A P3 Comparator Trial in Community Acquired Bacterial Pneumonia

NCT ID: NCT02269644

Last Updated: 2016-01-22

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-11-30
• Study Completion Date: 2016-12-31

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).

Conditions

Community Acquired Pneumonia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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

Group Type: EXPERIMENTAL

Dalbavancin

Intervention Type: DRUG

dalbavancin 1500 mg IV over 30 minutes on Day 1

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.

Group Type: ACTIVE_COMPARATOR

Linezolid

Intervention Type: DRUG

linezolid 600 mg every 12 hours for a minimum of 10 days and a maximum of 14 days

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.

Group Type: OTHER

Linezolid Placebo

Intervention Type: DRUG

Dalbavancin randomized subjects after Day 1, 1st dose will receive linezolid placebo every 12 hours for a minimum of 10 days and a maximum of 14 days

Azithromycin

Dalbavancin and linezolid randomized subjects on Day 1, 1st dose will also receive 500 mg of IV azithromycin

Group Type: OTHER

Azithromycin

Intervention Type: DRUG

Dalbavancin and linezolid randomized subjects on Day 1, 1st dose receive 500 mg of IV azithromycin

Interventions

Dalbavancin

dalbavancin 1500 mg IV over 30 minutes on Day 1

Intervention Type: DRUG

Linezolid

linezolid 600 mg every 12 hours for a minimum of 10 days and a maximum of 14 days

Intervention Type: DRUG

Linezolid Placebo

Dalbavancin randomized subjects after Day 1, 1st dose will receive linezolid placebo every 12 hours for a minimum of 10 days and a maximum of 14 days

Intervention Type: DRUG

Azithromycin

Dalbavancin and linezolid randomized subjects on Day 1, 1st dose receive 500 mg of IV azithromycin

Intervention Type: DRUG

Other Intervention Names

Dalvance; Zyvox

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Durata Therapeutics Inc., an affiliate of Allergan plc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Urania Rappo, MD

Role: STUDY_DIRECTOR

Durata Therapeutics Inc., an affiliate of Allergan plc

Locations

Mercury Street Medical Group

Butte, Montana, United States

Countries

United States

Other Identifiers

2014-002683-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

DUR001-305

Identifier Type: -

Identifier Source: org_study_id