Itraconazole and Cyclosporine for Drug Interaction Study

Recruiting at 1 trial location

Overseen By Pfizer CT.gov Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Pfizer

Must not be taking: GLP-1R agonists, Itraconazole, Cyclosporine

Disqualifiers: HIV, Hepatitis B/C, MTC, others

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

Compensation: Varies

Number of Visits: 13

Duration: 13 days

16 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires participants to stop using prescription or nonprescription drugs and dietary and herbal supplements within 14 days or 5 half-lives before the first dose of the study medicine. This means you may need to stop taking your current medications, but it's best to discuss this with the study team for specific guidance.

What data supports the effectiveness of the drug combination of Itraconazole and Cyclosporine?

The combination of Itraconazole and Cyclosporine shows a beneficial interaction in renal transplant recipients, as Itraconazole is often used to prevent fungal infections in these patients who also need Cyclosporine. This combination can affect drug levels and costs, indicating a complex but potentially useful interaction. ^{1 2 3 4 5}

Is the combination of Itraconazole and Cyclosporine safe for humans?

The combination of Itraconazole and Cyclosporine can lead to serious and potentially life-threatening complications, especially in transplant patients, due to drug interactions that affect how the body processes these medications. Close monitoring and possible adjustments in medication are necessary to manage these risks. ^{1 2 3 6 7}

How does the drug combination of itraconazole and cyclosporine differ from other treatments?

The combination of itraconazole and cyclosporine is unique because itraconazole can increase the effectiveness of cyclosporine by enhancing its absorption, potentially allowing for lower doses of cyclosporine to be used. This interaction is particularly beneficial in transplant patients who need both drugs, as it can help manage drug costs and reduce side effects associated with higher doses of cyclosporine. ^{1 2 4 8 9}

What is the purpose of this trial?

The purpose of this study is to see how single dose of cyclosporine and multiple doses of itraconazole affect the level of the study medicine danuglipron in the blood of healthy adult participants. The information from this study may inform how danuglipron will be used in the future with medicines like cyclosporine and itraconazole.

Research Team

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Eligibility Criteria

This trial is for healthy adults over 18 years old with a BMI of 16-32 kg/m2 and weight above 50 kg. Participants must be in good health as confirmed by medical history, physical exams, lab tests, blood pressure, pulse rate, and ECG readings.

Inclusion Criteria

I am 18 or older and in good health as confirmed by a medical exam.

My BMI is between 16 and 32, and I weigh more than 110 pounds.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants receive danuglipron, cyclosporine, and itraconazole in a fixed sequence to evaluate pharmacokinetics

13 days

13 days of staying in the study clinic

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-5 weeks

Follow-up contact

Treatment Details

Interventions

• Cyclosporine
• Itraconazole

Trial Overview The study is testing how the body processes danuglipron when taken with cyclosporine (a single dose) and itraconazole (multiple doses). This will help understand future use of danuglipron alongside these medications.

Participant Groups

Group I: Period 3: Itraconazole + Danuglipron Experimental Treatment 2 Interventions

Participants will receive itraconazole daily for 6 days plus a single dose of danuglipron on Day 4.

Group II: Period 2: Cyclosporine + Danuglipron Experimental Treatment 2 Interventions

Participants will receive a single 20 mg dose of danuglipron and a single 600 mg dose of cyclosporine on Day 1.

Group III: Period 1: Danuglipron Active Control 1 Intervention

Participants will receive a single 20 mg dose of danuglipron on Day 1.

Who Is Running the Clinical Trial?

Pfizer

Lead Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

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

Beneficial pharmacokinetic interaction between cyclosporine and itraconazole in renal transplant recipients. [2019]

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

Effects of cyclosporine a on single-dose pharmacokinetics of intravenous itraconazole in patients with hematologic malignancies. [2018]

3. Canada pubmed.ncbi.nlm.nih.gov

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

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

Pharmacokinetic evaluation of the drug interaction between intravenous itraconazole and intravenous tacrolimus or intravenous cyclosporin A in allogeneic hematopoietic stem cell transplant recipients. [2013]

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

Factors influencing the magnitude and clinical significance of drug interactions between azole antifungals and select immunosuppressants. [2018]

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

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

7. Denmark pubmed.ncbi.nlm.nih.gov

Adverse drug interactions as a high-risk factor for lethal post-transplant complications in Chinese population. [2019]

8. England pubmed.ncbi.nlm.nih.gov

Effects of multiple oral dosing of itraconazole on the pharmacokinetics of cyclosporine in cats. [2013]

9. England pubmed.ncbi.nlm.nih.gov

Diltiazem does not always increase blood cyclosporin concentration. [2013]