Mycoplasma Genitalium Infection, Urethritis
Conditions
Keywords
Omadacycline
Brief summary
Urethritis from Mycoplasma genitalium is difficult to treat and often does not respond to first line therapy. In this case series study, individuals who have failed first line therapy will receive omadacycline (provided by Paratek Pharmaceuticals) to determine the safety and feasibility of using this agent for this condition.
Detailed description
Treatment refractory Mycoplasma genitalium (Mgen) urethritis is an extremely difficult-to-manage clinical entity with inadequate therapeutic options. There are no guidelines for management of patients who fail first-line therapy, with case reports and case series providing limited data into second-line/salvage therapy. In vitro data suggests omadacycline may be active against Mgen and a recent case report provided details on the first refractory case of Mgen cured after omadacycline. In this study individuals with symptomatic Mgen urethritis who have failed first-line therapy (doxycycline followed by moxifloxacin) will receive treatment with omadacycline. The goals of the study are to further explore the efficacy and safety of omadacycline as second-line/salvage therapy in similar cases and to potentially build a foundation for subsequent studies.
Interventions
Patients will receive 28 tablets of 150 milligrams (mg) of omadacycline, taken as 300 mg daily for 14 days.
Sponsors
Montefiore Medical Center
Paratek Pharmaceuticals Inc
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥18 years * Symptomatic urethritis (dysuria, urethral discomfort, pain, or discharge) from Mgen (exclusion of Chlamydia trachomatis, Neisseria gonorrhea, and Trichomonas vaginalis by NAAT) * Treatment-refractory infection, defined as persistent symptoms and Mgen NAAT positivity ≥21 days after completion of initial treatment. Initial treatment based on Centers for Disease Control and Prevention (CDC) guidelines: doxycycline (100 mg twice daily for seven days) followed by moxifloxacin (400 mg once daily for seven days)
Exclusion criteria
* Pregnancy or breast feeding * Allergy or severe intolerance to omadacycline or any of its components * Baseline alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 3 × upper limit of normal (ULN), as determined on screening visit liver function tests (LFTs). * Baseline total bilirubin \> 1.5 × ULN * Suspected or confirmed clinical evidence of end-stage liver disease (e.g., ascites, hepatic encephalopathy) * Patient reported condomless sexual activity occurring between completion of first-line Mgen treatment and subsequent positive NAAT test * Inability of the patient to reasonably expect to avoid condomless sex during the study's 35-day follow-up period between starting study omadacycline and date of follow up test * Based on investigator judgement, significant uncertainty about adherence to prior first-line treatments * Based on investigator judgement, significant uncertainty about the subject's interest in or ability to adhere to omadacycline
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants with Microbiological Cure of Mycoplasma genitalium | Day 35 (+/- 7 days), 21 days after completion of the 14-day omadacycline course | Microbiological cure is defined as having a negative nucleic acid amplification test (NAAT) for Mycoplasma genitalium at the Day 35 test of cure visit. The NAAT is performed on a self-collected urine specimen or a urogenital swab. Participants with a positive NAAT result are classified as not cured (continue to have an active infection). Participants who do not attend the Day 35 (+/- 7 days) visit or from whom no evaluable specimen is obtained are classified as not cured. The denominator is all enrolled participants who received at least one dose of omadacycline. If any participants included in the study are unable to complete the full 14 days of the medication for any reason they will be evaluated based on their outcome from their Day 35 NAAT. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability of omadacycline | At 14 (+/- 5 days) and 35 days (+/- 7 days) after study drug administration | Safety and tolerability of omadacycline will be assessed in tandem using the 20-item PHArmacotherapeutical Symptom Evaluation (PHASE-20) rating scale. The scale consists of 19 specific potential drug-related symptoms plus 1 open-ended category and evaluates whether symptoms experienced during the follow-up period may be related to the medication. For each item, participants will be asked to "tick the box" that best describes symptoms they experienced over the last 2 weeks and circle the appropriate term(s) when a multi-symptom item is presented if all symptoms don't apply. Each of the 20 items is rated on a 4-point ordinal scale: 0 (No problem), 1 (Minor problem), 2 (Moderate problem), and 3 (Severe problem), yielding an overall possible score of 0-60 with higher scores being indicative of a greater burden of possible medication-related symptoms. The scale is administered by telephone at Day 14 and in person at Day 35. Scores are reported separately at each time point. |
| Number of Participants with One or More Treatment-Emergent Adverse Events | Day 1 (first dose administration) through Day 35 (+/- 7 days) | A treatment-emergent adverse event (TEAE) is defined as any adverse event with onset on or after the first dose of omadacycline. Events are identified by the investigator team assessment during the Day 14 (+/- 5 days) telephone contact and the Day 35 (+/- 7 days) clinic visit, and by participant-initiated reporting at any time during the study period. Each event is characterized by severity and by investigator-assessed relationship to omadacycline. Participants reporting more than one event are counted once. |
Countries
United States
Contacts
CONTACTEric A Meyerowitz, MD
CONTACTCaroline Mullis, MD, MS
PRINCIPAL_INVESTIGATOREric A Meyerowitz, MD
Montefiore Medical Center
Outcome results
None listed