Trial Outcomes & Findings for Delafloxacin Versus Vancomycin and Aztreonam for the Treatment of Acute Bacterial Skin and Skin Structure Infections (NCT NCT01811732)

Last Updated: 2017-09-27

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

660 participants

Primary outcome timeframe

48 to 72 hours after starting treatment

Results posted on

2017-09-27

Participant Flow

Participant milestones

Participant milestones
Measure	Delafloxacin Plus Placebo 300 mg IV every 12 hours, for a minimum of 10 and up to a maximum of 28 doses Delafloxacin: Delafloxacin Placebo: Placebo	Vancomycin Plus Aztreonam + Placebo Vancomycin 15 mg/kg IV plus two grams Aztreonam every 12 hours for a minimum of 10 and up to a maximum of 28 doses Vancomycin: Vancomycin Aztreonam: Aztreonam Placebo: Placebo
Overall Study STARTED	331	329
Overall Study COMPLETED	276	271
Overall Study NOT COMPLETED	55	58

Reasons for withdrawal

Reasons for withdrawal
Measure	Delafloxacin Plus Placebo 300 mg IV every 12 hours, for a minimum of 10 and up to a maximum of 28 doses Delafloxacin: Delafloxacin Placebo: Placebo	Vancomycin Plus Aztreonam + Placebo Vancomycin 15 mg/kg IV plus two grams Aztreonam every 12 hours for a minimum of 10 and up to a maximum of 28 doses Vancomycin: Vancomycin Aztreonam: Aztreonam Placebo: Placebo
Overall Study Lost to Follow-up	24	30
Overall Study Withdrawal by Subject	16	10
Overall Study Adverse Event	3	9
Overall Study Lack of Efficacy	3	1
Overall Study Non-compliance with study drug/procedure	3	3
Overall Study Physician Decision	2	0
Overall Study Death	1	1
Overall Study Insufficient venous access	0	1
Overall Study Protocol Violation	0	1
Overall Study Subject incarcerated	1	2
Overall Study Admitted to another facility	1	0
Overall Study Correct study drug not available on site	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Delafloxacin + Placebo n=331 Participants 300mg iv every 12 hours for a minimum of 10 and up to a maximum of 28 doses Delafloxacin: Delafloxacin Placebo: Placebo	Vancomycin Plus Aztreonam + Placebo n=329 Participants Vancomycin 15mg/kg iv plus two grams Aztreonam every 12 hours for a minimum of 10 and up to a maximum of 28 doses Vancomycin: Vancomycin Aztreonam: Aztreonam Placebo: Placebo	Total n=660 Participants Total of all reporting groups
Age, Continuous	46.3 years STANDARD_DEVIATION 13.91 • n=5 Participants	45.3 years STANDARD_DEVIATION 14.44 • n=7 Participants	45.8 years STANDARD_DEVIATION 14.18 • n=5 Participants
Age, Customized <= 65 years	309 Participants n=5 Participants	309 Participants n=7 Participants	618 Participants n=5 Participants
Age, Customized > 65 years	22 Participants n=5 Participants	20 Participants n=7 Participants	42 Participants n=5 Participants
Age, Customized > 75 years	7 Participants n=5 Participants	10 Participants n=7 Participants	17 Participants n=5 Participants
Sex: Female, Male Female	125 Participants n=5 Participants	120 Participants n=7 Participants	245 Participants n=5 Participants
Sex: Female, Male Male	206 Participants n=5 Participants	209 Participants n=7 Participants	415 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	101 Participants n=5 Participants	103 Participants n=7 Participants	204 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	230 Participants n=5 Participants	226 Participants n=7 Participants	456 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	5 Participants n=5 Participants	2 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Black or African American	27 Participants n=5 Participants	19 Participants n=7 Participants	46 Participants n=5 Participants
Race (NIH/OMB) White	297 Participants n=5 Participants	304 Participants n=7 Participants	601 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment North America	268 participants n=5 Participants	274 participants n=7 Participants	542 participants n=5 Participants
Region of Enrollment Europe	63 participants n=5 Participants	55 participants n=7 Participants	118 participants n=5 Participants
BMI (Body Mass Index)	28.36 kg/m2 STANDARD_DEVIATION 6.423 • n=5 Participants	27.86 kg/m2 STANDARD_DEVIATION 6.363 • n=7 Participants	28.11 kg/m2 STANDARD_DEVIATION 6.393 • n=5 Participants
BMI ranges < 25	113 Participants n=5 Participants	125 Participants n=7 Participants	238 Participants n=5 Participants
BMI ranges >= 25	218 Participants n=5 Participants	204 Participants n=7 Participants	422 Participants n=5 Participants
BMI ranges >= 30	120 Participants n=5 Participants	94 Participants n=7 Participants	214 Participants n=5 Participants
BMI ranges >= 35	53 Participants n=5 Participants	42 Participants n=7 Participants	95 Participants n=5 Participants
Presence of Diabetes	30 Participants n=5 Participants	27 Participants n=7 Participants	57 Participants n=5 Participants

PRIMARY outcome

Timeframe: 48 to 72 hours after starting treatment

Population: ITT Population

Outcome measures

Outcome measures
Measure	Delafloxacin Plus Placebo n=331 Participants 300mg iv every 12 hours for a minimum of 10 and up to a maximum of 28 doses Delafloxacin: Delafloxacin Placebo: Placebo	Vancomycin Plus Aztreonam + Placebo n=329 Participants Vancomycin 15mg/kg iv plus two grams Aztreonam every 12 hours for a minimum of 10 and up to a maximum of 28 doses Vancomycin: Vancomycin Aztreonam: Aztreonam Placebo: Placebo
Objective Response at 48 to 72 Hours (FDA Primary Endpoint) Responder	259 Participants	266 Participants
Objective Response at 48 to 72 Hours (FDA Primary Endpoint) Non-Responder	72 Participants	63 Participants

SECONDARY outcome

Timeframe: Study Day 14 +/- 1 day

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 Plus Placebo n=331 Participants 300mg iv every 12 hours for a minimum of 10 and up to a maximum of 28 doses Delafloxacin: Delafloxacin Placebo: Placebo	Vancomycin Plus Aztreonam + Placebo n=329 Participants Vancomycin 15mg/kg iv plus two grams Aztreonam every 12 hours for a minimum of 10 and up to a maximum of 28 doses Vancomycin: Vancomycin Aztreonam: Aztreonam Placebo: Placebo
Investigator Assessment at the Follow-up Visit (EMA Primary Endpoint) Cure	172 Participants	166 Participants
Investigator Assessment at the Follow-up Visit (EMA Primary Endpoint) Improved	98 Participants	108 Participants
Investigator Assessment at the Follow-up Visit (EMA Primary Endpoint) Failure	9 Participants	7 Participants
Investigator Assessment at the Follow-up Visit (EMA Primary Endpoint) Indeterminate	52 Participants	48 Participants

SECONDARY outcome

Timeframe: Study Day 21 to 28

Population: ITT Population

Outcome measures

Outcome measures
Measure	Delafloxacin Plus Placebo n=331 Participants 300mg iv every 12 hours for a minimum of 10 and up to a maximum of 28 doses Delafloxacin: Delafloxacin Placebo: Placebo	Vancomycin Plus Aztreonam + Placebo n=329 Participants Vancomycin 15mg/kg iv plus two grams Aztreonam every 12 hours for a minimum of 10 and up to a maximum of 28 doses Vancomycin: Vancomycin Aztreonam: Aztreonam Placebo: Placebo
Investigator Assessment at the Late Follow-up Visit Improved	32 Participants	48 Participants
Investigator Assessment at the Late Follow-up Visit Cure	233 Participants	219 Participants
Investigator Assessment at the Late Follow-up Visit Failure	9 Participants	6 Participants
Investigator Assessment at the Late Follow-up Visit Indeterminate/Missing	57 Participants	56 Participants

Adverse Events

Delafloxacin Plus Placebo

Serious events: 12 serious events

Other events: 91 other events

Deaths: 1 deaths

Vancomycin Plus Aztreonam + Placebo

Serious events: 12 serious events

Other events: 111 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Delafloxacin Plus Placebo n=324 participants at risk 300mg iv every 12 hours, for a minimum of 10 and up to a maximum of 28 doses Delafloxacin: Delafloxacin Placebo: Placebo	Vancomycin Plus Aztreonam + Placebo n=326 participants at risk Vancomycin 15mg/kg iv plus two grams Aztreonam every 12 hours for a minimum of 10 and up to a maximum of 28 doses Vancomycin: Vancomycin Aztreonam: Aztreonam Placebo: Placebo
Infections and infestations Infection	8.6% 28/324 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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.	7.7% 25/326 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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.
General disorders Infusion site extravasation	8.6% 28/324 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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.	13.5% 44/326 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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 Diarrhea	8.3% 27/324 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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.	3.1% 10/326 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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	7.4% 24/324 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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.	8.6% 28/326 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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.
Nervous system disorders Headache	3.1% 10/324 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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.	7.7% 25/326 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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

Measure	Delafloxacin Plus Placebo n=324 participants at risk 300mg iv every 12 hours, for a minimum of 10 and up to a maximum of 28 doses Delafloxacin: Delafloxacin Placebo: Placebo	Vancomycin Plus Aztreonam + Placebo n=326 participants at risk Vancomycin 15mg/kg iv plus two grams Aztreonam every 12 hours for a minimum of 10 and up to a maximum of 28 doses Vancomycin: Vancomycin Aztreonam: Aztreonam Placebo: Placebo
Infections and infestations Cellulitis	0.62% 2/324 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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.	0.31% 1/326 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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.
Infections and infestations Hepatitis C	0.31% 1/324 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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.	0.00% 0/326 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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.
Infections and infestations Infection	0.31% 1/324 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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.	0.61% 2/326 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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.
Infections and infestations Peritonitis	0.00% 0/324 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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.	0.31% 1/326 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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.
Infections and infestations Sepsis	0.00% 0/324 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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.	0.31% 1/326 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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.
Infections and infestations Septic Shock	0.31% 1/324 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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.	0.00% 0/326 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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.
Infections and infestations Skin bacterial infection	0.31% 1/324 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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.	0.00% 0/326 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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.
Infections and infestations Staphylococcal sepsis	0.31% 1/324 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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.	0.00% 0/326 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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.
Psychiatric disorders Depression	0.31% 1/324 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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.	0.00% 0/326 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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.
Psychiatric disorders Major depression	0.31% 1/324 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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.	0.00% 0/326 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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.
Psychiatric disorders Polysubstance dependence	0.31% 1/324 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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.	0.00% 0/326 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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.
Psychiatric disorders Substance-induced mood disorder	0.31% 1/324 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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.	0.00% 0/326 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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 Diarrhea	0.31% 1/324 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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.	0.00% 0/326 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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 Gastric ulcer perforation	0.00% 0/324 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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.	0.31% 1/326 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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.
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	0.31% 1/324 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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.	0.00% 0/326 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.31% 1/324 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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.	0.00% 0/326 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/324 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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.	0.31% 1/326 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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.
Skin and subcutaneous tissue disorders Pyoderma gangrenosum	0.31% 1/324 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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.	0.00% 0/326 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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.
Hepatobiliary disorders Hepatic cirrhosis	0.00% 0/324 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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.	0.31% 1/326 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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.
Injury, poisoning and procedural complications Overdose	0.00% 0/324 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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.	0.31% 1/326 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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.
Injury, poisoning and procedural complications Stab wound	0.00% 0/324 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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.	0.31% 1/326 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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.
Musculoskeletal and connective tissue disorders Soft tissue necrosis	0.00% 0/324 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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.	0.31% 1/326 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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.
Nervous system disorders Cervical radiculopathy	0.00% 0/324 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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.	0.31% 1/326 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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.
Renal and urinary disorders Renal failure acute	0.00% 0/324 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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.	0.31% 1/326 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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.
Vascular disorders Peripheral ischemia	0.00% 0/324 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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.	0.31% 1/326 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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.
Vascular disorders Peripheral vascular disorder	0.00% 0/324 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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.	0.31% 1/326 • Adverse event data were collected from the time the patient signed the ICF through the follow-up telephone contact 30 days after the last dose of study drug (up to 45 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.