Study to Evaluate Eye Function in Patients Taking Linezolid for Six Weeks or Greater

Study Overview
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Brief Summary
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To understand and characterize the effects of linezolid on the optic nerve by observing and following patients who have been treated with linezolid for six weeks or longer for the development of signs or symptoms of visual disturbance or eye disorders.

Detailed Description
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Characterize Optic Side Effect

Official Title
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Prospective Study Of Ophthalmologic Function In Patients Receiving Linezolid For Six Weeks Or Greater

Conditions
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Optic Nerve Diseases

Intervention / Treatment
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* Drug: Zyvox - linezolid
* Drug: Matched control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects who are 18 years of age or older. Subjects in Treated Group: Subjects must have received linezolid 600 mg BID for six weeks or greater and be currently on drug (or have received linezolid within 7 days of baseline evaluation). Subjects who have current signs or symptoms compatible with linezolid toxicity (i.e. optic or peripheral neuropathy) may be enrolled in the study if they are on linezolid at time of baseline evaluation (or have received linezolid within 7 days of baseline evaluation). Linezolid may be discontinued at any time at the primary physician's discretion and remain on the study. Women of childbearing potential must use adequate contraception Subjects in Control Group: Subjects will have a diagnosis similar to patients in the treated group and similar important co-morbidities and epidemiologic factors if possible. Exclusion Criteria: Subject in Treated Group: Subjects with a known presence of optic or peripheral nerve damage due to another illness, condition or medication. Subjects with a pre-existing or a diagnosis at time of screening visit of an ophthalmologic condition that would adversely affect the study testing protocol (e.g. dense cataracts, macular degeneration, retinitis pigmentosa). Subjects who are currently receiving or anticipated to receive another medication, antibiotic or other, that has known potential to produce ocular or neurologic toxicity indistinguishable from that caused by linezolid or lactic acidosis. Subjects with a history of significant exposure, in the opinion of the investigator and with prior discussion with the medical monitor, to medications known to produce optic or peripheral neuropathy. Subjects with an active communicable disease (i.e., tuberculosis assessed as currently communicable) and subjects on active treatment for tuberculosis or other mycobacterial disease that include drugs that have known potential to produce ocular or neurologic toxicity. Subjects with severe liver disease or abnormal liver function test. Subjects in Control Group: Subjects must not currently be taking linezolid or have received it for more than 7 days at any time. Subjects with a known presence of optic or peripheral nerve damage due to another illness, condition or medication. Subjects with a pre-existing or a diagnosis at the screening visit of an ophthalmologic condition that would adversely affect the study testing protocol (e.g. dense cataracts, macular degeneration, retinitis pigmentosa). Subjects who are currently receiving another medication, antibiotic or other, that has known potential to produce ocular or neurologic toxicity indistinguishable from that caused by linezolid or lactic acidosis. Subjects with a history of significant exposure, in the opinion of the investigator and with prior discussion with the medical monitor, to medications known to produce optic or peripheral neuropathy. Subjects with an active communicable disease (i.e., tuberculosis assessed as currently communicable) and subjects on active treatment for tuberculosis or other mycobacterial disease that include drugs that have known potential to produce ocular or neurologic toxicity.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Linezolid<br>Subjects have received at least 6 weeks of linezolid therapy (600 mg BID). Continued duration of linezolid treatment is based on treating physician's benefit/risk assessment. A matching control who did not receive linezolid will be selected for each linezolid treated subject. | Drug: Zyvox - linezolid<br>* Observation and testing in patients for whom their treating physician has determined linezolid is an appropriate therapy. Eye tests performed for subjects who have received linezolid for at least 6 weeks and matching controls who have received other antibiotics for similar types of infections.<br>|
| Active Comparator: Matched control<br>Control subjects individually matched to linezolid subjects (on age, gender and type of infection) who received at least 6 weeks of antibiotics other than linezolid. Control group assessed only at baseline visit to assess presence of background abnormalities in the study test panel. | Drug: Matched control<br>* Matched controls received an antibiotic other than linezolid for at least 6 weeks prior to baseline visit. The control group had only a baseline visit and there were no post baseline study visits.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With an Adverse Event |  | Through and including 28 calendar days after the last administration of the investigational product | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants by Clinical Outcome of Infection at End of Study | Clinical response was evaluated at the End of Study visit (30 days after last dose) as Cure, Improvement, Failure, Unknown or Other. Clinical response was based primarily on the global assessment of the clinical presentation of the subject made by the investigator at that evaluation timepoint. The clinical response classifications were defined as follows. Cure: Resolution of the clinical signs and symptoms of infection, when compared to Baseline. No additional antimicrobial treatment is required for the disease under study. Improvement: Improvement in 2 or more, but not all, of the clinical signs and symptoms of infection, when compared with Baseline. No additional antimicrobial treatment is required for the disease under study. Failure: Persistence or progression of Baseline clinical signs and symptoms of infection, or development of new clinical findings consistent with active infection. Unknown: Inability to assess clinical response. | At End of Study visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Optic neuropathy following long-term linezolid use