Efficacy and Safety Study of Eravacycline Compared With Levofloxacin in Complicated Urinary Tract Infections

• Sponsor: Tetraphase Pharmaceuticals, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01978938
• Collaborator: (none)
• Enrollment: 908
• Locations: 99
• Arms: 2
• Actual Duration (Months): 10.5
• Patients Per Site: 9.2
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

This is a phase 3, randomized, double-blind, double-dummy, multicenter, prospective study to assess the efficacy and safety of eravacycline compared with levofloxacin in participants with complicated urinary tract infections (cUTI).

Condition or Disease	Intervention/Treatment	Phase
cUTI	Drug: Eravacycline; Drug: Levofloxacin	Phase 3

Detailed Description

This study began with a 3-arm Lead-in portion to determine the oral (PO) dosing (200 or 250 milligrams [mg]) of eravacycline to be used with intravenously (IV) administered eravacycline for the Pivotal portion (2 arms). A PO dose of 200 mg was selected based on the unblinded Lead-in analysis.

Study Design

• Study Type: Interventional
• Actual Enrollment: 908 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Masking Description: Except for the responsible study site pharmacist or designee and separate unblinded clinical research associates to monitor drug supply and adherence to study drug blinding and randomization procedures, all study staff and participants were blinded to treatment assignment.
• Primary Purpose: Treatment
• Official Title: A Phase 3, Randomized, Double-blind, Double-dummy, Multicenter, Prospective Study to Assess the Efficacy and Safety of Eravacycline Compared With Levofloxacin in Complicated Urinary Tract Infections
• Actual Study Start Date: Oct 6, 2014
• Actual Primary Completion Date: Jun 3, 2015
• Actual Study Completion Date: Aug 21, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Eravacycline Eravacycline was administered IV at a dose of 1.5 mg per kilogram (kg) of body weight every 24 hours (q24h). At minimum, the first 3 doses were administered IV. After an IV-to-PO transition, provided adequate clinical improvement, participants were administered 200 mg PO twice a day for a total therapy of 7 dosing cycles.	Drug: Eravacycline; Other Names: TP-434
Active Comparator: Levofloxacin Levofloxacin (750 mg) was administered IV q24h. At minimum, the first 3 doses were administered IV. After an IV-to-PO transition, provided adequate clinical improvement, participants were administered 750 mg PO once a day for a total therapy of 7 dosing cycles.	Drug: Levofloxacin; Other Names: Levaquin

Outcome Measures

Primary Outcome Measures

1. Participants In The Microbiological Intent-To-Treat (Micro-ITT) Population With A Responder Outcome At The Post-Treatment (PT) Visit [PT Visit]

   This was the primary outcome measure for the Food and Drug Administration (FDA). The primary objective was to demonstrate the non-inferiority (NI) of eravacycline to levofloxacin in responder outcome, which was derived from both clinical and microbiological responses, in the micro-ITT population. Clinical responses were either cure, failure, or indeterminate/missing; microbiological responses were characterized programmatically as either success, failure, or indeterminate/missing. Clinical cure was defined as complete resolution or significant improvement of signs or symptoms of the infection; microbiological success was a reduction of the baseline pathogen(s) to <10^4 colony-forming units/milliliter (CFU/mL). An outcome of Responder required a clinical response of cure and a microbiological response of success. Any other combination of the clinical and microbiological responses was considered either Non-responder or Indeterminate.

Secondary Outcome Measures

1. Participants In The Microbiological Modified ITT (Micro-MITT) Population With A Microbiological Response [PT Visit]

   This outcome measure (FDA and the European Medicines Agency [EMA]) compared the microbiological responses of eravacycline to levofloxacin for both treatment groups in the micro-MITT population. Responses were success, failure, or indeterminate/missing. Success was considered a reduction of the baseline pathogen(s) to <10^4 CFU/mL. Failure required blood cultures at or beyond end of therapy (EOT) to be positive for baseline pathogen(s), or urine culture to grow ≥10^4 CFU/mL of the baseline pathogen(s). Indeterminate/missing indicated no interpretable culture data available.

2. Participants In The Microbiologically Evaluable (ME) Population With A Microbiological Response [PT Visit]

   This outcome measure (FDA and EMA) compared the microbiological responses of eravacycline to levofloxacin for both treatment groups in the ME population. Responses were either success or failure. Indeterminate/missing responses were not included. Success was considered a reduction of the baseline pathogen(s) to <10^4 CFU/mL. Failure required blood cultures at or beyond EOT to be positive for baseline pathogen(s), or urine culture to grow ≥10^4 CFU/mL of the baseline pathogen(s). Indeterminate/missing indicated no interpretable culture data available. Populations: ME, all micro-ITT and clinically-evaluable (CE) participants with a suitable urine specimen and an interpretable urine culture; micro-ITT, all participants with ≥1 baseline bacterial pathogen from a urine or blood culture that caused a UTI against which eravacycline had expected antibacterial activity; ITT, all randomized participants, regardless of receiving study drug or not.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Male and female participants with either:

1. Pyelonephritis and normal urinary tract anatomy (approximately 50% of the total population), OR b. cUTI with at least 1 of the following conditions associated with a risk for developing cUTI: i. Indwelling urinary catheter ii. Urinary retention (approximately 100 milliliters of residual urine after voiding) iii. Neurogenic bladder iv. Partial obstructive uropathy (such as, nephrolithiasis, bladder stones, and ureteral strictures) v. Azotemia of renal origin (not congestive heart failure or volume related) such that the serum blood urea nitrogen (BUN) is elevated (>20 mg/deciliters) AND the serum BUN: creatinine ratio is <15 vi. Surgically modified or abnormal urinary tract anatomy (such as, bladder diverticula, redundant urine collection system) EXCEPT surgery within the last month

Exclusion Criteria:

1. Concurrent use of non-study antibacterial drug therapy that would have a potential effect on outcome evaluations in participants with cUTI, including:

2. Participants with a history of a levofloxacin-resistant urinary tract infection

3. Likely to receive ongoing antibacterial drug prophylaxis prior to the late Post-Treatment visit (such as, participants with vesiculo-ureteral reflux)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	San Diego Clinical Trials	San Diego	California	United States
2	Harbor-UCLA Medical Center	Torrance	California	United States
3	Tampa General Hospital	Tampa	Florida	United States
4	Henry Ford Hospital	Detroit	Michigan	United States	48202
5	Sunrise Hospital and Medical Centre	Las Vegas	Nevada	United States	89109
6	Columbus Regional Research Institute	Columbus	Ohio	United States
7	Multiprofile Hospital for Active Treatment "Dr. Tota Venkova", Gabrovo, Department of Nephrology	Gabrovo		Bulgaria
8	Multiprofile Hospital for Active Treatment "Dr. Stamen Iliev", Montana, Department of Nephrology and Dialysis	Montana		Bulgaria
9	University Multiprofile Hospital for Active Treatment "Dr. Georgi Stranski", Pleven, Urology Clinic	Pleven		Bulgaria
10	Multiprofile Hospital for Active Treatment, Ruse, Department of Urology	Rousse		Bulgaria
11	Multiprofile Hospital for Active Treatment, Sofia at Military Medical Academy, General Urology Clinic	Sofia		Bulgaria
12	University Multiprofile Hospital for Active Treatment "Aleksandrovska", Sofia, Department of Laparoscopic Urology	Sofia		Bulgaria
13	University Multiprofile Hospital for Active Treatment and Emergency Medicine "N.I. Pirogov", Sofia, Urology Clinic	Sofia		Bulgaria
14	Multiprofile Regional Hospital for Active Treatment "Dr. Stefan Cherkezov", Veliko Tarnovo, Department of Urology	Veliko Tarnovo		Bulgaria
15	Fundacion Cardiomet	Armenia		Colombia
16	De la Costa Clinic. Ltd. Research Centre	Barranquilla		Colombia
17	University Hospital Brno, Clinic of Urology	Brno		Czechia
18	University Hospital Hradec Kralove, Clinic of Urology	Hradec Kralove		Czechia
19	Hospital Novy Jicin, Department of Urology	Novy Jicin		Czechia
20	University Hospital Olomouc	Olomouc		Czechia
21	Thomayer Hospital, Department of Urology	Prague		Czechia
22	East Viru Central Hospital, Surgery Clinic	Kohtla-Jarve		Estonia
23	East Tallinn Central Hospital, Department of Internal Medicine	Tallinn		Estonia
24	West Tallinn Central Hospital, Department of Urology	Tallinn		Estonia
25	Tartu University Hospital, Surgery Clinic, Department of Urology and Renal Transplantation	Tartu		Estonia
26	Western Georgia National Medical Center	Kutaisi		Georgia
27	Aversi Clinic	Tbilisi		Georgia
28	Modern Medical Technologies - Guram Karazanashvili's clinic	Tbilisi		Georgia
29	Research Institute of Clinical Medicine	Tbilisi		Georgia
30	Tsulukidze National Center of Urology	Tbilisi		Georgia
31	Evaggelismos Hospital	Kolonaki		Greece
32	Papageorgiou General Hospital	Thessaloníki		Greece
33	Principal SMO Kft.	Baja		Hungary
34	Jahn Ferenc South Pest Hospital, Department of Urology	Budapest		Hungary
35	Petz Aladar County Teaching Hospital, Department of Urology	Gyor		Hungary
36	Elisabeth Teaching Hospital and Rehabilitation Institute of Sopron, Department of Urology	Sopron		Hungary
37	Csongrad County Dr. Bugyi Istvan Hospital, Department of Urology	Szentes		Hungary
38	St. Borbala Hospital, Department of Urology	Tatabanya		Hungary
39	Zion Medical Center	Haifa		Israel
40	Hospital Mater Domini	Castellanza		Italy
41	Liepajas Regional Hospital	Liepaja		Latvia
42	P. Stradins Clinical University Hospital	Riga		Latvia
43	Riga East University Hospital, LLC	Riga		Latvia
44	SIA 'URO' Clinic	Riga		Latvia
45	Vidzemes Hospital	Valmiera		Latvia
46	Hospital Civil Fray Antonio Alcalde	Guadalajara		Mexico
47	Hospital Civil Guadalajara Dr. Juan I. Mendoza	Guadalajara		Mexico
48	National Scientific Practical Center for Emergency Medicine, Department of Urology	Chisinau		Moldova, Republic of
49	Republican Clinical Hospital, Department of Urology	Chisinau		Moldova, Republic of
50	Boni Fratres Catoviensis Sp. z o.o., Department of Internal Diseases with Cardiologic Diagnostics Unit	Katowice		Poland
51	Military Medical Academy University Teaching Hospital - Central Veterans' Hospital, Clinical and Didactic Center of the Medical University of Lodz, Teaching Department of Nephrology, Hypertension and Renal Transplantation	Lodz		Poland
52	Medicome Sp. z o.o.	Oswiecim		Poland
53	HEUREKA Hanna Szalecka	Piaseczno		Poland
54	Pope John Paul 2nd Independent Public Provincial Hospital	Zamość		Poland
55	Emergency Clinical County Hospital Brasov	Brasov		Romania
56	"Prof. Dr. Th. Burghele" Clinical Hospital	Bucharest		Romania
57	Delta Hospital	Bucharest		Romania
58	Craiova Emergency Clinical County Hospital	Craiova		Romania
59	Clinical Hospital "Dr. C. I. Parhon"	Iași		Romania
60	Oradea Clinical Municipal Hospital "Dr. Gavril Curteanu"	Oradea		Romania
61	Sibiu County Emergency Clinical Hospital	Sibiu		Romania
62	Central Clinical Hospital of Civil Aviation	Moscow		Russian Federation
63	City Clinical Hospital #57 under Moscow Healthcare Department	Moscow		Russian Federation
64	Federal Clinical Center for High Medical Technologies	Moscow		Russian Federation
65	City Clinical Hospital of Emergency Care #2	Novosibirsk		Russian Federation
66	Penza Regional Clinical Hospital n.a. N.N. Burdenko	Penza		Russian Federation
67	Rostov State Medical University	Rostov-on-Don		Russian Federation
68	North-Western State Medical University n.a. I.I. Mechnikov	Saint Petersburg		Russian Federation
69	Saint-Petersburg Scientific Research Institute for Phthisiopulmonology	Saint Petersburg		Russian Federation
70	St. Petersburg Clinical Hospital under the Russian Academy of Sciences	Saint Petersburg		Russian Federation
71	St. Petersburg State Healthcare Institution: City Hospital #15	Saint Petersburg		Russian Federation
72	St. Petersburg State Healthcare Institution: St. George the Martyr City Hospital	Saint Petersburg		Russian Federation
73	St. Petersburg State-Funded Healthcare Institution: City Hospital #26	Saint Petersburg		Russian Federation
74	Saratov State Medical University n.a. V.I. Razumovsky	Saratov		Russian Federation
75	Smolensk Regional Clinical Hospital	Smolensk		Russian Federation
76	Novgorod Regional Clinical Hospital	Veliky Novgorod		Russian Federation
77	Vsevolozhsk Clinical Central District Hospital	Vsevolozhsk		Russian Federation
78	Lakeview Hospital	Benoni		South Africa
79	Clinresco Centres	Kempton Park		South Africa
80	Mzansi Ethical Research Centre	Middleburg		South Africa
81	St. Georges Hospital	Port Elizabeth		South Africa
82	Regional Municipal Institution "Chernivtsi Regional Hospital"	Chernivtsi		Ukraine
83	Dnipropetrovsk City Multispecialty Clinical Hospital #4	Dnipropetrovsk		Ukraine
84	Dnipropetrovsk I.I. Mechnikov Regional Clinical Hospital	Dnipropetrovsk		Ukraine
85	Ivano-Frankivsk City Clinical Hospital #1	Ivano-Frankivs'k		Ukraine
86	Ivano-Frankivsk Regional Clinical Hospital	Ivano-Frankivs'k		Ukraine
87	O.I. Meschaninov Clinical Hospital of Emergency and Urgent Medical Care	Kharkiv		Ukraine
88	Shapoval Regional Clinical Center of Urology and Nephrology	Kharkiv		Ukraine
89	Khmelnytskyi Regional Hospital	Khmel'nyts'kyy		Ukraine
90	Institute of Urology	Kyiv		Ukraine
91	Lviv Regional Clinical Hospital	L'viv		Ukraine
92	Volyn Regional Clinical Hospital	Luts'k		Ukraine
93	Mykolaiv Regional Hospital, Center for Nephrology and Dialysis	Mykolaiv		Ukraine
94	City Clinical Hospital #10, Urology Department #1	Odesa		Ukraine
95	Odesa Regional Clinical Hospital	Odessa		Ukraine
96	Poltava M.V. Sklifosovskyi Regional Clinical Hospital	Poltava		Ukraine
97	State Institution: Uzhhorod Railway Station Clinical Hospital under State Territorial Industry-Specific Association:Lviv Railway	Uzhhorod		Ukraine
98	Vinnytsia M.I. Pyrohov Regional Clinical Hospital	Vinnytsya		Ukraine
99	Municipal Institution "Zaporizhzhia Reqional Clinical Hospital" of Zaporizhzhia Regional Councill	Zaporizhzhya		Ukraine

Sponsors and Collaborators

• Tetraphase Pharmaceuticals, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Tetraphase Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT01978938
• Other Study ID Numbers: TP-434-010
• First Posted: Nov 8, 2013
• Last Update Posted: Jan 11, 2022
• Last Verified: Dec 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Urinary Tract Infections; Levofloxacin; Ofloxacin

Study Results

Participant Flow

Recruitment Details	Participants with a diagnosis of complicated urinary tract infection (cUTI), including participants with acute pyelonephritis, were recruited into this study.
Pre-assignment Detail	Screening and baseline assessments were performed after informed consent was obtained and within 36 hours prior to enrollment.

Arm/Group Title	Eravacycline	Levofloxacin
Arm/Group Description	Eravacycline was administered intravenously (IV) at a dose of 1.5 milligrams per kilogram (mg/kg) of body weight every 24 hours (q24h). At minimum, the first 3 doses were administered IV. After an IV-to-oral (PO) transition, provided adequate clinical improvement, participants were administered 200 mg PO twice a day (BID) for a total therapy of 7 dosing cycles.	Levofloxacin (750 mg) was administered IV q24h. At minimum, the first 3 doses were administered IV. After an IV-to-PO transition, provided adequate clinical improvement, participants were administered 750 mg PO once a day (QD) for a total therapy of 7 dosing cycles.
Period Title: Overall Study
STARTED	455	453
Received at Least 1 Dose of Study Drug	454	451
COMPLETED	432	439
NOT COMPLETED	23	14

Baseline Characteristics

Arm/Group Title	Eravacycline	Levofloxacin	Total
Arm/Group Description	Eravacycline was administered IV at a dose of 1.5 mg/kg of body weight q24h. At minimum, the first 3 doses were administered IV. After an IV-to-PO transition, provided adequate clinical improvement, participants were administered 200 mg PO BID for a total therapy of 7 dosing cycles.	Levofloxacin (750 mg) was administered IV q24h. At minimum, the first 3 doses were administered IV. After an IV-to-PO transition, provided adequate clinical improvement, participants were administered 750 mg PO QD for a total therapy of 7 dosing cycles.	Total of all reporting groups
Overall Participants	455	453	908
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	291 64%	301 66.4%	592 65.2%
>=65 years	164 36%	152 33.6%	316 34.8%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.7 (18.82)	51.7 (19.81)	52.7 (19.3)
Sex: Female, Male (Count of Participants)
Female	291 64%	302 66.7%	593 65.3%
Male	164 36%	151 33.3%	315 34.7%

Outcome Measures

1. Primary Outcome

Title	Participants In The Microbiological Intent-To-Treat (Micro-ITT) Population With A Responder Outcome At The Post-Treatment (PT) Visit
Description	This was the primary outcome measure for the Food and Drug Administration (FDA). The primary objective was to demonstrate the non-inferiority (NI) of eravacycline to levofloxacin in responder outcome, which was derived from both clinical and microbiological responses, in the micro-ITT population. Clinical responses were either cure, failure, or indeterminate/missing; microbiological responses were characterized programmatically as either success, failure, or indeterminate/missing. Clinical cure was defined as complete resolution or significant improvement of signs or symptoms of the infection; microbiological success was a reduction of the baseline pathogen(s) to <10^4 colony-forming units/milliliter (CFU/mL). An outcome of Responder required a clinical response of cure and a microbiological response of success. Any other combination of the clinical and microbiological responses was considered either Non-responder or Indeterminate.
Time Frame	PT Visit

Outcome Measure Data

Analysis Population Description

micro-ITT included all participants in the ITT population who had at least 1 baseline bacterial pathogen from a urine or blood culture that caused a urinary tract infection (UTI) against which eravacycline had expected antibacterial activity. ITT included all randomized participants, regardless of receiving study drug or not.

Arm/Group Title	Eravacycline	Levofloxacin
Arm/Group Description	Eravacycline was administered IV at a dose of 1.5 mg/kg of body weight q24h. At minimum, the first 3 doses were administered IV. After an IV-to-PO transition, provided adequate clinical improvement, participants were administered 200 mg PO BID for a total therapy of 7 dosing cycles.	Levofloxacin (750 mg) was administered IV q24h. At minimum, the first 3 doses were administered IV. After an IV-to-PO transition, provided adequate clinical improvement, participants were administered 750 mg PO QD for a total therapy of 7 dosing cycles.
Measure Participants	298	302
Responder	180 39.6%	202 44.6%
Non-responder	100 22%	91 20.1%
Indeterminate	18 4%	9 2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Eravacycline, Levofloxacin
	Comments	For the FDA, an NI margin of 10% was used, which was based on historical data regarding the treatment effect of antibiotics. A 10% NI margin for the Responder outcome is robust and can sufficiently confirm a clinically meaningful treatment effect of eravacycline in the treatment of cUTI.
	Type of Statistical Test	Non-Inferiority
	Comments	The NI test was based on the lower limit of the 2-sided 95% confidence interval (CI), using the method proposed without stratification by Miettinen and Nurminen. If the lower limit of the 95% CI for the difference in Responder (clinical cure and microbiologic success) rates in the micro-ITT population exceeded -10%, then the null hypothesis was rejected and the NI of eravacycline to levofloxacin was declared.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	-6.5
	Confidence Interval	(2-Sided) 95%; -14.1 to 1.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Participants In The Microbiological Modified ITT (Micro-MITT) Population With A Microbiological Response
Description	This outcome measure (FDA and the European Medicines Agency [EMA]) compared the microbiological responses of eravacycline to levofloxacin for both treatment groups in the micro-MITT population. Responses were success, failure, or indeterminate/missing. Success was considered a reduction of the baseline pathogen(s) to <10^4 CFU/mL. Failure required blood cultures at or beyond end of therapy (EOT) to be positive for baseline pathogen(s), or urine culture to grow ≥10^4 CFU/mL of the baseline pathogen(s). Indeterminate/missing indicated no interpretable culture data available.
Time Frame	PT Visit

Outcome Measure Data

Analysis Population Description

micro-MITT included all micro-ITT participants who received ≥1 dose of study drug. micro-ITT: all ITT participants with ≥1 baseline bacterial pathogen from a urine or blood culture that caused a UTI against which eravacycline had expected antibacterial activity. ITT: all randomized participants, regardless of receiving study drug or not.

Arm/Group Title	Eravacycline	Levofloxacin
Arm/Group Description	Eravacycline was administered IV at a dose of 1.5 mg/kg of body weight q24h. At minimum, the first 3 doses were administered IV. After an IV-to-PO transition, provided adequate clinical improvement, participants were administered 200 mg PO BID for a total therapy of 7 dosing cycles.	Levofloxacin (750 mg) was administered IV q24h. At minimum, the first 3 doses were administered IV. After an IV-to-PO transition, provided adequate clinical improvement, participants were administered 750 mg PO QD for a total therapy of 7 dosing cycles.
Measure Participants	297	302
Success	194 42.6%	213 47%
Failure	85 18.7%	78 17.2%
Indeterminate/missing	18 4%	11 2.4%

3. Secondary Outcome

Title	Participants In The Microbiologically Evaluable (ME) Population With A Microbiological Response
Description	This outcome measure (FDA and EMA) compared the microbiological responses of eravacycline to levofloxacin for both treatment groups in the ME population. Responses were either success or failure. Indeterminate/missing responses were not included. Success was considered a reduction of the baseline pathogen(s) to <10^4 CFU/mL. Failure required blood cultures at or beyond EOT to be positive for baseline pathogen(s), or urine culture to grow ≥10^4 CFU/mL of the baseline pathogen(s). Indeterminate/missing indicated no interpretable culture data available. Populations: ME, all micro-ITT and clinically-evaluable (CE) participants with a suitable urine specimen and an interpretable urine culture; micro-ITT, all participants with ≥1 baseline bacterial pathogen from a urine or blood culture that caused a UTI against which eravacycline had expected antibacterial activity; ITT, all randomized participants, regardless of receiving study drug or not.
Time Frame	PT Visit

Outcome Measure Data

Analysis Population Description

ME: all micro-ITT and CE participants with a suitable urine specimen and an interpretable urine culture. CE: all randomized participants dosed with no other antimicrobials (unless allowed by protocol), had an investigator clinical response assessment of "success" or "failure" at the assessment visit, and had no other major protocol violations.

Arm/Group Title	Eravacycline	Levofloxacin
Arm/Group Description	Eravacycline was administered IV at a dose of 1.5 mg/kg of body weight q24h. At minimum, the first 3 doses were administered IV. After an IV-to-PO transition, provided adequate clinical improvement, participants were administered 200 mg PO BID for a total therapy of 7 dosing cycles.	Levofloxacin (750 mg) was administered IV q24h. At minimum, the first 3 doses were administered IV. After an IV-to-PO transition, provided adequate clinical improvement, participants were administered 750 mg PO QD for a total therapy of 7 dosing cycles.
Measure Participants	255	276
Success	180 39.6%	203 44.8%
Failure	75 16.5%	73 16.1%

Adverse Events

Time Frame	The time frame for adverse event reporting was from the first dose of study drug through 30 days after the last dose of study drug or the late post-treatment visit (whichever was later).
Adverse Event Reporting Description	The safety population was all randomized subjects who receive any amount of study drug. All safety analyses were conducted in this population and are presented by treatment actually received (not as randomized). One subject was randomized to levofloxacin but received eravacycline, therefore Eravacycline N = 455; Levofloxacin N= 450
Arm/Group Title	Eravacycline		Levofloxacin
Arm/Group Description	Eravacycline was administered IV at a dose of 1.5 mg/kg of body weight q24h. At minimum, the first 3 doses were administered IV. After an IV-to-PO transition, provided adequate clinical improvement, participants were administered 200 mg PO BID for a total therapy of 7 dosing cycles.		Levofloxacin (750 mg) was administered IV q24h. At minimum, the first 3 doses were administered IV. After an IV-to-PO transition, provided adequate clinical improvement, participants were administered 750 mg PO QD for a total therapy of 7 dosing cycles.
All Cause Mortality
	Eravacycline		Levofloxacin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/455 (0.2%)		0/450 (0%)
Serious Adverse Events
	Eravacycline		Levofloxacin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/455 (1.5%)		6/450 (1.3%)
Blood and lymphatic system disorders
Disseminated intravascular coagulation	1/455 (0.2%)		0/450 (0%)
Cardiac disorders
Pericardial effusion	0/455 (0%)		1/450 (0.2%)
Gastrointestinal disorders
Diarrhoea	0/455 (0%)		1/450 (0.2%)
Pancreatitis acute	1/455 (0.2%)		0/450 (0%)
Infections and infestations
Orchitis	0/455 (0%)		1/450 (0.2%)
Pneumonia	0/455 (0%)		1/450 (0.2%)
Psoas abscess	0/455 (0%)		1/450 (0.2%)
Psychiatric disorders
Suicide attempt	1/455 (0.2%)		0/450 (0%)
Renal and urinary disorders
Renal colic	1/455 (0.2%)		0/450 (0%)
Urinary retention	0/455 (0%)		1/450 (0.2%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/455 (0.2%)		0/450 (0%)
Pneumonia aspiration	1/455 (0.2%)		0/450 (0%)
Vascular disorders
Deep vein thrombosis	1/455 (0.2%)		0/450 (0%)
Other (Not Including Serious) Adverse Events
	Eravacycline		Levofloxacin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	129/455 (28.4%)		26/450 (5.8%)
Gastrointestinal disorders
Nausea	82/455 (18%)		14/450 (3.1%)
Vomiting	33/455 (7.3%)		6/450 (1.3%)
Nervous system disorders
Headache	14/455 (3.1%)		6/450 (1.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Publications should include input from the PI, his/her colleagues, other PIs in this trial and the Sponsor's personnel; such input should be reflected in the authorship. Agreement of order of authors should be established before writing a manuscript. The PI interested in participating in writing the manuscript should contact the Sponsor. The PI shall not make any publication without the Sponsor's prior written approval, which may be withheld or granted by the Sponsor, in its sole discretion.