Clinical Data & Safety

Image depicting bacterial cell death1

EFFICACY

CONTEPO™ was studied in a multicenter, randomized, double blind phase 2/3 trial in adult hospitalized patients with cUTIs (included acute phylonephritis). This study evaluated the safety and efficacy of CONTEPO vs piperacillin/tazobactam.2

Screening
(≤48 hours before 1st dose)
1:1

N = 464

Fosfomycin for injection
6 grams IV q8h
1-hour Infusion

n = 233

7 days, up to 14 days with concurrent bacteremia, no oral switch

Piperacillin / Tazobactam
4.5 grams IV q8h
1-hour infusion

n = 231

EOT

TOC

Day 19-21

LFU

Day 24-28

TOC = Test of Cure Day 19-21 after randomization, EOT = End of Therapy, LFU = Late Follow Up Day 24-28 after randomization

CONTEPO achieved high clinical cure rates and microbiological eradication

Demonstrated noninferiority in overall clinical response vs piperacillin/tazobactam2,3

Overall Response Rates at TOC in the mMITT Population3*

Treatment Difference 7.9% CI (-3.1, 18.9)

Overall Success (%)

  • 100
  • 90
  • 80
  • 70
  • 60
  • 50
  • 40
  • 30
  • 20
  • 10
  • 0

63.5%

n = 170

CONTEPO

55.6%

n = 169

PIP / TAZ

* Overall success was defined as clinical cure plus microbiological eradication (baseline uropathogens with growth in urine ≥105 CFU/mL were reduced to <104 CFU /mL) at the test-of-cure (TOC) visit, 19 (+2) days after randomization.

Response†
CONTEPO‡ n/N (%)
Piperacillin/Tazobactam§ n/N (%) Piperacillin/
Tazobactam§
n/N (%)
Treatment Difference (95% CI)
Clinical Cure
154 / 170 (90.6)
155 / 169 (91.7)
-1.1 (-7.8, 5.5)
Microbiological
Eradication
110 / 170 (64.7)
97 / 169 (57.4)
7.3 (-3.6, 18.3)

† Patients with an organism resistant to study drugs at baseline were to be excluded. All of the patients excluded (CONTEPO, n = 14; piperacillin /tazobactam, n = 9) had an organism resistant to piperacillin/tazobactam.
‡ CONTEPO 6 g intravenously every 8 hours
§ Piperacillin/tazobactam 4.5 g every 8 hours

Efficacy maintained in challenging infections with resistant pathogens

Overall Response Rates at Test-of-Cure Visit by Baseline Pathogen in cUTI Patients in ZEUS Trial (mMITT Population)3

Pathogen*
CONTEPO n/N (%)
Piperacillin/Tazobactam n/N (%) Piperacillin/
Tazobactam
n/N (%)
E. coli
87 / 130 (66.9)
75 / 130 (57.7)
K. pneumoniae
8 / 18 (44.4)
11 / 20 (55.0)

* Patients with an organism resistant to study drugs at baseline were to be excluded. All of the patients excluded (CONTEPO, n = 14; piperacillin/tazobactam, n = 9) had an organism resistant to piperacillin/tazobactam.

Microbiological Eradication at TOC2*†

Pre-planned Sub-group Analysis

Microbiological Eradication (%)

  • 100
  • 90
  • 80
  • 70
  • 60
  • 50
  • 40
  • 30
  • 20
  • 10
  • 0

72.9%

N = 133

63.2%

N = 133

E. coli

66.7%

N = 27

56.0%

N = 25

K. pneumoniae

* Percentages were calculated using N as the denominator, where N was the number of patients with the specified pathogens. If both a urine and blood sample had the same pathogen at baseline, eradication was defined as baseline bacterial pathogen was reduced to <104 colony-forming unit /mL on urine culture and was negative on repeat blood culture.
† Not powered for noninferiority

CONTEPO

PIP / TAZ

SAFETY PROFILE

Adverse Reactions Occurring in 2% or Greater of Patients with cUTIs Receiving CONTEPO in ZEUS (Trial 1)3

Complicated Urinary Tract Infections, Including Acute Pyelonephritis

Adverse Reaction
CONTEPO n = 233, %
Piperacillin/Tazobactam n = 231, %
Gastrointestinal Disorders
Nausea
4.3
1.3
Diarrhea
3.9
4.8
Vomiting
3.9
0.4
Laboratory Investigations
Transaminase elevations*
10.3
4.8
Hypokalemia
9.9
1.7
Hypophosphatemia
2.1
0.0
Hypocalcemia
3.9
2.6
Hypernatremia
3.4
0.9
Blood & Lymphatic System Disorders
Neutropenia†
6.4
3.9
Nervous System Disorders
Headache
2.6
2.2

* Transaminase elevations include increased ALT and AST ≥ 3x ULN
† Neutropenia includes absolute neutrophil count < 1500 cells/mm3


Serious adverse reactions occurred in 2.1% (5/233) CONTEPO and 2.6% (6/231) piperacillin/tazobactam- treated patients, respectively. Treatment was discontinued due to adverse reactions in 3% (7/233) of patients receiving CONTEPO and in 2.6% (7/231) of patients receiving piperacillin/tazobactam.