A Study to Assess the Mass Balance Recovery, Metabolite Profile and Metabolite Identification of [14C]AZD9833

NCT05364255 | Completed Phase 1

• 2 other identifiers: D8532C000052022-000834-40
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

The Sponsor is developing the test medicine, AZD9833 for the potential treatment of estrogen receptor (ER)-positive breast cancer. This single-part, healthy volunteer study will try to identify how the test medicine is taken up, broken down and removed from the body. To help investigate this, the test medicine is radiolabelled, which means that the test medicine has a radioactive component (carbon-14) which helps us to track where the test medicine is in the body. The safety and tolerability of the test medicine will also be studied. This study will take place at one non-NHS site, and will consist of a single study period involving up to 6 post-menopausal female volunteers, aged between 50 to 70 years.

Conditions

ER-positive, HER2-negative Breast Cancer

Keywords

Breast cancer

Outcome Measures

Primary Outcomes (5)

• The cumulative amount of AZD9833 excreted (CumAe)

  Assessment of the total radioactivity by measuring the cumulative amount of AZD9833 excreted

  Urine and faecal samples collected from pre-dose until 168 hours post-dose

• The cumulative amount of AZD9833 excreted, expressed as a percentage of the radioactive dose administered (Cum%Ae)

  Assessment of the total radioactivity, expressed as a percentage, by measuring the cumulative amount of AZD9833 excreted

  Urine and faecal samples collected from pre-dose until 168 hours post-dose

• Assessment of metabolites in plasma by liquid chromatography-radiochemical-detection and subsequent mass spectrometry

  Assessment of metabolites in plasma by liquid chromatography-radiochemical-detection and subsequent mass spectrometry

  Plasma samples collected from pre-dose until 168 hours post-dose

• Assessment of metabolites in urine by liquid chromatography-radiochemical-detection and subsequent mass spectrometry

  Assessment of metabolites in urine by liquid chromatography-radiochemical-detection and subsequent mass spectrometry

  Urine samples collected from pre-dose until 168 hours post-dose

• Assessment of metabolites in faeces by liquid chromatography-radiochemical-detection and subsequent mass spectrometry

  Assessment of metabolites in faeces by liquid chromatography-radiochemical-detection and subsequent mass spectrometry

  Faeces samples collected from pre-dose until 168 hours post-dose

Secondary Outcomes (20)

• The amount of total radioactivity eliminated in urine (Ae)

  Urine samples collected from pre-dose until 168 hours post-dose

• The amount of total radioactivity eliminated in urine expressed as a percentage of the radioactive dose administered (%Ae)

  Urine samples collected from pre-dose until 168 hours post-dose

• The cumulative amount of AZD9833 excreted in urine (CumAe)

  Urine samples collected from pre-dose until 168 hours post-dose

• The cumulative amount of AZD9833 excreted in urine, expressed as a percentage of the radioactive dose administered (Cum%Ae)

  Urine samples collected from pre-dose until 168 hours post-dose

• The amount of total radioactivity eliminated in faeces (Ae)

  Faeces samples collected from pre-dose until 168 hours post-dose

Study Arms (1)

[14C]AZD9833 (D8532C00005)

EXPERIMENTAL

Oral Solution, 75 mg (NMT 0.67 MBq)

Drug: [14C]AZD9833 Oral Solution, 75 mg

Interventions

[14C]AZD9833 Oral Solution, 75 mg DRUG

Oral Solution, 75 mg (NMT 0.67 MBq) - oral, fasted

[14C]AZD9833 (D8532C00005)

Eligibility Criteria

• Age: 50 Years - 70 Years
• Sex: female
• Healthy Volunteers: Yes
• 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
• Aged between 50 to 70 years inclusive at the time of signing informed consent
• Healthy post-menopausal females, defined as post-menopausal by fulfilling the following criterion:
• (a) amenorrhoea for at least 12 months following cessation of all exogenous hormonal treatments and without an alternative medical or surgical cause and confirmed by an FSH result of ≥30 IU/L
• Must be willing and able to communicate and participate in the whole study
• Have a body mass index (BMI) between 19.0 to 35.0 kg/m2, weigh at least 50 kg and no more than 100 kg inclusive as measured at screening.
• Must have regular bowel movements (i.e. average stool production of ≥1 and ≤3 stools per day)

You may not qualify if:

• History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the volunteer at risk because of participation in the study, or influence the results or the volunteer's ability to participate in the study
• History or presence of GI, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs
• Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP
• History of or ongoing clinically significant visual disturbances including but not limited to visual hallucinations, migraine with visual symptoms, blurred vision, frequent floaters/flashes associated with other symptoms such as dizziness
• Any clinically significant abnormalities in clinical chemistry, haematology, or urinalysis results, at screening as judged by the Investigator
• Any clinically significant abnormal findings in vital signs at screening as judged by the Investigator, including systolic BP \<100 mmHg, diastolic BP \<50 mmHg or heart rate \<50 bpm. Vital signs outside these limits can be repeated once for confirmation
• Any clinically significant abnormalities on 12-lead ECG at screening, as judged by the Investigator, including non-sinus rhythms, PR interval \<120 msec or \>220 msec, ventricular rate \<50 bpm or \>100 bpm, QRS interval \>120 msec, or QTcF \>470 msec as a mean of triplicate. ECGs can be repeated once in triplicate if parameters are outside these limits for confirmation
• Evidence of renal impairment at screening, as indicated by an estimated creatinine clearance (CLcr) of \<60 mL/min/1.73m2 using the Cockcroft-Gault equation
• Any positive result on screening for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV Ab), and human immunodeficiency virus (HIV) 1 and 2 antibodies
• Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 4 weeks prior to Day 1, or less than 5 elimination half-lives + 6 days prior to Day 1, whichever is longer. Note: subjects consented and screened, but not administered IMP in this study or a previous Phase I study, are not excluded
• Plasma donation within 1 month of screening or any blood donation/loss more than 500 mL during the 3 months prior to screening
• History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the Investigator or history of hypersensitivity to drugs with a similar chemical structure or class to AZD9833. Hay fever is allowed unless it is active
• Any known or suspected hypersensitivity or contraindication to the components of the study drug, AZD9833, judged to be clinically relevant by the investigator
• Current smokers or those who have smoked or used nicotine products (including e-cigarettes) within the 3 months prior to screening
• A confirmed breath carbon monoxide reading of greater than 10 ppm at screening or admission

Sponsors & Collaborators

• AstraZeneca: lead
• Quotient Sciences: collaborator

Study Sites (1)

Research Site

Ruddington, NG11 6JS, United Kingdom

Location

Related Links

• Redacted CSR Synopsis

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Somasekhara Menakuru, MBBS, MS, MRCS, DPM, MFPM

  Quotient Sciences

  PRINCIPAL INVESTIGATOR

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: May 4, 2022
• First Posted: May 6, 2022
• Study Start: May 10, 2022
• Primary Completion: June 20, 2022
• Study Completion: June 20, 2022
• Last Updated: June 21, 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 deidentified individual patient-level data in an approved sponsored 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

GB (1)