A Study to Investigate the Absolute Bioavailability, Absorption, Metabolism, Distribution and Excretion of [14C]AZD5363 (Capivasertib)

NCT05419401 | Completed Phase 1

• 1 other identifier: D3614C00007
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

The Sponsor is developing the test medicine, Capivasertib, for the potential treatment of primary breast and prostate cancer. This two-part healthy volunteer study will try to identify the absolute bioavailability (amount of the test medicine that enters the blood stream), mass balance recovery (how much radioactivity can be recovered from the urine and faeces) and the rates and routes of elimination of the test medicine.

Conditions

Healthy Volunteer

Keywords

Healthy volunteer

Outcome Measures

Primary Outcomes (23)

• Absolute bioavailability (F)

  Absolute bioavailability (F) of oral capivasertib compared to \[14C\]-capivasertib (part 1)

  Plasma sample collection from pre-dose to 72 hours post dose

• tmax

  PK of capivasertib and \[14C\]AZD5363 (capivasertib) in plasma (part 1)

  Plasma sample collection from pre-dose to 72 hours post dose

• Cmax

  PK of capivasertib and \[14C\]AZD5363 (capivasertib) in plasma (part 1)

  Plasma samples collection from pre-dose to 72 hours post dose

• AUC0-t

  PK of capivasertib and \[14C\]AZD5363 (capivasertib) in plasma (Part 1)

  Plasma samples collection from pre-dose to 72 hours post dose

• AUC0-inf

  PK of capivasertib and \[14C\]AZD5363 (capivasertib) in plasma (Part 1)

  Plasma samples collection from pre-dose to 72 hours post dose

• t1/2

  PK of capivasertib and \[14C\]AZD5363 (capivasertib) in plasma (Part 1)

  Plasma samples collection from pre-dose to 72 hours post dose

• λz

  PK of capivasertib and \[14C\]AZD5363 (capivasertib) in plasma (Part 1)

  Plasma samples collection from pre-dose to 72 hours post dose

• CL/F

  PK of capivasertib and \[14C\]AZD5363 (capivasertib) in plasma (Part 1)

  Plasma samples collection from pre-dose to 72 hours post dose

• Vz/F

  PK of capivasertib and \[14C\]AZD5363 (capivasertib) in plasma (Part 1)

  Plasma samples collection from pre-dose to 72 hours post dose

• tmax

  PK (plasma) and total radioactivity (whole blood and plasma) of capivasertib (Part 2)

  Plasma sample collection from pre-dose to 168 hours post dose

• Cmax

  PK (plasma) and total radioactivity (whole blood and plasma) of capivasertib (Part 2)

  Plasma sample collection from pre-dose to 168 hours post dose

• AUC0-t

  PK (plasma) and total radioactivity (whole blood and plasma) of capivasertib (Part 2)

  Plasma sample collection from pre-dose to 168 hours post dose

• AUC0-inf

  PK (plasma) and total radioactivity (whole blood and plasma) of capivasertib (Part 2)

  Plasma sample collection from pre-dose until 168 hours post-dose

• t1/2

  PK (plasma) and total radioactivity (whole blood and plasma) of capivasertib (Part 2)

  Plasma sample collection from pre-dose until 168 hours post-dose

• λz

  PK (plasma) and total radioactivity (whole blood and plasma) of capivasertib (Part 2)

  Plasma sample collection from pre-dose until 168 hours post-dose

• CL/F

  PK (plasma) and total radioactivity (whole blood and plasma) of capivasertib (Part 2)

  Plasma sample collection from pre-dose until 168 hours post-dose

• Vz/F

  PK (plasma) and total radioactivity (whole blood and plasma) of capivasertib (Part 2)

  Plasma sample collection from pre-dose until 168 hours post-dose

• CLR

  PK (plasma and urine) and total radioactivity (whole blood and plasma) of capivasertib (Part 2)

  Plasma sample collection from pre-dose to 72 hours post dose and urine samples collected from pre-dose until 168 hours post-dose

• CumAe

  Mass balance recovery of \[14C\]AZD5365 (capivasertib) from urine and faecal samples (Part 2)

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

• Cum%Ae

  Mass balance recovery of \[14C\]AZD5365 (capivasertib) from urine and faecal samples (Part 2)

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

• Ae

  Mass balance recovery of \[14C\]AZD5365 (capivasertib) from urine and faecal samples (Part 2)

  Urine and faecal sample collection from pre-dose until 168 hours post-dose

• %Ae

  Mass balance recovery of \[14C\]AZD5365 (capivasertib) from urine and faecal samples (Part 2)

  Urine and faecal sample collection from pre-dose until 168 hours post-dose

• Blood:plasma concentration ratios

  Blood:plasma concentration ratios of total radioactivity (Part 2)

  Whole blood samples collected up to 24 hours post dose. Plasma sample collection from pre-dose until 72 hours post-dose

Secondary Outcomes (1)

• Number of subjects with treatment-related adverse events

  Through study duration, an average of 9 weeks.

Study Arms (2)

Capivasertib

EXPERIMENTAL

film-coated tablet, 200 mg

Drug: Capivasertib film-coated tablet, 200 mg

[14C]AZD5363 (Capivasertib)

EXPERIMENTAL

Solution for Infusion 20 µg/mL (NMT 37.0 kBq/5 mL) and Oral Solution, 400 mg (NMT 4.8 MBq)

Drug: [14C]AZD5363 (Capivasertib)

Interventions

Capivasertib film-coated tablet, 200 mg DRUG

400mg dose, oral, fasted

Capivasertib

[14C]AZD5363 (Capivasertib) DRUG

Solution for Infusion 20 µg/mL (NMT 37.0 kBq/5 mL) - 100 µg; 5 mL, Intravenous Oral Solution, 400 mg (NMT 4.8 MBq) - 400mg; 100mL, oral, fasted

[14C]AZD5363 (Capivasertib)

Eligibility Criteria

• Age: 30 Years - 65 Years
• Sex: male
• 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.
• Must be willing and able to communicate and participate in the whole study.
• Healthy males aged 30 to 65 years inclusive at the time of signing informed consent.
• Must be vasectomised (at least 6 months prior to screening) and must agree to adhere to the contraception requirements of the study.
• Have a body mass index (BMI) between 18.0 and 30.0 kg/m2 inclusive and 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)
• Provision of signed, written and dated informed consent for optional genetic research. If a subject declines to participate in the genetic component of the study, there will be no penalty or loss of benefit to the subject.

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 of any clinically significant disease or disorder (e.g. cardiovascular, pulmonary, GI (including but not limited to refractory nausea and vomiting, malabsorption syndrome, chronic GI diseases, previous cholecystectomy, inability to swallow the formulated product or previous significant bowel resection, or other condition that would preclude adequate absorption of capivasertib), liver, renal, neurological, musculoskeletal, endocrine, metabolic, malignant, psychiatric, major physical impairment, skin abnormalities and glucose metabolism abnormalities) which, in the opinion of the investigator, may either put the subject at risk because of participation in the study, or influence the ADME of drugs.
• History of latent or chronic infections (e.g. tuberculosis, recurrent sinusitis, genital herpes, urinary tract infections) or at risk of infection (surgery, trauma or significant infection within previous 90 days, history of skin abscesses within previous 90 days).
• Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP.
• 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 capivasertib. Hay fever is allowed unless it is active
• Any known or suspected hypersensitivity or contraindication to the components of the study drug, capivasertib, judged to be clinically relevant by the investigator.
• History of severe COVID-19 (e.g. hospitalisation, extracorporeal membrane oxygenation, mechanically ventilated) in the last 6 months.
• Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator or delegate at screening
• Any clinically significant abnormal findings in vital signs, at screening or pre-dose, as judged by the investigator.
• QTcF \>450 msec or QT \>500 msec or other clinically significant ECG abnormality, as judged by the investigator, at screening or pre-dose, or a history of additional risk factors for Torsades de Points (e.g. heart failure, hypokalaemia, family history of long QT syndrome), which in the opinion of the Investigator may put the volunteer at risk.
• Evidence of current SARS-CoV-2 infection within 2 weeks of first IMP administration.
• Any clinically significant abnormalities in clinical chemistry, haematology, or urinalysis results, as judged by the investigator
• Total bilirubin (TBL) ≥1.5×the ULN or ≥3×ULN in the presence of documented Gilbert's syndrome (unconjugated hyperbilirubinemia)
• Clinically significant abnormal fasting blood glucose or triglycerides at screening.
• Any positive result on screening for serum hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab), and human immunodeficiency virus (HIV) 1 and 2 antibody.

Sponsors & Collaborators

• AstraZeneca: lead
• Quotient Sciences: collaborator

Study Sites (1)

Research Site

Ruddington, NG11 6JS, United Kingdom

Location

MeSH Terms

Interventions

capivasertib

Study Officials

• Sharan Sidhu, MBChB, BAO, MRCS, MFPM

  Quotient Sciences

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: April 11, 2022
• First Posted: June 15, 2022
• Study Start: April 11, 2022
• Primary Completion: July 12, 2022
• Study Completion: July 12, 2022
• Last Updated: July 22, 2022

Record last verified: 2022-07

Locations

GB (1)