Drug-drug Interaction Study With AZD5305 and Itraconazole in Patients With Advanced Solid Malignancies

NCT05573724 | Completed Phase 1

• 2 other identifiers: D9720C000052022-001450-33
• Study Type: interventional
• Target: 16
• Locations: 2 countries
• Sites: 2

Brief Summary

This study is a single-arm, open-label, multi-centre drug-drug interaction (DDI) study of AZD5305 administered orally in patients with advanced solid tumours.

Conditions

Advanced Solid Malignancies

Keywords

Tumors; Pharmacokinetics; Itraconazole; AZD5305; Safety; Tolerability

Outcome Measures

Primary Outcomes (7)

• Part A: Area under the concentration-time curve from time zero to infinity (AUCinf)

  The effect of Itraconazole on the AUCinf of AZD5305 will be assessed. The ratios of geometric means of test intervention (AZD5305 + Itraconazole; parent and metabolite\[s\], if applicable) relative to reference intervention (AZD5305 alone) of AUCinf will be presented.

  Day 1-4, Day 7-13

• Part A: AUC from time zero to time of last measurable concentration (AUClast)

  The effect of Itraconazole on the AUClast of AZD5305 will be assessed. The ratios of geometric means of test intervention (AZD5305 + Itraconazole; parent and metabolite\[s\], if applicable) relative to reference intervention (AZD5305 alone) of AUClast will be presented.

  Day 1-4, Day 7-13

• Part A: Maximum plasma drug concentration (Cmax)

  The effect of Itraconazole on the Cmax of AZD5305 will be assessed. The ratios of geometric means of test intervention (AZD5305 + Itraconazole; parent and metabolite\[s\], if applicable) relative to reference intervention (AZD5305 alone) of Cmax will be presented.

  Day 1-4, Day 7-13

• Part A: Apparent total body clearance of drug from plasma (CL/F)

  The effect of Itraconazole on the PK of AZD5305 will be assessed.

  Day 1-4, Day 7-13

• Part A: Terminal elimination half-life (t½λz)

  The effect of Itraconazole on the PK of AZD5305 will be assessed.

  Day 1-4, Day 7-13

• Part A: Time to maximum observed concentration (Tmax)

  The effect of Itraconazole on the PK of AZD5305 will be assessed.

  Day 1-4, Day 7-13

• Part A: Apparent volume of distribution based on the terminal phase (Vz/F)

  The effect of Itraconazole on the PK of AZD5305 will be assessed.

  Day 1-4, Day 7-13

Secondary Outcomes (5)

• Part A and Part B: Number of participants with Adverse Events (AEs) and Serious Adverse events (SAEs)

  Part A: From screening until post-treatment follow-up (28 days after last dose) (approximately 13 days if continuing into Part B); Part B: From Cycle 1 day 1 until Post treatment follow up (28 days after last dose) (approximately 12 months)

• Part A and Part B: Number of Participants with Laboratory Value Abnormalities and/or AEs

  Part A: From screening until post-treatment follow-up (28 days after last dose) (approximately 13 days if continuing into Part B); Part B: From Cycle 1 Day 1 until Post treatment follow-up (28 days after last dose) (approximately 12 months)

• Part A and Part B: Number of Participants with Vital Sign Abnormalities and/or AEs

  Part A: From screening until post-treatment follow-up (28 days after last dose) (approximately 13 days if continuing into Part B); Part B: From Cycle 1 Day 1 until Post treatment follow-up (28 days after last dose) (approximately 12 months)

• Part A and Part B: Number of Participants with Electrocardiogram (ECG) Abnormalities and/or AEs

  Part A: From screening until post-treatment follow-up (28 days after last dose) (approximately 13 days if continuing into Part B); Part B: From Cycle 1 Day 1 until Post treatment follow-up (28 days after last dose) (approximately 12 months)

• Part A and Part B: Number of Participants with Eastern Cooperative Oncology Group Performance Status (ECOG PS) Abnormalities and/or AEs

  Part A: From screening until post-treatment follow-up (28 days after last dose) (approximately 13 days if continuing into Part B); Part B: From Cycle 1 Day 1 until Post treatment follow-up (28 days after last dose) (approximately 12 months)

Study Arms (1)

Treatment Arm

EXPERIMENTAL

Part A: The participants will receive a single oral dose of AZD5305 on Day 1, followed by a 2-day washout. Then Itraconazole will be dosed for 3 days \[BD\] on Day 4 and \[OD\] on Days 5 and 6, then a single oral dose of AZD5305 administered concurrently with Itraconazole on Day 7 and only Itraconazole on Days 8 to 12. Part B: Patients proceeding to Part B after completing Part A of the study will receive AZD5305 OD as monotherapy.

Drug: AZD5305; Drug: Itraconazole

Interventions

AZD5305 DRUG

In Part A, the participants will receive a single dose of AZD5305 on Day 1 and Day 7. In Part B, the participants will receive AZD5305 once daily.

Treatment Arm

Itraconazole DRUG

In Part A, the participants will receive Itraconazole twice daily on Day 4 and once daily on Days 5-12

Treatment Arm

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed and dated, written informed consent prior to any study specific procedures, sampling and analyses.
• Males and females aged ≥ 18 years at the time of screening.
• Patients with documented evidence of locally advanced unresectable or metastatic solid tumours, excluding lymphoma, who have exhausted standard of care options (or for which no standard therapies exist) and may be suitable for AZD5305 monotherapy treatment.
• Adequate organ and marrow function.
• An Eastern Cooperative Oncology Group Performance Status (ECOG PS): 0 to 2 with no deterioration over the previous 2 weeks.
• Life expectancy ≥ 12 weeks.
• Female patients of childbearing potential. Must have a negative pregnancy test result at screening and prior to each Part of study intervention.
• Female patients must not breastfeed and must not donate or retrieve ova for their own use from screening to approximately 6 months after the last dose of study intervention.

You may not qualify if:

• Previous enrolment in the present study (ie, dosing with AZD5305 previously initiated in this study).
• Positive for detection of drugs of abuse or alcohol at screening.
• Concomitant use of medications or herbal supplements known to be cytochrome P450 3A4 enzyme (CYP3A4) substrates, strong, and moderate inhibitors or inducers.
• Patients with germline Breast cancer gene-mutated relapsed advanced ovarian cancer who have received three or more previous lines of chemotherapy.
• Using of proton pump inhibitors, histamine H2 receptor antagonists and other antiacid agents.
• Using of calcium channel blockers.
• Concomitant use of drugs that are known to prolong or shorten QT and have a known risk of Torsade's de Pointes (TdP).
• During the 4 weeks prior to the first dose, receiving continuous corticosteroids.
• Major surgery within 4 weeks of the first dose of study intervention.
• Radiotherapy with a wide field of radiation within 4 weeks or radiotherapy with a limited field of radiation for palliation within 2 weeks of the first dose of study intervention.
• Treatment with any of the following: any investigational agents or study interventions from a previous clinical study within 5 half-lives or 3 weeks (whichever is shorter) of the first dose of study intervention; any other anticancer treatment within the following time periods prior to the first dose of study intervention: Cytotoxic and non-cytotoxic treatment: 3 weeks or five half-lives (whichever is shorter); Biological products including immuno-oncology agents: 4 weeks before enrolment.; any live virus or bacterial vaccine within 28 days of the first dose of study intervention.
• Any concurrent anticancer therapy or concurrent use of prohibited medications.
• With the exception of alopecia, and peripheral neuropathy; any unresolved toxicities from prior therapy greater than CTCAE Grade 1.
• Any known history of persisting (\> 2 weeks) severe pancytopenia.
• Spinal cord compression, or brain metastases unless asymptomatic and treated and stable and not requiring continuous corticosteroids at a dose of \> 10 mg prednisone/day or equivalent.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (2)

Research Site

Chisinau, MD-2025, Moldova

Location

Research Site

Cluj-Napoca, 400015, Romania

Location

MeSH Terms

Conditions

Neoplasms

Interventions

AZD5305; Itraconazole

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 7, 2022
• First Posted: October 10, 2022
• Study Start: November 7, 2022
• Primary Completion: April 17, 2023
• Study Completion: May 17, 2024
• Last Updated: June 18, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will share
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in a sponsor approved tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

MO (1); RO (1)