequately such that alternative antibiotics were needed, the BE discontinued test article due to an adverse event that was possibly/probably related to test article, the primary site of infection was surgically removed, or the par. received potentially effective antibiotics for treatment of the primary infection site on >2 days after study enrollment. A classification of indeterminate is used for any outcome that was not classified as CS or CF.

2. Number of Participants With Clinical Response in the Clinically Evaluable (CE) Population [10 to 17 days after the last dose of test article (intravenous or oral) (total treatment of up to 14 days)]

   Clinical response is defined as CS, which was categorized as a determination by a BE that the infection had sufficiently resolved such that antibiotics were no longer needed, the participant received ≥1 dose of test article, the participant did not receive non-study antibiotics on >2 calendar days from Day 1 to the Test of Cure assessment, and the participant did not meet any of the criteria for clinical failure. CF was categorized as a determination by a BE that the infection had responded inadequately such that alternative antibiotics were needed, the BE discontinued test article due to an adverse event that was possibly/probably related to test article, the primary site of infection was surgically removed, or the participant received potentially effective antibiotics for treatment of the primary infection site on >2 days after study enrollment. A classification of indeterminate is used for any outcome that was not classified as CS or CF.

Secondary Outcome Measures

1. Number of Participants With Microbiologic Response in the mITT Population [10 to 17 days after the last dose of test article (intravenous or oral) (total treatment of up to 14 days)]

   Microbiological response to treatment was determined using the following classification: (a) microbiologic success: all infecting pathogens isolated at Baseline were eradicated or presumed eradicated at the Test of Cure evaluation and no superinfecting pathogen was isolated from the site of infection under study; (b) microbiological failure: persistence or presumed persistence of one or more infecting pathogens or isolation of a superinfecting pathogen from the site of infection under study.

2. Number of Participants With Microbiologic Response in the Microbiologically Evaluable (ME) Population [10 to 17 days after the last dose of test article (intravenous or oral) (total treatment of up to 14 days)]

   Microbiological response to treatment was determined using the following classification: (a) microbiologic success: all infecting pathogens isolated at Baseline were eradicated or presumed eradicated at the Test of Cure evaluation and no superinfecting pathogen was isolated from the site of infection under study; (b) microbiological failure: persistence or presumed persistence of one or more infecting pathogens or isolation of a superinfecting pathogen from the site of infection under study.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Patients, ages 18 years to 80 years

2. Has an acute complicated skin and skin structure infection

3. 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:

1. Has received an investigational drug within past 1 month

2. Has been previously enrolled in this protocol

3. Has received >48 hr of a potentially effective systemic antibiotic immediately prior to study drug

4. Is nursing

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Paratek Recruiting Site	Anaheim	California	United States	92804
2	Paratek Recruiting Site	Buena Park	California	United States	90620
3	Paratek Recruiting Site	Chula Vista	California	United States	91911
4	Paratek Recruiting Site	Hawaiian Gardens	California	United States	90716
5	Paratek Recruiting Site	Oceanside	California	United States	92056
6	Paratek Recruiting Site	San Jose	California	United States	95124
7	Paratek Recruiting Site	Indianapolis	Indiana	United States	46280
8	Paratek Recruiting Site	Butte	Montana	United States	59701
9	Paratek Recruiting Site	Electra	Texas	United States	76360
10	Paratek Recruiting Site	Houston	Texas	United States	77074
11	Paratek Recruiting Site	Wichita Falls	Texas	United States	76301

Sponsors and Collaborators

• Paratek Pharmaceuticals Inc

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Paratek Pharmaceuticals Inc
• ClinicalTrials.gov Identifier: NCT03716024
• Other Study ID Numbers: PTK0796-CSSI-0702
• First Posted: Oct 23, 2018
• Last Update Posted: Oct 12, 2020
• Last Verified: Sep 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Paratek Pharmaceuticals Inc: CSSSI
• Additional relevant MeSH terms: Skin Diseases, Bacterial; Skin Diseases, Infectious; Skin Diseases; Linezolid

Study Results

Participant Flow

Arm/Group Title	Omadacycline	Linezolid
Arm/Group Description	Participants received intravenous (IV) omadacycline 100 milligrams (mg) infused over 30 minutes, every 24 hours (q24h), with the option to switch to two 100-mg capsules via oral administration q24h at the discretion of the investigator. All participants received up to 7 days of IV therapy and up to 14 days of IV and oral therapy combined.	Participants received IV linezolid 600 mg infused over 30 minutes, every 12 hours (q12h), with the option to switch to one 600-mg tablet via oral administration q12h at the discretion of the investigator. All participants received up to 7 days of IV therapy and up to 14 days of IV and oral therapy combined.
Period Title: Overall Study
STARTED	118	116
COMPLETED	107	98
NOT COMPLETED	11	18

Baseline Characteristics

Arm/Group Title	Omadacycline	Linezolid	Total
Arm/Group Description	Participants received intravenous (IV) omadacycline 100 milligrams (mg) infused over 30 minutes, every 24 hours (q24h), with the option to switch to two 100-mg capsules via oral administration q24h at the discretion of the investigator. All participants received up to 7 days of IV therapy and up to 14 days of IV and oral therapy combined.	Participants received IV linezolid 600 mg infused over 30 minutes, every 12 hours (q12h), with the option to switch to one 600-mg tablet via oral administration q12h at the discretion of the investigator. All participants received up to 7 days of IV therapy and up to 14 days of IV and oral therapy combined.	Total of all reporting groups
Overall Participants	111	108	219
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	44.4 (14.06)	45.4 (13.34)	44.9 (13.69)
Sex: Female, Male (Count of Participants)
Female	45 40.5%	51 47.2%	96 43.8%
Male	66 59.5%	57 52.8%	123 56.2%
Race/Ethnicity, Customized (participants) [Number]
Caucasian	97 87.4%	99 91.7%	196 89.5%
Black or African American	8 7.2%	6 5.6%	14 6.4%
Asian Hawaiian or Other Pacific Islander	5 4.5%	1 0.9%	6 2.7%
American Indian or Alaska Native	0 0%	1 0.9%	1 0.5%
Recorded as Other	1 0.9%	1 0.9%	2 0.9%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Clinical Response in the Modified Intent-to-Treat (mITT) Population
Description	Clinical response is defined as clinical success (CS), which is categorized as a determination by a blinded evaluator (BE) that the infection had sufficiently resolved such that antibiotics were no longer needed, the participant (par.) received ≥1 dose of test article, the par. did not receive non-study antibiotics on >2 calendar days from Day 1 to the Test of Cure assessment, and the par. did not meet any of the criteria for clinical failure. Clinical failure (CF) is categorized as a determination by a BE that the infection had responded inadequately such that alternative antibiotics were needed, the BE discontinued test article due to an adverse event that was possibly/probably related to test article, the primary site of infection was surgically removed, or the par. received potentially effective antibiotics for treatment of the primary infection site on >2 days after study enrollment. A classification of indeterminate is used for any outcome that was not classified as CS or CF.
Time Frame	10 to 17 days after the last dose of test article (intravenous or oral) (total treatment of up to 14 days)

Outcome Measure Data

Analysis Population Description

mITT Population: all enrolled participants who received at least 1 dose of test article and who had at least 1 infecting pathogen isolated at the Baseline evaluation. Non-evaluable participants are included as clinical failures.

Arm/Group Title	Omadacycline	Linezolid
Arm/Group Description	Participants received intravenous (IV) omadacycline 100 milligrams (mg) infused over 30 minutes, every 24 hours (q24h), with the option to switch to two 100-mg capsules via oral administration q24h at the discretion of the investigator. All participants received up to 7 days of IV therapy and up to 14 days of IV and oral therapy combined.	Participants received IV linezolid 600 mg infused over 30 minutes, every 12 hours (q12h), with the option to switch to one 600-mg tablet via oral administration q12h at the discretion of the investigator. All participants received up to 7 days of IV therapy and up to 14 days of IV and oral therapy combined.
Measure Participants	84	78
Clinical success	75 67.6%	59 54.6%
Clinical failure	9 8.1%	19 17.6%
Clinical failure: failure	2 1.8%	4 3.7%
Clinical failure: non-evaluable	7 6.3%	15 13.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Omadacycline, Linezolid
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	13.6
	Confidence Interval	(2-Sided) 95%; 1.3 to 26.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	omadacycline minus linezolid

2. Primary Outcome

Title	Number of Participants With Clinical Response in the Clinically Evaluable (CE) Population
Description	Clinical response is defined as CS, which was categorized as a determination by a BE that the infection had sufficiently resolved such that antibiotics were no longer needed, the participant received ≥1 dose of test article, the participant did not receive non-study antibiotics on >2 calendar days from Day 1 to the Test of Cure assessment, and the participant did not meet any of the criteria for clinical failure. CF was categorized as a determination by a BE that the infection had responded inadequately such that alternative antibiotics were needed, the BE discontinued test article due to an adverse event that was possibly/probably related to test article, the primary site of infection was surgically removed, or the participant received potentially effective antibiotics for treatment of the primary infection site on >2 days after study enrollment. A classification of indeterminate is used for any outcome that was not classified as CS or CF.
Time Frame	10 to 17 days after the last dose of test article (intravenous or oral) (total treatment of up to 14 days)

Outcome Measure Data

Analysis Population Description

CE Population: all enrolled participants who received at least 1 dose of test article and who had a qualifying skin and skin structure infection, received the correct test article for at least 5 calendar days, had the necessary clinical evaluations performed, and did not receive potentially confounding non-study antibiotics

Arm/Group Title	Omadacycline	Linezolid
Arm/Group Description	Participants received intravenous (IV) omadacycline 100 milligrams (mg) infused over 30 minutes, every 24 hours (q24h), with the option to switch to two 100-mg capsules via oral administration q24h at the discretion of the investigator. All participants received up to 7 days of IV therapy and up to 14 days of IV and oral therapy combined.	Participants received IV linezolid 600 mg infused over 30 minutes, every 12 hours (q12h), with the option to switch to one 600-mg tablet via oral administration q12h at the discretion of the investigator. All participants received up to 7 days of IV therapy and up to 14 days of IV and oral therapy combined.
Measure Participants	100	88
Clinical success	98 88.3%	82 75.9%
Clinical failure	2 1.8%	6 5.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Omadacycline, Linezolid
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	4.8
	Confidence Interval	(2-Sided) 95%; -1.7 to 11.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	omadacycline minus linezolid

3. Secondary Outcome

Title	Number of Participants With Microbiologic Response in the mITT Population
Description	Microbiological response to treatment was determined using the following classification: (a) microbiologic success: all infecting pathogens isolated at Baseline were eradicated or presumed eradicated at the Test of Cure evaluation and no superinfecting pathogen was isolated from the site of infection under study; (b) microbiological failure: persistence or presumed persistence of one or more infecting pathogens or isolation of a superinfecting pathogen from the site of infection under study.
Time Frame	10 to 17 days after the last dose of test article (intravenous or oral) (total treatment of up to 14 days)

Outcome Measure Data

Analysis Population Description

mITT Population. Non-evaluable participants are included as microbiological failures.

Arm/Group Title	Omadacycline	Linezolid
Arm/Group Description	Participants received intravenous (IV) omadacycline 100 milligrams (mg) infused over 30 minutes, every 24 hours (q24h), with the option to switch to two 100-mg capsules via oral administration q24h at the discretion of the investigator. All participants received up to 7 days of IV therapy and up to 14 days of IV and oral therapy combined.	Participants received IV linezolid 600 mg infused over 30 minutes, every 12 hours (q12h), with the option to switch to one 600-mg tablet via oral administration q12h at the discretion of the investigator. All participants received up to 7 days of IV therapy and up to 14 days of IV and oral therapy combined.
Measure Participants	84	78
Microbiological success	73 65.8%	57 52.8%
Microbiological failure	11 9.9%	21 19.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Omadacycline, Linezolid
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	13.8
	Confidence Interval	(2-Sided) 95%; 0.9 to 26.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	omadacycline minus linezolid

4. Secondary Outcome

Title	Number of Participants With Microbiologic Response in the Microbiologically Evaluable (ME) Population
Description	Microbiological response to treatment was determined using the following classification: (a) microbiologic success: all infecting pathogens isolated at Baseline were eradicated or presumed eradicated at the Test of Cure evaluation and no superinfecting pathogen was isolated from the site of infection under study; (b) microbiological failure: persistence or presumed persistence of one or more infecting pathogens or isolation of a superinfecting pathogen from the site of infection under study.
Time Frame	10 to 17 days after the last dose of test article (intravenous or oral) (total treatment of up to 14 days)

Outcome Measure Data

Analysis Population Description

ME Population: all participants in the CE cohort who had an infecting pathogen identified at Baseline

Arm/Group Title	Omadacycline	Linezolid
Arm/Group Description	Participants received intravenous (IV) omadacycline 100 milligrams (mg) infused over 30 minutes, every 24 hours (q24h), with the option to switch to two 100-mg capsules via oral administration q24h at the discretion of the investigator. All participants received up to 7 days of IV therapy and up to 14 days of IV and oral therapy combined.	Participants received IV linezolid 600 mg infused over 30 minutes, every 12 hours (q12h), with the option to switch to one 600-mg tablet via oral administration q12h at the discretion of the investigator. All participants received up to 7 days of IV therapy and up to 14 days of IV and oral therapy combined.
Measure Participants	77	63
Microbiological success	73 65.8%	57 52.8%
Microbiological failure	4 3.6%	6 5.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Omadacycline, Linezolid
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	4.3
	Confidence Interval	(2-Sided) 95%; -5.3 to 14.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	from enrollment to 10 to 17 days after the last dose of test article (intravenous or oral administration) (up to approximately 27 days)
Adverse Event Reporting Description	Adverse events are reported for members of the omadacycline Safety Population, comprised of all participants who received 1 or more doses of omadacycline, and members of the linezolid Safety Population, comprised of all participants who received only linezolid as intravenous test article.
Arm/Group Title	Omadacycline		Linezolid
Arm/Group Description	Participants received intravenous (IV) omadacycline 100 milligrams (mg) infused over 30 minutes, every 24 hours (q24h), with the option to switch to two 100-mg capsules via oral administration q24h at the discretion of the investigator. All participants received up to 7 days of IV therapy and up to 14 days of IV and oral therapy combined.		Participants received IV linezolid 600 mg infused over 30 minutes, every 12 hours (q12h), with the option to switch to one 600-mg tablet via oral administration q12h at the discretion of the investigator. All participants received up to 7 days of IV therapy and up to 14 days of IV and oral therapy combined.
All Cause Mortality
	Omadacycline		Linezolid
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/111 (0%)		0/108 (0%)
Serious Adverse Events
	Omadacycline		Linezolid
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/111 (0.9%)		2/108 (1.9%)
Infections and infestations
Soft tissue infection	0/111 (0%)		1/108 (0.9%)
Wound infection	0/111 (0%)		1/108 (0.9%)
Psychiatric disorders
Confusional state	1/111 (0.9%)		0/108 (0%)
Other (Not Including Serious) Adverse Events
	Omadacycline		Linezolid
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	44/111 (39.6%)		54/108 (50%)
Cardiac disorders
Tachycardia	3/111 (2.7%)		0/108 (0%)
Gastrointestinal disorders
Nausea	13/111 (11.7%)		8/108 (7.4%)
Constipation	5/111 (4.5%)		2/108 (1.9%)
Vomiting	5/111 (4.5%)		4/108 (3.7%)
Abdominal pain	3/111 (2.7%)		0/108 (0%)
Abdominal pain upper	3/111 (2.7%)		0/108 (0%)
Diarrhoea	3/111 (2.7%)		6/108 (5.6%)
Dyspepsia	3/111 (2.7%)		1/108 (0.9%)
General disorders
Fatigue	5/111 (4.5%)		2/108 (1.9%)
Infections and infestations
Abscess	3/111 (2.7%)		1/108 (0.9%)
Nasopharyngitis	0/111 (0%)		3/108 (2.8%)
Investigations
Alanine aminotransferase (ALT) increased	3/111 (2.7%)		7/108 (6.5%)
Aspartate aminotransaminase (AST) increased	3/111 (2.7%)		5/108 (4.6%)
Blood creatine phosphokinase increased	3/111 (2.7%)		1/108 (0.9%)
Metabolism and nutrition disorders
Hypoglycaemia	4/111 (3.6%)		1/108 (0.9%)
Dehydration	3/111 (2.7%)		0/108 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	3/111 (2.7%)		0/108 (0%)
Nervous system disorders
Headache	6/111 (5.4%)		8/108 (7.4%)
Dizziness	4/111 (3.6%)		5/108 (4.6%)
Psychiatric disorders
Insomnia	2/111 (1.8%)		3/108 (2.8%)
Skin and subcutaneous tissue disorders
Rash	5/111 (4.5%)		0/108 (0%)
Pruritus	3/111 (2.7%)		4/108 (3.7%)
Pruritus generalised	1/111 (0.9%)		3/108 (2.8%)

Limitations/Caveats

[Not Specified]

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.