Trial Outcomes & Findings for Efficacy and Safety Study of Eravacycline Compared With Ertapenem in Participants With Complicated Urinary Tract Infections (NCT NCT03032510)

Last Updated: 2022-01-06

Results Overview

This was the co-primary outcome measure for the Food and Drug Administration (FDA). The primary objective was to demonstrate the non-inferiority (NI) of eravacycline to ertapenem 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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1205 participants

Primary outcome timeframe

End of Infusion

Results posted on

2022-01-06

Participant Flow

Participant milestones

Participant milestones
Measure	Eravacycline (Intravenous)/Levofloxacin (Oral) Eravacycline 1.5mg/kg IV q24h Placebo IV q24h Levofloxacin (PO)	Ertapenem (Intravenous)/Levofloxacin (Oral) Ertapenem 1g IV q24h Placebo IV q24h Levofloxacin (PO)
Overall Study STARTED	603	602
Overall Study COMPLETED	576	584
Overall Study NOT COMPLETED	27	18

Reasons for withdrawal

Reasons for withdrawal
Measure	Eravacycline (Intravenous)/Levofloxacin (Oral) Eravacycline 1.5mg/kg IV q24h Placebo IV q24h Levofloxacin (PO)	Ertapenem (Intravenous)/Levofloxacin (Oral) Ertapenem 1g IV q24h Placebo IV q24h Levofloxacin (PO)
Overall Study Adverse Event	5	2
Overall Study Lost to Follow-up	8	7
Overall Study Withdrawal by Subject	8	7
Overall Study Subject noncompliance	4	2
Overall Study Physician Decision	2	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Eravacycline (Intravenous)/Levofloxacin (Oral) n=603 Participants Eravacycline 1.5 mg/kg IV q24h Placebo IV Levofloxacin PO	Ertapenem (Intravenous)/Levofloxacin (Oral) n=602 Participants Ertapenem 1.0g IV q24h Placebo IV Levofloxacin PO	Total n=1205 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	338 Participants n=5 Participants	331 Participants n=7 Participants	669 Participants n=5 Participants
Age, Categorical >=65 years	265 Participants n=5 Participants	271 Participants n=7 Participants	536 Participants n=5 Participants
Age, Continuous	57.1 years STANDARD_DEVIATION 18.16 • n=5 Participants	56.5 years STANDARD_DEVIATION 19.34 • n=7 Participants	56.8 years STANDARD_DEVIATION 18.7 • n=5 Participants
Sex: Female, Male Female	330 Participants n=5 Participants	343 Participants n=7 Participants	673 Participants n=5 Participants
Sex: Female, Male Male	273 Participants n=5 Participants	259 Participants n=7 Participants	532 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	11 Participants n=5 Participants	15 Participants n=7 Participants	26 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	592 Participants n=5 Participants	587 Participants n=7 Participants	1179 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	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) White	600 Participants n=5 Participants	601 Participants n=7 Participants	1201 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	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment Latvia	36 participants n=5 Participants	39 participants n=7 Participants	75 participants n=5 Participants
Region of Enrollment Austria	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Region of Enrollment Romania	54 participants n=5 Participants	59 participants n=7 Participants	113 participants n=5 Participants
Region of Enrollment Hungary	56 participants n=5 Participants	66 participants n=7 Participants	122 participants n=5 Participants
Region of Enrollment United States	9 participants n=5 Participants	13 participants n=7 Participants	22 participants n=5 Participants
Region of Enrollment Ukraine	148 participants n=5 Participants	137 participants n=7 Participants	285 participants n=5 Participants
Region of Enrollment Georgia	33 participants n=5 Participants	40 participants n=7 Participants	73 participants n=5 Participants
Region of Enrollment Slovakia	18 participants n=5 Participants	13 participants n=7 Participants	31 participants n=5 Participants
Region of Enrollment Bulgaria	61 participants n=5 Participants	42 participants n=7 Participants	103 participants n=5 Participants
Region of Enrollment Estonia	21 participants n=5 Participants	20 participants n=7 Participants	41 participants n=5 Participants
Region of Enrollment Russia	126 participants n=5 Participants	143 participants n=7 Participants	269 participants n=5 Participants
Region of Enrollment Poland	23 participants n=5 Participants	17 participants n=7 Participants	40 participants n=5 Participants
Region of Enrollment Moldova	18 participants n=5 Participants	12 participants n=7 Participants	30 participants n=5 Participants

PRIMARY outcome

Timeframe: End of Infusion

Population: 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 and ertapenem had expected antibacterial activity.

Outcome measures

Outcome measures
Measure	Eravacycline (Intravenous) n=428 Participants Eravacycline was administered IV at a dose of 1.5 mg/kg of body weight q24h. At minimum, the first 5 doses were administered IV. An IV-to-PO transition could occur after dose 5. During PO administration, subjects received 750 mg of levofloxacin once daily. Total treatment duration was 7 or 10 days.	Ertapenem (Intravenous) n=403 Participants Ertapenem was administered IV at a dose of 1 g q24h. At minimum, the first 5 doses were administered IV. An IV-to-PO transition could occur after dose 5. During PO administration, subjects received 750 mg of levofloxacin once daily. Total treatment duration was 7 or 10 days.
Proportion of Participants in the Micro-ITT Population Demonstrating Clinical Cure and Microbiologic Success at the EOI Visit Responder	363 Participants	382 Participants
Proportion of Participants in the Micro-ITT Population Demonstrating Clinical Cure and Microbiologic Success at the EOI Visit Non-responder	51 Participants	7 Participants
Proportion of Participants in the Micro-ITT Population Demonstrating Clinical Cure and Microbiologic Success at the EOI Visit Indeterminate	14 Participants	14 Participants

PRIMARY outcome

Timeframe: TOC visit (14-17 days after randomization)

This was the co-primary outcome measure for the Food and Drug Administration (FDA). The primary objective was to demonstrate the non-inferiority (NI) of eravacycline to ertapenem 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.

Outcome measures

Outcome measures
Measure	Eravacycline (Intravenous) n=428 Participants Eravacycline was administered IV at a dose of 1.5 mg/kg of body weight q24h. At minimum, the first 5 doses were administered IV. An IV-to-PO transition could occur after dose 5. During PO administration, subjects received 750 mg of levofloxacin once daily. Total treatment duration was 7 or 10 days.	Ertapenem (Intravenous) n=403 Participants Ertapenem was administered IV at a dose of 1 g q24h. At minimum, the first 5 doses were administered IV. An IV-to-PO transition could occur after dose 5. During PO administration, subjects received 750 mg of levofloxacin once daily. Total treatment duration was 7 or 10 days.
Proportion of Participants in the Micro-ITT Population Demonstrating Clinical Cure and Microbiologic Success at the Test-Of-Cure (TOC) Visit Responder	293 Participants	302 Participants
Proportion of Participants in the Micro-ITT Population Demonstrating Clinical Cure and Microbiologic Success at the Test-Of-Cure (TOC) Visit Non-responder	116 Participants	86 Participants
Proportion of Participants in the Micro-ITT Population Demonstrating Clinical Cure and Microbiologic Success at the Test-Of-Cure (TOC) Visit Indeterminate	19 Participants	15 Participants

SECONDARY outcome

Timeframe: TOC visit (14-17 days after randomization)

Population: ITT included all randomized participants, regardless of receiving study drug or not.

Clinical cure: A complete resolution or significant improvement of signs or symptoms of the infection such that no rescue/non-study antibacterial medication was required to treat the cUTI that presented at study entry. Clinical failure: Subjects were classified as clinical failure in the event of * Death related to cUTI at any timepoint * Persistence of clinical symptoms of cUTI or new symptoms developed * Initiation of rescue/non-study antibacterial medication for cUTI Indeterminate: Study data were listed as indeterminate if the outcome was other than clinical cure or clinical failure. The reason for an indeterminate designation had to be provided Missing: Study data were listed as missing if the Investigator did not complete an assessment or if the subject did not complete the study visit.

Outcome measures

Outcome measures
Measure	Eravacycline (Intravenous) n=603 Participants Eravacycline was administered IV at a dose of 1.5 mg/kg of body weight q24h. At minimum, the first 5 doses were administered IV. An IV-to-PO transition could occur after dose 5. During PO administration, subjects received 750 mg of levofloxacin once daily. Total treatment duration was 7 or 10 days.	Ertapenem (Intravenous) n=602 Participants Ertapenem was administered IV at a dose of 1 g q24h. At minimum, the first 5 doses were administered IV. An IV-to-PO transition could occur after dose 5. During PO administration, subjects received 750 mg of levofloxacin once daily. Total treatment duration was 7 or 10 days.
Proportion of Participants in the ITT Population With Favorable Clinical Outcomes at TOC Visit Clinical Cure	547 Participants	566 Participants
Proportion of Participants in the ITT Population With Favorable Clinical Outcomes at TOC Visit Clinical Failure	31 Participants	20 Participants
Proportion of Participants in the ITT Population With Favorable Clinical Outcomes at TOC Visit Indeterminate/missing	25 Participants	16 Participants

Adverse Events

Eravacycline (Intravenous)

Serious events: 11 serious events

Other events: 174 other events

Deaths: 3 deaths

Ertapenem (Intravenous)

Serious events: 6 serious events

Other events: 52 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Eravacycline (Intravenous) n=601 participants at risk Eravacycline 1.5 mg/kg IV -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 randomized to the ertapenem group received a dose of eravacycline and was included in the eravacycline group in the safety analysis.	Ertapenem (Intravenous) n=600 participants at risk Ertapenem 1 g IV-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 randomized to the ertapenem group received a dose of eravacycline and was included in the eravacycline group in the safety analysis.
Gastrointestinal disorders Nausea	14.0% 84/601 • 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 FU visit (whichever was later). 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 randomized to the ertapenem group received a dose of eravacycline and was included in the eravacycline group in the safety analysis.	1.7% 10/600 • 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 FU visit (whichever was later). 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 randomized to the ertapenem group received a dose of eravacycline and was included in the eravacycline group in the safety analysis.
Gastrointestinal disorders Vomiting	5.2% 31/601 • 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 FU visit (whichever was later). 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 randomized to the ertapenem group received a dose of eravacycline and was included in the eravacycline group in the safety analysis.	0.67% 4/600 • 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 FU visit (whichever was later). 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 randomized to the ertapenem group received a dose of eravacycline and was included in the eravacycline group in the safety analysis.
General disorders Infusion site phlebitis	4.0% 24/601 • 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 FU visit (whichever was later). 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 randomized to the ertapenem group received a dose of eravacycline and was included in the eravacycline group in the safety analysis.	0.50% 3/600 • 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 FU visit (whichever was later). 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 randomized to the ertapenem group received a dose of eravacycline and was included in the eravacycline group in the safety analysis.
Gastrointestinal disorders Diarrhoea	3.0% 18/601 • 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 FU visit (whichever was later). 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 randomized to the ertapenem group received a dose of eravacycline and was included in the eravacycline group in the safety analysis.	2.8% 17/600 • 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 FU visit (whichever was later). 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 randomized to the ertapenem group received a dose of eravacycline and was included in the eravacycline group in the safety analysis.
General disorders Headache	2.8% 17/601 • 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 FU visit (whichever was later). 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 randomized to the ertapenem group received a dose of eravacycline and was included in the eravacycline group in the safety analysis.	3.0% 18/600 • 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 FU visit (whichever was later). 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 randomized to the ertapenem group received a dose of eravacycline and was included in the eravacycline group in the safety analysis.

Additional Information

Chief Development Officer

La Jolla Pharmaceutical Company

Phone: 617-715-3600

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place