Absolute Bioavailability and ADME Study of [14C]AZD9977 in Healthy Male Subjects

NCT04686591 | Completed Phase 1 FDA Drug

• 1 other identifier: D6402C00002
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

Study to Assess the Absorption, Metabolism, and Excretion of \[14C\]AZD9977 after a Single-Dose Oral Administration

Conditions

Cardiovascular Disease

Keywords

Chronic Heart Failure

Outcome Measures

Primary Outcomes (6)

• Absolute bioavailability of AZD9977

  Absolute bioavailability based on AUC0-inf of oral formulation compared to IV adjusted for dose

  Collection of plasma samples from pre-dose until 72 hours post-dose.

• The cumulative amount of AZD9977 excreted (CumAe)

  Assessment of the total radioactivity by measuring the cumulative amount of AZD9977 excreted (CumAe)

  Collection of urine and faecal samples from pre-dose until 168 hours post-dose.

• The cumulative amount of AZD9977 excreted and expressed as a percentage of the administered dose (CumFe)

  Assessment of the rates and routes of elimination by measuring the cumulative amount excreted and expressed as a percentage of the administered dose (CumFe)

  Collection of urine and faecal samples 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

  Collection of plasma samples from pre-dose until 72 hours post-dose in period 1 and from pre-dose to 168 hours post-dose in period 2.

• 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

  Collection of urine samples from pre-dose until 72 hours post-dose in period 1 and from pre-dose to 168 hours post-dose in period 2.

• 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

  Collection of faecal samples from pre-dose until 168 hours post-dose.

Secondary Outcomes (18)

• Number of adverse events (AEs) experienced by subjects

  Approximately 8 weeks

• Time prior to the first measurable concentration (AZD9977) (tlag)

  Collection of plasma samples from pre-dose to 72 hours post-dose in period 1 and pre-dose to 168 hours post-dose in period 2.

• Time of maximum observed concentration (tmax)

  Collection of plasma samples from pre-dose to 72 hours post-dose in period 1 and pre-dose to 168 hours post-dose in period 2.

• Maximum observed concentration (cmax)

  Collection of plasma samples from pre-dose to 72 hours post-dose in period 1 and pre-dose to 168 hours post-dose in period 2.

• Area under the curve from time 0 to the time of last measurable concentration (AUC0-t)

  Collection of plasma samples from pre-dose to 72 hours post-dose in period 1 and pre-dose to 168 hours post-dose in period 2.

Study Arms (1)

AZD9977

EXPERIMENTAL

In Period 1, one 100 mg dose of AZD9977 capsule 50 mg (as 2 x 50 mg capsules) and one 100 µg dose of \[14C\]AZD9977 Solution for Infusion, 20 µg/mL (NMT 37.0 kBq/5 mL). In Period 2, one 100 mg dose of \[14C\]AZD9977 Oral Suspension, 100 mg (NMT 9.9 MBq).

Drug: AZD9977 capsule 50 mg; Drug: [14C]AZD9977 Solution for Infusion, 20 µg/mL (NMT 37.0 kBq/5 mL); Drug: [14C]AZD9977 Oral Suspension, 100 mg (NMT 9.9 MBq)

Interventions

AZD9977 capsule 50 mg DRUG

100 mg dose of AZD9977 capsule 50 mg (as 2 x 50 mg capusles)

Also known as: AZD9977

AZD9977

[14C]AZD9977 Solution for Infusion, 20 µg/mL (NMT 37.0 kBq/5 mL) DRUG

One 100 µg dose of \[14C\]AZD9977 Solution for Infusion, 20 µg/mL (NMT 37.0 kBq/5 mL)

Also known as: [14C]AZD9977

AZD9977

[14C]AZD9977 Oral Suspension, 100 mg (NMT 9.9 MBq) DRUG

One 100 mg dose of \[14C\]AZD9977 Oral Suspension, 100 mg (NMT 9.9 MBq)

Also known as: [14C]AZD9977

AZD9977

Eligibility Criteria

• Age: 30 Years - 60 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Provision of signed and dated, written informed consent prior to any study specific procedures.
• Healthy male subjects aged 30 to 60 years at the time of signing informed consent with suitable veins for cannulation or repeated venepuncture.
• Body mass index (BMI) of 18.0 to 30.0 kg/m2 (body weight at least 50 kg), as measured at screening.
• Must be willing and able to communicate and participate in the whole study.
• Must have regular bowel movements (i.e., average stool production of ≥1 and ≤3 stools per day).
• Must agree to adhere to the contraception requirements defined in the clinical protocol

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 gastrointestinal, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
• Clinically significant history of recent depression, seizures or other hyperactive central nervous system condition or ongoing treatment for the same.
• 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 AZD9977 or the formulation excipients. Hay fever is allowed unless it is active.
• Acute diarrhoea or constipation in the 7 days before administration of IMP in the study. If screening occurs \>7 days before the first study day, this criterion will be determined on the first study day.
• Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP.
• Any clinically significant abnormalities in clinical chemistry, haematology, or urinalysis results, as judged by the investigator.
• Serum potassium \>5.0 mmol/L or fasting blood glucose \> upper limit of normal (ULN) at screening.
• Evidence of renal impairment at screening, as indicated by an estimated eGFR of \<80 mL/min/1.73m2 using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation or other evidence of renal impairment.
• Subjects with known Gilbert's Syndrome or elevated unconjugated hyperbilirubinaemia or subjects with a history of cholecystectomy or gall stones.
• Abnormal resting vital signs (after 5 min rest) of supine systolic BP \>140 mmHg and/or diastolic BP \>90 mmHg and/or \<50 mmHg and/or HR \<45 or \>90 bpm at screening or Period 1 Day 1 pre-dose. Vital signs can be repeated once if abnormal, as judged by the investigator.
• Subjects with clinically significant history of recurrent syncope/blackouts or previous history of orthostatic hypotension or those who are noted to have a fall in systolic BP ≥20 mmHg or diastolic BP ≥10 mmHg or elevation in HR of more than 30 bpm when checked between 2 and 5 min after change of posture at screening or at Period 1 Day 1 pre-dose.
• Any clinically significant abnormalities on 12-lead ECG, including those which can increase the risk of arrhythmias including QTcF\>450 msec, as judged by the investigator.
• 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 in the past 2 years, as judged by the investigator.

Sponsors & Collaborators

• AstraZeneca: lead
• Quotient Sciences: collaborator

Study Sites (1)

Research Site

Ruddington, NG11 6JS, United Kingdom

Location

MeSH Terms

Conditions

Cardiovascular Diseases

Interventions

AZD9977

Study Officials

• Somasekhara Menakuru, MBBS, MS, MRCS, DPM

  Quotient Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2020
• First Posted: December 29, 2020
• Study Start: December 21, 2020
• Primary Completion: February 4, 2021
• Study Completion: February 4, 2021
• Last Updated: March 9, 2021

Record last verified: 2021-03

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. URL:

Locations

GB (1)