Posaconazole for Fungal Infection

Recruiting in Palo Alto (17 mi)

+16 other locations

Age: < 18

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Merck Sharp & Dohme Corp.

Must not be taking: Azole antifungals

Disqualifiers: Cystic fibrosis, Cardiac arrhythmia, others

No Placebo Group

Prior Safety Data

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This study aims to estimate the pharmacokinetics (PK) of posaconazole (POS, MK-5592) intravenous (IV) and powder for oral suspension (PFS) formulations in pediatric participants \<2 years of age with invasive fungal infection (IFI).

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it mentions that certain medications are prohibited before starting the study. It's best to discuss your current medications with the study team to see if any need to be adjusted.

What data supports the effectiveness of the drug Posaconazole for fungal infections?

Posaconazole has been shown to be effective against a wide range of fungal infections, including those resistant to other treatments, and is particularly useful for preventing serious fungal infections in high-risk patients. Clinical trials and studies have demonstrated its effectiveness in treating infections like aspergillosis and candidiasis, and it is well-tolerated with few side effects. ^{1 2 3 4 5}

Is posaconazole generally safe for humans?

Posaconazole, also known as Noxafil, is generally well tolerated by patients and is approved for use in treating and preventing fungal infections. It is available in different forms, including oral suspension, tablets, and intravenous solution, and has been shown to have good tolerability in clinical settings. ^{1 2 3 5 6}

How is the drug Posaconazole different from other treatments for fungal infections?

Posaconazole is unique because it is a triazole antifungal drug that can be taken orally or intravenously and is effective against a wide range of fungi, including those resistant to other antifungal drugs like fluconazole and amphotericin B. It also offers a gastro-resistant tablet form that provides better absorption and consistent plasma levels, making it a preferred option for treating invasive fungal infections. ^{1 2 3 5 7}

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

This trial is for children under 2 years old with invasive fungal infections. They must have symptoms of an acute IFI episode, weigh at least 500g, and have a central line in place. Kids can't join if they've had posaconazole recently, cystic fibrosis, certain metabolic disorders, active COVID-19, liver dysfunction or known severe reactions to similar antifungals.

Inclusion Criteria

I have a fungal infection that is not candidiasis, and it responds to POS medication.

The participant (or legally acceptable representative) has provided documented informed consent for the study

I have had symptoms of a fungal infection for less than 30 days.

Exclusion Criteria

Has QTc prolongation at screening >500 msec

I have or might have Gilbert's syndrome.

I have a hereditary sugar digestion problem.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive posaconazole IV and/or PFS formulations. In Panel A, a single dose of IV POS is administered. In Panel B, participants receive IV POS for a minimum of 7 days, then transition to PFS for up to 84 days.

Up to 84 days

Daily visits for IV administration initially, then weekly visits for monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Posaconazole (Azole Antifungal)

Trial Overview The study tests how the body processes two forms of posaconazole: intravenous (IV) and oral suspension (PFS), in young kids with fungal infections. It aims to understand the appropriate dosing by observing how the drug moves through their bodies.

Participant Groups

Group I: Panel B: POS PFS Experimental Treatment 1 Intervention

Following a minimum of 7 days IV dosing, participants as clinically able will be transitioned from POS IV to POS PFS nominal 6 mg/kg body weight based on weight bands administered on Day 8, once daily to a maximum 84 days.

Group II: Panel B: POS IV Experimental Treatment 1 Intervention

Posaconazole 6 mg/kg body weight administered twice daily by IV infusion on Day 1, and then once daily from Day 2 to a maximum 84 days.

Group III: Panel A: POS IV Experimental Treatment 1 Intervention

Posaconazole 6 mg/kg body weight administered in a single dose by IV infusion on Day 1.

Posaconazole is already approved in Canada for the following indications:

Approved in Canada as Noxafil for:

• Invasive Aspergillus infections
• Candidemia
• Oropharyngeal Candidiasis

Who Is Running the Clinical Trial?

Merck Sharp & Dohme Corp.

Lead Sponsor

Trials

2,287

Recruited

4,582,000+

Chirfi Guindo

Merck Sharp & Dohme Corp.

Chief Medical Officer

Engineering degree from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme Corp.

Chief Executive Officer since 2021

J.D. from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Merck Sharp & Dohme LLC

Lead Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

A study using MRI on adult and juvenile Beagle dogs showed that the intravenous administration of posaconazole (Noxafil) did not affect brain ventricle volume over three months, indicating its safety regarding brain development in older dogs.

The research highlighted significant natural variability in brain ventricle sizes among dogs, which is important for accurately interpreting the effects of treatments like posaconazole and supports its potential use in children over two years of age.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic resonance imaging assessment of the ventricular system in the brains of adult and juvenile beagle dogs treated with posaconazole IV Solution. Hines, CD., Song, X., Kuruvilla, S., et al.[2015]

Posaconazole is an effective antifungal agent for preventing invasive fungal infections, particularly in high-risk patients, and has shown efficacy in treating azole-refractory infections, based on randomized trials and clinical reports.

It has a favorable safety profile, with gastrointestinal disturbances being the most common side effects, and is well tolerated even in long-term use, making it a promising option for managing serious fungal infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Posaconazole: when and how? The clinician's view. Katragkou, A., Tsikopoulou, F., Roilides, E., et al.[2013]

Posaconazole is an effective antifungal agent approved for preventing and treating invasive fungal infections, particularly in patients with weakened immune systems, such as those undergoing stem cell transplants.

The new gastro-resistant tablet formulation of posaconazole offers significant pharmacokinetic advantages over the oral suspension, including improved absorption, less variability between patients, and the convenience of once-daily dosing, making it the preferred choice for optimizing treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Posaconazole: a review of the gastro-resistant tablet and intravenous solution in invasive fungal infections. McKeage, K.[2018]

Posaconazole is a newly approved antifungal medication with a wide range of effectiveness against various yeasts and filamentous fungi, making it a valuable option for treating fungal infections.

While generally well tolerated, there are concerns about its gastrointestinal absorption, which can affect its efficacy in treating serious infections, particularly in immunosuppressed patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of posaconazole in the treatment of oropharyngeal candidiasis. Ianas, V., Matthias, KR., Klotz, SA.[2021]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Posaconazole: SCH 56592. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

In vitro activities of posaconazole, fluconazole, itraconazole, voriconazole, and amphotericin B against a large collection of clinically important molds and yeasts. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Magnetic resonance imaging assessment of the ventricular system in the brains of adult and juvenile beagle dogs treated with posaconazole IV Solution. [2015]

4. Germany pubmed.ncbi.nlm.nih.gov

Posaconazole: when and how? The clinician's view. [2013]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Posaconazole: a review of the gastro-resistant tablet and intravenous solution in invasive fungal infections. [2018]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Role of posaconazole in the treatment of oropharyngeal candidiasis. [2021]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Posaconazole. [2018]