E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Community acquired bacterial pneumonia |
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E.1.1.1 | Medical condition in easily understood language |
Infection of the lungs acquired from normal social contact in the community |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10010120 |
E.1.2 | Term | Community acquired pneumonia |
E.1.2 | System Organ Class | 100000004862 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To compare the efficacy of a single 1500 mg dose of intravenous dalbavancin at 72-120 hours after randomization to the comparator regimen (linezolid ) for the treatment of CABP due to susceptible organisms in the ITT population. |
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E.2.2 | Secondary objectives of the trial |
To test the efficacy of dalbavancin to the comparator regimen at a variety of time points, and using a variety of alternative outcome measures, and to test the safety profile of dalbavancin 1500 mg versus the comparator regimen.
To assess the population PK profile of dalbavancin using a sparse sampling approach. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Title, date and version as main protocol.
Objective: To assess the population PK profile of dalbavancin |
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E.3 | Principal 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. |
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E.4 | Principal exclusion criteria |
1. Contra-indication to the administration of any of the study treatments, such as hypersensitivity to any of the glycopeptide agents, aztreonam, 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 (≥ 20 mg prednisone per day or equivalent) for ≥ 2 weeks (within the past month), 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1) Treatment response at Day 4-5. Success is defined as improvement in at least 2 of the following symptoms: chest pain, frequency or severity of cough, amount of productive sputum, and difficulty breathing |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1) Improvement at Day 4-5 in at least two of the following symptoms with no worsening in any of these symptoms of CABP compared to baseline: chest pain, frequency or severity of cough, amount of productive sputum, and difficulty breathing and improvement in vital signs (i.e. temperature, heart rate, respiratory rate or blood pressure);
2) Clinical outcome (using primary response criteria) at Day 14
3) Investigator Assessment of Outcome at Day 14 and Day 28, with success defined as complete resolution of symptoms and signs attributable to CABP and did not receive non trial antibacterial drugs for treatment of CABP
4) All-cause mortality at Day 28 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) Day 4-5
2) At day 14
3) At day 14 and day 28
4) At day 28 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Brazil |
Bulgaria |
Chile |
France |
Hungary |
Italy |
Korea, Republic of |
Mexico |
Poland |
Romania |
Russian Federation |
South Africa |
Spain |
Ukraine |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |