Clinical trial NCT02269644: A P3 Comparator Trial in Community Acquired Bacterial Pneumonia
Official title: 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Community Acquired Pneumonia
Lead sponsor: Durata Therapeutics Inc., an affiliate of Allergan plc
Sponsor class: INDUSTRY
First posted: 2014-10-21
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility criteria: Inclusion Criteria:

1. Adults aged 18 to 85, inclusive
2. Has given written, informed consent
3. Has acute illness with onset within previous 7 days
4. Has at least 2 of the following symptoms:

   * Difficulty breathing or shortness of breath
   * Cough
   * Production of purulent sputum
   * Pleuritic chest pain
5. Has at least 2 vital sign abnormalities:

   * Fever (\> 38°C or \< 35°C)
   * Hypotension (systolic BP \< 90 mm Hg)
   * Tachycardia (\> 100 beats /min)
   * Tachypnea (\> 24 breaths /min)
6. Has at least one other clinical or laboratory abnormalities:

   * Hypoxemia (room air SaO2 \< 90% )
   * Clinical evidence of pulmonary consolidation
   * Elevated WBC count or neutropenia (\> 12,000/mm3 or \< 4,000/mm3)
7. Has new lobar or multi-lobar infiltrates on chest radiograph
8. Has CURB-65 risk category 1 to 4. Patients with CURB-65 risk category 1 will be limited to 20% of the total patient population

Exclusion Criteria:

1. 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)
2. 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
3. Has aspiration pneumonia
4. Has hospital acquired or ventilator associated pneumonia, or healthcare associated pneumonia, or 2 or more days in hospital in the previous 90 days
5. Has cystic fibrosis or known or suspected Pneumocystis pneumonia or known or suspected active tuberculosis
6. 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
7. Has primary or metastatic lung cancer
8. Has known bronchial obstruction or a history of post-obstructive pneumonia
9. Requires admission to ICU at baseline
10. Has empyema requiring drainage
11. Infection due to an organism known prior to study entry to be resistant to either treatment regimen
12. Has known or suspected infection due solely to an atypical pathogen such as Mycoplasma sp., Chlamydia sp. or Legionella sp. or positive Legionella urinary antigen at baseline
13. Absolute neutrophil count \< 500 cells/mm3
14. Known or suspected human immunodeficiency virus (HIV) infected patients with a CD4 cell count \< 200 cells/mm3 or with a past or current acquired immunodeficiency syndrome (AIDS)-defining condition and unknown CD4 count
15. Patients with a recent bone marrow transplant (in post-transplant hospital stay)
16. Patients receiving oral steroids \> 40 mg prednisolone per day (or equivalent) or receiving immunosuppressant drugs after organ transplantation
17. Patients with a rapidly fatal illness, who are not expected to survive for 3 months
18. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study
19. Has participated in another trial of an investigational pharmaceutical product in the 30 days prior to enrollment
20. Prior participation in this trial.

Primary outcomes:
measure: Treatment Response of CABP Symptoms
timeFrame: Change from Baseline to 72-120 hours after randomization
Secondary outcomes:
measure: Efficacy of dalbavancin to the comparator regimen
timeFrame: Change from baseline to 72-120 hours after randomization, Day 14 and Day 28
measure: Safety Analysis
timeFrame: Safety will be assessed at all time-points through Day 28
Other outcomes:
Locations:
city: Butte
country: United States
facility: Mercury Street Medical Group
state: Montana
Study officials:
affiliation: Durata Therapeutics Inc., an affiliate of Allergan plc
name: Urania Rappo, MD
role: STUDY_DIRECTOR
References: