In cUTI, Fetroja demonstrated significantly higher efficacy vs high-dose imipenem/cilastatin1,2

Studied in a multinational, double-blind trial vs imipenem/cilastatin in cUTI1

Study design1,2

Clinical trial assessment timeline Fetroja vs imipenem/cilastatin primary efficacy endpoint TOC 7 days post therapy ± 2 days Clinical trial assessment timeline Fetroja vs imipenem/cilastatin primary efficacy endpoint TOC 7 days post therapy ± 2 days

cUTI Clinical trial assessment timeline: Fetroja vs imipenem/cilastatin primary efficacy endpoint—composite of clinical response and microbiological eradication 7 days post therapy ± 2 days
Assessments:
Day 1 (Baseline)
Day 4 (Early assessment [±1 day])

In vitro activity does not necessarily correlate with clinical efficacy.

  • Non-inferiority study in patients with cUTI ± pyelonephritis (N=448)1,2
  • Randomized 2:1 to receive Fetroja (n=300) or imipenem/cilastatin (n=148) for 7-14 days1*†
    • High dosage of imipenem/cilastatin used to allow for inclusion of patients with Pseudomonas aeruginosa infection2
    • Carbapenem-resistant pathogens excluded as ethical necessity due to carbapenem comparator2
  • Study was designed to capture a complicated patient population with comorbidities who are at greater risk of multidrug-resistant Gram-negative infections2
    • Allowed immunosuppressed patients, including renal transplant2
    • Limited patients with acute uncomplicated pyelonephritis to 30% maximum2
    • Step-down to oral therapy not permitted1
*
Dosages used were Fetroja 2 grams every 8 hours (infused over 1 hour), imipenem/cilastatin 1 gram/1 gram every 8 hours (infused over 1 hour).1
†
Recommended dosing of Fetroja is 2 grams every 8 hours by intravenous (IV) infusion over 3 hours in patients with creatinine clearance (CLcr) ≥60 to <120 mL/min.1
q8h=every 8 hours.

Primary endpoint

Primary endpointa: Composite clinical responseb and microbiological eradicationc at TOC1,2

Fetroja 72.6 % (n=183/252); Imipenem/cilastatin 54.6% (n=65/119); Treatment difference 18.6% (95% CI, 8.2, 28.9) P=0.0004

a
Microbiological intent-to-treat (micro-ITT) population, which included all patients who received at least a single dose of study medication and had at least 1 baseline Gram-negative uropathogen.1
b
Clinical response defined as resolution or improvement of cUTI symptoms and no new symptoms assessed by the investigator.1
c
Microbiological eradication defined as all Gram-negative uropathogens found at baseline at ≥105 CFU/mL were reduced to <104 CFU/mL.1

CI=confidence interval; TOC=test of cure.

Fetroja demonstrated significantly higher efficacy vs high-dose imipenem/cilastatin in cUTI1,2

See Fetroja clinical data in HABP/VABP

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Secondary endpoints

Secondary endpointsd: Microbiological eradication and clinical response at TOC1,2

Microbiological eradicatione at TOC

Fetroja 73.0% (n=184/252); Imipenem/cilastatin 56.3% (n=67/119); Treatment difference 17.3% (95% CI, 6.9, 27.6)

Clinical responsef at TOC

Fetroja 89.7% (n=226/252); Imipenem/cilastatin 87.4% (n=104/119); Treatment difference 2.4% (95% CI, -4.7, 9.4)

Secondary endpointsd: Follow-up2,3

  • Composite of microbiological eradication and clinical response at follow-up: Fetroja 54.4% (n=137/252) vs imipenem/cilastatin 39.5% (n=47/119)
  • Treatment difference was 15.31% (95% CI, 4.69, 25.92)

Microbiological eradicatione at follow-up

Fetroja 57.1% (n=144/252); Imipenem/cilastatin 43.7% (n=52/119); Treatment difference 13.92% (95% CI, 3.21, 24.63)

Clinical responsef at follow-up

Fetroja 81.3% (n=205/252); Imipenem/cilastatin 72.3% (n=86/119); Treatment difference 9.02% (95% CI, -0.37, 18.41)

d
Microbiological intent-to-treat (micro-ITT) population, which included all patients who received at least a single dose of study medication and least 1 baseline Gram-negative uropathogen.1
e
Microbiologic eradication defined as all Gram-negative uropathogens found at baseline at ≥105 CFU/mL were reduced to <104.1
f
Clinical response defined as resolution or improvement of cUTI symtpoms and no new symptoms assessed by the investigator.1

Adverse reactions

Selected adverse reactions occurring in ≥2% of patients receiving Fetroja in the cUTI trial1

Serious adverse reactions and adverse reactions leading to discontinuation
Adverse reaction FETROJAg
(n=300)		 Imipenem/
cilastatinh
(n=148)
Serious adverse reactions 4.7% 8.1%
Death 0.3% 0%
Discontinuation of treatment due to adverse reaction 1.7% 2.0%
In patients who received Fetroja, discontinuation of treatment due to adverse reaction included diarrhea (0.3%), drug hypersensitivity (0.3%), and increased hepatic enzymes (0.3%).
Selected adverse reactions occurring in ≥2% of patients receiving Fetroja
Adverse reaction FETROJAg
(n=300)		 Imipenem/
cilastatinh
(n=148)
Diarrhea 4% 6%
Infusion site reactionsi 4% 5%
Constipation 3% 4%
Rashj 3% <1%
Candidiasisk 2% 3%
Cough 2% <1%
Elevations in liver testsl 2% <1%
Headache 2% 5%
Hypokalemiam 2% 3%
Nausea 2% 4%
Vomiting 2% 1%
Swipe table for more
g
2 grams IV over 1 hour every 8 hours (with dosing adjustment based on renal function).1
h
1 gram IV over 1 hour every 8 hours (with dosing adjustment based on renal function and body weight).1
i
Infusion site reactions include infusion site erythema, inflammation, pain, pruritus, injection site pain, and phlebitis.1
j
Rash includes rash macular, rash maculopapular, erythema, skin irritation.1
k
Candidiasis includes oral or vulvovaginal candidiasis, candiduria.1
l
Elevations in liver tests include alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, blood alkaline phosphatase, hepatic enzyme increased.1
m
Hypokalemia includes blood potassium decreased.1