Study Evaluating the Pharmacokinetic and Mass Balance of Single Dose [14C] AZD5718 in Volunteers

NCT03948451 | Completed Phase 1

• 1 other identifier: D7550C00007
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

The Sponsor is developing the test medicine, AZD5718, for the potential treatment of cardiovascular disease. The study is an open-label, single dose study involving 6 healthy male subjects. The volunteers will receive a single dose of 200 mg radiolabelled AZD5718 (14C-AZD5718 Oral Suspension) containing not more than 9.9 MBq of radiocarbon. Volunteers will attend the clinic for 9 days (Day -1 to Day 8) to receive a single dose of the test medicine. It is planned that the volunteers will be discharged as a group once all volunteers have reached the discharge criteria. This may result in the subjects being discharged as a group prior to completion of the planned residency period. If the discharge criteria are not met by volunteers by Day 8, the individual volunteers who have not met the criteria will remain in the clinical unit for a further 48 h (until Day 10). A follow-up call will take place 7 to 10 days after discharge to ensure the ongoing wellbeing of volunteers.

Conditions

Cardiovascular Disease

Keywords

Coronary Artery Disease

Outcome Measures

Primary Outcomes (17)

• The amount of AZD5718 excreted (Ae)

  Assessment of the total radioactivity by measuring the amount of AZD5718 excreted (Ae)

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

• Amount of AZD5718 excreted and expressed as a percentage of the administered dose (Fe)

  Assessment of the total radioactivity by measuring the amount of AZD5718 excreted and expressed as a percentage of the administered dose (Fe)

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

• The cumulative amount of AZD5718 excreted (CumAe)

  Assessment of the total radioactivity by measuring the cumulative amount of AZD5718 excreted (CumAe)

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

• The cumulative amount of AZD5718 excreted and expressed as a percentage of the administered dose (CumFe)

  Assessment of the total radioactivity by measuring the cumulative amount of AZD5718 excreted and expressed as a percentage of the administered dose (CumFe)

  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 and structural identification by assessing liquid chromatography-radiochemical-detection and subsequent mass spectrometry

  Collection of plasma samples 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 and structural identification by assessing liquid chromatography-radiochemical-detection and subsequent mass spectrometry

  Collection of urine samples 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 and structural identification by assessing liquid chromatography-radiochemical-detection and subsequent mass spectrometry

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

• Time to maximum concentration (tmax) for AZD5718 and total radioactivity

  Assessment of AZD5718 and total radioactivity by measuring the time to maximum concentration (tmax)

  Collection of plasma samples from pre-dose until 168 hours post-dose

• Maximum plasma concentration (cmax) for AZD5718 and total radioactivity

  Assessment of AZD5718 and total radioactivity by measuring the maximum plasma concentration (cmax)

  Collection of plasma samples from pre-dose until 168 hours post-dose

• Area under the concentration time curve to the last quantifiable concentration (AUC last) for AZD5718 and total radioactivity

  Assessment of AZD5718 and total radioactivity by measuring the concentration time curve to the last quantifiable concentration (AUC last)

  Collection of plasma samples from pre-dose until 168 hours post-dose

• Area under the concentration time curve from time zero to the last quantifiable concentration (AUC0-inf) for AZD5718 and total radioactivity

  Assessment of AZD5718 and total radioactivity by measuring the concentration time curve from time zero to the last quantifiable concentration (AUC0-inf)

  Collection of plasma samples from pre-dose until 168 hours post-dose

• Apparent terminal Elimination Half-life (t1/2,λz) for AZD5718 and total radioactivity

  Assessment of AZD5718 and total radioactivity by measuring the Elimination Half-life (t1/2,λz)

  Collection of plasma samples from pre-dose until 168 hours post-dose

• Oral clearance (CL/F) of AZD5718

  Assessment of the oral clearance of AZD5718 by measuring the apparent oral clearance (CL/F)

  Collection of plasma samples from pre-dose until 168 hours post-dose

• Apparent Volume of Distribution (Vz/F) of AZD5718

  Assessment of the oral PK (pharmacokinetics) of AZD5718by measuring the Apparent Volume of Distribution (Vz/F)

  Collection of plasma samples from pre-dose until 168 hours post-dose

• The amount of AZD5718 excreted (Ae)

  Assessment of the oral PK (pharmacokinetics) of AZD5718 by measuring the amount of AZD5718 excreted (Ae)

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

• Amount of AZD5718 excreted and expressed as a percentage of the administered dose (Fe)

  Assessment of the oral PK (pharmacokinetics) of AZD5718 by measuring the amount of AZD5718 excreted and expressed as a percentage of the administered dose (Fe)

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

• Renal clearance (Clr) in urine of AZD5718

  Assessment of the oral PK (pharmacokinetics) by measuring the renal clearance (Clr)

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

Secondary Outcomes (2)

• Evaluation of whole blood:plasma concentration ratios for total radioactivity

  Blood samples collected until 168 hours post-dose

• Number of adverse events (AE) experienced by subjects

  AEs recorded from the time of informed consent until discharge from the study (168 hours post-dose)

Study Arms (1)

[14C]AZD5718 Oral Suspension

EXPERIMENTAL

One 200 mg dose of \[14C\]AZD5718 Oral Suspension

Drug: [14C]AZD5718 Oral Suspension

Interventions

[14C]AZD5718 Oral Suspension DRUG

200 mg dose of \[14C\]AZD5718 Oral Suspension

Also known as: [14C]AZD5718

[14C]AZD5718 Oral Suspension

Eligibility Criteria

• Age: 30 Years - 65 Years
• Gender Eligibility Details: Healthy male subjects aged 30 to 65 years
• 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.
• Healthy male subjects aged 30 to 65 years with suitable veins for cannulation or repeated venepuncture.
• Have a body mass index of 18.5 to 35.0 kg/m2, and weigh at least 50 kg and no more than 100 kg, as measured at screening.
• Must have regular bowel movements (ie, average stool production of ≥1 and ≤3 stools per day).
• Must be willing and able to communicate and participate in the whole study.
• Must be surgically sterile or agree to adhere to the contraception requirements.

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 of 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.
• Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP.
• Subjects with Gilbert's syndrome or subjects with a history of cholecystectomy or gall stones.
• Any confirmed clinically significant abnormalities in clinical chemistry, haematology or urinalysis as judged by the investigator.
• Any confirmed clinically significant abnormal findings in vital signs, as judged by the investigator.
• Any confirmed clinically significant abnormal findings in 12-lead ECG, as judged by the investigator.
• Any positive result at screening for serum hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results.
• Known or suspected history of drug or alcohol abuse within the past 2 years, as judged by the investigator.
• Plasma donation within 1 month of screening or any blood donation/loss of more than 500 mL of blood 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 AZD5718 or the formulation excipients. Hay fever is allowed unless it is active.
• Current smokers and those who have smoked within the last 12 months. A breath carbon monoxide reading of greater than 10 ppm at screening and admission.
• Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months.
• Confirmed 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.
• Herbal preparations/medications are not allowed throughout the study. These herbal medications include, but are not limited to, St. John's wort, kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone, yohimbe, saw palmetto, and ginseng. Subjects should stop using these herbal medications 14 days prior to administration of \[14C\]AZD5718.

Sponsors & Collaborators

• AstraZeneca: lead
• Quotient Sciences: collaborator

Study Sites (1)

Research Site

Ruddington, NG11 6JS, United Kingdom

Location

MeSH Terms

Conditions

Cardiovascular Diseases; Coronary Artery Disease

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Study Officials

• Sharan Sidhu, MBChB, BAO, MRCS, MFPM

  Quotient Sciences Limited (indemnified by Medical Protection Society)

  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: April 1, 2019
• First Posted: May 14, 2019
• Study Start: April 30, 2019
• Primary Completion: July 2, 2019
• Study Completion: July 2, 2019
• Last Updated: July 15, 2019

Record last verified: 2019-07

Locations

GB (1)