Itraconazole and AZD5004 for Drug Interaction Study

Recruiting at 1 trial location

Overseen By AstraZeneca Clinical Study Information Center

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: AstraZeneca

Must not be taking: Prescribed medications

Disqualifiers: HIV, Hepatic disease, Psychosis, others

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

Compensation: Varies

Number of Visits: 1

38 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that participants have not used any prescribed or non-prescribed medication within 3 months prior to screening, so you will likely need to stop taking your current medications.

Is itraconazole generally safe for humans?

Itraconazole is generally safe for humans, but it can interact with other medications, especially those processed by the liver. These interactions can sometimes lead to increased side effects or reduced effectiveness of the drugs involved, so it's important to monitor and adjust dosages if necessary. ^{1 2 3 4 5}

How does the drug Itraconazole differ from other treatments?

Itraconazole is unique because it is an azole antifungal that can interact with many other drugs due to its metabolism by the cytochrome P450 system, which can lead to significant drug interactions. This makes it important to monitor and adjust dosages when used with other medications, especially in patients with complex treatment regimens. ^{1 2 3 5 6}

What is the purpose of this trial?

The purpose of this study is to assess the impact of multiple doses of itraconazole on the pharmacokinetics (PK) of AZD5004 in healthy participants (Part A), and to assess the impact of multiple doses of AZD5004 on the PK of Combined Oral Contraceptives (COCs) in healthy female participants (Part B).

Eligibility Criteria

This trial is for healthy individuals. Part A includes any gender, while Part B is specifically for healthy females who are eligible to take combined oral contraceptives.

Inclusion Criteria

Part B - Females of non-childbearing potential must be confirmed at the Screening Visit by fulfilling one of the following criteria: Postmenopausal defined as amenorrhoea for at least 12 months following cessation of all exogenous hormonal treatments and Follicle-stimulating hormone (FSH) levels (> 40 mIU/mL), Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy but not tubal ligation or tubal occlusion, Have a BMI between ≥ 23 kg/m2 and ≤ 35 kg/m2 and weigh at least 55 kg

My veins can be used for repeated needle insertions.

I have tested negative for pregnancy before starting the trial.

Exclusion Criteria

Part A and Part B - History of any clinically important disease or disorder which, in the opinion of the Investigator, may either put the participant at risk because of participation in the study

Known smoker, history of alcohol, drug abuse or caffeine intake

Vulnerable participants, e.g., kept in detention, protected adults under guardianship

Timeline

Screening

Participants are screened for eligibility to participate in the trial

27 days

Treatment Part A

Participants receive AZD5004, followed by Itraconazole, and then a combination of both

10 days

Multiple visits for drug administration and monitoring

Follow-up Part A

Participants are monitored for safety and effectiveness after treatment

17 to 24 days

Treatment Part B

Participants receive combined oral contraceptives and AZD5004

78 days

Visits on Day 1, Day 8, Day 50, and Day 78

Follow-up Part B

Participants are monitored for safety and effectiveness after treatment

Up to 96 days

Treatment Details

Interventions

• AZD5004
• Itraconazole

Trial Overview The study tests how multiple doses of the antifungal drug Itraconazole affect AZD5004 in participants (Part A), and how AZD5004 affects the body's handling of birth control pills containing Ethinyl Oestradiol and Levonorgestrel in female participants (Part B).

Participant Groups

Group I: Part B: Ethinyl Estradiol/ Levonorgestrel (EE/LNG) + AZD5004 Experimental Treatment 2 Interventions

Participants will receive one tablet of combined 0.03/0.15 mg EE/LNG and AZD5004 orally.

Group II: Part A: AZD5004 + Itraconazole Experimental Treatment 2 Interventions

Participants will receive oral dose of AZD5004 on Period 1, followed by Itraconazole capsule orally in Period 2, and then will receive oral dose of AZD5004 combination with Itraconazole capsule in Period 3.

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

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

Update on drug interactions with azole antifungal agents. [2017]

2. Canada pubmed.ncbi.nlm.nih.gov

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

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

Management of drug and food interactions with azole antifungal agents in transplant recipients. [2010]

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

Clinical relevance of the pharmacokinetic interactions of azole antifungal drugs with other coadministered agents. [2009]

5. England pubmed.ncbi.nlm.nih.gov

In vivo CYP3A4 activity does not predict the magnitude of interaction between itraconazole and tacrolimus from an extended release formulation. [2019]

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

Inhibition of in vitro metabolism of simvastatin by itraconazole in humans and prediction of in vivo drug-drug interactions. [2019]