Safety and Efficacy Study of a Fluoroquinolone to Treat Complicated Skin Infections

• Sponsor: Melinta Therapeutics, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00719810
• Collaborator: (none)
• Enrollment: 150
• Locations: 14
• Arms: 3
• Duration (Months): 4
• Patients Per Site: 10.7
• Patients Per Site Per Month: 2.7

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the efficacy, safety and tolerability of RX-3341 (delafloxacin), a fluoroquinolone, versus tigecycline, a glycylcycline antibacterial drug, in the treatment of complicated skin and skin structure infections.

Condition or Disease	Intervention/Treatment	Phase
Skin Structure Infections; Bacterial Skin Diseases; Staphylococcal Skin Infections	Drug: delafloxacin; Drug: delafloxacin; Drug: tigecycline	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 150 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Multicenter Study of the Safety and Efficacy of RX 3341 Compared With Tigecycline for the Treatment of Complicated Skin and Skin Structure Infections
• Study Start Date: Jun 1, 2008
• Actual Primary Completion Date: Oct 1, 2008
• Actual Study Completion Date: Oct 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: delafloxacin; 300 mg intravenous every 12 hours
Experimental: 2	Drug: delafloxacin; 450 mg intravenous every 12 hours
Active Comparator: 3	Drug: tigecycline; 100 mg then 50 mg intravenous tigecycline every 12 hours

Outcome Measures

Primary Outcome Measures

1. Clinical Response at Test of Cure (TOC) in the Clinically Evaluable (CE) Population [14-21 days after the last dose of study drug]

   A Cure was defined as resolution of baseline signs and symptoms, or improvement to an extent that no additional antibiotic treatment is necessary. Failure was defined as the need for additional antibiotics, either because of lack of efficacy after at least 2 days (i.e., 4 doses) of study treatment or because of treatment-related adverse events (AEs), and/or the need for surgical intervention greater than 48 hours after study entry.

Secondary Outcome Measures

1. Clinical Response in Patients With Methicillin-resistant Staphylococcus Aureus (MRSA) [14-21 days after the last dose of study drug]

   A Cure was defined as resolution of baseline signs and symptoms, or improvement to an extent that no additional antibiotic treatment is necessary. Failure was defined as the need for additional antibiotics, either because of lack of efficacy after at least 2 days (i.e., 4 doses) of study treatment or because of treatment-related adverse events (AEs), and/or the need for surgical intervention greater than 48 hours after study entry.

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 cSSSI

• Diagnosis of one of the following 3 types of cSSSI: wound infection that has developed within 30 days of surgery, trauma, or a bite injury; abscess that has developed in the 7 days before enrollment; or cellulitis that has developed in the 7 days before enrollment

• Sexually active men and women 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

• The patient must be willing to comply with protocol requirements

Exclusion Criteria:

• Medical history of hypersensitivity or allergic reaction to quinolones, tetracycline or tetracycline derivatives

• Chronic or underlying skin condition at the site of infection

• Infection involving prosthetic materials or foreign bodies (unless prosthetic material will be removed within 24 hours), infection associated with a human bite, osteomyelitis, decubitus ulcer, diabetic foot ulcer, septic arthritis, mediastinitis, necrotizing fasciitis, myositis, tendinitis, endocarditis, toxic shock syndrome, gangrene or gas gangrene, burns covering ≥10% of body surface area, severely impaired arterial blood supply, current evidence of deep vein thrombosis or superficial thrombophlebitis

• An infection that would normally have a high cure rate after surgical incision alone

• Any infection expected to require other antimicrobial agents in addition to study drug

• Receipt of >24 hours of systemic antibiotic therapy in the 7 days before enrollment

• A severely compromised immune system

• History of Child-Pugh Class B or C liver disease or severe renal impairment (creatinine clearance of <30 mL/minute)

• Pregnancy or lactation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Physician Alliance Research Center	Anaheim	California	United States
2	Quality of Life Medical Center, LLC	Hawaiian Gardens	California	United States
3	Tri City Medical Center	Oceanside	California	United States
4	Crest Clinical Trials	Santa Ana	California	United States
5	Internal Medicine Associates of Lee County	Fort Myers	Florida	United States
6	Joseph M. Still Research Foundation, Inc.	Augusta	Georgia	United States
7	Southeast Regional Research Group	Columbus	Georgia	United States
8	Southeast Regional Research Group	Ludowici	Georgia	United States
9	Southeast Regional Research Group	Savannah	Georgia	United States
10	St. James Health Care	Butte	Montana	United States
11	Riverside Methodist Hospital	Columbus	Ohio	United States
12	West Houston Clinical Research Services	Houston	Texas	United States
13	Westbury Medical Clinic	Houston	Texas	United States
14	Clinical Research Puerto Rico, Inc	San Juan		Puerto Rico

Sponsors and Collaborators

• Melinta Therapeutics, Inc.

Investigators

• Study Director: Jeanne Breen, MD, Melinta Therapeutics, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Melinta Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT00719810
• Other Study ID Numbers: RX-3341-201
• First Posted: Jul 22, 2008
• Last Update Posted: Jul 14, 2014
• Last Verified: Jun 1, 2014

• Keywords provided by Melinta Therapeutics, Inc.: complicated; skin
• Additional relevant MeSH terms: Infections; Communicable Diseases; Cellulitis; Skin Diseases, Infectious; Staphylococcal Skin Infections; Skin Diseases, Bacterial; Skin Diseases; Tigecycline; Fluoroquinolones

Study Results

Participant Flow

Recruitment Details	This study targeted participants with complicated skin and skin structure infections (cSSSI), i.e. infections involving subcutaneous tissues or requiring surgical intervention. Patients could have one of three infection types: wound infection, abscess, or cellulitis.

Arm/Group Title	Delafloxacin 300 mg IV q12h	Delafloxacin 450 mg IV q12h	Tigecycline 100 mg IV x 1, Followed by 50 mg IV q12h
Arm/Group Description
Period Title: Overall Study
STARTED	49	51	50
COMPLETED	46	47	42
NOT COMPLETED	3	4	8

Baseline Characteristics

Arm/Group Title	Delafloxacin 300 mg IV q12h	Delafloxacin 450 mg IV q12h	Tigecycline 100 mg IV x 1, Followed by 50 mg IV q12h	Total
Arm/Group Description	Total of all reporting groups
Overall Participants	49	51	50	150
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42.7 (15.10)	37.2 (14.35)	40.4 (13.83)	40.1 (14.51)
Sex: Female, Male (Count of Participants)
Female	18 36.7%	15 29.4%	15 30%	48 32%
Male	31 63.3%	36 70.6%	35 70%	102 68%

Outcome Measures

1. Primary Outcome

Title	Clinical Response at Test of Cure (TOC) in the Clinically Evaluable (CE) Population
Description	A Cure was defined as resolution of baseline signs and symptoms, or improvement to an extent that no additional antibiotic treatment is necessary. Failure was defined as the need for additional antibiotics, either because of lack of efficacy after at least 2 days (i.e., 4 doses) of study treatment or because of treatment-related adverse events (AEs), and/or the need for surgical intervention greater than 48 hours after study entry.
Time Frame	14-21 days after the last dose of study drug

Outcome Measure Data

Analysis Population Description

The CE population included patients with a diagnosis of cSSSI who received at least 80% of study drug, had a test of cure (TOC) visit 14-21 days after the last dose of study drug, and who did not receive any concomitant, systemic antibacterial therapy with activity against the causative pathogen.

Arm/Group Title	Delafloxacin 300 mg IV q12h	Delafloxacin 450 mg IV q12h	Tigecycline 100 mg IV x 1, Followed by 50 mg IV q12h
Arm/Group Description
Measure Participants	35	40	34
Number [Participants]	33 67.3%	37 72.5%	31 62%

2. Secondary Outcome

Title	Clinical Response in Patients With Methicillin-resistant Staphylococcus Aureus (MRSA)
Description	A Cure was defined as resolution of baseline signs and symptoms, or improvement to an extent that no additional antibiotic treatment is necessary. Failure was defined as the need for additional antibiotics, either because of lack of efficacy after at least 2 days (i.e., 4 doses) of study treatment or because of treatment-related adverse events (AEs), and/or the need for surgical intervention greater than 48 hours after study entry.
Time Frame	14-21 days after the last dose of study drug

Outcome Measure Data

Analysis Population Description

Clinically Evaluable (CE) patients (see previous definition) with MRSA isolated from screening culture of primary infection.

Arm/Group Title	Delafloxacin 300 mg IV q12h	Delafloxacin 450 mg IV q12h	Tigecycline 100 mg IV x 1, Followed by 50 mg IV q12h
Arm/Group Description
Measure Participants	14	20	14
Number [Participants]	13 26.5%	19 37.3%	12 24%

Adverse Events

Time Frame	All adverse events (AEs) that occurred from the time the patient signed the informed consent form (ICF) were to be reported on the appropriate electronic case report form (eCRF).
Arm/Group Title	Delafloxacin 300 mg IV q12h		Delafloxacin 450 mg IV q12h		Tigecycline 100 mg IV x 1, Followed by 50 mg IV q12h
Arm/Group Description
All Cause Mortality
	Delafloxacin 300 mg IV q12h		Delafloxacin 450 mg IV q12h		Tigecycline 100 mg IV x 1, Followed by 50 mg IV q12h
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Delafloxacin 300 mg IV q12h		Delafloxacin 450 mg IV q12h		Tigecycline 100 mg IV x 1, Followed by 50 mg IV q12h
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/49 (2%)		3/51 (5.9%)		3/50 (6%)
Cardiac disorders
Bradycardia	0/49 (0%)	0	1/51 (2%)	1	0/50 (0%)	0
Gastrointestinal disorders
Duodenal ulcer hemorrhage	0/49 (0%)	0	0/51 (0%)	0	1/50 (2%)	1
Infections and infestations
Cellulitis	0/49 (0%)	0	0/51 (0%)	0	1/50 (2%)	1
Osteomyelitis	0/49 (0%)	0	1/51 (2%)	1	0/50 (0%)	0
Injury, poisoning and procedural complications
Femoral neck fracture	1/49 (2%)	1	0/51 (0%)	0	0/50 (0%)	0
Nervous system disorders
Cerebellar infarction	0/49 (0%)	0	0/51 (0%)	0	1/50 (2%)	1
Convulsion	0/49 (0%)	0	1/51 (2%)	1	0/50 (0%)	0
Vascular disorders
Subclavian vein thrombosis	0/49 (0%)	0	0/51 (0%)	0	1/50 (2%)	1
Other (Not Including Serious) Adverse Events
	Delafloxacin 300 mg IV q12h		Delafloxacin 450 mg IV q12h		Tigecycline 100 mg IV x 1, Followed by 50 mg IV q12h
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/49 (28.6%)		32/51 (62.7%)		36/50 (72%)
Gastrointestinal disorders
Constipation	0/49 (0%)	0	0/51 (0%)	0	4/50 (8%)	4
Diarrhea	5/49 (10.2%)	5	12/51 (23.5%)	12	5/50 (10%)	5
Nausea	6/49 (12.2%)	6	13/51 (25.5%)	13	23/50 (46%)	23
Vomiting	0/49 (0%)	0	6/51 (11.8%)	6	14/50 (28%)	14
General disorders
Fatigue	0/49 (0%)	0	4/51 (7.8%)	4	0/50 (0%)	0
Infusion site pain	0/49 (0%)	0	7/51 (13.7%)	7	0/50 (0%)	0
Infections and infestations
Subcutaneous abscess	0/49 (0%)	0	4/51 (7.8%)	4	0/50 (0%)	0
Injury, poisoning and procedural complications
Skin laceration	0/49 (0%)	0	0/51 (0%)	0	3/50 (6%)	3
Investigations
Alanine aminotransferase increased	3/49 (6.1%)	3	0/51 (0%)	0	0/50 (0%)	0
Nervous system disorders
Dizziness	0/49 (0%)	0	1/51 (2%)	1	4/50 (8%)	4
Headache	0/49 (0%)	0	4/51 (7.8%)	4	6/50 (12%)	6
Skin and subcutaneous tissue disorders
Rash	0/49 (0%)	0	2/51 (3.9%)	2	3/50 (6%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The sponsor retains control of all publication rights.