A Study of Plazomicin Compared With Meropenem for the Treatment of Complicated Urinary Tract Infection (cUTI) Including Acute Pyelonephritis (AP) (EPIC)

Achaogen

Status and phase: Completed; Phase 3

Conditions: Acute Pyelonephritis; Complicated Urinary Tract Infection

Treatments: Drug: levofloxacin (oral); Drug: plazomicin; Drug: meropenem

Study type: Interventional

Funder types: Industry

Identifiers

NCT02486627

U1111-1171-1554 (Other Identifier)

ACHN-490-009

2015-001588-37 (EudraCT Number)

Details and patient eligibility

About

This was a randomized, multicenter, multinational, double-blind study comparing the efficacy and safety of plazomicin compared with meropenem followed by optional oral (PO) therapy in the treatment of cUTI, including AP, in adults.

Enrollment: 609 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Pyuria
• Have a pretreatment baseline urine culture obtained within 36 hours before the start of administration of the first dose of study drug
• Clinical signs and/or symptoms of acute pyelonephritis or complicated urinary tract infection
• Normal renal function or moderate renal impairment

Key Exclusion Criteria:

• Confirmed fungal urinary tract infection at the time of randomization
• Known urinary tract infection or colonization with Gram-positive pathogens
• Current cUTI or AP is known to be caused by a pathogen resistant to meropenem
• Female participants of childbearing potential if they are known to be pregnant or have a positive pregnancy test at screening, breastfeeding, or unable or unwilling to use a highly effective method of birth control during the study and for at least 30 days following the last dose of study medication
• Any rapidly progressing disease or immediately life-threatening illness
• Documented presence of immunodeficiency or an immunocompromised condition
• Documented or known history of otologic surgery or disease including use of hearing aid, head injury leading to otologic damage, Ménière's disease, tumor of the head, neck, or auditory system, perilymphatic fistula, or autoimmune disease of the inner ear, or family history of hearing loss (excluding age-related hearing loss [onset after age of 65 years])

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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609 participants in 2 patient groups

Plazomicin

Experimental group

Description:

Patients received 15 milligrams per kilogram (mg/kg) plazomicin as an intravenous (IV) infusion once daily followed by matching placebo infusions 8 and 16 hours later. After a minimum of 4 days of IV plazomicin, patients could switch to 250 or 500 mg oral levofloxacin for a total duration of 7 to 10 days (IV plus oral).

Treatment:

Drug: levofloxacin (oral)

Drug: plazomicin

Meropenem

Active Comparator group

Description:

Patients received 1.0 g meropenem as an IV infusion every 8 hours (q8h). After a minimum of 4 days of IV meropenem, patients could switch to 250 or 500 mg oral levofloxacin for a total duration of 7 to 10 days (IV plus oral).

Treatment:

Drug: meropenem

Drug: levofloxacin (oral)