A Study Of Intravenous Sulopenem And Oral PF-03709270 In Community Acquired Pneumonia That Requires Hospitalization

A Phase 2 Randomized, Double-blind, Double-dummy Efficacy, Safety And Tolerability Study Of Iv Sulopenem With Switch To Oral Pf-03709270 Compared To Ceftriaxone With Step Down To Amoxicillin/Clavulanate Potassium (Augmentin) In Subjects With Community Acquired Pneumonia (Cap) Requiring Hospitalization

The purpose of this study is to test if intravenous sulopenem and an oral drug, PF-03709270 are safe and effective in patients that are hospitalized with community acquired pneumonia.

Study Overview

• Status: Completed
• Conditions: Pneumonia, Bacterial
• Intervention / Treatment: Drug: sulopenem and PF-03709270; Drug: Sulopenem and PF-03709270; Drug: Ceftriaxone and amoxicillin/clavulanate

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Brisbane, Queensland, Australia, 4102
      • Infection Management Services, Building 17, Level 1
• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
      • Hamilton Health Sciences - General Site
    • Hamilton, Ontario, Canada, L8N 3Z5
      • Hamilton Health Sciences- McMaster Site
    • Hamilton, Ontario, Canada, L8V 1C3
      • Hamilton Health Sciences - Henderson Site
• Korea, Republic of
  • Seoul, Korea, Republic of, 138-736
    • Asan Medical Center, Division of Infectious Diseases
• Poland
  • Bialystok, Poland, 15-003
    • Oddzial Chorob Wewnetrznych i Gastroenterologii
  • Brzesko, Poland, 32-800
    • Oddzial Chorob Pluc
  • Krakow, Poland, 30-901
    • Kliniczny Oddzial Gruzlicy i Chorob Pluc
  • Lodz, Poland, 90-153
    • Oddzial Kliniczny Pulmonologii i Alergologii
  • Poznan, Poland, 60-569
    • Oddzial Pulmonologiczny III
  • Proszowice, Poland, 32-100
    • Oddzial Pulmonologiczny
  • Warszawa, Poland, 03-401
    • II Oddzial Chorob Wewnetrznych
• United States
  • California
    • Chula Vista, California, United States, 91911
      • eStudySite, Inc.
    • Chula Vista, California, United States, 91911
      • Sharp Chula Vista Medical Center
    • Oceanside, California, United States, 92056
      • Tri-City Medical Center
    • Oceanside, California, United States, 92056
      • eStudySite, Inc.
  • Illinois
    • Moline, Illinois, United States, 61265
      • Medical Arts Associates, Ltd
    • Rock Island, Illinois, United States, 61201
      • Trinity Medical Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55422
      • Infectious Disease Minneapolis Limited
  • Ohio
    • Akron, Ohio, United States, 44304
      • Summa Health System
    • Akron, Ohio, United States, 44309
      • Summa Health System
    • Akron, Ohio, United States, 44310
      • Summa Health System
  • Utah
    • Provo, Utah, United States, 84604
      • Utah Valley Regional Medical Center
    • Provo, Utah, United States, 84604
      • Utah Valley Pulmonary Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Hospitalized male or female patients 18 years of age or older.
• Female patients of childbearing potential must not be pregnant.
• Must exhibit at least two pre-specified clinical symptoms/signs of pneumonia.
• Must require hospitalization for the pneumonia.
• Chest Xray must be suggestive of a pneumonia.

Exclusion Criteria:

• Hospital or ventilator associated pneumonia.
• Patients with cystic fibrosis, pneumocystis carinii pneumonia or active tuberculosis.
• Previous treatment for the current pneumonia episode received for more than 24 hours.
• Allergies to penems or beta lactams.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Loading dose of IV sulopenem with switch to oral PF-03709270	Drug: sulopenem and PF-03709270; Sulopenem - 600 mg infused over 1 hour, single loading dose and switch to oral PF-03709270 - 1000 mg twice a day
Experimental: 2; IV sulopenem with switch to oral PF-03709270	Drug: Sulopenem and PF-03709270; Sulopenem - 600 mg infused over 1 hour twice daily for a minimum of 2 days and switch to oral PF-03709270 - 1000 mg twice a day
Active Comparator: 3; IV ceftriaxone with switch to oral amoxicillin/clavulanate potassium comparator	Drug: Ceftriaxone and amoxicillin/clavulanate; IV ceftriaxone (2g) infused over 30 minutes QD (once daily) for minimum of 2 days Step down oral amoxicillin/clavulanate potassium suspension (400 mg/5 ml) BID (every 12 hours)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Clinical Response at Test of Cure (TOC) Visit	Clinical response (CR) was based primarily on global assessment of clinical presentation of participant made by investigator at evaluation time point. At TOC (7 to 14 days after end of treatment [EOT]) CR was evaluated as "cure"=resolution of clinical signs and symptoms related to the acute infection, or clinical improvement in which no additional antibiotics were deemed necessary when compared to baseline; "failure"=persistence or progression of baseline signs and symptoms of pneumonia (for example: body temperature, white blood cell [WBC] count, respiratory rate, auscultatory findings, cough, sputum production), development of new pulmonary or extrapulmonary clinical findings consistent with active infection and those participants that were not assessed for clinical response due to early discontinuation; "indeterminate"=extenuating circumstances precluded classification to 1 of the above.	7 to 14 days after end of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Clinical Response at End of Treatment (EOT) and Follow-up Visit	CR was based primarily on global assessment of clinical presentation of participant made by investigator at evaluation time point. At EOT (Day 7 to 10) and follow-up (15 to 28 days after EOT), CR was evaluated as "cure"=resolution of clinical signs and symptoms related to the acute infection, or clinical improvement in which no additional antibiotics were deemed necessary when compared to baseline; "failure"=persistence or progression of baseline signs and symptoms of pneumonia, development of new pulmonary or extrapulmonary clinical findings consistent with active infection and those participants that were not assessed for clinical response due to early discontinuation; with additional CR evaluated as "improvement"= of few not all signs and symptoms of pneumonia when compared to baseline and no additional antibacterial treatment required at EOT and "indeterminate"=extenuating circumstances precluded classification to 1 of the above at follow-up.	EOT (Day 7 to 10) , Follow-up (15 to 28 days after EOT)
Number of Participants With Microbiological Response at Test of Cure (TOC) Visit	Microbiological response assessed at participant level. Eradication=the absence of the original pathogens from the post-treatment TOC culture of specimen from the original site of infection. Presumed eradication=the complete resolution of signs and symptoms associated with cessation of culturable specimen (for example, sputum). Persistence=the presence of the original pathogen in the post-treatment TOC culture specimen from the original site of infection. Presumed persistence=in a participant who was judged to be a clinical failure and a culture of specimen was not possible or was not done, it was presumed that there was persistence of the pathogen. Not applicable microbiologic response included participants that did not have post-treatment microbiologic cultures due to early discontinuation. Data reported for eradication is combination of eradication and presumed eradication data and data reported for persistence is combination of persistence and presumed persistence data.	7 to 14 days after EOT
Change From Baseline in Community Acquired Pneumonia (CAP) Symptom Questionnaire at Test of Cure (TOC) and Follow-up Visit	The CAP Symptom Questionnaire was a participant reported questionnaire administered by interview. It consisted of 12 items (coughing, chest pains, shortness of breath, sweating, chills, headache, nausea, muscle pain, lack of appetite, trouble concentrating, trouble sleeping, and fatigue). Depending on if the participant had or not had symptoms/problems, they were asked how much they had been bothered by the symptoms/problems over the previous 24 hours. CAP items were rated on the 6-point response scale (0 = participant did not have symptom/problem: 1 = not at all, 2 = a little, 3 = moderately, 4 = quite a bit, 5 = extremely; if the participant had the symptom/problem and were bothered). All 12 items score were summed and averaged to produce a CAP symptom score (range, 0 to 6). High values indicated poorer outcomes (higher symptom bothersomeness).	Baseline, TOC (7 to 14 days after end of treatment), Follow-up (15 to 28 days after EOT)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Died		Baseline up to 15 to 28 days after EOT
Number of Participants With Abnormal Laboratory Test Findings	Criteria for laboratory abnormalities: hemoglobin (Hb), hematocrit, red blood cell (RBC) (less than [<] 0.8*lower limit of normal [LLN]); reticulocyte (absolute and percentage) (<0.5*LLN or greater than [>] 1.5*upper LN [ULN]); platelet (<0.5*LLN or >1.75*ULN); white blood cell (WBC) (<0.6*LLN or >1.5*ULN); lymphocyte, neutrophil (<0.8*LLN or >1.2*ULN); eosinophil, monocyte, basophil (>1.2*ULN); bilirubin (BR) (>1.5*ULN); aspartate and alanine aminotransferase, gamma-glutamyl transpeptidase, alkaline phosphatase, lactate dehydrogenase (>3.0*ULN); total protein, albumin (<0.8*LLN or >1.2*ULN);blood urea nitrogen, creatinine (>1.3*ULN); sodium (<0.95*LLN or >1.05*ULN); potassium, chloride, calcium, magnesium, bicarbonate (<0.9*LLN or >1.1*ULN); glucose (<0.6*LLN or >1.5*ULN); urine (pH [<4.5 or >8], glucose, protein, blood, ketone [>=1]). Total number of participants with abnormal laboratory values were reported.	Baseline up to 15 to 28 days after EOT
Number of Participants With Abnormal Physical Examination Findings	A physical examination included an examination of the general appearance, skin, heart, head, eyes, ears, nose, throat, breasts, abdomen, musculoskeletal, neck, neurological, extremities, and others. Criteria for abnormal physical findings were based on investigator's discretion.	Last observation (up to 15-28 days after EOT, approximately 38 days)
Number of Participants With Categorical Change From Baseline in Vital Signs	Participants who met the categorical criteria for increase in vital signs data were reported. Categorical criteria for increase from baseline vital signs data: supine and sitting systolic blood pressure (BP) of greater than or equal to (>=) 30 millimeter of mercury (mmHg); supine and sitting diastolic BP of >=20 mmHg.	Baseline up to 15 to 28 days after EOT
Population Pharmacokinetics	Data for this Outcome Measure are not reported here because the analysis population includes participants who were not enrolled in this study.	0.5 to 1 hours, 1.5 to 3 hours, 3 to 5 hours after initiation of first intravenous dose; 0.5 to 2.5 hours, 4 to 6 hours following administration of oral dose on the day of IV to oral switch (minimum of 2 days equivalent on intravenous dose)
Number of Participants With Healthcare Resource Utilization	Healthcare resource utilization was to be evaluated using the assessment of the following: date and duration of index admission, duration of hospitalization, date of discharge, location of discharge, type/length of treatment inside and outside of the hospital, healthcare professional visits outside of the hospital, emergency room visits, and other hospitalizations.	Baseline up to 15 to 28 days after EOT

Collaborators and Investigators

• Sponsor: Pfizer

Study record dates

Study Major Dates

• Study Start: January 1, 2009
• Primary Completion (Actual): June 1, 2009
• Study Completion (Actual): June 1, 2009

Study Registration Dates

• First Submitted: November 24, 2008
• First Submitted That Met QC Criteria: November 24, 2008
• First Posted (Estimate): November 25, 2008

Study Record Updates

• Last Update Posted (Estimate): March 10, 2016
• Last Update Submitted That Met QC Criteria: February 11, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Pneumonia; Pneumonia, Bacterial; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Ceftriaxone; Amoxicillin; Clavulanic Acid; Clavulanic Acids; Amoxicillin-Potassium Clavulanate Combination; Lactams
• Other Study ID Numbers: A8811020; 2008-006307-23 (EudraCT Number)