A Multicenter, Randomized, Double-blind, Parallel-group, Clinical Study of S-649266 Compared With Meropenem for the Treatment of Hospital-acquired Bacterial Pneumonia, Ventilator-associated Bacterial Pneumonia, or Healthcare-associated Bacterial Pneumonia Caused by Gram-negative Pathogens

Clinical Study of S-649266 for the Treatment of Nosocomial Pneumonia Caused by Gram-negative Pathogens

Sponsors

Lead sponsor: Shionogi

Source Shionogi Inc.
Brief Summary

To compare all-cause mortality at Day 14 in participants receiving S-649266 with participants receiving the comparator, meropenem, in adults with hospital-acquired bacterial pneumonia (HABP), ventilator-associated bacterial pneumonia (VABP), or healthcare-associated bacterial pneumonia (HCABP) caused by Gram-negative pathogens.

Overall Status Completed
Start Date October 24, 2017
Completion Date April 1, 2019
Primary Completion Date February 26, 2019
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
All-cause Mortality at Day 14 Day 14
Secondary Outcome
Measure Time Frame
Percentage of Participants with a Clinical Outcome of Clinical Cure at Test of Cure (TOC) Test of cure, defined as 7 days after end of treatment (treatment duration is 7-14 days)
Percentage of Participants with a Microbiologic Outcome of Eradication at TOC Test of cure, defined as 7 days after end of treatment (treatment duration is 7-14 days)
Percentage of Participants with a Clinical Outcome of Clinical Cure at Early Assessment (EA) Early assessment, defined as 3-4 days after the start of treatment.
Percentage of Participants with a Clinical Outcome of Clinical Cure at End of Treatment (EOT) End of treatment, defined as the last day of study treatment (7-14 days)
Percentage of Participants with a Clinical Outcome of Sustained Clinical Cure at Follow-up (FU) Follow-up, defined as 14 days after the end of treatment (treatment duration is 7-14 days)
Percentage of Participants with a Microbiologic Outcome of Eradication at EA Early assessment, defined as 3-4 days after the start of treatment.
Percentage of Participants with a Microbiologic Outcome of Eradication at EOT End of treatment, defined as the last day of study treatment (7-14 days)
Percentage of Participants with a Microbiologic Outcome of Sustained Eradication at FU Follow-up, defined as 14 days after the end of treatment (treatment duration is 7-14 days)
All-cause Mortality at Day 28 Day 28
All-cause Mortality Over the Full Duration of the Study From start of treatment through study completion (up to 42 days)
Number of 24-hour Days Associated with the Treatment of the Infection Treatment period (7-14 days)
Number of Participants with Adverse Events From baseline through study completion (up to 42 days)
Enrollment 300
Condition
Intervention

Intervention type: Drug

Intervention name: S-649266

Description: 2000 mg intravenously every 8 hours for a period of 7 to14 days (dosage adjustment is necessary based on renal function)

Arm group label: S-649266

Other name: Cefiderocol

Intervention type: Drug

Intervention name: Meropenem

Description: 2000 mg intravenously every 8 hours for a period of 7 to 14 days (dosage adjustment is necessary based on renal function)

Arm group label: Meropenem

Other name: Merrem®

Intervention type: Drug

Intervention name: Linezolid

Description: 600 mg of Linezolid will be administered intravenously over 30 minutes to 2 hours, every 12 hours.

Other name: Zyvox®

Eligibility

Criteria:

Inclusion Criteria:

- Subjects 18 years or older at the time of signing informed consent

- Subjects who have provided written informed consent or their informed consent has been provided by a legally authorized representative

- Subjects who meet the clinical diagnosis criteria for hospital-acquired bacterial pneumonia (HABP),ventilator-associated bacterial pneumonia (VABP), or healthcare-associated bacterial pneumonia (HCABP)

- All subjects must fulfill at least 1 of the following clinical criteria at screening:

1. New onset or worsening of pulmonary symptoms or signs, such as cough, dyspnea, tachypnea (eg, respiratory rate > 25 breaths/minute), expectorated sputum production, or requirement for mechanical ventilation

2. Hypoxemia (eg, a partial pressure of oxygen [PaO2] < 60 mm Hg while the subject is breathing room air, as determined by arterial blood gas [ABG], or worsening of the ratio of the PaO2 to the fraction of inspired oxygen [PaO2/FiO2])

3. Need for acute changes in the ventilator support system to enhance oxygenation, as determined by worsening oxygenation (ABG or PaO2/FiO2) or needed changes in the amount of positive end-expiratory pressure

4. New onset of or increase in (quantity or characteristics) suctioned respiratory secretions, demonstrating evidence of inflammation and absence of contamination

- All subjects must have at least 1 of the following signs:

1. Documented fever (ie, core body temperature [tympanic, rectal, esophageal] ≥ 38°C [100.4°F], oral temperature ≥ 37.5°C, or axillary temperature ≥ 37°C)

2. Hypothermia (ie, core body temperature [tympanic, rectal, esophageal] ≤ 35°C [95.0°F], oral temperature ≤ 35.5°C and axillary temperature ≤ 36°C)

3. Leukocytosis with a total peripheral white blood cell (WBC) count ≥ 10,000 cells/mm³

4. Leukopenia with total peripheral WBC count ≤ 4500 cells/mm³

5. Greater than 15% immature neutrophils (bands) noted on peripheral blood smear

- All subjects must have a chest radiograph during screening showing the presence of new or progressive infiltrate(s) suggestive of bacterial pneumonia. A computed tomography (CT) scan in the same time window showing the same findings could also be acceptable

- All subjects must have a suspected Gram-negative infection involving the lower respiratory tract

Exclusion Criteria:

- Subjects who have known or suspected community-acquired bacterial pneumonia (CABP), atypical pneumonia, viral pneumonia, or chemical pneumonia (including aspiration of gastric contents, inhalation injury)

- Other exclusions based on the prescribing information of meropenem or linezolid, prior antibiotic usage, age, and pregnancy.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
Shionogi Clinical Trials Administrator Clinical Support Help Line Study Director Shionogi
Location
facility
Shionogi Research Site | New Haven, Connecticut, 06511, United States
Shionogi Research Site | DeLand, Florida, 32720, United States
Shionogi Research Site | Chicago, Illinois, 60612, United States
Shionogi Research Site | Council Bluffs, Iowa, 51503, United States
Shionogi Research Site | Louisville, Kentucky, 40202, United States
Shionogi Research Site | Baton Rouge, Louisiana, 70808, United States
Shionogi Research Site | Shreveport, Louisiana, 71103, United States
Shionogi Research Site | Annapolis, Maryland, 21404, United States
Shionogi Research Site | Detroit, Michigan, 48201, United States
Shionogi Research Site | Saint Louis, Missouri, 63110-0250, United States
Shionogi Research Site | Cleveland, Ohio, 44106, United States
Shionogi Research Site | Columbus, Ohio, 43210-1267, United States
Shionogi Research Site | Bethlehem, Pennsylvania, 18105, United States
Shionogi Research Site | Philadelphia, Pennsylvania, 19141, United States
Shionogi Research Site | Salt Lake City, Utah, 84132, United States
Shionogi Research Site | Brussels, 1020, Belgium
Shionogi Research Site | Brussels, 1070, Belgium
Shionogi Research Site | Halifax, Nova Scotia, B3H3A7, Canada
Shionogi Research Site | Kingston, Ontario, K7L 2V7, Canada
Shionogi Research Site | Brno, 65693, Czechia
Shionogi Research Site | Hradec Kralove, 50005, Czechia
Shionogi Research Site | Kolin, 28000, Czechia
Shionogi Research Site | Kyjov, 69701, Czechia
Shionogi Research Site | Ostrava-Poruba, 708 52, Czechia
Shionogi Research Site | Prague, 15006, Czechia
Shionogi Research Site | Pribram, 26101, Czechia
Shionogi Research Site | Kohtla-Jarve, 31025, Estonia
Shionogi Research Site | Parnu, 80010, Estonia
Shionogi Research Site | Tallin, 13419, Estonia
Shionogi Research Site | Tartu, 51014, Estonia
Shionogi Research Site | Angers, 49933, France
Shionogi Research Site | Argenteuil, 95100, France
Shionogi Research Site | Bron, 69677, France
Shionogi Research Site | LaRoche-sur-Yon, 85925, France
Shionogi Research Site | Lyon Cedex, 69437, France
Shionogi Research Site | Nice, 06202, France
Shionogi Research Site | Paris Cedex, 75018, France
Shionogi Research Site | Batumi, 6010, Georgia
Shionogi Research Site | Kutaisi, 4600, Georgia
Shionogi Research Site | Kutaisi, 4601, Georgia
Shionogi Research Site | Tbilisi, 0160, Georgia
Shionogi Research Site | Bonn, 53127, Germany
Shionogi Research Site | Hamburg, 20246, Germany
Shionogi Research Site | Heidelberg, 69120, Germany
Shionogi Research Site | Leipzig, 04103, Germany
Shionogi Research Site | Budapest, 1121, Hungary
Shionogi Research Site | Budapest, 1125, Hungary
Shionogi Research Site | Debrecen, H-4031, Hungary
Shionogi Research Site | Fehergyarmat, 4900, Hungary
Shionogi Research Site | Szekesfehervar, 8000, Hungary
Shionogi Research Site | Holon, 58100, Israel
Shionogi Research Site | Jerusalem, 9103102, Israel
Shionogi Research Site | Tel Aviv, 64239, Israel
Shionogi Research Site | Tel Hashomer, 52621, Israel
Shionogi Research Site | Tikva, 49100, Israel
Shionogi Research Site | Maebashi, Gunma, 371-8511, Japan
Shionogi Research Site | Tsuchiura, Ibaraki, 300-8585, Japan
Shionogi Research Site | Tsu-city, Mie, 514-8507, Japan
Shionogi Research Site | Shimajiri-gun, Okinawa, 901-1193, Japan
Shionogi Research Site | Itabashi-ku, Tokyo, 173-8610, Japan
Shionogi Research Site | Kumamoto, 860-0008, Japan
Shionogi Research Site | Daugavpils, LV-5417, Latvia
Shionogi Research Site | Liepaja, LV-3414, Latvia
Shionogi Research Site | Riga, LV-1006, Latvia
Shionogi Research Site | Saldus Novads, LV-1002, Latvia
Shionogi Research Site | Jaro, Iloilo City, 5000, Philippines
Shionogi Research Site | Tondo, Manila, 1012, Philippines
Shionogi Research Site | Caloocan, Metro Manila, 1400, Philippines
Shionogi Research Site | Quezon City, Metro Manila, 1104, Philippines
Shionogi Research Site | Quezon City, Metro Manila, 1109, Philippines
Shionogi Research Site | Caloocan City, 1427, Philippines
Shionogi Research Site | Iloilo City, 5000, Philippines
Shionogi Research Site | Manila, 1000, Philippines
Shionogi Research Site | San Juan, 00921, Puerto Rico
Shionogi Research Site | Barnaul, 656024, Russian Federation
Shionogi Research Site | Barnaul, 656045, Russian Federation
Shionogi Research Site | Chelyabinsk, 454000, Russian Federation
Shionogi Research Site | Krasnodar, 350012, Russian Federation
Shionogi Research Site | Moscow, 105203, Russian Federation
Shionogi Research Site | Moscow, 115280, Russian Federation
Shionogi Research Site | Moscow, 127015, Russian Federation
Shionogi Research Site | Novosibirsk, 630051, Russian Federation
Shionogi Research Site | Novosibirsk, 630075, Russian Federation
Shionogi Research Site | Sait-Petersburg, 194354, Russian Federation
Shionogi Research Site | Smolensk, 214019, Russian Federation
Shionogi Research Site | St. Petersburg, 192242, Russian Federation
Shionogi Research Site | St. Petersburg, 196247, Russian Federation
Shionogi Research Site | St. Petersburg, 197706, Russian Federation
Shionogi Research Site | St. Petersburg, 454091, Russian Federation
Shionogi Research Site | Tomsk, 634063, Russian Federation
Shionogi Research Site | Belgrade, 11000, Serbia
Shionogi Research Site | Kragujev Ac, 34000, Serbia
Shionogi Research Site | Sremska Kamenica, 21204, Serbia
Shionogi Research Site | Alicante, 03010, Spain
Shionogi Research Site | Barcelona, 08003, Spain
Shionogi Research Site | Barcelona, 08026, Spain
Shionogi Research Site | Barcelona, 8036, Spain
Shionogi Research Site | Madrid, 28007, Spain
Shionogi Research Site | Madrid, 28922, Spain
Shionogi Research Site | Torrejon de Ardoz, 28850, Spain
Shionogi Research Site | Torrevieja, 03186, Spain
Shionogi Research Site | Valencia, 46010, Spain
Shionogi Research Site | New Taipei City, 235, Taiwan
Shionogi Research Site | Taichung, 40705, Taiwan
Shionogi Research Site | Taipei, 10002, Taiwan
Shionogi Research Site | Taipei, 11696, Taiwan
Shionogi Research Site | Chernivtsi, 58001, Ukraine
Shionogi Research Site | Dnipropetrovsk, 49000, Ukraine
Shionogi Research Site | Ivano Frankivsk, 76008, Ukraine
Shionogi Research Site | Kharkiv, 61037, Ukraine
Shionogi Research Site | Kharkiv, 61103, Ukraine
Shionogi Research Site | Kherson, 73000, Ukraine
Shionogi Research Site | Kiev, 01133, Ukraine
Shionogi Research Site | Kiev, 041112, Ukraine
Shionogi Research Site | Kremenchuk, 39617, Ukraine
Shionogi Research Site | Poltava, 36038, Ukraine
Shionogi Research Site | Sumy, 40031, Ukraine
Shionogi Research Site | Vinnitsya, 21029, Ukraine
Shionogi Research Site | Zaporizhzhya, 69035, Ukraine
Location Countries

Belgium

Canada

Czechia

Estonia

France

Georgia

Germany

Hungary

Israel

Japan

Latvia

Philippines

Puerto Rico

Russian Federation

Serbia

Spain

Taiwan

Ukraine

United States

Verification Date

February 2020

Responsible Party

Responsible party type: Sponsor

Keywords
Has Expanded Access Yes
Condition Browse
Number Of Arms 2
Arm Group

Arm group label: S-649266

Arm group type: Experimental

Description: Participants will receive 2 g S-649266 administered intravenously every 8 hours for 7 to 14 days and 600 mg linezolid administered intravenously every 12 hours for at least 5 days.

Arm group label: Meropenem

Arm group type: Active Comparator

Description: Participants will receive 2 g meropenem administered intravenously every 8 hours for 7 to 14 days and 600 mg linezolid administered intravenously every 12 hours for at least 5 days.

Acronym APEKS-NP
Patient Data No
Study Design Info

Allocation: Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: Triple (Participant, Care Provider, Investigator)

Source: ClinicalTrials.gov