Trial Outcomes & Findings for Delafloxacin vs Vancomycin and Aztreonam for the Treatment of Acute Bacterial Skin and Skin Structure Infections (NCT NCT01984684)

NCT ID: NCT01984684

Last Updated: 2017-11-17

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

850 participants

Primary outcome timeframe

48 to 72 hrs after starting treatment

Results posted on

2017-11-17

Participant Flow

Participant milestones

Participant milestones
Measure	Delafloxacin 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 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
Overall Study STARTED	423	427
Overall Study COMPLETED	366	368
Overall Study NOT COMPLETED	57	59

Reasons for withdrawal

Reasons for withdrawal
Measure	Delafloxacin 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 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
Overall Study Lost to Follow-up	25	24
Overall Study Adverse Event	8	12
Overall Study Withdrawal by Subject	9	9
Overall Study Lack of Efficacy	3	6
Overall Study Physician Decision	4	2
Overall Study Protocol Violation	4	2
Overall Study Death	0	1
Overall Study Noncompliance with study drug	2	1
Overall Study Subject incarcerated	1	0
Overall Study Study drug not available at site	1	1
Overall Study Subject had inadequate IV access	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Delafloxacin n=423 Participants 300mg iv Q12H for 6 doses, 450mg oral tablet Q12H for a minimum of 10 up to a maximum of 28 doses total	Vancomycin Plus Aztreonam n=427 Participants 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 n=850 Participants Total of all reporting groups
Region of Enrollment Europe	165 Participants n=5 Participants	173 Participants n=7 Participants	338 Participants n=5 Participants
Region of Enrollment North America	202 Participants n=5 Participants	196 Participants n=7 Participants	398 Participants n=5 Participants
Region of Enrollment Mexico	8 Participants n=5 Participants	4 Participants n=7 Participants	12 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	37 Participants n=5 Participants	30 Participants n=7 Participants	67 Participants n=5 Participants
Age, Continuous	51.2 years STANDARD_DEVIATION 15.98 • n=5 Participants	50.2 years STANDARD_DEVIATION 16.03 • n=7 Participants	50.7 years STANDARD_DEVIATION 16.00 • n=5 Participants
Age, Customized <= 65 years	344 Participants n=5 Participants	352 Participants n=7 Participants	696 Participants n=5 Participants
Age, Customized > 65 years	79 Participants n=5 Participants	75 Participants n=7 Participants	154 Participants n=5 Participants
Age, Customized > 75 years	35 Participants n=5 Participants	31 Participants n=7 Participants	66 Participants n=5 Participants
Sex: Female, Male Female	161 Participants n=5 Participants	151 Participants n=7 Participants	312 Participants n=5 Participants
Sex: Female, Male Male	262 Participants n=5 Participants	276 Participants n=7 Participants	538 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	132 Participants n=5 Participants	99 Participants n=7 Participants	231 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	291 Participants n=5 Participants	328 Participants n=7 Participants	619 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	12 Participants n=5 Participants	7 Participants n=7 Participants	19 Participants n=5 Participants
Race (NIH/OMB) Asian	11 Participants n=5 Participants	15 Participants n=7 Participants	26 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Black or African American	13 Participants n=5 Participants	18 Participants n=7 Participants	31 Participants n=5 Participants
Race (NIH/OMB) White	348 Participants n=5 Participants	355 Participants n=7 Participants	703 Participants n=5 Participants
Region of Enrollment Brazil	0 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants
Region of Enrollment Chile	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment Peru	34 Participants n=5 Participants	29 Participants n=7 Participants	63 Participants n=5 Participants
Region of Enrollment South Korea	8 Participants n=5 Participants	13 Participants n=7 Participants	21 Participants n=5 Participants
Region of Enrollment Taiwan	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment Argentina	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
BMI (Body Mass Index)	30.4 kg/m2 STANDARD_DEVIATION 7.44 • n=5 Participants	30.7 kg/m2 STANDARD_DEVIATION 7.54 • n=7 Participants	30.5 kg/m2 STANDARD_DEVIATION 7.49 • n=5 Participants
BMI category < 30 kg/m2	212 Participants n=5 Participants	213 Participants n=7 Participants	425 Participants n=5 Participants
BMI category >= 30 kg/m2	211 Participants n=5 Participants	214 Participants n=7 Participants	425 Participants n=5 Participants
Presence of diabetes	53 Participants n=5 Participants	54 Participants n=7 Participants	107 Participants n=5 Participants

PRIMARY outcome

Timeframe: 48 to 72 hrs after starting treatment

Population: ITT Population

Outcome measures

Outcome measures
Measure	Delafloxacin n=423 Participants 300mg iv Q12H for 6 doses, 450mg oral tablet Q12H for a minimum of 10 up to a maximum of 28 doses total	Vancomycin Plus Aztreonam n=427 Participants Vancomycin 15mg/kg iv plus two grams Aztreonam every 12 hours for a minimum of 10 up to a maximum of 28 doses total
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. Responder	354 Participants	344 Participants
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. Nonresponder	69 Participants	83 Participants

SECONDARY outcome

Timeframe: Study Day 14 ± 1

Population: ITT Population

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).

Outcome measures

Outcome measures
Measure	Delafloxacin n=423 Participants 300mg iv Q12H for 6 doses, 450mg oral tablet Q12H for a minimum of 10 up to a maximum of 28 doses total	Vancomycin Plus Aztreonam n=427 Participants Vancomycin 15mg/kg iv plus two grams Aztreonam every 12 hours for a minimum of 10 up to a maximum of 28 doses total
Investigator-assessed Response of Signs and Symptoms of Infection at the Follow up Visit (European Medicines Agency [EMA] Primary Endpoint) Cure	244 Participants	255 Participants
Investigator-assessed Response of Signs and Symptoms of Infection at the Follow up Visit (European Medicines Agency [EMA] Primary Endpoint) Improved	125 Participants	107 Participants
Investigator-assessed Response of Signs and Symptoms of Infection at the Follow up Visit (European Medicines Agency [EMA] Primary Endpoint) Failure	17 Participants	21 Participants
Investigator-assessed Response of Signs and Symptoms of Infection at the Follow up Visit (European Medicines Agency [EMA] Primary Endpoint) Indeterminate/Missing	37 Participants	44 Participants

SECONDARY outcome

Timeframe: Study Day 21 to 28

Outcome measures

Outcome measures
Measure	Delafloxacin n=423 Participants 300mg iv Q12H for 6 doses, 450mg oral tablet Q12H for a minimum of 10 up to a maximum of 28 doses total	Vancomycin Plus Aztreonam n=427 Participants Vancomycin 15mg/kg iv plus two grams Aztreonam every 12 hours for a minimum of 10 up to a maximum of 28 doses total
Investigator-assessed Response of Signs and Symptoms of Infection at the Late Follow-up Visit Cure	287 Participants	303 Participants
Investigator-assessed Response of Signs and Symptoms of Infection at the Late Follow-up Visit Improved	66 Participants	48 Participants
Investigator-assessed Response of Signs and Symptoms of Infection at the Late Follow-up Visit Failure	21 Participants	24 Participants
Investigator-assessed Response of Signs and Symptoms of Infection at the Late Follow-up Visit Indeterminate/Missing	49 Participants	52 Participants

Adverse Events

Delafloxacin

Serious events: 16 serious events

Other events: 55 other events

Deaths: 0 deaths

Vancomycin Plus Aztreonam

Serious events: 17 serious events

Other events: 32 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Delafloxacin n=417 participants at risk 300mg iv Q12H for 6 doses, 450mg oral tablet Q12H for a minimum of 10 up to a maximum of 28 doses total	Vancomycin Plus Aztreonam n=425 participants at risk Vancomycin 15mg/kg iv plus two grams Aztreonam every 12 hours for a minimum of 10 up to a maximum of 28 doses total
Gastrointestinal disorders Diarrhea	7.7% 32/417 • 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). 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.	3.3% 14/425 • 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). 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.
Gastrointestinal disorders Nausea	7.7% 32/417 • 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). 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.	4.5% 19/425 • 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). 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.

Additional Information

Sue Cammarata (Chief Medical Officer)

Melinta Therapeutics, Inc.

Phone: 1-844-MELINTA (1-844-635-4682)

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER