Omadacycline for Bone and Joint Infections

(CORGI Trial)

Recruiting at 1 trial location

Overseen By Donna Phan Tran, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Must not be taking: Tetracyclines

Disqualifiers: Pregnancy, Fungi, Mycobacteria, Endocarditis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 4-12 weeks

180 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new antibiotic, omadacycline, for treating bone and joint infections. The goal is to determine if omadacycline is as effective and easier to take than standard antibiotics, particularly because it can be taken orally once daily. Individuals with a bone or joint infection requiring 4 to 12 weeks of treatment and without a long-term antibiotic plan might be suitable candidates. Participants will be randomly assigned to either take omadacycline or follow their usual antibiotic treatment. The trial aims to assess whether omadacycline can improve treatment adherence and outcomes. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important medical advancements.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with your doctor to understand how your current medications might interact with the trial treatment.

Is there any evidence suggesting that omadacycline is likely to be safe for humans?

Research shows that patients usually tolerate omadacycline well. In a study of individuals with community-acquired bacterial pneumonia, only 1% of those taking omadacycline experienced diarrhea, compared to 8% of those on another antibiotic. This suggests omadacycline might cause fewer stomach issues.

However, some individuals may still experience nausea or vomiting. Doctors recommend taking it on an empty stomach for this reason. Omadacycline is approved for treating other infections, which supports its safety profile. As a pill, it is easier to use for bone and joint infections since it does not require injection.

Overall, while research indicates that omadacycline is safe, individual reactions to medications can vary. Consulting a healthcare provider is always advisable if there are any concerns. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for bone and joint infections?

Omadacycline is unique because it offers a new approach to treating bone and joint infections by using a tetracycline-class antibiotic that can be taken orally. Unlike standard treatments, which often involve intravenous antibiotics like vancomycin or ceftriaxone, omadacycline can be administered without a loading dose and has specific guidelines to avoid food interactions, enhancing its practicality and ease of use. Researchers are excited because omadacycline's oral administration could simplify treatment regimens and improve patient compliance, potentially leading to better outcomes in managing these challenging infections.

What evidence suggests that omadacycline might be an effective treatment for bone and joint infections?

Research has shown that omadacycline, a treatment under study in this trial, may effectively treat bone and joint infections (BJIs). Participants may receive omadacycline, an oral antibiotic that is easy to take and may help people adhere to their treatment plan for better results. It is already approved for treating other infections, such as community-acquired bacterial pneumonia, supporting its safety and effectiveness. Overall, early evidence suggests that omadacycline could be a reliable choice for treating BJIs, offering a simpler and effective treatment option. ^{1 3 6 7 8}

Who Is on the Research Team?

Amy Y. Kang, PharmD, BCIDP

Principal Investigator

Chapman Univeristy

Loren G Miller

Principal Investigator

The Lundquist Institute For Biomedical Innovation at Harbor-UCLA Medical Center

Are You a Good Fit for This Trial?

Adults aged 18-85 with bone and joint infections (BJI) suspected to be caused by gram-positive bacteria, needing 4-12 weeks of outpatient treatment. Participants must be able to take oral medication and attend clinic visits. Women of childbearing age must use two forms of contraception during the study.

Inclusion Criteria

I can attend all required follow-up visits at the research clinic.

If a woman is of childbearing potential, she must consistently use two acceptable methods of contraception (IUD, injectable contraceptive, birth control patch, OCP, barrier method, abstinence) from baseline through the course of antibiotics (4-12 weeks). If a male patient's sexual partner is of childbearing potential, the male patient must acknowledge that they will consistently use an acceptable method of contraception as defined above from baseline through the course of antibiotics (4-12 weeks)

I am on a short-term antibiotics course, not for chronic use.

Exclusion Criteria

Pregnancy or breast feeding. Women of childbearing potential must have a negative urine or serum pregnancy test result within 1 day prior to initiation of study drug

I have completed both surgeries and 6 weeks of IV therapy for my prosthetic joint infection.

My bone and joint infection is complicated by heart infection or brain abscesses.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either omadacycline or standard of care antibiotics for bone and joint infections, with therapy lasting between 4 and 12 weeks as decided by the treating physician.

4-12 weeks

In-person visits at weeks 0, 2, 4, 8, and 12

Follow-up

Participants are monitored for safety and effectiveness after treatment, including a final in-person visit 2 weeks post-treatment and a phone survey 3 months post-treatment.

16-24 weeks

1 in-person visit, 1 phone survey

Extension

If necessary, participants may transition to other standard of care antibiotics after 12 weeks of omadacycline treatment.

What Are the Treatments Tested in This Trial?

Interventions

• Omadacycline
• Standard of Care

Trial Overview

This trial is testing omadacycline pills against standard antibiotics for treating BJIs. Patients' treatments are chosen before they join, then randomly assigned to either the new pill or their pre-chosen standard care, followed up through clinic visits and phone surveys.

How Is the Trial Designed?

Group I: standard of care antibiotic Experimental Treatment 1 Intervention

Standard of care as determined by primary care team

Group II: omadacycline Experimental Treatment 1 Intervention

Omadacycline will be administered 300 mg orally daily without the loading dose. We chose to omit the loading dose given that many of the enrolled subjects would have received an IV therapy prior to omadacycline initiation and notable gastrointestinal intolerabilities (nausea/vomiting) based on Phase-3 trial data. Subjects receiving omadacycline will be counseled on appropriate timing of administration (fast for 4 hours before dosing and no food for 2 hours after dosing) in light of the known food effects on drug absorption. They will be instructed to avoid use of products containing aluminum, calcium, or magnesium, bismuth subsalicylate, and iron containing preparations such as dairy, antacids, and multivitamins for 4 hours post-dosing.

Omadacycline is already approved in United States for the following indications:

Approved in United States as Nuzyra for:

• Community-acquired bacterial pneumonia
• Acute bacterial skin and skin structure infections

Who Is Running the Clinical Trial?

Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Lead Sponsor

Trials

105

Recruited

46,600+

Paratek Pharmaceuticals Inc

Industry Sponsor

Trials

17

Recruited

4,000+

Chapman University

Collaborator

Trials

10

Recruited

920+

Published Research Related to This Trial

A review of over 30 antibiotics showed that most, including amoxicillin, vancomycin, and fluoroquinolones, effectively penetrate bone and joint tissues, reaching concentrations that exceed the minimum inhibitory concentrations (MIC) for common pathogens associated with infections.

However, some antibiotics like penicillin and metronidazole demonstrated poor penetration into bone and joint spaces, suggesting they may be less effective for treating these types of infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibiotic penetration into bone and joints: An updated review. Thabit, AK., Fatani, DF., Bamakhrama, MS., et al.[2019]

Omadacycline, approved by the FDA in 2018, is an effective new antibiotic for treating community-acquired pneumonia and acute bacterial skin infections, showing promise against a wide range of bacteria.

This drug is a semisynthetic derivative of minocycline that can overcome common bacterial resistance mechanisms, making it a valuable option in the fight against resistant infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omadacycline: A Newly Approved Antibacterial from the Class of Tetracyclines. Durães, F., Sousa, E.[2020]

Linezolid, daptomycin, and telavancin show potential as treatment options for osteomyelitis caused by resistant gram-positive bacteria, with linezolid demonstrating significant bone penetration in human studies, but its use may be limited by side effects.

Daptomycin and telavancin may serve as alternatives to vancomycin for treating osteomyelitis, while tigecycline and ceftaroline lack sufficient clinical data and show poor bone penetration, limiting their effectiveness in this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The potential role of newer gram-positive antibiotics in the setting of osteomyelitis of adults. Moenster, RP., Linneman, TW., Call, WB., et al.[2013]

Omadacycline (NUZYRA™) is a newly approved oral and intravenous antibiotic that effectively treats community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI) in adults.

This first-in-class aminomethylcycline antibiotic has a broad spectrum of antibacterial activity, marking a significant advancement in the treatment options available for various bacterial infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omadacycline: First Global Approval. Markham, A., Keam, SJ.[2020]

A multidisciplinary team developed evidence-based algorithms for antibiotic therapy in bone and joint infections (BJIs), addressing various clinical scenarios such as vertebral osteomyelitis and prosthetic joint infections.

The algorithms consider important factors like the spectrum of antibiotic activity, pharmacokinetics, and the ability to penetrate bone, aiming to improve treatment outcomes for patients with BJIs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic and pharmacodynamic considerations for optimizing antimicrobial therapy used to treat bone and joint infections: an evidence-based algorithmic approach. Gatti, M., Tedeschi, S., Zamparini, E., et al.[2023]

In a study of 39 patients with Staphylococcus aureus periprosthetic joint infections, oral doxycycline as suppressive antibiotic therapy showed good tolerability, with only 15.4% experiencing adverse events, and 74.4% remaining free of complications after treatment.

Doxycycline demonstrated effectiveness in managing these infections, with 25.6% of patients experiencing treatment failure, primarily due to relapses related to doxycycline-susceptible pathogens, indicating it can be a viable option for patients at high risk of infection failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Suppressive antibiotic therapy with oral doxycycline for Staphylococcus aureus prosthetic joint infection: a retrospective study of 39 patients. Pradier, M., Nguyen, S., Robineau, O., et al.[2018]

Omadacycline is a newly approved antibiotic effective against a wide range of bacteria, including drug-resistant strains like MRSA, making it a valuable option for treating community-acquired pneumonia and skin infections.

It has a favorable safety profile with minimal drug interactions, and the most common side effects are gastrointestinal symptoms, indicating it is generally well-tolerated by patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omadacycline: A Novel Tetracycline Derivative With Oral and Intravenous Formulations. Watkins, RR., Deresinski, S.[2020]

Omadacycline is a new antibiotic derived from the tetracycline class that remains effective against many resistant bacteria, making it a promising option for treating community-acquired infections like skin infections and pneumonia.

It has a favorable safety profile similar to other tetracyclines, does not require dose adjustments for different patient demographics, and can be taken orally, which may lower hospitalization costs compared to intravenous antibiotics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omadacycline: A Modernized Tetracycline. Gallagher, JC.[2023]

Omadacycline is an effective antibiotic against both methicillin-susceptible and methicillin-resistant Staphylococcus aureus, as demonstrated in a study using a neutropenic murine thigh model.

The study found specific pharmacodynamic parameters, with AUC/MIC values of 21.9 for net stasis and 57.7 for a 1-log kill, indicating the concentration levels needed for effective bacterial control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In Vivo Pharmacodynamics of Omadacycline against Staphylococcus aureus in the Neutropenic Murine Thigh Infection Model. Lepak, AJ., Zhao, M., Marchillo, K., et al.[2020]

Treating bone and joint infections is challenging and typically requires a combination of long-term antibiotic therapy and surgery, but there is no standardized approach for these treatments.

Due to the lack of high-quality clinical evidence, it is difficult to provide clear, evidence-based recommendations for the optimal antimicrobial therapy, which must be tailored to both the specific microorganisms involved and the individual patient.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Antibiotic therapy of osteoarticular infections in the adult]. Galpérine, T., Bernard, L.[2007]

Tetracycline antibiotics, especially minocycline, significantly reduce disease activity in rheumatoid arthritis (RA) after 3 months of treatment, with a notable effect on tender joint count and inflammatory markers like ESR.

There was no increased risk of adverse events associated with tetracyclines, indicating they are a safe option for RA treatment, although they did not show benefits in preventing radiological progression of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Should tetracycline treatment be used more extensively for rheumatoid arthritis? Metaanalysis demonstrates clinical benefit with reduction in disease activity. Stone, M., Fortin, PR., Pacheco-Tena, C., et al.[2013]

Citations

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sciencedirect.com

sciencedirect.com/science/article/pii/S2213716525001031

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2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10398854/

Real-world effectiveness of omadacycline and impact ...

Patients with unfilled omadacycline prescriptions were more likely to have 30-day ED/hospital visits relative to patients with filled prescriptions.

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clinicaltrials.gov

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Controlled Trial of Omadacycline Randomized Treatment ...

To compare the treatment success, as defined by lack of definite treatment failure, of omadacycline versus standard of care (SOC) antibiotics for bone and joint ...

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firstwordpharma.com

firstwordpharma.com/story/6323887

Paratek Pharmaceuticals to Present New Data on NUZYRA ...

NUZYRA (omadacycline) is a once-daily oral and intravenous antibiotic indicated for adults with community-acquired bacterial pneumonia (CABP) ...

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11778859/

P-67. Safety of Omadacycline Versus ...

Background. The incidence of bone and joint infections (BJIs) continues to increase, and existing oral BJI antibiotics have limitations.

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nuzyra.com

nuzyra.com/hcp/safety/cabp/

NUZYRA® (omadacycline) Safety in CABP Patients

In OPTIC, 4 (1%) patients experienced diarrhea in the NUZYRA treatment group as compared to 31 (8%) patients in the moxifloxacin group.

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digitalcommons.chapman.edu

digitalcommons.chapman.edu/cgi/viewcontent.cgi?article=2110&context=pharmacy_articles

Safety of Omadacycline Versus Standard-of-Care Oral ...

The incidence of bone and joint infections (BJIs) continues to in- crease, and existing oral BJI antibiotics have limitations. Omadacycline may ...

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accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2018/209816_209817lbl.pdf

NUZYRA (omadacycline) - accessdata.fda.gov

safety and effectiveness of NUZYRA in treating clinical infections due to these microorganisms have not been established in adequate and well controlled ...