AZD2389 + Itraconazole for Healthy Subjects

Overseen By AstraZeneca Clinical Study Information Center

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: AstraZeneca

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

Disqualifiers: Gastrointestinal, Hepatic, Renal, others

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

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how the body processes a new drug, AZD2389, both alone and in combination with itraconazole, an antifungal medication. This understanding helps researchers determine how the drug behaves in healthy individuals. Participants who are generally healthy, have a body mass index (BMI) between 18 and 32, and weigh at least 50 kg may be suitable for this study. As a Phase 1 trial, this research focuses on understanding the treatment's effects in people, offering participants the opportunity to be among the first to receive this new drug.

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.

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

Research has shown that itraconazole is generally safe, and most people tolerate it well. It has a good safety record, typically causing fewer side effects than similar drugs. In contrast, AZD2389 is a newer drug still under study to determine its safety and effectiveness. This trial is in its early stages, providing limited information about responses to AZD2389. Early-stage trials primarily focus on safety, so researchers closely monitor any possible side effects. Participants in these trials help gather crucial information on how the treatment works in the body and whether it causes any side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about AZD2389 because it offers a novel approach by potentially working in synergy with itraconazole to enhance drug efficacy. Unlike other treatments that stick to conventional pathways, AZD2389 might interact with new biological targets, possibly leading to improved therapeutic outcomes. This innovative mechanism is what sets AZD2389 apart from current treatment options, and it could provide a fresh alternative for conditions where these drugs are applicable.

What evidence suggests that AZD2389 and itraconazole could be effective?

Currently, solid proof is lacking on how well AZD2389 treats any specific condition. Previous studies have mainly focused on how the body processes the drug. In this trial, participants will receive both AZD2389 and itraconazole to examine how AZD2389 behaves alone and in combination with itraconazole. Scientists are still learning basic details about how AZD2389 moves through the body and interacts with other drugs. Although direct information about its effectiveness for a health condition is not yet available, this study helps researchers understand the drug better for future testing. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

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

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

Interventions

• AZD2389
• Itraconazole

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

Itraconazole is an effective oral antifungal medication that works against a wide range of fungal infections, including serious ones caused by Aspergillus species, when taken once or twice daily.

Preliminary evidence suggests that itraconazole may also be beneficial in preventing opportunistic fungal infections in high-risk patients, such as those with recurrent vaginal candidiasis, AIDS, or those on immunosuppressant therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Itraconazole - a potent antifungal drug. Panda, NK.[2021]

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]

Itraconazole is highly effective against a wide range of fungal infections, showing potent activity against over 6,500 strains from more than 260 species, including Candida and Aspergillus, with no drug-related side effects reported in studies involving guinea pigs.

In comparative studies, itraconazole outperformed fluconazole, amphotericin B, and flucytosine in treating various fungal infections, demonstrating superior efficacy in candidosis, cryptococcosis, sporotrichosis, and aspergillosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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

Itraconazole is an effective antifungal treatment for various systemic infections, with tissue levels often much higher than plasma levels, which is important for determining the appropriate therapeutic approach.

While generally safe, itraconazole absorption can be reduced in some patients, particularly those undergoing chemotherapy or with altered stomach pH, and it can interact with other medications, necessitating caution in patients on anticoagulants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacokinetics of itraconazole]. Cauwenbergh, G.[2013]

Itraconazole is an effective oral antifungal medication, achieving over 80% cure rates for superficial infections and good to excellent response rates for serious fungal infections like aspergillosis and cryptococcosis, based on non-comparative clinical trials.

The drug is generally well tolerated, with only 1-2% of patients experiencing transient liver function changes, and it shows promise for preventing opportunistic fungal infections in at-risk patients, although further controlled trials are needed to fully establish its role compared to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06846528

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

2. withpower.com withpower.com/trial/phase-1-healthy-subjects-hs-1-2025-a2729

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

3. plpl.www.astrazenecaclinicaltrials.com plpl.www.astrazenecaclinicaltrials.com/study/D7930C00005/

A Study to Investigate the Pharmacokinetics of AZD2389 ... The purpose of this study is to assess the pharmacokinetics (PK) of AZD2389 when administered alone and in combination with itraconazole in ...

4. trial.medpath.com trial.medpath.com/clinical-trial/fb50f7d1134a9cf0/nct06846528-azd2389-pharmacokinetics-itraconazole-combination

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

5. adisinsight.springer.com adisinsight.springer.com/trials/700380677

An Open-label, Fixed Sequence Study in Healthy Participants ... The purpose of this study is to assess the pharmacokinetics (PK) of AZD2389 when administered alone and in combination with itraconazole in ...