A Study to Assess the Rel Bioavailability, Food Effect and Absolute Bioavailability on the Pharmacokinetics of AZD9833

NCT04546347 | Completed Phase 1

• 1 other identifier: D8530C00004
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

AstraZeneca AB is developing the test medicine, AZD9833, for the potential treatment of oestrogen receptor (ER) positive breast cancer. ER-positive breast cancer is where the cancer cells grow in response to the hormone oestrogen. The study will try to identify and compare how much of the test medicine formulations (recipes) are taken up into the blood when given as a tablet, a solution and as an injection directly into the vein. The dose given directly into the vein will be radiolabelled, meaning that it contains a radioactive component in order to track where the drug is in the body. This study will also look at the effect of food when taking the test medicine in the form of the tablet. The test medicine safety and tolerability will also be assessed. This is a one-part study involving up to 32 healthy post-menopausal female volunteers aged 50 to 70. Volunteers will be randomly assigned to a group of up to 8, two groups will partake in four study periods and two groups will partake in three study periods. Volunteers will be admitted to the clinical unit on the day before dosing (Day -1) for each study period. On Day 1 of each study period, volunteers will receive either a single oral dose (tablet or solution) of AZD9833 or a single oral dose (tablet) of AZD9833 co-administered with a single radiolabelled IV dose of \[14C\]AZD9833, in either the fed or fasted state. There will be a minimum 7 day washout between periods. Volunteers will remain resident until 72 hours post dose (Day 4) of each study period. A follow-up phone call will take place 5 to 7 days post-final dose to ensure the ongoing wellbeing of the volunteers.

Conditions

Healthy Volunteers

Keywords

oestrogen receptor (ER) positive breast cancer; breast cancer

Outcome Measures

Primary Outcomes (3)

• Relative bioavailability of AZD9833 based on Area under the curve from time 0 to the time of last measurable concentration (AUC0-t)

  Assessment of the PK (pharmacokinetics) on AZD9833 by measuring relative bioavailability based on AUC0-t

  Collection of plasma samples from pre-dose to 72 hours post-dose

• Relative bioavailability of AZD9833 based on area under the concentration time curve from time zero to the last quantifiable concentration (AUC0-inf)

  Assessment of the PK (pharmacokinetics) on AZD9833 by measuring relative bioavailability based on AUC0-inf

  Collection of plasma samples from pre-dose to 72 hours post-dose

• Relative bioavailability of AZD9833 based on Maximum observed concentration (Cmax)

  Assessment of the PK (pharmacokinetics) on AZD9833 by measuring relative bioavailability based on Cmax

  Collection of plasma samples from pre-dose to 72 hours post-dose

Secondary Outcomes (2)

• Area under the concentration time curve from time zero to the last quantifiable concentration (AUC0-inf) for AZD9833 vs [14C]-AZD9833 and total radioactivity

  Collection of plasma samples from pre-dose to 72 hours post-dose

• Number of adverse events (AE) experienced by subjects

  AEs recorded from the time of informed consent until discharge from the study (72 hours post-dose)

Other Outcomes (1)

• Evaluation on exposure differences between and including both dose levels of AZD9833

  Collection of plasma samples from pre-dose to 72 hours post-dose

Study Arms (6)

14CAZD9833 Infusion NMT 22.8 kBq/5mL

EXPERIMENTAL

Dose 1 14CAZD9833 Solution for Infusion

Radiation: [14C]AZD9833 Solution for Infusion, (NMT 22.8 kBq/5mL)

AZD9833 film-coated tablet A Dose 1

EXPERIMENTAL

Dose 1 AZD9833 film-coated tablet type A

Drug: AZD9833 film-coated tablet A Dose 1

AZD9833 Oral Solution

EXPERIMENTAL

Dose 1 AZD9833 oral solution

Drug: AZD9833 Oral Solution

AZD9833 film-coated tablet B Dose 1

EXPERIMENTAL

Dose 1 AZD9833 film-coated tablet type B

Drug: AZD9833 film-coated tablet B Dose 1

AZD9833 film-coated tablet A Dose 2

EXPERIMENTAL

Dose 2 AZD9833 film-coated tablet type A

Drug: AZD9833 film-coated tablet A Dose 2

AZD9833 film-coated tablet B Dose 2

EXPERIMENTAL

Dose 2 AZD9833 film-coated tablet type B

Drug: AZD9833 film-coated tablet B Dose 2

Interventions

[14C]AZD9833 Solution for Infusion, (NMT 22.8 kBq/5mL) RADIATION

Dose of \[14C\]AZD9833 Solution for Infusion

Also known as: [14C]AZD9833

14CAZD9833 Infusion NMT 22.8 kBq/5mL

AZD9833 film-coated tablet A Dose 1 DRUG

Dose 1 AZD9833 film-coated tablet A Dose 1

Also known as: AZD9833 film-coated tablet phase 1

AZD9833 film-coated tablet A Dose 1

AZD9833 Oral Solution DRUG

AZD9833 Oral Solution

AZD9833 Oral Solution

AZD9833 film-coated tablet B Dose 1 DRUG

AZD9833 film-coated tablet B Dose 1

Also known as: AZD9833 film-coated tablet late phase

AZD9833 film-coated tablet B Dose 1

AZD9833 film-coated tablet A Dose 2 DRUG

Dose 1 of AZD9833 film-coated tablet A Dose 2

Also known as: AZD9833 film-coated tablet phase 1

AZD9833 film-coated tablet A Dose 2

AZD9833 film-coated tablet B Dose 2 DRUG

Dose 1 of film-coated tablet B Dose 2

Also known as: AZD9833 film-coated tablet late phase

AZD9833 film-coated tablet B Dose 2

Eligibility Criteria

• Age: 50 Years - 70 Years
• Gender Eligibility Details: Healthy post-menopausal female volunteers aged 50 to 70
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy post-menopausal females, defined as amenorrhoea for at least 12 months or more following cessation of all exogenous hormonal treatments and FSH levels in the post menopausal range. Subjects taking prescribed medications are permitted on a case by case basis, as long as they have stable baseline conditions
• Between 50 and 70 years of age inclusive, at the time of signing informed consent
• Body mass index (BMI) of 19.0 to 35.0 kg/m2 and minimum weight 50 kg and maximum weight 100 kg, as measured at screening
• Must be willing and able to communicate and participate in the whole study
• Must provide written informed consent

You may not qualify if:

• History of any clinically significant disease or disorder which, in the opinion of the investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study
• Evidence of current SARS-CoV-2 infection
• 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 illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of the IMP
• Any clinically significant abnormalities in clinical chemistry, haematology, or urinalysis results, as judged by the investigator.
• Any clinically significant abnormal findings in vital signs at screening or pre dose, as judged by the investigator. Subjects with screening or pre-dose (Period 1 only) resting mean vital signs measurements (mean of three measurements separated by at least 2 min each) systolic BP \<100 mmHg, diastolic BP \<50 mmHg or heart rate \<50 bpm. Vital signs outside these limits can be repeated once in triplicate.
• Any clinically significant abnormalities at screening or pre-dose on 12-lead ECG as judged by the investigator, including non-sinus rhythms, PR interval \<120 msec or \>220 msec, ventricular rate \<50/min or \>100/min, QRS interval \>120 msec, or QTcF \>450 msec. ECGs can be repeated once if parameters are outside these limits for confirmation
• Any positive result on screening for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody, (HCV Ab) and human immunodeficiency virus (HIV) antibody.
• Known or suspected history of drug abuse within the past 2 years, as judged by the investigator
• Plasma donation within 1 month of screening or any blood donation/loss more than 500 mL during the 3 months prior to screening
• Subjects with history of significant allergy/hypersensitivity, as judged by the investigator or history of hypersensitivity to drugs with a similar chemical structure or class to AZD9833 or the formulation excipients. Hay fever is allowed unless it is active.
• Current smokers or those who have smoked or used nicotine products within the previous 12 months, as verified by a urine cotinine test at screening or admission.
• Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months.
• Positive screen for drugs of abuse at screening or admission to the clinical unit or positive screen for alcohol at screening or admission to the clinical unit.
• Known or suspected history of alcohol abuse or excessive intake of alcohol \>14 units per week (1 unit = ½ pint beer, or a 25 mL shot of 40% spirit, 1.5 to 2 units = 125 mL glass of wine, depending on type).

Sponsors & Collaborators

• AstraZeneca: lead
• Quotient Sciences: collaborator

Study Sites (1)

Research Site

Ruddington, NG11 6JS, United Kingdom

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

AZD9833

Condition Hierarchy (Ancestors)

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

Study Officials

• Somasekhara Menakuru, MBBS MS MRCS

  Quotient Sciences Limited (indemnified by Medical Protection Society)

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: September 8, 2020
• First Posted: September 14, 2020
• Study Start: September 17, 2020
• Primary Completion: January 7, 2021
• Study Completion: January 7, 2021
• Last Updated: January 20, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• 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)