AZD5305 hADME in Patients With Advanced Solid Malignancies

NCT06713369 | Recruiting Phase 1

• 1 other identifier: D9723C00004
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 2

Brief Summary

This Phase I, open-label study aims to study to absolute bioavailability of Saruparib (AZD5305) and the absorption, distribution, metabolism and excretion (ADME) of \[14C\]-Saruparib in patients with advanced solid malignancies. This will be done on an inpatient basis in 2 parts (single-dose oral administration with radiolabeled microtracer in Part A, single-dose IV radiolabeled administration in Part B) during which samples will be obtained of plasma, urine, feces and vomitus (where applicable).

Conditions

Locally Advanced or Metastatic Solid Tumor

Keywords

hADME; saruparib; AZD5305; advanced solid tumour / tumor; neoplasm

Outcome Measures

Primary Outcomes (17)

• Absolute bioavailability (F) of Saruparib

  Absolute bioavailability (F) of Saruparib

  Day 4

• Total radioactivity recovery in urine and faeces

  Total radioactivity recovery in urine and faeces

  Day 8

• Pharmacokinetics of Saruparib(Part B)

  AUCinf

  Day 8

• PK parameters characterized by AUCinf

  AUCinf

  Day 4

• Ratio of AUCinf of plasma Saruparib relative to AUCinf of metabolite

  Ratio of AUCinf of plasma Saruparib relative to AUCinf of metabolite

  Day 4

• Mass balance parameters as characterized by amount excreted and cumulative amount excreted in urine, faeces and total (urine and faeces combined)

  Cumulative amount excreted in urine, faeces and total (urine and faeces combined)

  Day 8

• Amount excreted and cumulative amount excreted in urine, faeces and total (urine and faeces combined) expressed as a percentage of the administered dose

  Amount excreted and cumulative amount excreted in urine, faeces and total (urine and faeces combined) expressed as a percentage of the administered dose.

  Day 8

• Pharmacokinetics of Saruparib(Part B)

  AUClast

  Day 8

• Pharmacokinetics of Saruparib(Part B)

  Cmax

  Day 8

• Pharmacokinetics of Saruparib(Part B)

  tmax

  Day 8

• Pharmacokinetics of Saruparib(Part B)

  t1/2(lambda)z

  Day 8

• Pharmacokinetics of Saruparib(Part B)

  Ratio of AUCinf of plasma Saruparib relative to AUCinf of plasma total radioactivity

  Day 8

• Pharmacokinetics of Saruparib(Part B)

  Ratio of AUCinf of whole blood total radioactivity relative to AUCinf of plasma total radioactivity

  Day 8

• PK parameters characterized by AUClast

  AUClast

  Day 4

• PK parameters characterized by Cmax

  Cmax

  Day 4

• PK parameters characterized by tmax

  tmax

  Day 4

• PK parameters characterized by t1/2(lambda)z

  t1/2(lambda)z

  Day 4

Secondary Outcomes (2)

• Metabolic profiling of a single oral dose of [14C]-Saruparib (Part B)

  Day 8

• Characterize the safety of Saruparib in participants with advanced solid malignancies by incidence and severity of AEs, laboratory abnormalities, 12-lead ECG abnormalities, vital signs abnormalities, physical examination findings

  Day 14

Study Arms (1)

Primary Treatment Arm - AZD5305

EXPERIMENTAL

Part A will assess absolute bioavailability via oral administration of Saruparib (AZD5305) and IV \[14C\]-saruparib microtracer. Part B will assess ADME via IV \[14C\]-saruparib administration

Drug: Saruparib (AZD5305); Drug: [14C]-AZD5305 microtracer; Drug: [14C]-AZD5305 (therapeutic dose)

Interventions

Saruparib (AZD5305) DRUG

PARP-inhibitor

Also known as: Saruparib

Primary Treatment Arm - AZD5305

[14C]-AZD5305 microtracer DRUG

IV radiolabeled microtracer

Also known as: IV [14C]-Saruparib microtracer

Primary Treatment Arm - AZD5305

[14C]-AZD5305 (therapeutic dose) DRUG

IV radiolabeled PARP inhibitor

Also known as: IV [14C]-Saruparib (therapeutic dose)

Primary Treatment Arm - AZD5305

Eligibility Criteria

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

You may qualify if:

• Male or female ≥ 18 years of age (or the legal age of consent in the jurisdiction in which the study is taking place), at the time of signing the ICF.
• Histologically or cytologically documented, locally advanced or metastatic solid tumour, excluding lymphoma, for which standard therapy does not exist or has proven ineffective or intolerable.
• ECOG performance status of 0 or 1 with no deterioration over the 2 weeks prior to dosing.
• Predicted life expectancy ≥ 12 weeks.
• Adequate organ and marrow function as defined in the protocol
• Willingness and ability to comply with study and follow-up procedures.
• Able and willing to stay in hospital for specified residential periods following administration of Saruparib/\[14C\]-Saruparib
• Regular bowel movements
• Body weight within normal range specified in protocol
• Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies Reproduction
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in the protocol

You may not qualify if:

• Participants with a history of MDS/AML or with features suggestive of MDS/AML (as determined by prior diagnostic investigation). Specific screening for MDS/AML is not required.
• Participants with any known predisposition to bleeding
• Any history of persisting severe cytopenia due to any cause
• Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption, distribution, metabolism, or excretion of Saruparib.
• History of another primary malignancy, with some exceptions
• Persistent toxicities (CTCAE Grade ≥ 2), excluding alopecia, caused by previous anticancer therapy.
• Spinal cord compression or brain metastases for at least 4 weeks prior to start of study intervention unless asymptomatic and stable
• History of arrhythmia
• Active HBV (positive HBsAg result) or HCV.
• Evidence of active and uncontrolled HIV infection.
• Active tuberculosis infection
• Major surgical procedure (excluding placement of vascular access) or significant traumatic injury within 4 weeks of the first dose of study intervention or an anticipated need for major surgery during the study.
• As judged by the investigator, any other evidence of diseases (such as severe or uncontrolled systemic diseases or active uncontrolled infections which, in the investigator's opinion, makes it undesirable for the participant to participate in the study or would jeopardise compliance with the protocol.
• Any prior treatment with a PARP inhibitor or platinum chemotherapy.
• Other anticancer therapy (chemotherapy, immunotherapy, hormonal anticancer therapy, radiotherapy \[except for palliative local radiotherapy\]), biological therapy or other novel agent is not permitted until the last PK sampling is completed.

Sponsors & Collaborators

• AstraZeneca: lead
• Fortrea: collaborator

Study Sites (2)

Research Site

Liverpool, L7 8YA, United Kingdom

RECRUITING

Research Site

Manchester, M20 4BX, United Kingdom

RECRUITING

MeSH Terms

Conditions

Neoplasm Metastasis; Neoplasms

Interventions

AZD5305

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

AstraZeneca Clinical Study Information Center

CONTACT

1-877-240-9479; information.center@astrazeneca.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: No masking
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Approximately 8 patients will be enrolled, all will be assigned to the same treatment arm with no randomization or masking. All eligible patients will begin dosing in Part A, followed by a washout period, followed by Part B.

Study Record Dates

• First Submitted: July 30, 2024
• First Posted: December 3, 2024
• Study Start: April 2, 2025
• Primary Completion (Estimated): October 2, 2026
• Study Completion (Estimated): October 2, 2026
• Last Updated: March 4, 2026

Record last verified: 2026-03

Locations

GB (2)