Lefamulin for M. Genitalium Treatment Failures

Study Overview
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Brief Summary
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The purpose of this drug study is to find out whether the antibiotic lefamulin (trade name Xenleta) will cure Mycoplasma genitalium infections that have not been cured by prior antibiotics while finding out whether it is more effective if the antibiotic doxycycline is taken first.

Detailed Description
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Study participants will be randomly chosen to receive either lefamulin alone or doxycycline followed by lefamulin in a 1:1 ratio. Each participant will receive 14 lefamulin pills or 14 doxycycline pills and 14 lefamulin pills in the mail and take them as directed for one week (each). Participants will collect one culture sample and one sample to confirm M. genitalium infection on the same day they take their first pill then mail the two samples to the laboratory. They will also answer questions about their symptoms, any side effects, and their behavior with their sex partners. Participants will collect samples two more times and answer questions three more times if they are randomly chosen to receive lefamulin alone or four more times if they are randomly chosen to receive doxycycline followed by lefamulin during the study. The study team will culture M. genitalium then determine minimum inhibitory concentrations (MICs) to three antibiotics (azithromycin, moxifloxacin, and lefamulin) to see whether it is resistant to any of these antibiotics. The study team will also test for M. genitalium to confirm whether the participants have an infection at baseline and see if lefamulin cured the infection upon completion of the lefamulin. After 20 patients have been enrolled, the study team will conduct an interim analysis to assess futility. Futility will be defined as less than five percent probability that true efficacy is greater than or equal to 60 percent (i.e., less than or equal to three of the first 10 participants experience microbiologic cure). If neither lefamulin alone nor doxycycline followed by lefamulin meets criteria for futility, the study team will continue the study. If one regimen meets criteria for futility, the study team will drop the regimen that met the criteria for futility and continue to administer the other regimen to the remaining 20 participants. If both regimens meet criteria for futility, the study team will halt the study. Study participants will be informed of their M. genitalium test of cure results. If the lefamulin does not cure the infection, the study physician will consult with the referring physician who will continue to treat the infection per clinic standard of care.

Official Title
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Lefamulin for Mycoplasma Genitalium Treatment Failures in the US

Conditions
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Mycoplasma Genitalium Infection

Intervention / Treatment
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* Drug: Lefamulin
* Drug: Doxycycline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Physician referral Persistent symptomatic urogenital M. genitalium infection documented by any nucleic acid amplification test (NAAT) 14-90 days after completion of the prior antimicrobial regimen for M. genitalium Low risk of reinfection, defined as no unprotected sex with an untreated sex partner since completion of the prior antimicrobial regimen for M. genitalium Living in the United States Male or female sex at birth At least 18 years of age English-speaking Able to provide written informed consent Able to undergo a test to confirm M. genitalium infection at baseline and tests of cure 21-28 days and 42-47 days after completion of the lefamulin Referring physician willing and able to provide needed patient information Exclusion Criteria: Rectal M. genitalium infection only Females with pelvic inflammatory disease (PID), pregnancy, or currently breastfeeding Females of reproductive age not on a highly effective method of contraception (i.e., intrauterine device (IUD), Nexplanon, progesterone only depot injection with last injection less than three months prior, oral contraceptive pill and last menstrual period less than 28 days prior) Known QT prolongation or ventricular arrhythmias including torsades de pointes Receiving concurrent drugs known to prolong QT interval (i.e., Class IA or III antiarrhythmics, antipsychotics, erythromycin, pimozide, moxifloxacin, tricyclic antidepressants) Receiving strong or moderate CYP3A or P-gp inducers, strong CYP3A or P-gp inhibitors, moderate CYP3A or P-gp inhibitors, or sensitive CYP3A4 substrates that prolong QT interval Moderate or severe liver impairment Known liver disease Renal failure requiring dialysis Known allergy to doxycycline, other tetracyclines, and/or lefamulin Unwilling or unable to undergo a test to confirm M. genitalium infection at baseline or tests of cure 21-28 days and 42-47 days after completion of the lefamulin Not fluent in English and/or not able to provide written informed consent Referring physician unwilling or unable to provide needed patient information At the study physician's discretion

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

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lefamulin alone<br>Lefamulin 600mg tablet orally twice daily for 7 days | Drug: Lefamulin<br>* 600mg tablet orally twice daily<br>* Other names: Xenleta;|
| Experimental: Doxycycline followed by lefamulin<br>Doxycycline 100mg tablet orally twice daily for 7 days followed by lefamulin 600mg tablet orally twice daily for 7 days | Drug: Lefamulin<br>* 600mg tablet orally twice daily<br>* Other names: Xenleta;Drug: Doxycycline<br>* 100mg tablet orally twice daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microbiologic cure | Defined as a negative Aptima Mycoplasma genitalium test 21-28 days after completion of the lefamulin | 21-28 days after completion of the lefamulin | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microbiologic cure after lefamulin alone compared to microbiologic cure after doxycycline followed by lefamulin | Defined as a negative Aptima Mycoplasma genitalium test 21-28 days after completion of the lefamulin | 21-28 days after completion of the lefamulin | 
| Clinical cure | Defined as the absence of symptoms, visible discharge, and other clinical signs (e.g., less than 5 PMNs/HPF on Gram stained smear where available) 21-28 days after completion of the lefamulin | 21-28 days after completion of the lefamulin | 
| Reported adherence to lefamulin | Defined by self-reported number of tablets taken | 7 days from initial study start if randomized to lefamulin alone; 14 days from initial study start if randomized to lefamulin and doxycycline | 
| Reported adverse events | Defined by self-reported adverse events | 42 days from initial study start if randomized to lefamulin alone; 49 days from initial study start if randomized to lefamulin and doxycycline | 
| Sustained microbiologic cure | Defined as a negative Aptima Mycoplasma genitalium test 42-47 days after completion of the lefamulin | 42-47 days after completion of the lefamulin | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lefamulin, Doxycycline, M. genitalium