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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00797108
First received: November 24, 2008
Last updated: February 11, 2016
Last verified: February 2016
  Purpose
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.

Condition Intervention Phase
Pneumonia, Bacterial
Drug: sulopenem and PF-03709270
Drug: Sulopenem and PF-03709270
Drug: Ceftriaxone and amoxicillin/clavulanate
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Percentage of Participants With Clinical Response at Test of Cure (TOC) Visit [ Time Frame: 7 to 14 days after end of treatment ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Percentage of Participants With Clinical Response at End of Treatment (EOT) and Follow-up Visit [ Time Frame: EOT (Day 7 to 10) , Follow-up (15 to 28 days after EOT) ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Microbiological Response at Test of Cure (TOC) Visit [ Time Frame: 7 to 14 days after EOT ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Community Acquired Pneumonia (CAP) Symptom Questionnaire at Test of Cure (TOC) and Follow-up Visit [ Time Frame: Baseline, TOC (7 to 14 days after end of treatment), Follow-up (15 to 28 days after EOT) ] [ Designated as safety issue: No ]
    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).


Other Outcome Measures:
  • Number of Participants Who Died [ Time Frame: Baseline up to 15 to 28 days after EOT ] [ Designated as safety issue: Yes ]
  • Number of Participants With Abnormal Laboratory Test Findings [ Time Frame: Baseline up to 15 to 28 days after EOT ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With Abnormal Physical Examination Findings [ Time Frame: Last observation (up to 15-28 days after EOT, approximately 38 days) ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With Categorical Change From Baseline in Vital Signs [ Time Frame: Baseline up to 15 to 28 days after EOT ] [ Designated as safety issue: Yes ]
    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.

  • Population Pharmacokinetics [ Time Frame: 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) ] [ Designated as safety issue: No ]
    Data for this Outcome Measure are not reported here because the analysis population includes participants who were not enrolled in this study.

  • Number of Participants With Healthcare Resource Utilization [ Time Frame: Baseline up to 15 to 28 days after EOT ] [ Designated as safety issue: No ]
    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.


Enrollment: 35
Study Start Date: January 2009
Study Completion Date: June 2009
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00797108

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

Additional Information:
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00797108     History of Changes
Other Study ID Numbers: A8811020  2008-006307-23 
Study First Received: November 24, 2008
Results First Received: July 8, 2015
Last Updated: February 11, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Pneumonia
Pneumonia, Bacterial
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Bacterial Infections
Amoxicillin
Ceftriaxone
Clavulanic Acid
Clavulanic Acids
Amoxicillin-Potassium Clavulanate Combination
Lactams
Anti-Bacterial Agents
Anti-Infective Agents
Beta-Lactamase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 29, 2016