Delafloxacin vs Vancomycin and Aztreonam for the Treatment of Acute Bacterial Skin and Skin Structure Infections

• Sponsor: Melinta Therapeutics, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01984684
• Collaborator: (none)
• Enrollment: 850
• Locations: 94
• Arms: 2
• Actual Duration (Months): 20
• Patients Per Site: 9
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the effects of Delafloxacin versus Vancomycin plus Aztreonam in the treatment of patients with acute bacterial skin and soft tissue infections.

Condition or Disease	Intervention/Treatment	Phase
Skin and Subcutaneous Tissue Bacterial Infections; Skin Structures and Soft Tissue Infections	Drug: delafloxacin; Drug: vancomycin; Drug: aztreonam	Phase 3

Detailed Description

The purpose of this study is to determine if delafloxacin, an investigational drug, is safe and effective in the treatment of skin and nearby tissue infections compared with a combination of other antibiotics, vancomycin and aztreonam.

Study Design

• Study Type: Interventional
• Actual Enrollment: 850 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Multicenter, Randomized, Double-blind, Active Controlled Study to Evaluate the Efficacy + Safety of IV + Oral Delafloxacin Compared With Vancomycin + Aztreonam in Patients With Acute Bacterial Skin and Skin Structure Infections (ABSSSI)
• Actual Study Start Date: May 1, 2014
• Actual Primary Completion Date: Dec 1, 2015
• Actual Study Completion Date: Jan 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Delafloxacin Delafloxacin 300 mg IV Q12H for 6 doses, then Delafloxacin 450 mg oral tablet Q12H for a minimum of 10 up to a maximum of 28 doses total	Drug: delafloxacin; Other Names: RX-3341
Active Comparator: Vancomycin plus Aztreonam Vancomycin 15 mg/kg IV plus two grams Aztreonam every 12 hours for a minimum of 10 up to a maximum of 28 doses total (Aztreonam was discontinued as soon as possible if a gram-negative organism was not identified in baseline cultures)	Drug: vancomycin; Drug: aztreonam

Outcome Measures

Primary Outcome Measures

1. Objective Response of ≥20% Reduction in Lesion Erythema Area Compared to Baseline at 48 to 72 Hours After Initiation of Treatment as Determined by Digital Measurements of the Leading Edge. [48 to 72 hrs after starting treatment]

   A patient was considered a responder if s/he had a ≥20% reduction in size of the area of erythema associated with the baseline ABSSSI, as determined by digital planimetry of the leading edge and had none of the reasons for clinical failure; a patient was considered a non-responder (failure) if s/he had <20% reduction in size of the area of erythema associated with the baseline ABSSSI as determined by digital planimetry of the leading edge, or had major intervention such as another antibiotic or surgical intervention or died within 74 hours after initiation of study drug.

Secondary Outcome Measures

1. Investigator-assessed Response of Signs and Symptoms of Infection at the Follow up Visit (European Medicines Agency [EMA] Primary Endpoint) [Study Day 14 ± 1]

   A patient was considered a Cure if all baseline signs and symptoms of ABSSSI had resolved; if some symptoms remained, but the patient was improved to the extent that no additional antibiotic treatment was necessary, the response was Improved. A patient was considered a Failure for any of the following reasons: nonstudy antibacterial drug therapy was required because of lack of efficacy after at least 4 doses of study drug or for a treatment-related AE; study antibacterial drug therapy was required for longer than 28 doses; and/or unplanned surgical intervention was needed after study entry except for limited bedside debridement and standard wound care. Improved and Indeterminate responses were considered failures in the primary analysis. A sensitivity analysis was also performed, in which the assigned responses were Success (Cure + Improved) or Failure (Failure + Indeterminate/Missing).

2. Investigator-assessed Response of Signs and Symptoms of Infection at the Late Follow-up Visit [Study Day 21 to 28]

   A patient was considered a Cure if all baseline signs and symptoms of ABSSSI had resolved; if some symptoms remained, but the patient was improved to the extent that no additional antibiotic treatment was necessary, the response was Improved. A patient was considered a Failure for any of the following reasons: nonstudy antibacterial drug therapy was required because of lack of efficacy after at least 4 doses of study drug or for a treatment-related AE; study antibacterial drug therapy was required for longer than 28 doses; and/or unplanned surgical intervention was needed after study entry except for limited bedside debridement and standard wound care. Improved and Indeterminate responses were considered failures in the primary analysis. A sensitivity analysis was also performed, in which the assigned responses were Success (Cure + Improved) or Failure (Failure + Indeterminate/Missing).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Adult (≥ 18 years of age) men or women with a diagnosis of ABSSSI (cellulitis/erysipelas, wound infection, major cutaneous abscess, or burn infection) with surrounding redness of a minimum surface area of 75 cm^2 and at least two signs of systemic infection

• In the opinion of the investigator, the subject must require and be a suitable candidate for IV antibiotic therapy, and the subject must be able and willing to comply with protocol requirements

Exclusion Criteria:

• A medical history of significant hypersensitivity or allergic reaction to quinolones, beta-lactams, vancomycin, or vancomycin derivatives according to the judgment of the investigator.

• Women who are pregnant or lactating.

• Any chronic or underlying skin condition at the site of infection that may complicate the assessment of response, including infection involving a prosthetic joint, human or animal bite, osteomyelitis, decubitus ulcer, diabetic foot ulcer, septic arthritis, mediastinitis, necrotizing fasciitis, anaerobic cellulitis, or synergistic necrotizing cellulitis, myositis, tendinitis, endocarditis, sustained shock, gangrene or gas gangrene; burns covering ≥10% of body surface area; severely compromised immune system, severely impaired arterial blood supply to an extremity with an ABSSSI, deep vein thrombosis or superficial thrombophlebitis, and requiring either an amputation or multiple debridement procedures.

• Receipt of systemic antibiotic therapy in the 14 days before enrollment unless 1 of the following was documented:

• Received ≥ 48 hours of antibiotic therapy for ABSSSI AND clinical progression is documented (i.e., not by patient history alone).

• Recently (within 14 days) completed a treatment course with an antibacterial drug for an infection other than ABSSSI and the drug does not have activity against bacterial pathogens that cause ABSSSI.

• Received only 1 dose of either a single, potentially effective, short-acting antimicrobial drug or drug regimen for ABSSSI.

• Any underlying disease that, in the opinion of the investigator, could interfere with the subject's ability to participate in the study including severe cardiac disease, known history of liver disease, end-stage renal disease, malignancy, psychiatric disorder, ongoing treatment for seizures or untreated history of seizures, or life expectancy of < 3 months.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Melinta 303 Study Site	Mobile	Alabama	United States	36607
2	Melinta 303 Study Site	Montgomery	Alabama	United States
3	Melinta 303 Study Site	Anaheim	California	United States
4	Melinta 303 Study Site	Chula Vista	California	United States	91911
5	Melinta 303 Study Site	La Mesa	California	United States	91942
6	Melinta 303 Study Site	Long Beach	California	United States
7	Melinta 303 Study Site	Modesto	California	United States
8	Melinta 303 Study Site	Oceanside	California	United States	92056
9	Melinta 303 Study Site	San Diego	California	United States	92114
10	Melinta 303 Study Site	Stockton	California	United States
11	Melinta 303 Study Site	Torrance	California	United States	90509
12	Melinta 303 Study Site	DeLand	Florida	United States
13	Melinta 303 Study Site	Orlando	Florida	United States
14	Melinta 303 Study Site	Columbus	Georgia	United States	31904
15	Melinta 303 Study Site	Savannah	Georgia	United States	31405
16	Melinta 303 Study Site	Eunice	Louisiana	United States	70535
17	Melinta 303 Study Site	Springfield	Massachusetts	United States
18	Melinta 303 Study Site	Minneapolis	Minnesota	United States	55422
19	Melinta 303 Study Site	Butte	Montana	United States
20	Melinta 303 Study Site	Lincoln	Nebraska	United States
21	Melinta 303 Study Site	Las Vegas	Nevada	United States	89109
22	Melinta 303 Study Site	Somers Point	New Jersey	United States	08244
23	Melinta 303 Study Site	Teaneck	New Jersey	United States
24	Melinta 303 Study Site	Columbus	Ohio	United States
25	Melinta 303 Study Site	Toledo	Ohio	United States
26	Melinta 303 Study Site	Rapid City	South Dakota	United States
27	Melinta 303 Study Site	Jackson	Tennessee	United States
28	Melinta 303 Study Site	Smyrna	Tennessee	United States
29	Melinta 303 Study Site	Channelview	Texas	United States	77530
30	Melinta 303 Study Site	Houston	Texas	United States	77024
31	Melinta 303 Study Site	San Antonio	Texas	United States
32	Melinta 303 Study Site	La Plata	Buenos Aires	Argentina
33	Melinta 303 Study Site	Rosario	Santa Fe	Argentina
34	Melinta 303 Study Site	Cordoba		Argentina
35	Melinta 303 Study Site	Santa Fe		Argentina
36	Melinta 303 Study Site	Salvador	Bahia	Brazil
37	Melinta 303 Study Site	Belo Horizonte	Minas Gerais	Brazil
38	Melinta 303 Study Site	Lavras	Minas Gerais	Brazil
39	Melinta 303 Study Site	Passo Fundo	Rio Grande Do Sul	Brazil
40	Melinta 303 Study Site	Campinas	Sao Paulo	Brazil
41	Melinta 303 Study Site	São José Do Rio Preto	Sao Paulo	Brazil
42	Melinta 303 Study Site	Sao Paulo		Brazil
43	Melinta 303 Study Site	Pleven		Bulgaria
44	Melinta 303 Study Site	Plovdiv		Bulgaria
45	Melinta 303 Study Site	Ruse		Bulgaria
46	Melinta 303 Study Site	Sofia		Bulgaria
47	Melinta 303 Study Site	Varna		Bulgaria
48	Melinta 303 Study Site	Santiago		Chile
49	Melinta 303 Study Site	Temuco		Chile
50	Melinta 303 Study Site	Kohtla-Järve		Estonia
51	Melinta 303 Study Site	Tallinn		Estonia
52	Melinta 303 Study Site	Tartu		Estonia
53	Melinta 303 Study Site	Voru		Estonia
54	Melinta 303 Study Site	Batumi		Georgia
55	Melinta 303 Study Site	Kutaisi		Georgia
56	Melinta 303 Study Site	Tbilisi		Georgia
57	Melinta 303 Study Site	Zugdidi		Georgia
58	Melinta 303 Study Site	Kaposvar		Hungary
59	Melinta 303 Study Site	Kecskemét		Hungary
60	Melinta 303 Study Site	Nyiregyhaza		Hungary
61	Melinta 303 Study Site	Szeged		Hungary
62	Melinta 303 Study Site	Veszprem		Hungary
63	Melinta 303 Study Site	Wŏnju	Gang'weondo	Korea, Republic of
64	Melinta 303 Study Site	Ansan	Gyeonggido	Korea, Republic of
65	Melinta 303 Study Site	Goyang	Gyeonggido	Korea, Republic of
66	Melinta 303 Study Site	Daegu		Korea, Republic of
67	Melinta 303 Study Site	Daejeon		Korea, Republic of
68	Melinta 303 Study Site	Gwangju		Korea, Republic of
69	Melinta 303 Study Site	Incheon		Korea, Republic of
70	Melinta 303 Study Site	Seoul		Korea, Republic of
71	Melinta 303 Study Site	Daugavpils		Latvia
72	Melinta 303 Study Site	Liepaja		Latvia
73	Melinta 303 Study Site	Rezekne		Latvia
74	Melinta 303 Study Site	Riga		Latvia
75	Melinta 303 Study Site	Guadalajara	Jalisco	Mexico
76	Melinta 303 Study Site	Monterrey	Nuevo Leon	Mexico
77	Melinta 303 Study Site	Chisinau		Moldova, Republic of
78	Melinta 303 Study Site	Trujillo	La Libertad	Peru
79	Melinta 303 Study Site	Cusco		Peru
80	Melinta 303 Study Site	Lima		Peru
81	Melinta 303 Study Site	Loreto		Peru
82	Melinta 303 Study Site	Cluj-Napoca	Cluj	Romania
83	Melinta 303 Study Site	Craiova	Dolj	Romania
84	Melinta 303 Study Site	Timisoara	Timis	Romania
85	Melinta 303 Study Site	Bucharest		Romania
86	Melinta 303 Study Site	Targu mures		Romania
87	Melinta 303 Study Site	Banska Bystrica		Slovakia
88	Melinta 303 Study Site	Presov		Slovakia
89	Melinta 303 Study Site	Kaohsiung		Taiwan
90	Melinta 303 Study Site	New Taipei City		Taiwan
91	Melinta 303 Study Site	Taichung		Taiwan
92	Melinta 303 Study Site	Tainan City		Taiwan
93	Melinta 303 Study Site	Taipei		Taiwan
94	Melinta 303 Study Site	Zhonghe		Taiwan

Sponsors and Collaborators

• Melinta Therapeutics, Inc.

Investigators

• Study Director: Sue K Cammarata, MD, Melinta Therapeutics, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Melinta Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT01984684
• Other Study ID Numbers: RX-3341-303
• First Posted: Nov 15, 2013
• Last Update Posted: Nov 17, 2017
• Last Verified: Nov 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Melinta Therapeutics, Inc.: Bacterial skin infection; infection; skin; delafloxacin; vancomycin; aztreonam; methicillin-resistant Staphylococcus aureus (MRSA) bacteria; bacterial infection; Anti-Infective Agents
• Additional relevant MeSH terms: Infections; Communicable Diseases; Bacterial Infections; Soft Tissue Infections; Vancomycin; Aztreonam

Study Results

Participant Flow

Arm/Group Title	Delafloxacin	Vancomycin Plus Aztreonam
Arm/Group Description	300 mg IV Q12H for 6 doses, 450 mg oral tablet Q12H for a minimum of 10 up to a maximum of 28 doses total	Vancomycin 15 mg/kg IV plus two grams Aztreonam every 12 hours for a minimum of 10 up to a maximum of 28 doses total
Period Title: Overall Study
STARTED	423	427
COMPLETED	366	368
NOT COMPLETED	57	59

Baseline Characteristics

Arm/Group Title	Delafloxacin	Vancomycin Plus Aztreonam	Total
Arm/Group Description	300mg iv Q12H for 6 doses, 450mg oral tablet Q12H for a minimum of 10 up to a maximum of 28 doses total	Vancomycin 15mg/kg iv plus two grams Aztreonam every 12 hours for a minimum of 10 up to a maximum of 28 doses total	Total of all reporting groups
Overall Participants	423	427	850
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51.2 (15.98)	50.2 (16.03)	50.7 (16.00)
Age, Customized (Count of Participants)
<= 65 years	344 81.3%	352 82.4%	696 81.9%
> 65 years	79 18.7%	75 17.6%	154 18.1%
> 75 years	35 8.3%	31 7.3%	66 7.8%
Sex: Female, Male (Count of Participants)
Female	161 38.1%	151 35.4%	312 36.7%
Male	262 61.9%	276 64.6%	538 63.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	132 31.2%	99 23.2%	231 27.2%
Not Hispanic or Latino	291 68.8%	328 76.8%	619 72.8%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	12 2.8%	7 1.6%	19 2.2%
Asian	11 2.6%	15 3.5%	26 3.1%
Native Hawaiian or Other Pacific Islander	2 0.5%	2 0.5%	4 0.5%
Black or African American	13 3.1%	18 4.2%	31 3.6%
White	348 82.3%	355 83.1%	703 82.7%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	37 8.7%	30 7%	67 7.9%
Region of Enrollment (Count of Participants)
Europe	165 39%	173 40.5%	338 39.8%
North America	202 47.8%	196 45.9%	398 46.8%
Mexico	8 1.9%	4 0.9%	12 1.4%
Brazil	0 0%	5 1.2%	5 0.6%
Chile	1 0.2%	1 0.2%	2 0.2%
Peru	34 8%	29 6.8%	63 7.4%
South Korea	8 1.9%	13 3%	21 2.5%
Taiwan	1 0.2%	1 0.2%	2 0.2%
Argentina	4 0.9%	5 1.2%	9 1.1%
BMI (Body Mass Index) (kg/m2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m2]	30.4 (7.44)	30.7 (7.54)	30.5 (7.49)
BMI category (Count of Participants)
< 30 kg/m2	212 50.1%	213 49.9%	425 50%
>= 30 kg/m2	211 49.9%	214 50.1%	425 50%
Presence of diabetes (Count of Participants)
Count of Participants [Participants]	53 12.5%	54 12.6%	107 12.6%

Outcome Measures

1. Primary Outcome

Title	Objective Response of ≥20% Reduction in Lesion Erythema Area Compared to Baseline at 48 to 72 Hours After Initiation of Treatment as Determined by Digital Measurements of the Leading Edge.
Description	A patient was considered a responder if s/he had a ≥20% reduction in size of the area of erythema associated with the baseline ABSSSI, as determined by digital planimetry of the leading edge and had none of the reasons for clinical failure; a patient was considered a non-responder (failure) if s/he had <20% reduction in size of the area of erythema associated with the baseline ABSSSI as determined by digital planimetry of the leading edge, or had major intervention such as another antibiotic or surgical intervention or died within 74 hours after initiation of study drug.
Time Frame	48 to 72 hrs after starting treatment

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Delafloxacin	Vancomycin Plus Aztreonam
Arm/Group Description	300mg iv Q12H for 6 doses, 450mg oral tablet Q12H for a minimum of 10 up to a maximum of 28 doses total	Vancomycin 15mg/kg iv plus two grams Aztreonam every 12 hours for a minimum of 10 up to a maximum of 28 doses total
Measure Participants	423	427
Responder	354 83.7%	344 80.6%
Nonresponder	69 16.3%	83 19.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Delafloxacin, Vancomycin Plus Aztreonam
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	A 2-sided 95% confidence interval (CI) for noninferiority testing was computed based on the difference in responder rates for vancomycin + aztreonam and delafloxacin at the primary endpoint. If the upper limit (UL) of the CI was less than 0.10, delafloxacin would be considered noninferior to vancomycin + aztreonam.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Responder Rates
	Estimated Value	3.1
	Confidence Interval	(2-Sided) 95%; -2.0 to 8.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Investigator-assessed Response of Signs and Symptoms of Infection at the Follow up Visit (European Medicines Agency [EMA] Primary Endpoint)
Description	A patient was considered a Cure if all baseline signs and symptoms of ABSSSI had resolved; if some symptoms remained, but the patient was improved to the extent that no additional antibiotic treatment was necessary, the response was Improved. A patient was considered a Failure for any of the following reasons: nonstudy antibacterial drug therapy was required because of lack of efficacy after at least 4 doses of study drug or for a treatment-related AE; study antibacterial drug therapy was required for longer than 28 doses; and/or unplanned surgical intervention was needed after study entry except for limited bedside debridement and standard wound care. Improved and Indeterminate responses were considered failures in the primary analysis. A sensitivity analysis was also performed, in which the assigned responses were Success (Cure + Improved) or Failure (Failure + Indeterminate/Missing).
Time Frame	Study Day 14 ± 1

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Delafloxacin	Vancomycin Plus Aztreonam
Arm/Group Description	300mg iv Q12H for 6 doses, 450mg oral tablet Q12H for a minimum of 10 up to a maximum of 28 doses total	Vancomycin 15mg/kg iv plus two grams Aztreonam every 12 hours for a minimum of 10 up to a maximum of 28 doses total
Measure Participants	423	427
Cure	244 57.7%	255 59.7%
Improved	125 29.6%	107 25.1%
Failure	17 4%	21 4.9%
Indeterminate/Missing	37 8.7%	44 10.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Delafloxacin, Vancomycin Plus Aztreonam
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Analysis of the investigator's assessment of response of signs and symptoms of infection (cure only) was performed using the Miettinen-Nurminen method without stratification for the ITT analysis set.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Cure Rates
	Estimated Value	-2.0
	Confidence Interval	(2-Sided) 95%; -8.6 to 4.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Investigator-assessed Response of Signs and Symptoms of Infection at the Late Follow-up Visit
Description	A patient was considered a Cure if all baseline signs and symptoms of ABSSSI had resolved; if some symptoms remained, but the patient was improved to the extent that no additional antibiotic treatment was necessary, the response was Improved. A patient was considered a Failure for any of the following reasons: nonstudy antibacterial drug therapy was required because of lack of efficacy after at least 4 doses of study drug or for a treatment-related AE; study antibacterial drug therapy was required for longer than 28 doses; and/or unplanned surgical intervention was needed after study entry except for limited bedside debridement and standard wound care. Improved and Indeterminate responses were considered failures in the primary analysis. A sensitivity analysis was also performed, in which the assigned responses were Success (Cure + Improved) or Failure (Failure + Indeterminate/Missing).
Time Frame	Study Day 21 to 28

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Delafloxacin	Vancomycin Plus Aztreonam
Arm/Group Description	300mg iv Q12H for 6 doses, 450mg oral tablet Q12H for a minimum of 10 up to a maximum of 28 doses total	Vancomycin 15mg/kg iv plus two grams Aztreonam every 12 hours for a minimum of 10 up to a maximum of 28 doses total
Measure Participants	423	427
Cure	287 67.8%	303 71%
Improved	66 15.6%	48 11.2%
Failure	21 5%	24 5.6%
Indeterminate/Missing	49 11.6%	52 12.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Delafloxacin, Vancomycin Plus Aztreonam
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Analysis of the investigator's assessment of response (cure only) at the Late Follow-up Visit was assessed using the Miettinen-Nurminen method without stratification.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Cure Rates
	Estimated Value	-3.1
	Confidence Interval	(2-Sided) 95%; -9.3 to 3.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Adverse event data were collected from the time the patient signed informed consent through the follow-up telephone contact 30 (+3) days after the last dose of study drug (up to 48 days).
Adverse Event Reporting Description	AE data are only included for the safety population which included all patients in the ITT population who received at least 1 dose of study drug.
Arm/Group Title	Delafloxacin		Vancomycin Plus Aztreonam
Arm/Group Description	300mg iv Q12H for 6 doses, 450mg oral tablet Q12H for a minimum of 10 up to a maximum of 28 doses total		Vancomycin 15mg/kg iv plus two grams Aztreonam every 12 hours for a minimum of 10 up to a maximum of 28 doses total
All Cause Mortality
	Delafloxacin		Vancomycin Plus Aztreonam
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/417 (0%)		2/425 (0.5%)
Serious Adverse Events
	Delafloxacin		Vancomycin Plus Aztreonam
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/417 (3.8%)		17/425 (4%)
Cardiac disorders
Myocardial infarction	0/417 (0%)		1/425 (0.2%)
Gastrointestinal disorders
Colitis	0/417 (0%)		1/425 (0.2%)
Intestinal ischemia	0/417 (0%)		1/425 (0.2%)
Nausea	0/417 (0%)		1/425 (0.2%)
General disorders
Pyrexia	0/417 (0%)		1/425 (0.2%)
Systemic inflammatory response symdrome	0/417 (0%)		1/425 (0.2%)
Infections and infestations
Abscess limb	1/417 (0.2%)		0/425 (0%)
Arthritis bacterial	0/417 (0%)		1/425 (0.2%)
Cellulitis	1/417 (0.2%)		3/425 (0.7%)
Erysipelas	0/417 (0%)		1/425 (0.2%)
Infection	1/417 (0.2%)		1/425 (0.2%)
Osteomyelitis	1/417 (0.2%)		0/425 (0%)
Pneumonia	1/417 (0.2%)		1/425 (0.2%)
Skin infection	4/417 (1%)		0/425 (0%)
Injury, poisoning and procedural complications
Clavicle fracture	0/417 (0%)		1/425 (0.2%)
Laceration	0/417 (0%)		1/425 (0.2%)
Subdural hematoma	1/417 (0.2%)		1/425 (0.2%)
Toxicity to various agents	1/417 (0.2%)		0/425 (0%)
Wound	0/417 (0%)		2/425 (0.5%)
Investigations
ALT increased	1/417 (0.2%)		0/425 (0%)
AST increased	1/417 (0.2%)		0/425 (0%)
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis	0/417 (0%)		1/425 (0.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of the colon	1/417 (0.2%)		0/425 (0%)
Neoplasm malignant	0/417 (0%)		1/425 (0.2%)
Psychiatric disorders
Schizophrenia	0/417 (0%)		1/425 (0.2%)
Suicidal ideation	0/417 (0%)		1/425 (0.2%)
Renal and urinary disorders
Renal failure	0/417 (0%)		2/425 (0.5%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	1/417 (0.2%)		0/425 (0%)
Pulmonary embolism	2/417 (0.5%)		0/425 (0%)
Skin and subcutaneous tissue disorders
Dermatitis	0/417 (0%)		1/425 (0.2%)
Rash	0/417 (0%)		1/425 (0.2%)
Urticaria	1/417 (0.2%)		0/425 (0%)
Other (Not Including Serious) Adverse Events
	Delafloxacin		Vancomycin Plus Aztreonam
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	55/417 (13.2%)		32/425 (7.5%)
Gastrointestinal disorders
Diarrhea	32/417 (7.7%)		14/425 (3.3%)
Nausea	32/417 (7.7%)		19/425 (4.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Melinta has the right to first publication of results, which would be made in conjunction with the PIs from all appropriate sites. Thereafter, PIs may publish results provided the PI submits the proposed publication to Melinta for review at least 60 days prior to the date of the proposed publication. Melinta may remove any information that is considered confidential and/or proprietary. If a publication is not submitted within 12 months of study conclusion, the PI may publish results.