A Phase 3, Double-blinded, Randomized, Comparator Trial of the Safety and Efficacy of a Single Dose of Dalbavancin to Twice Daily Linezolid for the Treatment of Community Acquired Bacterial Pneumonia
Overview
- Phase
- Phase 3
- Intervention
- Dalbavancin
- Conditions
- Community Acquired Pneumonia
- Sponsor
- Durata Therapeutics Inc., an affiliate of Allergan plc
- Locations
- 1
- Primary Endpoint
- Treatment Response of CABP Symptoms
- Status
- Withdrawn
- Last Updated
- 10 years ago
Overview
Brief Summary
This study will be a double-blind, randomized, multicenter trial to assess the safety and efficacy of a single 1500 mg IV dose of dalbavancin plus a single 500 mg IV dose of azithromycin in comparison to an approved antibiotic regimen of linezolid 600 mg every 12 hours for 10-14 days plus a single 500 mg IV dose of azithromycin for the treatment of Community Acquired Bacterial Pneumonia.
Detailed Description
This study will be a double-blind, randomized, multicenter trial to assess the safety and efficacy of a single 1500 mg IV dose of dalbavancin plus a single 500 mg IV dose of azithromycin in comparison to an approved antibiotic regimen of linezolid 600 mg every 12 hours for 10-14 days plus a single 500 mg IV dose of azithromycin for the treatment of CABP. Adult patients who meet all inclusion and none of the exclusion criteria will be randomized to one of the two treatment arms. Dosing will commence on Day 1, and all patients will receive a minimum of 10 days of therapy. Patients will be assessed on Day 1, Day 4-5, Day 7, Day 14 (End of Therapy, EOT), and Day 28 (Follow up).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Adults aged 18 to 85, inclusive
- •Has given written, informed consent
- •Has acute illness with onset within previous 7 days
- •Has at least 2 of the following symptoms:
- •Difficulty breathing or shortness of breath
- •Production of purulent sputum
- •Pleuritic chest pain
- •Has at least 2 vital sign abnormalities:
- •Fever (\> 38°C or \< 35°C)
- •Hypotension (systolic BP \< 90 mm Hg)
Exclusion Criteria
- •Contra-indication to the administration of any of the study treatments, such as hypersensitivity to any of the glycopeptide agents, beta-lactam agents, linezolid or macrolide antibiotics, or current or recent (within 2 weeks) use of MAO inhibitors or serotonergic antidepressants (within 5 weeks for fluoxetine) (see Section 5.5.1)
- •Has received antibiotic therapy in the 4 days prior to screening, with the following exception: up to 25% of patients may have received a single dose of a short acting (half life \< 8 hours) antibiotic
- •Has aspiration pneumonia
- •Has hospital acquired or ventilator associated pneumonia, or healthcare associated pneumonia, or 2 or more days in hospital in the previous 90 days
- •Has cystic fibrosis or known or suspected Pneumocystis pneumonia or known or suspected active tuberculosis
- •Females of child-bearing potential who are unable to take adequate contraceptive precautions, have a positive pregnancy result within 24 hours prior to study entry, are known to be pregnant, or are currently breastfeeding an infant
- •Has primary or metastatic lung cancer
- •Has known bronchial obstruction or a history of post-obstructive pneumonia
- •Requires admission to ICU at baseline
- •Has empyema requiring drainage
Arms & Interventions
Dalbavancin
Dalbavancin randomized subjects will receive one dose of dalbavancin 1500 mg IV over 30 minutes on Day 1 plus azithromycin 500 mg IV on Day 1. Dalbavancin dose will be adjusted for subjects with significant renal insufficiency who are not receiving regular hemodialysis. All patients in the dalbavancin group will receive placebo linezolid infusions or tablets to maintain the blinding. Dalbavancin dose will be adjusted for subjects with significant renal insufficiency who are not receiving regular hemodialysis
Intervention: Dalbavancin
Linezolid
Linezolid randomized subjects will receive linezolid 600 mg every 12 hours for a minimum of 10 days, and a maximum of 14 days. All patients will receive at least one IV dose of linezolid initially plus azithromycin 500 mg IV only on Day 1. Subjects then may then be switched to oral linezolid at the discretion of the investigator, if clinical improvement in the signs and symptoms of pneumonia is observed, to complete the 10-14 day course of therapy,. No dose adjustment is required for renal insufficiency.
Intervention: Linezolid
Linezold Placebo IV and Oral Capsules
Dalbavancin randomized subjects after the 1st dose on Day 1 will receive placebo linezolid every 12 hours for a minimum of 10 days and a maximum of 14 days. Dalbavancin randomized subjects may be switched to oral linezolid placebo therapy to complete the 10-14 day course of therapy.
Intervention: Linezolid Placebo
Azithromycin
Dalbavancin and linezolid randomized subjects on Day 1, 1st dose will also receive 500 mg of IV azithromycin
Intervention: Azithromycin
Outcomes
Primary Outcomes
Treatment Response of CABP Symptoms
Time Frame: Change from Baseline to 72-120 hours after randomization
Compare the efficacy of a single 1500 mg dose of intravenous dalbavancin plus azithromycin to the comparator regimen (linezolid plus azithromycin). Response will be based on resolution of symptoms; including chest pain, shortness of breath (difficulty breathing), frequency/severity of cough and amount of sputum production. Each of these symptoms will be assessed on a 4 point scale (absent, mild, moderate or severe). A patient will be defined as a clinical responder if there is at least a 1 point improvement in 2 or more of these symptoms at 72-120 hours after randomization compared to baseline.
Secondary Outcomes
- Efficacy of dalbavancin to the comparator regimen(Change from baseline to 72-120 hours after randomization, Day 14 and Day 28)
- Safety Analysis(Safety will be assessed at all time-points through Day 28)