AZD2389 + Itraconazole for Healthy Subjects

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: AstraZeneca

Must not be taking: Antacids, Analgesics, Enzyme inducers, others

Disqualifiers: Gastrointestinal, Hepatic, Renal, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

The purpose of this study is to assess the pharmacokinetics (PK) of AZD2389 when administered alone and in combination with itraconazole in healthy participants.

Will I have to stop taking my current medications?

The trial requires that participants do not use any prescribed or nonprescribed medication, including antacids and pain relievers, so you will likely need to stop taking your current medications.

What data supports the effectiveness of the drug Itraconazole?

Itraconazole is a well-studied antifungal drug that has been shown to be effective in treating a wide range of fungal infections, including those affecting the skin, nails, and deep organs. It is particularly useful for conditions like blastomycosis, histoplasmosis, and certain types of Candida infections, with a good safety profile and few serious side effects. ^{1 2 3 4 5}

Is itraconazole generally safe for humans?

Itraconazole is generally considered safe with a good safety profile, showing fewer side effects compared to other similar drugs, and has been used effectively in treating various fungal infections. ^{1 2 3 5 6}

How does the drug AZD2389 + Itraconazole differ from other treatments?

Itraconazole is a unique antifungal drug because it has a broad spectrum of activity and can be taken orally, making it effective for both superficial and deep fungal infections. It is particularly notable for its ability to reach high concentrations in tissues, which helps in treating systemic fungal infections more effectively than some other antifungal drugs. ^{1 7 8 9 10}

Eligibility Criteria

This trial is for healthy individuals who meet specific health criteria set by the researchers. The exact inclusion and exclusion details are not provided, but typically participants must have no significant medical conditions and be within a certain age range.

Inclusion Criteria

All females must have a negative pregnancy test at the Screening Visit and on admission to the Clinical Unit

I am a woman who cannot have children because I am postmenopausal for over a year or have had surgery to prevent pregnancy.

I am a man who can father children and will use birth control.

Exclusion Criteria

I have no conditions that affect how my body handles medicine.

Abnormal laboratory values, clinically important abnormalities or abnormal vital signs

Any positive result on screening for serum Hepatitis B surface antigen/antibody, Hepatitis C, or Human Immunodeficiency Virus

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Period 1

Participants receive AZD2389 alone to assess baseline pharmacokinetics

1 week

Daily visits for dosing and PK sampling

Period 2

Participants receive AZD2389 in combination with itraconazole to assess drug-drug interaction

1 week

Daily visits for dosing and PK sampling

Period 3

Continuation of combination treatment to further assess pharmacokinetics

1 week

Daily visits for dosing and PK sampling

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

1 visit (in-person)

Treatment Details

Interventions

• AZD2389 (Other)
• Itraconazole (Other)

Trial Overview The study is testing AZD2389, a drug whose effects in the body (pharmacokinetics) are being measured when taken alone or with another medication called Itraconazole. This will help understand how these drugs interact when used together.

Participant Groups

Group I: AZD2389 and Itraconazole Experimental Treatment 2 Interventions

AZD2389 is dosed on days 1 and 6. Itraconazole is dosed on days 3,4,5,6,7, with the dose on day 6 coming after AZD2389.

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Parexel

Industry Sponsor

Trials

322

Recruited

137,000+

Peyton Howell

Parexel

Chief Executive Officer

Master of Healthcare Administration from The Ohio State University, Bachelor of Arts in Health Communications from the University of Illinois

Dr. Austin Smith

Parexel

Chief Medical Officer since 2023

MD from the Royal College of Surgeons in Ireland

Findings from Research

Itraconazole is a broad-spectrum antifungal that is more effective than ketoconazole due to its higher affinity for fungal enzymes, leading to reduced treatment times for infections like vaginal candidiasis and effective treatment for serious conditions such as aspergillosis.

Currently approved in 42 countries, itraconazole is being further developed for antifungal prophylaxis and new formulations, including an oral solution and intravenous options, enhancing its usability in treating systemic fungal infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Itraconazole: pharmacology, clinical experience and future development. De Beule, K.[2019]

Fluconazole and itraconazole are promising new antifungal medications that are effective against systemic fungal infections and have shown high efficacy in treating cryptococcal meningitis.

These drugs have favorable pharmacokinetics and lower toxicity compared to existing azole antifungals, along with a reduced risk of drug interactions, making them safer options for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The triazole antifungal agents: a review of itraconazole and fluconazole. Bailey, EM., Krakovsky, DJ., Rybak, MJ.[2013]

Itraconazole and fluconazole are promising new oral antifungal agents with lower toxicity compared to older azoles, making them safer options for treating fungal infections.

Fluconazole is particularly effective against cryptococcal meningitis and urinary tract infections caused by Candida species, highlighting its potential in treating serious fungal diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Azole antifungal agents: emphasis on new triazoles. Saag, MS., Dismukes, WE.[2022]

Itraconazole is an effective antifungal agent for a variety of superficial fungal infections, with successful treatment regimens ranging from 1-day for vaginal candidosis to 1-week pulse therapy for onychomycosis, demonstrating its versatility and efficacy.

While itraconazole shows promising results for deep mycoses, it is less effective for certain infections like chromomycosis, but remains a valuable option due to its good tolerance and low incidence of serious side effects, although potential drug interactions should be monitored.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Itraconazole. Piérard, GE., Arrese, JE., Piérard-Franchimont, C.[2019]

Itraconazole is an effective antifungal agent with a broad spectrum of action, proven to be the drug of choice for several systemic fungal infections, including blastomycosis and histoplasmosis, based on clinical trials.

It has a strong safety profile, with very few significant side effects reported in a large patient population, making it a valuable treatment option for various fungal infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraconazole--a new oral antifungal agent with a very broad spectrum of activity in superficial and systemic mycoses. Odds, FC.[2019]

A retrospective review of patients treated with itraconazole revealed that low serum levels of the drug were linked to treatment failures in serious fungal infections, such as disseminated histoplasmosis and invasive aspergillosis.

Factors like concurrent use of rifampin, medications that reduce stomach acid, and specific administration methods (like nasogastric tubes) contributed to these low levels, suggesting that monitoring serum itraconazole levels is crucial for patients at risk of treatment failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Itraconazole: Precautions regarding drug interactions and bioavailability. Puttick, MP., Phillips, P.[2021]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Itraconazole: pharmacology, clinical experience and future development. [2019]

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

The triazole antifungal agents: a review of itraconazole and fluconazole. [2013]

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

Azole antifungal agents: emphasis on new triazoles. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Itraconazole. [2019]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Intraconazole--a new oral antifungal agent with a very broad spectrum of activity in superficial and systemic mycoses. [2019]

6. Canada pubmed.ncbi.nlm.nih.gov

Itraconazole: Precautions regarding drug interactions and bioavailability. [2021]

7. Switzerland pubmed.ncbi.nlm.nih.gov

In vitro antifungal spectrum of itraconazole and treatment of systemic mycoses with old and new antimycotic agents. [2018]

8. Germany pubmed.ncbi.nlm.nih.gov

[Pharmacokinetics of itraconazole]. [2013]

9. India pubmed.ncbi.nlm.nih.gov

Itraconazole - a potent antifungal drug. [2021]

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

Itraconazole. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in superficial and systemic mycoses. [2018]