Community-Acquired Pneumonia (CAP)
Conditions
Brief summary
The purpose of this study is to determine whether RX-1741, an oxazolidinone antibiotic, is safe and effective in the treatment of mild to moderate community acquired pneumonia (CAP).
Interventions
DRUGRadezolid
300 mg/day, orally for 7-10 days
Sponsors
Melinta Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Adult patients with mild to moderate CAP. * Adult men and women ≥18 years. * Females must be post-menopausal for at least 1 year or surgically sterile (hysterectomy or tubal ligation). * Sexually active males must use a barrier method of birth control during and for 30 days after the study. Their female partner should also use an additional reliable method of contraception during and for 30 days after the study. * The patient must present with an acute respiratory illness (≤7 days duration) with which history and physical examination is consistent with a diagnosis of CAP. Patients requiring immediate study drug therapy before serology or culture results are known may be entered with a presumptive diagnosis of CAP based on: A chest radiograph at baseline, which shows a new infiltrate(s) consistent with pneumonia as interpreted by the radiologist or the investigator and subsequently confirmed by the radiologist. AND at least 2 of the following signs and symptoms: New or increased cough. Purulent sputum or change in sputum character. Auscultatory findings consistent with pneumonia. New onset or progressive dyspnea or tachypnea. Fever \>38ºC oral or \>38.5ºC tympanic. White blood cell (WBC) count greater than 10,000 cells/mm3 or \>15% immature neutrophils (bands), regardless of total peripheral WBC count, or less than 4,500 cells/mm3. Patient must be able to swallow large capsules intact. A written, voluntarily signed informed consent must be obtained from the patient prior to the initiation of any study-related procedures.
Exclusion criteria
* Hypersensitivity to linezolid. * Patients are excluded if they have taken oral or parenteral antibiotics as follows: long-acting penicillin within 28 days of enrollment azithromycin, ceftriaxone, or telithromycin within 14 days prior to enrollment any other antibiotics for \>24 hours within 3 days of enrollment * Require parenteral antibiotics for the treatment for CAP. * Patient should not have been hospitalized or resided in a long-term facility for at least 14 days before the onset of symptoms. * Evidence of other pulmonary disease that precluded evaluation of therapeutic response. Patients with known bronchial obstruction or a history of postobstructive pneumonia. (This does not exclude patients who have chronic obstructive pulmonary disease). * Experienced a recent clinically significant coagulopathy. * History of cystic fibrosis, active tuberculosis, meningitis, endocarditis, or osteomyelitis. * Immunocompromised patients including, but not limited to patients with a CD4+ cell count of \<350 cells/mm3 secondary to human immunodeficiency virus (HIV) infection, neutropenic patients with granulocytes \<1000/mm3 or immunosuppression secondary to drugs such as corticosteroid therapy (\>10 mg/day of prednisone or equivalent for at least the past 3 months), splenectomized patients or patients with known hyposplenia or asplenia. * Patients who have severe liver disease. * Treatment with an investigational drug within 4 weeks prior to study drug administration. * Any underlying condition or disease state that would interfere with the completion of the study procedures and evaluation of the absorption of study drug. * Patients with bronchiectasis and a history of recent respiratory infection caused by Pseudomonas aeruginosa. * Any infection which requires the use of a concomitant antimicrobial agent, in addition to study drug. * Patients taking serotonergic agents, selective serotonin reuptake inhibitors (SSRIs) or monoamine oxidase inhibitors (MAOIs).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Cure in the Clinically Evaluable (CE) Population at Test of Cure (TOC) | Study days 14-38 | Patients were considered cured if all systemic signs and symptoms of CAP present at screening were improved or resolved and no further antibiotic therapy was necessary. In addition, the follow-up chest X-ray was to be either stable or improved. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Per Patient Microbiological Response of Eradicated in the Microbiologically Evaluable (ME) Population at Test of Cure (TOC) | Study Days 14-38 | The number of ME patients (defined as those CE patients with evidence of 1 or more of 7 key CAP pathogens: S. pneumoniae, H. influenzae, M. catarrhalis, M. pneumoniae, C. pneumoniae, and L. pneumophila) with a microbiologic response of eradicated, i.e. either documented eradication of the baseline pathogen(s), or presumed eradication in the setting of clinical cure with no material to culture. |
Countries
Canada, Russia, United States
Participant flow
Recruitment details
This study targeted adult patients with mild to moderate (i.e., CURB-65 score of 0 or 1) community-acquired pneumonia (CAP).
Participants by arm
| Arm | Count |
|---|---|
| Radezolid 300 mg PO Daily (QD) | 53 |
| Radezolid 450 mg PO Daily (QD) | 52 |
| Radezolid 450 mg PO Twice Daily (BID) | 53 |
| Total | 158 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 3 | 2 |
| Overall Study | Lack of Efficacy | 0 | 2 | 1 |
| Overall Study | Lost to Follow-up | 3 | 1 | 2 |
| Overall Study | Protocol Violation | 2 | 0 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | Radezolid 300 mg PO Daily (QD) | Radezolid 450 mg PO Daily (QD) | Radezolid 450 mg PO Twice Daily (BID) | Total |
|---|---|---|---|---|
| Age, Continuous | 49.6 years STANDARD_DEVIATION 18.37 | 50.4 years STANDARD_DEVIATION 14.55 | 52.1 years STANDARD_DEVIATION 15.61 | 50.7 years STANDARD_DEVIATION 16.2 |
| Region of Enrollment Canada | 14 participants | 16 participants | 21 participants | 51 participants |
| Region of Enrollment Russian Federation | 15 participants | 15 participants | 15 participants | 45 participants |
| Region of Enrollment United States | 24 participants | 21 participants | 17 participants | 62 participants |
| Sex: Female, Male Female | 22 Participants | 17 Participants | 22 Participants | 61 Participants |
| Sex: Female, Male Male | 31 Participants | 35 Participants | 31 Participants | 97 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 11 / 53 | 17 / 52 | 28 / 53 |
| serious Total, serious adverse events | 3 / 53 | 2 / 52 | 5 / 53 |
Outcome results
Primary
Clinical Cure in the Clinically Evaluable (CE) Population at Test of Cure (TOC)
Patients were considered cured if all systemic signs and symptoms of CAP present at screening were improved or resolved and no further antibiotic therapy was necessary. In addition, the follow-up chest X-ray was to be either stable or improved.
Time frame: Study days 14-38
Population: Clinically evaluable patients were those that had a diagnosis of CAP, as defined in the inclusion criteria; who received an appropriate course of therapy; who did not receive any other concomitant antibiotics, and who returned for a TOC visit in the appropriate time frame.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Radezolid 300 mg PO Daily (QD) | Clinical Cure in the Clinically Evaluable (CE) Population at Test of Cure (TOC) | 34 Participants |
| Radezolid 450 mg PO Daily (QD) | Clinical Cure in the Clinically Evaluable (CE) Population at Test of Cure (TOC) | 37 Participants |
| Radezolid 450 mg PO Twice Daily (BID) | Clinical Cure in the Clinically Evaluable (CE) Population at Test of Cure (TOC) | 32 Participants |
Other Pre-specified
Per Patient Microbiological Response of Eradicated in the Microbiologically Evaluable (ME) Population at Test of Cure (TOC)
The number of ME patients (defined as those CE patients with evidence of 1 or more of 7 key CAP pathogens: S. pneumoniae, H. influenzae, M. catarrhalis, M. pneumoniae, C. pneumoniae, and L. pneumophila) with a microbiologic response of eradicated, i.e. either documented eradication of the baseline pathogen(s), or presumed eradication in the setting of clinical cure with no material to culture.
Time frame: Study Days 14-38
Population: Microbiologically evaluable (ME) patients were defined as CE patients with evidence of 1 or more of 7 key CAP pathogens: S. pneumoniae, H. influenzae, M. catarrhalis, M. pneumoniae, C. pneumoniae, and L. pneumophila.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Radezolid 300 mg PO Daily (QD) | Per Patient Microbiological Response of Eradicated in the Microbiologically Evaluable (ME) Population at Test of Cure (TOC) | 16 Participants |
| Radezolid 450 mg PO Daily (QD) | Per Patient Microbiological Response of Eradicated in the Microbiologically Evaluable (ME) Population at Test of Cure (TOC) | 20 Participants |
| Radezolid 450 mg PO Twice Daily (BID) | Per Patient Microbiological Response of Eradicated in the Microbiologically Evaluable (ME) Population at Test of Cure (TOC) | 18 Participants |