A Study to Assess Objective Endpoint Measurements of Resp... | NCT01283581

NCT01283581

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Delafloxacin	Experimental	300 mg IV (intravenous) every 12 hours for 5-14 days	Drug: Delafloxacin
Vancomycin	Active Comparator	15 mg/kg, up to 1250 mg, IV every 12 hours for 5-14 dyas	Drug: Vancomycin
Linezolid	Active Comparator	600 mg IV every 12 hours for 5-14 days	Drug: Linezolid

Name	Type	Description	Arm Group Labels	Other Names
Delafloxacin	Drug	300mg IV every 12 hours for 5-14 days	Delafloxacin

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Investigator's Assessment of Clinical Response in the ITT (Intent-to-treat) Population at Follow-up	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.	Follow-up (Day 14 ± 1)

Secondary Outcomes

Measure	Description	Time Frame
Erythema Clinical Success	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%.	48 - 72 hours

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Adult (≥ 18 years of age) men or women
Sexually active women and men with partners of childbearing potential must agree to use an acceptable form of contraception as determined by the investigator during participation in the study and for 30 days after the final dose of study drug
Female partners of male subjects should also use an additional reliable method of contraception during study and for 30 days after the final dose of study drug
Subjects must have a diagnosis of ABSSSI - one or more of the following 4 infection types: cellulitis/erysipelas, wound infection, major cutaneous abscess, or burn infection
Subjects must have lymph node enlargement due to the present infection or at least one of the following symptoms of systemic infection: fever ≥ 38°C, lymphangitis, WBC (white blood cell) count ≥ 15,000 cells/μL, elevated C-reactive protein (> 5.0mg/L)
In the opinion of the investigator, the subject must require and be a suitable candidate for IV antibiotic therapy

Exclusion Criteria:

A medical history of significant hypersensitivity or allergic reaction to quinolones, linezolid, vancomycin, or vancomycin derivatives
Women who are pregnant or lactating
Any chronic or underlying skin condition at the site of infection that may complicate the assessment of response
Subjects with any of the following: infection involving prosthetic materials or foreign bodies, infection associated with a human or animal bite, osteomyelitis, decubitus ulcer, diabetic foot ulcer, septic arthritis, mediastinitis, necrotizing fasciitis, anaerobic cellulitis, or synergistic necrotizing cellulitis, myositis, tendinitis, endocarditis, toxic shock syndrome, gangrene, burns covering ≥ 10% of body surface area, severely impaired arterial blood supply, current evidence of deep vein thrombosis or superficial thrombophlebitis
Minor abscesses, unless present with one of the ABSSSI types
Any infection expected to require other antimicrobial agents in addition to study drug
Receipt of > 24 hours of systemic antibiotic therapy in the 14 days before enrollment unless one of the following is documented: the subject received a single dose of a short-acting antibacterial drug 3 or more days before clinical trial enrollment for surgical prophylaxis or recently completed treatment with an antibacterial drug for an infection other than ABSSSI and the drug does not have antibacterial activity against bacterial pathogens that cause ABSSSI
Receipt of more than 1 dose of a potentially effective antibacterial agent for treatment of the ABSSSI under study prior to enrollment
Receipt of chronic anti-inflammatory therapy for longer than 14 days before enrollment
Severely compromised immune systems
Subjects taking any medicinal product which inhibits monoamine oxidases A or B or within 2 weeks of Screening
Hypertension as defined by a systolic blood pressure of ≥ 180 mmHg or a diastolic blood pressure of ≥110 mmHg with confirmed re-check within 20 minutes of initial reading
Subjects with pheochromocytoma, thyrotoxicosis and/or subjects taking any of the following types of medications: sympathomimetic agents, vasopressive agents, dopaminergic agents, or other agents with the potential for serotonergic interactions
Subjects with carcinoid syndrome and/or subjects taking any of the following medications: serotonin re-uptake inhibitors, tricyclic antidepressants, serotonin 5-HT1 (serotonin receptor) receptor agonists, meperidine, or buspirone
Known history of liver disease
History of severe renal impairment
Life expectancy of < 3 months
Any underlying disease that, in the opinion of the investigator, could interfere with the subject's ability to participate in the study
Subjects previously randomized in this study or in who have received a dose of an investigational drug within 30 days of randomization
Subjects > 140 kg in body weight

Contacts/Locations Module

Name	Affiliation	Role
Scott Hopkins, MD		Study Director

Facility	Status	City	State	ZIP	Country	Contacts
University of South Alabama Medical Center		Mobile	Alabama	36617	United States
Drug Research and Analysis Corp

References Module

Citations

PubMed Identifier	Type	Citation
	Result	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
	Result	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
	Result	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
26679243

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

ID	Title	Description
FG000	Delafloxacin IV (Intravenous)	Delafloxacin 300 mg, BID (twice a day)
FG001	Linezolid IV	Linezolid 600 mg, BID

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

No data available

No data is available for this block.

Intervention Browse Module

Masking Info

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

Arm/Group Information

ID	Title	Description
BG000	Delafloxacin IV (Intravenous)	Delafloxacin 300 mg, BID (twice a day)
BG001	Linezolid	Linezolid 600 mg, BID
BG002	Vancomycin	Vancomycin 15 mg/kg or up to 1250 mg/dose, BID
BG003	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00039.7± 14.26 BG00144.8± 14.91 BG00244.8± 15.54 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00032 BG00125 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG00019 BG00111 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0003 BG0012 BG002

Baseline Infection Category

Categories of infection included major cutaneous abscess, cellulitis/erysipelas, wound infection, or burn infection

Number

Participants

Title

Denominators

Categories

Major cutaneous abscess

Title	Measurements
	BG00022 BG00124

Pathogens isolated at baseline

Number

Participants

Title

Denominators

Categories

Subjects with at least 1 pathogen

Title	Measurements
	BG00051 BG00157 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Investigator's Assessment of Clinical Response in the ITT (Intent-to-treat) Population at Follow-up

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.

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

Posted

Number

Participants

Follow-up (Day 14 ± 1)

ID	Title	Description
OG000	Delafloxacin IV	Delafloxacin 300 mg, BID
OG001	Linezolid	Linezolid 600 mg, BID
OG002	Vancomycin	Vancomycin 15 mg/kg or up to 1250 mg/dose, BID

Units	Counts
Participants	OG00081 OG00177 OG00298

Title

Denominators

Categories

Title	Measurements
	OG00057 OG00150 OG00253

Secondary

Erythema Clinical Success

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%.

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

Posted

Number

Participants

48 - 72 hours

ID	Title	Description
OG000	Delafloxacin IV	Delafloxacin 300 mg, BID
OG001	Linezolid	Linezolid 600 mg, BID
OG002	Vancomycin	Vancomycin 15 mg/kg or up to 1250 mg/dose, BID

Units	Counts
Participants	OG000

Secondary

Pharmacokinetic (PK) Parameter, Area Under Curve, (AUCinf, ug*h/mL), in Subjects Administered Delafloxacin, Vancomycin, and Linezolid

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).

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

Posted

Mean

Standard Deviation

ug*h/mL

Through Day 3 (± 1 day)

ID	Title	Description
OG000	Delafloxacin	300 mg IV every 12 hours for 5-14 days Delafloxacin: 300mg IV every 12 hours for 5-14 days
OG001	Vancomycin	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
OG002	Linezolid	600 mg IV every 12 hours for 5-14 days Linezolid: 600mg IV every 12 hours for 5-14 days

Secondary

The Levels of Inflammation Were Examined by Measuring a Surrogate, C-Reactive Protein (CRP)

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.

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

Posted

Mean

Standard Deviation

g/m3

Baseline, Days 1, 5, Follow-up (FU), and late Follow-up (LFU)

ID	Title	Description
OG000	Delafloxacin	300 mg IV every 12 hours for 5-14 days Delafloxacin: 300mg IV every 12 hours for 5-14 days
OG001	Vancomycin	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
OG002	Linezolid	600 mg IV every 12 hours for 5-14 days Linezolid: 600mg IV every 12 hours for 5-14 days

Secondary

Microbiological Response Rate in All Subjects (Microbiological Evaluable Population)

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.

Microbiologically Evaluable (ME) Population - All Subjects

Posted

Count of Participants

Participants

Follow-up (Day 14 ± 1)

ID	Title	Description
OG000	Delafloxacin	300 mg IV every 12 hours for 5-14 days Delafloxacin: 300mg IV every 12 hours for 5-14 days
OG001	Vancomycin	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
OG002	Linezolid	600 mg IV every 12 hours for 5-14 days Linezolid: 600mg IV every 12 hours for 5-14 days

Units	Counts
Participants

Secondary

Microbiological Response Rate in Subjects With MRSA (Methicillin Resistant Staphylococcus Aureus) in Microbiological Evaluable (ME) Population

Microbiologically Evaluable (ME) Population - MRSA Subjects

Posted

Count of Participants

Participants

Follow-up (Day 14 ± 1)

ID	Title	Description
OG000	Delafloxacin	300 mg IV every 12 hours for 5-14 days Delafloxacin: 300mg IV every 12 hours for 5-14 days
OG001	Vancomycin	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
OG002	Linezolid	600 mg IV every 12 hours for 5-14 days Linezolid: 600mg IV every 12 hours for 5-14 days

Units	Counts

Secondary

Clinical Response in Subjects With Infections Caused by MRSA - Microbiological ITT (MITT) Population

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.

Microbiological ITT Population (MITT)

Posted

Count of Participants

Participants

Follow-up (Day 14 ± 1)

ID	Title	Description
OG000	Delafloxacin	300 mg IV every 12 hours for 5-14 days Delafloxacin: 300mg IV every 12 hours for 5-14 days
OG001	Vancomycin	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
OG002	Linezolid	600 mg IV every 12 hours for 5-14 days Linezolid: 600mg IV every 12 hours for 5-14 days

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Delafloxacin IV	Delafloxacin 300 mg, BID	5	78	59	78
EG001	Linezolid	Linezolid 600 mg, BID	2	75	54	75
EG002	Vancomycin	Vancomycin 15 mg/kg or up to 1250 mg/dose, BID	6	96	62	96

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected78 at risk EG0010 events0 affected75 at risk EG0021 events1 affected96 at risk
Cardiac Failure Congestive	Cardiac disorders	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected78 at risk EG0010 events0 affected75 at risk EG0021 events1 affected96 at risk
Abdominal Pain	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected78 at risk EG0011 events1 affected75 at risk EG0021 events1 affected96 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected78 at risk EG0010 events0 affected75 at risk EG0021 events1 affected96 at risk
Nausea	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected78 at risk EG0010 events0 affected75 at risk EG0021 events1 affected96 at risk
Vomiting	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected78 at risk EG0010 events0 affected75 at risk EG0021 events1 affected96 at risk
Chest Pain	General disorders	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected78 at risk EG0010 events0 affected75 at risk EG0021 events1 affected96 at risk
Pyrexia	General disorders	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected78 at risk EG0010 events0 affected75 at risk EG0021 events1 affected96 at risk
Abscess	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected78 at risk EG0010 events0 affected75 at risk EG0020 events0 affected96 at risk
Bacteraemia	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected78 at risk EG0010 events0 affected75 at risk EG0020 events0 affected96 at risk
Cellulitis	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected78 at risk EG0011 events1 affected75 at risk EG0021 events1 affected96 at risk
Infection	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected78 at risk EG0010 events0 affected75 at risk EG0021 events1 affected96 at risk
Osteomyelitis	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected78 at risk EG0010 events0 affected75 at risk EG0021 events1 affected96 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected78 at risk EG0010 events0 affected75 at risk EG0021 events1 affected96 at risk
Convulsion	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG0002 events2 affected78 at risk EG0010 events0 affected75 at risk EG0020 events0 affected96 at risk
Renal Failure Acute	Renal and urinary disorders	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected78 at risk EG0010 events0 affected75 at risk EG0021 events1 affected96 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Constipation	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected78 at risk EG0015 events5 affected75 at risk EG0024 events4 affected96 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG00012 events12 affected78 at risk EG0015 events5 affected75 at risk EG0024 events4 affected96 at risk
Nausea	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG00017 events17 affected78 at risk EG00116 events16 affected75 at risk EG00213 events13 affected96 at risk
Vomiting	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG00010 events10 affected78 at risk EG0016 events6 affected75 at risk EG0028 events8 affected96 at risk
Fatigue	General disorders	MedDRA 13.1	Systematic Assessment	EG0005 events5 affected78 at risk EG0013 events3 affected75 at risk EG0026 events6 affected96 at risk
Infusion Site Pain	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0004 events4 affected78 at risk EG0017 events7 affected75 at risk EG0025 events5 affected96 at risk
Abscess Limb	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0002 events2 affected78 at risk EG0014 events4 affected75 at risk EG0022 events2 affected96 at risk
Cellulitis	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0003 events3 affected78 at risk EG0013 events3 affected75 at risk EG0025 events5 affected96 at risk
Skin Infection	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0002 events2 affected78 at risk EG0014 events4 affected75 at risk EG0022 events2 affected96 at risk
Vulvovaginal Mycotic Infection	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0004 events4 affected78 at risk EG0010 events0 affected75 at risk EG0020 events0 affected96 at risk
Dizziness	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG0005 events5 affected78 at risk EG0011 events1 affected75 at risk EG0021 events1 affected96 at risk
Headache	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG0005 events5 affected78 at risk EG0015 events5 affected75 at risk EG0025 events5 affected96 at risk
Pruritis	Skin and subcutaneous tissue disorders	MedDRA 13.1	Systematic Assessment	EG0006 events6 affected78 at risk EG0016 events6 affected75 at risk EG00220 events20 affected96 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 13.1	Systematic Assessment	EG0002 events2 affected78 at risk EG0015 events5 affected75 at risk EG0022 events2 affected96 at risk

ID	Term
C477891	delafloxacin
D000069349	Linezolid
D014640	Vancomycin

Ancestor Terms

ID	Term
D000081	Acetamides
D000577	Amides
D009930	Organic Chemicals
D000085	Acetates
D000144	Acids, Acyclic
D002264	Carboxylic Acids
D023303	Oxazolidinones
D010080	Oxazoles
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D006020	Glycopeptides
D006001	Glycoconjugates
D002241	Carbohydrates
D010455	Peptides
D000602	Amino Acids, Peptides, and Proteins

Units	Counts
Participants	OG00081 OG00198 OG00277