A Study to Assess Objective Endpoint Measurements of Response in Bacterial Skin Infections

• ClinicalTrials.gov Identifier: NCT01283581
• Recruitment Status: Completed
• First Posted: January 26, 2011
• Results First Posted: October 29, 2013
• Last Update Posted: October 16, 2019
• Sponsor: Melinta Therapeutics, Inc.
• Information provided by (Responsible Party): Melinta Therapeutics, Inc.

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Skin and Subcutaneous Tissue Bacterial Infections
• Interventions: Drug: Delafloxacin; Drug: Linezolid; Drug: Vancomycin
• Enrollment: 256

Participant Flow

Recruitment Details	This study targeted patients with ABSSSI (acute bacterial skin and skin structure infections), defined as cellulitis/erysipelas, wound infection, major cutaneous abscess, or burn infection; the minimum surface area was to be 75 square centimeters.
Pre-assignment Details

Arm/Group Title	Delafloxacin IV (Intravenous)	Linezolid IV	Vancomycin IV
Arm/Group Description	Delafloxacin 300 mg, BID (twice a day)	Linezolid 600 mg, BID	Vancomycin 15 mg/kg or up to 1250 mg/dose, BID
Period Title: Overall Study
Started	81	77	98
Completed	69	63	78
Not Completed	12	14	20
Reason Not Completed
Lost to Follow-up	8	6	8
Withdrawal by Subject	2	5	2
Adverse Event	1	1	4
Physician Decision	0	1	2
Protocol Violation	0	1	2
Noncompliance	1	0	0
Investigator unblinded	0	0	1
"Early termination"	0	0	1

Baseline Characteristics

Arm/Group Title		Delafloxacin IV (Intravenous)	Linezolid	Vancomycin	Total
Arm/Group Description		Delafloxacin 300 mg, BID (twice a day)	Linezolid 600 mg, BID	Vancomycin 15 mg/kg or up to 1250 mg/dose, BID	Total of all reporting groups
Overall Number of Baseline Participants		81	77	98	256
Baseline Analysis Population Description		ITT (intent-to-treat) population, defined as all subjects who were randomized.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	81 participants	77 participants	98 participants	256 participants
		39.7 (14.26)	44.8 (14.91)	44.8 (15.54)	43.2 (15.08)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	81 participants	77 participants	98 participants	256 participants
	Female	32 39.5%	25 32.5%	47 48.0%	104 40.6%
	Male	49 60.5%	52 67.5%	51 52.0%	152 59.4%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	81 participants	77 participants	98 participants	256 participants
	Hispanic or Latino	19 23.5%	11 14.3%	27 27.6%	57 22.3%
	Not Hispanic or Latino	62 76.5%	66 85.7%	71 72.4%	199 77.7%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	81 participants	77 participants	98 participants	256 participants
	American Indian or Alaska Native	3 3.7%	2 2.6%	2 2.0%	7 2.7%
	Asian	0 0.0%	1 1.3%	3 3.1%	4 1.6%
	Native Hawaiian or Other Pacific Islander	3 3.7%	0 0.0%	0 0.0%	3 1.2%
	Black or African American	10 12.3%	15 19.5%	15 15.3%	40 15.6%
	White	63 77.8%	58 75.3%	74 75.5%	195 76.2%
	More than one race	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	2 2.5%	1 1.3%	4 4.1%	7 2.7%
Baseline Infection Category [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	81 participants	77 participants	98 participants	256 participants
Major cutaneous abscess		22	24	29	75
Cellulitis/erysipelas		38	31	44	113
Wound infection		19	20	23	62
Burn infection		2	2	1	5
Not assessed		0	0	1	1
		[1] Measure Description: Categories of infection included major cutaneous abscess, cellulitis/erysipelas, wound infection, or burn infection
Pathogens isolated at baseline; Measure Type: Number; Unit of measure: Participants	Number Analyzed	81 participants	77 participants	98 participants	256 participants
Subjects with at least 1 pathogen		51	57	67	175
Subjects with multiple pathogens		6	15	8	29
Subjects with positive blood cultures		0	6	1	7
Subjects without pathogens		30	20	31	81
Subjects with at least 1 Staphylococcus aureus		45	53	61	159
Subjects with at least 1 MRSA		34	37	35	106
Subjects with at least 1 MSSA		11	16	26	53

Outcome Measures

1. Primary Outcome

Title	Investigator's Assessment of Clinical Response in the ITT (Intent-to-treat) Population at Follow-up
Description	The primary efficacy endpoint was the success rate, defined as (cure)/(cure + failure), and expressed as a percentage. Cure was defined as the complete resolution of all baseline signs and symptoms of ABSSSI and follow-up and late follow-up. If erythema was the only sign of infection present at follow-up and it was then absent at late follow-up, the case was classified as a Cure.
Time Frame	Follow-up (Day 14 ± 1)

Outcome Measure Data

Analysis Population Description

ITT (intent-to-treat) population, defined as all subjects who were randomized.

Arm/Group Title	Delafloxacin IV	Linezolid	Vancomycin
Arm/Group Description:	Delafloxacin 300 mg, BID	Linezolid 600 mg, BID	Vancomycin 15 mg/kg or up to 1250 mg/dose, BID
Overall Number of Participants Analyzed	81	77	98
Measure Type: Number; Unit of Measure: Participants
	57	50	53

2. Secondary Outcome

Title	Erythema Clinical Success
Description	The number of ITT subjects who had cessation of erythema within 48-72 hours, based on digital measurements, as well as resolution/absence of fever. Cessation was defined as a percentage change from baseline in total area of erythema/induration that is less than or equal to 0%.
Time Frame	48 - 72 hours

Outcome Measure Data

Analysis Population Description

ITT (intent-to-treat) population, defined as all subjects who were randomized.

Arm/Group Title	Delafloxacin IV	Linezolid	Vancomycin
Arm/Group Description:	Delafloxacin 300 mg, BID	Linezolid 600 mg, BID	Vancomycin 15 mg/kg or up to 1250 mg/dose, BID
Overall Number of Participants Analyzed	81	77	98
Measure Type: Number; Unit of Measure: Participants
	61	56	69

3. Secondary Outcome

Title	Pharmacokinetic (PK) Parameter, Area Under Curve, (AUCinf, ug*h/mL), in Subjects Administered Delafloxacin, Vancomycin, and Linezolid
Description	Blood samples for pharmacokinetic analyses were drawn from all subjects on Day 3 (± 1 day) of treatment within 2 hours before the first study drug infusion and at 1, 2, 3, 5, and 12 hours (ie, immediately before the second dose) after the start of the first study drug infusion. An analytical, validated method was used to analyze samples and determine human plasma concentrations. The primary pharmacokinetic parameter calculated was area under the plasma concentration - time curve from time 0 extrapolated to infinity (AUCinf, ug*h/mL).
Time Frame	Through Day 3 (± 1 day)

Outcome Measure Data

Analysis Population Description

AUCinf (ug*h/mL) for delafloxacin, linezolid, and vancomycin are presented only for those subjects with PK samples collected.

Arm/Group Title	Delafloxacin	Vancomycin	Linezolid
Arm/Group Description:	300 mg IV every 12 hours for 5-14 days Delafloxacin: 300mg IV every 12 hours for 5-14 days	15 mg/kg, up to 1250 mg, IV every 12 hours for 5-14 dyas Vancomycin: 15mg/kg, up to 1250 mg, IV every 12 hours for 5-14 days	600 mg IV every 12 hours for 5-14 days Linezolid: 600mg IV every 12 hours for 5-14 days
Overall Number of Participants Analyzed	57	35	42
Mean (Standard Deviation); Unit of Measure: ug*h/mL
	23.4 (11.70)	266.8 (88.63)	106.0 (47.33)

4. Secondary Outcome

Title	The Levels of Inflammation Were Examined by Measuring a Surrogate, C-Reactive Protein (CRP)
Description	CRP Levels (g/m3) were analyzed from blood samples collected from subjects at Baseline and various time points throughout the study. Change in baseline values were analyzed using an analysis of covariance (ANCOVA) model with treatment, infection category, and prior antimicrobial therapy as fixed effects and the baseline measure as the covariate.
Time Frame	Baseline, Days 1, 5, Follow-up (FU), and late Follow-up (LFU)

Outcome Measure Data

Analysis Population Description

Only subjects from ITT population with CRP levels evaluated were included in outcome measure analysis.

Arm/Group Title		Delafloxacin	Vancomycin	Linezolid
Arm/Group Description:		300 mg IV every 12 hours for 5-14 days Delafloxacin: 300mg IV every 12 hours for 5-14 days	15 mg/kg, up to 1250 mg, IV every 12 hours for 5-14 dyas Vancomycin: 15mg/kg, up to 1250 mg, IV every 12 hours for 5-14 days	600 mg IV every 12 hours for 5-14 days Linezolid: 600mg IV every 12 hours for 5-14 days
Overall Number of Participants Analyzed		81	98	77
Mean (Standard Deviation); Unit of Measure: g/m3
Baseline	Number Analyzed	71 participants	92 participants	71 participants
		46.6 (70.66)	55.2 (69.70)	49.3 (56.14)
Day 1	Number Analyzed	70 participants	90 participants	68 participants
		44.2 (67.63)	49.6 (58.56)	49.8 (61.66)
Day 5	Number Analyzed	76 participants	94 participants	72 participants
		19.6 (35.97)	19.5 (22.63)	26.5 (48.44)
FU	Number Analyzed	77 participants	94 participants	72 participants
		9.4 (17.65)	11.9 (28.71)	12.1 (26.04)
LFU	Number Analyzed	77 participants	94 participants	72 participants
		10.8 (17.47)	9.3 (16.46)	12.6 (27.10)

5. Secondary Outcome

Title	Microbiological Response Rate in All Subjects (Microbiological Evaluable Population)
Description	Based on the results of the baseline and follow up cultures and susceptibility testing, together with the clinical response assigned by the investigator, the sponsor determined a microbiological response for subjects in the ME population.
Time Frame	Follow-up (Day 14 ± 1)

Outcome Measure Data

Analysis Population Description

Microbiologically Evaluable (ME) Population - All Subjects

Arm/Group Title	Delafloxacin	Vancomycin	Linezolid
Arm/Group Description:	300 mg IV every 12 hours for 5-14 days Delafloxacin: 300mg IV every 12 hours for 5-14 days	15 mg/kg, up to 1250 mg, IV every 12 hours for 5-14 dyas Vancomycin: 15mg/kg, up to 1250 mg, IV every 12 hours for 5-14 days	600 mg IV every 12 hours for 5-14 days Linezolid: 600mg IV every 12 hours for 5-14 days
Overall Number of Participants Analyzed	34	52	39
Measure Type: Count of Participants; Unit of Measure: Participants
Documented Eradicated	0 0.0%	0 0.0%	0 0.0%
Presumed Eradicated	30 88.2%	42 80.8%	32 82.1%
Documented Persisted	0 0.0%	0 0.0%	1 2.6%
Presumed Persisted	4 11.8%	10 19.2%	6 15.4%

6. Secondary Outcome

Title	Microbiological Response Rate in Subjects With MRSA (Methicillin Resistant Staphylococcus Aureus) in Microbiological Evaluable (ME) Population
Description	Based on the results of the baseline and follow up cultures and susceptibility testing, together with the clinical response assigned by the investigator, the sponsor determined a microbiological response for subjects in the ME population.
Time Frame	Follow-up (Day 14 ± 1)

Outcome Measure Data

Analysis Population Description

Microbiologically Evaluable (ME) Population - MRSA Subjects

Arm/Group Title	Delafloxacin	Vancomycin	Linezolid
Arm/Group Description:	300 mg IV every 12 hours for 5-14 days Delafloxacin: 300mg IV every 12 hours for 5-14 days	15 mg/kg, up to 1250 mg, IV every 12 hours for 5-14 dyas Vancomycin: 15mg/kg, up to 1250 mg, IV every 12 hours for 5-14 days	600 mg IV every 12 hours for 5-14 days Linezolid: 600mg IV every 12 hours for 5-14 days
Overall Number of Participants Analyzed	21	26	25
Measure Type: Count of Participants; Unit of Measure: Participants
Documented Eradicated	0 0.0%	0 0.0%	0 0.0%
Presumed Eradicated	18 85.7%	23 88.5%	20 80.0%
Documented Persisted	0 0.0%	0 0.0%	1 4.0%
Presumed Persisted	3 14.3%	3 11.5%	4 16.0%

7. Secondary Outcome

Title	Clinical Response in Subjects With Infections Caused by MRSA - Microbiological ITT (MITT) Population
Description	The success rate, defined as (cure)/(cure + failure), and expressed as a percentage. Cure was defined as the complete resolution of all baseline signs and symptoms of ABSSSI and follow-up and late follow-up. If erythema was the only sign of infection present at follow-up and it was then absent at late follow-up, the case was classified as a Cure.
Time Frame	Follow-up (Day 14 ± 1)

Outcome Measure Data

Analysis Population Description

Microbiological ITT Population (MITT)

Arm/Group Title	Delafloxacin	Vancomycin	Linezolid
Arm/Group Description:	300 mg IV every 12 hours for 5-14 days Delafloxacin: 300mg IV every 12 hours for 5-14 days	15 mg/kg, up to 1250 mg, IV every 12 hours for 5-14 dyas Vancomycin: 15mg/kg, up to 1250 mg, IV every 12 hours for 5-14 days	600 mg IV every 12 hours for 5-14 days Linezolid: 600mg IV every 12 hours for 5-14 days
Overall Number of Participants Analyzed	29	32	34
Measure Type: Count of Participants; Unit of Measure: Participants
	19 65.5%	21 65.6%	21 61.8%

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	The safety population in this study was defined as all enrolled subjects who received at least 1 dose of study drug. The respective subjects numbers were 78 (delafloxacin), 75 (linezolid), and 96 (vancomycin).
Arm/Group Title	Delafloxacin IV		Linezolid		Vancomycin
Arm/Group Description	Delafloxacin 300 mg, BID		Linezolid 600 mg, BID		Vancomycin 15 mg/kg or up to 1250 mg/dose, BID
All-Cause Mortality
	Delafloxacin IV		Linezolid		Vancomycin
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--		--/--
Serious Adverse Events
	Delafloxacin IV		Linezolid		Vancomycin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/78 (6.41%)		2/75 (2.67%)		6/96 (6.25%)
Blood and lymphatic system disorders
Anaemia † 1	0/78 (0.00%)	0	0/75 (0.00%)	0	1/96 (1.04%)	1
Cardiac disorders
Cardiac Failure Congestive † 1	1/78 (1.28%)	1	0/75 (0.00%)	0	1/96 (1.04%)	1
Gastrointestinal disorders
Abdominal Pain † 1	0/78 (0.00%)	0	1/75 (1.33%)	1	1/96 (1.04%)	1
Diarrhoea † 1	0/78 (0.00%)	0	0/75 (0.00%)	0	1/96 (1.04%)	1
Nausea † 1	0/78 (0.00%)	0	0/75 (0.00%)	0	1/96 (1.04%)	1
Vomiting † 1	0/78 (0.00%)	0	0/75 (0.00%)	0	1/96 (1.04%)	1
General disorders
Chest Pain † 1	0/78 (0.00%)	0	0/75 (0.00%)	0	1/96 (1.04%)	1
Pyrexia † 1	1/78 (1.28%)	1	0/75 (0.00%)	0	1/96 (1.04%)	1
Infections and infestations
Abscess † 1	1/78 (1.28%)	1	0/75 (0.00%)	0	0/96 (0.00%)	0
Bacteraemia † 1	1/78 (1.28%)	1	0/75 (0.00%)	0	0/96 (0.00%)	0
Cellulitis † 1	1/78 (1.28%)	1	1/75 (1.33%)	1	1/96 (1.04%)	1
Infection † 1	0/78 (0.00%)	0	0/75 (0.00%)	0	1/96 (1.04%)	1
Osteomyelitis † 1	0/78 (0.00%)	0	0/75 (0.00%)	0	1/96 (1.04%)	1
Metabolism and nutrition disorders
Dehydration † 1	0/78 (0.00%)	0	0/75 (0.00%)	0	1/96 (1.04%)	1
Nervous system disorders
Convulsion † 1	2/78 (2.56%)	2	0/75 (0.00%)	0	0/96 (0.00%)	0
Renal and urinary disorders
Renal Failure Acute † 1	0/78 (0.00%)	0	0/75 (0.00%)	0	1/96 (1.04%)	1
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 13.1
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Delafloxacin IV		Linezolid		Vancomycin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	59/78 (75.64%)		54/75 (72.00%)		62/96 (64.58%)
Gastrointestinal disorders
Constipation † 1	1/78 (1.28%)	1	5/75 (6.67%)	5	4/96 (4.17%)	4
Diarrhoea † 1	12/78 (15.38%)	12	5/75 (6.67%)	5	4/96 (4.17%)	4
Nausea † 1	17/78 (21.79%)	17	16/75 (21.33%)	16	13/96 (13.54%)	13
Vomiting † 1	10/78 (12.82%)	10	6/75 (8.00%)	6	8/96 (8.33%)	8
Infusion Site Pain † 1	4/78 (5.13%)	4	7/75 (9.33%)	7	5/96 (5.21%)	5
General disorders
Fatigue † 1	5/78 (6.41%)	5	3/75 (4.00%)	3	6/96 (6.25%)	6
Infections and infestations
Abscess Limb † 1	2/78 (2.56%)	2	4/75 (5.33%)	4	2/96 (2.08%)	2
Cellulitis † 1	3/78 (3.85%)	3	3/75 (4.00%)	3	5/96 (5.21%)	5
Skin Infection † 1	2/78 (2.56%)	2	4/75 (5.33%)	4	2/96 (2.08%)	2
Vulvovaginal Mycotic Infection † 1	4/78 (5.13%)	4	0/75 (0.00%)	0	0/96 (0.00%)	0
Nervous system disorders
Dizziness † 1	5/78 (6.41%)	5	1/75 (1.33%)	1	1/96 (1.04%)	1
Headache † 1	5/78 (6.41%)	5	5/75 (6.67%)	5	5/96 (5.21%)	5
Skin and subcutaneous tissue disorders
Pruritis † 1	6/78 (7.69%)	6	6/75 (8.00%)	6	20/96 (20.83%)	20
Rash † 1	2/78 (2.56%)	2	5/75 (6.67%)	5	2/96 (2.08%)	2
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 13.1

Limitations and Caveats

[Not Specified]

More Information

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.

Results Point of Contact

• Name/Title: Dr. Sue Cammarata
• Organization: Melinta Therapeutics
• Phone: 312-724-9401
• EMail: scammarata@melinta.com

Publications of Results:

Results of a Phase 2 Study of Delafloxacin (DLX) Compared to Vancomycin (VAN) and Linezolid (LNZ) in Acute Bacterial Skin and Skin Structure Infections (ABSSSI) J. Longcor 1 , S. Hopkins 1 , L. Lawrence 1 , S. Green 2 , P. Mehra 2 , P. Manos 2 , W. Sears 2 , W. O'Riordan 2 1 Rib - X Pharmaceuticals, Inc., New Haven, CT; 2 eStudySite, San Diego, CA 52nd ICAAC, San Francisco, CA 2012

Characterization and In Vitro Activity of Delafloxacin (DLX) Against Isolates from a Phase 2 Study of Acute Bacterial Skin and Skin Structure Infections (ABSSSI) L. Lawrence 1 , S. Hopkins 1 , D. Sahm 2 , Jennifer Deane 2 , E. Burak 1 , J. Longcor 1 1 Rib - X Pharmaceuticals, Inc., New Haven, CT; 2 Eurofins Medinet, Chantilly, VA 52nd ICAAC, San Franciso, 2012

Pharmacokinetics (PK) of Delafloxacin (DLX), Vancomycin (VAN), and Linezolid (LNZ) in a Phase 2 Exploratory Study in Subjects with Acute Bacterial Skin and Skin Structure Infections (ABSSSI) R. Hoover 1 , L. Lawrence 1 , J. Longcor 1 , J. Greenfield 2 1 Rib - X Pharmaceuticals, New Haven, CT; 2 PharmaNet/i3, The Woodlands, TX 52nd ICAAC, San Francisco, CA, 2012

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Kingsley J, Mehra P, Lawrence LE, Henry E, Duffy E, Cammarata SK, Pullman J. A randomized, double-blind, Phase 2 study to evaluate subjective and objective outcomes in patients with acute bacterial skin and skin structure infections treated with delafloxacin, linezolid or vancomycin. J Antimicrob Chemother. 2016 Mar;71(3):821-9. doi: 10.1093/jac/dkv411. Epub 2015 Dec 17.

• Responsible Party: Melinta Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT01283581
• Other Study ID Numbers: RX-3341-202
• First Submitted: January 24, 2011
• First Posted: January 26, 2011
• Results First Submitted: August 23, 2013
• Results First Posted: October 29, 2013
• Last Update Posted: October 16, 2019