A Study to Investigate the Pharmacokinetics of RO7079901 and Meropenem in Participants With a Complicated Urinary Tract Infection

Phase 1

Completed

• Conditions: Urinary Tract Infections
• Interventions: Drug: RO7079901; Drug: Meropenem

• Registration Number: NCT03174795
• Lead Sponsor: Hoffmann-La Roche

Brief Summary

This is a non-randomized, open-label, one-treatment, one group study in participants with complicated urinary tract infection (cUTI) including pyelonephritis to characterize the pharmacokinetics of RO7079901 co-administered with meropenem.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-05-31
• Study First Submitted QC: 2017-05-31
• Study First Posted: 2017-06-05
• Study Start: 2017-07-11
• Primary Completion: 2017-12-04
• Study Completion: 2017-12-16
• Status Verified: 2018-05
• Last Update Submitted: 2018-05-11
• Last Update Posted: 2018-05-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

• Requiring hospitalization for IV antibacterial therapy for the treatment of presumed/confirmed cUTI (including pyelonephritis)
• Clinical signs and/or symptoms of pyelonephritis or a cUTI
• Urine culture taken within the 48 hours (hr) period immediately preceding the first dose of study drug contains greater than (>)1x10^5 colony forming units (CFU) per milliliter (CFU/mL) of a gram negative organism
• Negative urine pregnancy test result confirmed by a blood test
• Agreement to remain abstinent or use a contraceptive method

Exclusion Criteria

• Has a concomitant infection requiring antibacterial therapy, in addition to study drug
• Confirmed fungal urinary tract infection
• Moderate or severe renal impairment, or end-stage renal disease requiring renal replacement therapy or a recipient of a renal transplant
• Documented presence of immunodeficiency, or a severely immunocompromised condition or use of systemic immunosuppressant therapy
• Any rapidly progressing disease or immediately life-threatening illness, or other terminal illness or condition with high risk of mortality meaning that the participant is considered, in the opinion of the Investigator, unlikely to survive the study period
• Urinary tract surgery or clinically significant urogenital trauma in the one week immediately preceding study entry
• Urinary tract infection (UTI) symptoms potentially attributable to another process (sexually transmitted infections or prostatitis)
• Suspected or confirmed perinephric or intra renal abscess
• Complete obstruction of any portion of the urinary tract, or a permanent urinary diversion
• History of epilepsy, brain lesions or other significant neurological disorders
• Use of probenecid within the 7 days before enrollment
• Known history of clinically significant hypersensitivity or severe allergic reaction to meropenem or any other antibiotic
• Any other ongoing condition or disease, or clinically significant abnormalities in laboratory test results that the investigator considers would render the participant unsuitable for the study
• Women who are pregnant, planning to become pregnant, or lactating
• Participation in a clinical study of an investigational drug or device within one month prior to enrollment
• Prior enrollment in this study

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
RO7079901 and Meropenem	RO7079901	Participants will receive RO7079901 and meropenem. The duration of study drug treatment will be determined by the investigator after evaluation of the participant's response to study drug treatment. Participants should receive a minimum treatment period of 3 days and up to 14 days of intravenous (IV) study drug treatment.
RO7079901 and Meropenem	Meropenem	Participants will receive RO7079901 and meropenem. The duration of study drug treatment will be determined by the investigator after evaluation of the participant's response to study drug treatment. Participants should receive a minimum treatment period of 3 days and up to 14 days of intravenous (IV) study drug treatment.

Primary Outcome Measures

Name	Time	Method
Total Clearance (CL) of RO7079901	Pre-dose (0 hr), 1.5 hr (end of infusion [infusion duration=1.5 hr]), 3, 4.5, 6, 8 hr post dose on Days 1, 3; pre-dose (0 hr), 1.5 and 8 hr post dose on Days 5 and 7
Renal Clearance (CLr) of RO7079901	Days 1 and 3 (all urine passed in the 8-hour period after morning dose will be collected)
Maximum Observed Plasma Concentration (Cmax) of RO7079901	Pre-dose (0 hr), 1.5 hr (end of infusion [infusion duration=1.5 hr]), 3, 4.5, 6, 8 hr post dose on Days 1, 3; pre-dose (0 hr), 1.5 and 8 hr post dose on Days 5 and 7
Fraction Excreted into the Urine (Fe) of RO7079901	Days 1 and 3 (all urine passed in the 8-hour period after morning dose will be collected)
Time of Maximum Observed Plasma Concentration (Tmax) of RO7079901	Pre-dose (0 hr), 1.5 hr (end of infusion [infusion duration=1.5 hr]), 3, 4.5, 6, 8 hr post dose on Days 1, 3; pre-dose (0 hr), 1.5 and 8 hr post dose on Days 5 and 7
Steady State Volume of Distribution (Vss) of RO7079901	Pre-dose (0 hr), 1.5 hr (end of infusion [infusion duration=1.5 hr]), 3, 4.5, 6, 8 hr post dose on Days 1, 3; pre-dose (0 hr), 1.5 and 8 hr post dose on Days 5 and 7
Area Under the Plasma Concentration Versus Time Curve Over the Dosing Interval (AUC0-tau) of RO7079901	Pre-dose (0 hr), 1.5 hr (end of infusion [infusion duration=1.5 hr]), 3, 4.5, 6, 8 hr post dose on Days 1, 3; pre-dose (0 hr), 1.5 and 8 hr post dose on Days 5 and 7
Cumulative Amount Excreted in Urine Over the Dosing Interval (Ae) of RO7079901	Days 1 and 3 (all urine passed in the 8-hour period after morning dose will be collected)

Secondary Outcome Measures

Name	Time	Method
Cmax of Meropenem	Pre-dose (0 hr), 1.5 hr (end of infusion [infusion duration=1.5 hr]), 3, 4.5, 6, 8 hr post dose on Days 1, 3; pre-dose (0 hr), 1.5 and 8 hr post dose on Days 5 and 7
CL of Meropenem	Pre-dose (0 hr), 1.5 hr (end of infusion [infusion duration=1.5 hr]), 3, 4.5, 6, 8 hr post dose on Days 1, 3; pre-dose (0 hr), 1.5 and 8 hr post dose on Days 5 and 7
CLr of Meropenem	Days 1 and 3 (all urine passed in the 8-hour period after morning dose will be collected)
Ae of Meropenem	Days 1 and 3 (all urine passed in the 8-hour period after morning dose will be collected)
AUC0-tau of Meropenem	Pre-dose (0 hr), 1.5 hr (end of infusion [infusion duration=1.5 hr]), 3, 4.5, 6, 8 hr post dose on Days 1, 3; pre-dose (0 hr), 1.5 and 8 hr post dose on Days 5 and 7
Fe of Meropenem	Days 1 and 3 (all urine passed in the 8-hour period after morning dose will be collected)
Tmax of Meropenem	Pre-dose (0 hr), 1.5 hr (end of infusion [infusion duration=1.5 hr]), 3, 4.5, 6, 8 hr post dose on Days 1, 3; pre-dose (0 hr), 1.5 and 8 hr post dose on Days 5 and 7
Vss of Meropenem	Pre-dose (0 hr), 1.5 hr (end of infusion [infusion duration=1.5 hr]), 3, 4.5, 6, 8 hr post dose on Days 1, 3; pre-dose (0 hr), 1.5 and 8 hr post dose on Days 5 and 7

Trial Locations

Locations (14)

eStudySite; 🇺🇸 La Mesa, California, United States

Semmelweis University, First Dept of Medicine; 🇭🇺 Budapest, Hungary

Jacksonville Center For Clinical Research; 🇺🇸 Jacksonville, Florida, United States

P.Stradina Kliniska Uni Tes Slimnica; Latvian Center of Nephrology; 🇱🇻 Riga, Latvia

Szpital Kliniczny Dzieciątka Jezus; Oddział Urologii; 🇵🇱 Warszawa, Poland

Szent Imre Egyetemi Oktatokorhaz; 🇭🇺 Budapest, Hungary

Kenezy Gyula Korhaz-Rend. Eges. Szol.; Klinikai Farm. Infek. es Allerg. Intezet; 🇭🇺 Debrecen, Hungary

Liepaja Regional hospital; 🇱🇻 Liepaja, Latvia

Riga East clinical university hospital; 🇱🇻 Riga, Latvia

Klinika Urologii Ogólnej: Collegium Medicum Uniwersytetu Mikołaja Kopernika w Toruniu; Urology; 🇵🇱 Bydgoszcz, Poland

Uniwersytecki Szpital Kliniczny im WAM CSW; Klinika Nefrologii i Transplantologii Nerek; 🇵🇱 Łódź, Poland

Clinical Center of Serbia; Clinic of Urology; 🇷🇸 Belgrade, Serbia

Clinical Center Zemun; 🇷🇸 Belgrade, Serbia

Clinical Hospital Center Bezanijska Kosa; 🇷🇸 Belgrade, Serbia