E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hospital-Acquired Pneumonia with a Focus on Patients with Infections Due to Methicillin-Resistant Staphylococcus aureus |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 6.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10052596 |
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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 and safety of telavancin to vancomycin in the treatment of adults with Gram-positive hospital-acquired pneumonia (HAP) with an emphasis on patients with infections due to methicillin-resistant Staphylococcus aureus (MRSA). |
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E.2.2 | Secondary objectives of the trial |
To pool the data from this study with those from a second study of identical design (protocol 0015) and to assess the superiority of telavancin to vancomycin in patients with MRSA infection. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Patients who meet all of the following criteria will be eligible for study enrollment.
1. Male and female patients ≥ 18 years old. 2. Clinical signs and symptoms consistent with pneumonia acquired after at least 48 hours of continuous stay in an inpatient acute or chronic-care facility, or acquired within 7 days after being discharged from a hospitalization of ≥ 3 days duration. 3. A chest radiograph with findings consistent with a diagnosis of pneumonia (new or progressive infiltrates, consolidation, or pleural effusion) within 48 hours prior to randomization in the study. 4. Availability of appropriate respiratory or sputum specimens for Gram stain and culture, and venous access for IV dosing. 5. Willing to receive IV therapy for the duration of treatment. 6. Informed consent can be obtained for participation in this study as defined by the local Institutional Review Board or Ethics Committee. |
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E.4 | Principal exclusion criteria |
Patients who satisfy any of the following criteria are not eligible for study enrollment.
1. a) Received more than 24 hours of potentially effective systemic (IV/IM or PO) antibiotic therapy prior to randomization, (unless documented to be a treatment failure or if the isolated pathogen for the current pneumonia was resistant in vitro to previous treatment), and/or b) Requires non-study systemic antibiotic potentially effective against the baseline pathogen for another reason during the study 2. Respiratory tract specimens or sputum with only Gram-negative bacteria seen on Gram stain or culture. 3. Known infection with MSSA or S. pneumoniae and patient will require more than 24 hours of concomitant study medication therapy with an antibiotic for Gram-negative coverage that has activity versus MSSA or S. pneumoniae (e.g., piperacillin-tazobactam or imipenem). 4. Known or suspected pulmonary disease that precludes evaluation of therapeutic response (e.g., granulomatous diseases, lung cancer, or another malignancy metastatic to the lungs); cystic fibrosis or active tuberculosis. 5. Known or suspected Legionella pneumophila pneumonia. 6. Known or suspected infection with an organism that is not susceptible to medications permitted by the protocol should be excluded. 7. Documented or suspected meningitis, endocarditis, or osteomyelitis. 8. Sustained shock defined as supine systolic blood pressure < 90 mm Hg for > 2 hours despite adequate fluid resuscitation, with evidence of hypoperfusion or requirement for sympathomimetic agents to maintain blood pressure. 9. Baseline QTc > 500 msec, congenital long QT syndrome, uncompensated heart failure, or uncorrected abnormal K+ or Mg++ blood levels. 10. Severely neutropenic (absolute neutrophil count < 500/mm³) or anticipated to develop severe neutropenia during the study treatment period due to prior or planned chemotherapy, or have HIV with CD4 count < 100/mm³ during the last 6 months 11. Requirement for concomitant administration of intravenous Sporanox® (itraconazole) or Vfend® (voriconazole) or any other medication containing a cyclodextrin solubilizer 12. a) Female patients of childbearing potential if they are pregnant, nursing, or unable to use a highly effective method of birth control during the study and for at least one month following the last dose of study medication. A negative serum pregnancy result must be documented prior to treatment. A highly effective method of birth control is defined as one that results in a low failure rate (i.e., < 1% per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence, or a vasectomized partner. b) Male patients must agree to use medically acceptable birth control for a least three months following last dose of study medication. A vasectomy or a condom used with a spermicide is a medically acceptable birth control method for males. 13. Prior enrollment in a clinical trial of telavancin. 14. Known hypersensitivity to, or intolerance of, study medications or their formulation excipients. 15. Treatment with another investigational medication within 30 days of study entry 16. Considered unlikely to survive at least 7 days due to underlying illness 17. Considered unlikely to comply with the study procedures or to return for scheduled post-treatment evaluations. 18. Any other condition that in the opinion of an investigator, would confound or interfere with evaluation of safety or efficacy of the investigational medication, or prevent compliance with the study protocol. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the clinical response at the Test-of-Cure evaluation. For purpose of analysis, assessments of “failure” at End-of-Therapy will be carried forward to Test-of-Cure. |
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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 | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
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 | No |
E.8.2.3 | Other | No |
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.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
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 |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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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The Independent Data Monitoring Committee (IDMC) will be asked to make recommendations regarding the continuation and/or modification of the study.
Theravance expects to run the study to completion unless evidence of an unsatisfactory risk/benefit profile appears. It does not anticipate stopping the study early should telavancin appear more efficacious than standard therapy. |
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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 | 10 |
E.8.9.1 | In the Member State concerned days | |
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 | 10 |