Clinical trial NCT03174795: A Study to Investigate the Pharmacokinetics of RO7079901 and Meropenem in Participants With a Complicated Urinary Tract Infection
Official title: A Non-Randomized, Open-Label, One Treatment, One Group Study to Investigate the Pharmacokinetics of RO7079901 and Meropenem in Patients With a Complicated Urinary Tract Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Urinary Tract Infections
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2017-06-05
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Area Under the Plasma Concentration Versus Time Curve Over the Dosing Interval (AUC0-tau) of RO7079901
timeFrame: 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
measure: Total Clearance (CL) of RO7079901
timeFrame: 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
measure: Renal Clearance (CLr) of RO7079901
timeFrame: Days 1 and 3 (all urine passed in the 8-hour period after morning dose will be collected)
measure: Maximum Observed Plasma Concentration (Cmax) of RO7079901
timeFrame: 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
measure: Cumulative Amount Excreted in Urine Over the Dosing Interval (Ae) of RO7079901
timeFrame: Days 1 and 3 (all urine passed in the 8-hour period after morning dose will be collected)
measure: Fraction Excreted into the Urine (Fe) of RO7079901
timeFrame: Days 1 and 3 (all urine passed in the 8-hour period after morning dose will be collected)
measure: Time of Maximum Observed Plasma Concentration (Tmax) of RO7079901
timeFrame: 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
measure: Steady State Volume of Distribution (Vss) of RO7079901
timeFrame: 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
Secondary outcomes:
measure: AUC0-tau of Meropenem
timeFrame: 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
measure: CL of Meropenem
timeFrame: 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
measure: CLr of Meropenem
timeFrame: Days 1 and 3 (all urine passed in the 8-hour period after morning dose will be collected)
measure: Cmax of Meropenem
timeFrame: 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
measure: Ae of Meropenem
timeFrame: Days 1 and 3 (all urine passed in the 8-hour period after morning dose will be collected)
measure: Fe of Meropenem
timeFrame: Days 1 and 3 (all urine passed in the 8-hour period after morning dose will be collected)
measure: Tmax of Meropenem
timeFrame: 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
measure: Vss of Meropenem
timeFrame: 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
Other outcomes:
Locations:
city: La Mesa
country: United States
facility: eStudySite
state: California
city: Jacksonville
country: United States
facility: Jacksonville Center For Clinical Research
state: Florida
city: Budapest
country: Hungary
facility: Semmelweis University, First Dept of Medicine
city: Budapest
country: Hungary
facility: Szent Imre Egyetemi Oktatokorhaz
city: Debrecen
country: Hungary
facility: Kenezy Gyula Korhaz-Rend. Eges. Szol.; Klinikai Farm. Infek. es Allerg. Intezet
city: Liepaja
country: Latvia
facility: Liepaja Regional hospital
city: Riga
country: Latvia
facility: P.Stradina Kliniska Uni Tes Slimnica; Latvian Center of Nephrology
city: Riga
country: Latvia
facility: Riga East clinical university hospital
city: Bydgoszcz
country: Poland
facility: Klinika Urologii Ogólnej: Collegium Medicum Uniwersytetu Mikołaja Kopernika w Toruniu; Urology
city: Warszawa
country: Poland
facility: Szpital Kliniczny Dzieciątka Jezus; Oddział Urologii
city: Łódź
country: Poland
facility: Uniwersytecki Szpital Kliniczny im WAM CSW; Klinika Nefrologii i Transplantologii Nerek
city: Belgrade
country: Serbia
facility: Clinical Center of Serbia; Clinic of Urology
city: Belgrade
country: Serbia
facility: Clinical Center Zemun
city: Belgrade
country: Serbia
facility: Clinical Hospital Center Bezanijska Kosa
Study officials:
References: