Ceftazidime-Avibactam Compared With Doripenem Followed by Oral Therapy for Hospitalized Adults With Complicated UTIs (Urinary Tract Infections)

Condition(s) targeted: Complicated Urinary Tract Infection (cUTI) Including Acute Pyelonephritis

Intervention: CAZ-AVI (Drug); Doripenem (Drug); Either switch to oral therapy: 500 mg of Ciprofloxacin (oral) (Drug); or switch to oral therapy: 800 mg/160 mg of sulfamethoxazole/trimethoprim (oral) (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: AstraZeneca

Official(s) and/or principal investigator(s):
Paul Newell, MBBS, MRCP, Study Director, Affiliation: AstraZeneca

The purpose of this study is to evaluate the effects of Ceftazidime Avibactam compared to Doripenem for treating hospitalized patients with complicated urinary tract infections, including acute pyelonephritis

Official title: A Phase III, Randomized, Multicenter, Double-Blind, Double Dummy, Parallel Group, Comparative Study to Determine the Efficacy, Safety, and Tolerability of Ceftazidime Avibactam (CAZ-AVI, Formerly CAZ104) Versus Doripenem Followed by Appropriate Oral Therapy in the Treatment of Complicated Urinary Tract Infections, Including Acute Pyelonephritis, With a Gram Negative Pathogen in Hospitalized Adults

Study design: Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome:

The proportion of patients with resolved (or return to premorbid) UTI(Urinary Tract Infection)symptoms except flank pain and resolution or improvement in flank pain based on patient-reported symptom assessment response

The proportion of patients with a per patient microbiological eradication and resolution (or return to premorbid) of all UTI-specified symptoms based on patient-reported symptom assessment response.

Secondary outcome:

The proportion of patients with a favorable per patient microbiological response in the microbiological modified Intent-To-Treat analysis set

The proportion of patients with a favorable per patient microbiological response in the microbiologically evaluable analysis set.

The proportion of patients with a favorable per patient microbiological response in the extended microbiological evaluable analysis set

The proportion of patients with resolution (or return to premorbid) of all UTI-specific symptoms based on the patient-reported symptom assessment response in the microbiological modified Intent-To-Treat analysis set

The proportion of favorable per-pathogen microbiological response in the microbiological modified Intent-To-Treat analysis set

The proportion of favorable per-pathogen microbiological response in the microbiologically evaluable analysis set

The proportion of favorable per-pathogen microbiological response in the extended microbiologically evaluable analysis set

The proportion of patients with an investigator-determined clinical cure in the microbiological modified Intent-To-Treat analysis set

The proportion of patients with an investigator-determined clinical cure in the microbiologically evaluable analysis set

The proportion of patients with an investigator-determined clinical cure in the extended microbiologically evaluable analysis set

The proportion of patients with an investigator-determined clinical cure in the clinically evaluable analysis set

The favorable per pathogen microbiologic response by categories of minimum inhibitory concentration in the microbiological modified Intent-To-Treat analysis set

The favorable per pathogen microbiologic response by categories of minimum inhibitory concentration in the microbiologically evaluable analysis set

The favorable per pathogen microbiologic response by categories of minimum inhibitory concentration in the extended microbiologically evaluable analysis set

The proportion of patients with favorable investigator clinical response assessment in patients infected with a ceftazidime resistant pathogen in the microbiological modified Intent-To-Treat analysis set

The proportion of patients with an investigator-determined clinical cure in patients infected with a ceftazidime resistant pathogen in the microbiologically evaluable analysis set

The proportion of patients with an investigator-determined clinical cure in patients infected with a ceftazidime resistant pathogen in the extended microbiologically evaluable analysis set

The proportion of patients with favorable per-patient microbiological response for patients infected with a ceftazidime resistant pathogen in the microbiological modified Intent-To-Treat analysis set

The proportion of patients with favorable per-patient microbiological response for patients infected with a ceftazidime resistant pathogen in the microbiologically evaluable analysis set

The proportion of patients with favorable per-patient microbiological response for patients infected with a ceftazidime resistant pathogen in the extended microbiologically evaluable analysis set

The proportion of patients with symptomatic resolution (defined in the co-primary variables) for patients infected with a ceftazidime resistant pathogen in the microbiological modified Intent-To-Treat analysis set

The time to first defervescence while on IV (intravenous)study therapy in patients in the microbiological modified Intent-To-Treat analysis set who have fever at study entry

The time to first defervescence while on IV (intravenous) study therapy in patients in the microbiologically evaluable analysis set who have fever at study entry

The time to first defervescence while on IV (intravenous) study therapy in patients in the extended microbiologically evaluable analysis set who have fever at study entry

The time to first defervescence while on IV (intravenous) study therapy in patients in the clinically evaluable analysis set who have fever at study entry

Profile of pharmacokinetic (PK) of the individual components of CAZ-AVI (avibactam and ceftazidime)- maximum plasma concentration (Cmax)

Profile of pharmacokinetic (PK) of the individual components of CAZ-AVI (avibactam and ceftazidime)- minimum plasma concentration (Cmin)

Profile of pharmacokinetic (PK) of the individual components of CAZ-AVI (avibactam and ceftazidime)- area under the plasma concentration time curve at steady state (AUCss)

Profile of pharmacokinetic (PK) of the individual components of CAZ-AVI (avibactam and ceftazidime)- terminal half-life (t½ )

The safety and tolerability profile by incidence and severity of adverse events and serious adverse events, vital signs, clinical laboratory tests, ECGs and physical exams

Detailed description: A Phase III, Randomized, Multicenter, Double-Blind, Double Dummy, Parallel Group, Comparative Study to Determine the Efficacy, Safety, and Tolerability of Ceftazidime Avibactam (CAZ-AVI, formerly CAZ104) Versus Doripenem Followed by Appropriate Oral Therapy in the Treatment of Complicated Urinary Tract Infections, Including Acute Pyelonephritis, With a Gram Negative Pathogen in Hospitalized Adults

Minimum age: 18 Years. Maximum age: 90 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- 18 to 90 years of age inclusive

- Female patients can participate if they are surgically sterile or completed menopause

or females capable of having children and agree not to attempt pregnancy while receiving IV study therapy and for a period of 7 days after

- Has pyuria with >/= 10 WBCs (white blood cell) and has a positive urine culture

within 48 hours of enrollment containing >/=10 to the fifth CFU (colony forming unit ) /ml of a recognized uropathogen known to be susceptible to IV study therapy (CAZ-AVI and doripenem)

- Demonstrates either acute pyelonephritis or complicated lower UTI without

pyelonephritis. Exclusion Criteria:

- Urine pathogen is a Gram-positive pathogen or a uropathogen resistant to CAZ-AVI or

doripenem

- Patient's urine culture at study entry isolates more than 2 microorganisms regardless

of colony count or patient has a confirmed fungal UTI

- Patient is receiving hemodialysis or peritoneal dialysis or had a renal transplant

- Patient is immunocompromised

- Patient is considered unlikely to survive the 6- to 8-week study period or has a

rapidly progressive or terminal illness including septic shock which is associated with a high risk of mortality

Research Site, Cordoba, Argentina

Research Site, Corrientes, Argentina

Research Site, Córdoba, Argentina

Research Site, Mendoza, Argentina

Research Site, Santa Fe, Argentina

Research Site, Belo Horizonte, Brazil

Research Site, Campinas/SP, Brazil

Research Site, Salvador, Brazil

Research Site, São José do Rio Preto - SP, Brazil

Research Site, São Paulo, Brazil

Research Site, Vila Clementino, Brazil

Research Site, Pleven, Bulgaria

Research Site, Ruse, Bulgaria

Research Site, Sofia, Bulgaria

Research Site, Zagreb, Croatia

Research Site, Kyjov, Czech Republic

Research Site, Opava, Czech Republic

Research Site, Jena, Germany

Research Site, Wuppertal, Germany

Research Site, Athens, Greece

Research Site, Budapest, Hungary

Research Site, Nagykanizsa, Hungary

Research Site, Nyíregyháza, Hungary

Research Site, Zalaegerszeg, Hungary

Research Site, Jerusalem, Israel

Research Site, Petach-Tikva, Israel

Research Site, Safed, Israel

Research Site, Fukuoka-shi, Japan

Research Site, Koshigaya-shi,, Japan

Research Site, Kyoto-shi, Japan

Research Site, Nagoya-shi, Japan

Research Site, Nara-shi, Japan

Research Site, Oita-shi, Japan

Research Site, Sendai-shi, Japan

Research Site, Sunto-gun, Japan

Research Site, Tokushima-shi, Japan

Research Site, Ueda-shi, Japan

Research Site, Utsunomiya-shi, Japan

Research Site, Busan, Korea, Republic of

Research Site, Seoul, Korea, Republic of

Research Site, Wonju, Korea, Republic of

Research Site, Guadalajara, Jalisco, Mexico

Research Site, Inowrocław, Poland

Research Site, Krakow, Poland

Research Site, Warszawa, Poland

Research Site, Lisboa, Portugal

Research Site, Brasov, Romania

Research Site, Bucharest, Romania

Research Site, Bucuresti, Romania

Research Site, Cluj, Romania

Research Site, Craiova, Romania

Research Site, Iasi, Romania

Research Site, Arkhangelsk, Russian Federation

Research Site, Krasnodar, Russian Federation

Research Site, Moscow, Russian Federation

Research Site, Novosibirsk, Russian Federation

Research Site, Penza, Russian Federation

Research Site, Rostov-on-Don, Russian Federation

Research Site, Saratov, Russian Federation

Research Site, St. Petersburg, Russian Federation

Research Site, St.Petersburg, Russian Federation

Research Site, Vsevolozhsk, Russian Federation

Research Site, Belgrade, Serbia

Research Site, Kragujevac, Serbia

Research Site, Poprad, Slovakia

Research Site, Presov, Slovakia

Research Site, Trnava, Slovakia

Research Site, Zilina, Slovakia

Research Site, Chiayi, Taiwan

Research Site, Taipei, Taiwan

Research Site, Diyarbakir, Turkey

Research Site, Cherkasy, Ukraine

Research Site, Dnipropetrovsk, Ukraine

Research Site, Kharkiv, Ukraine

Research Site, Kyiv, Ukraine

Research Site, Lviv, Ukraine

Research Site, Mykolaiv, Ukraine

Research Site, Odesa, Ukraine

Research Site, Odessa, Ukraine

Research Site, Uzhhorod, Ukraine

Research Site, Zaporizhzhya, Ukraine

Research Site, Sylmar, California, United States

Research Site, Royal Oak, Michigan, United States

Research Site, Lima, Ohio, United States

Starting date: October 2012
Last updated: October 20, 2014