Mass Balance Recovery, Pharmacokinetics and Metabolite Profile and Identification of [14C]AZD7594

NCT04002427 | Completed Phase 1

• 1 other identifier: D3741C00010
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

AZD7594 is in clinical development for the treatment of asthma. This is a single centre, open-label, single period study in 6 healthy subjects, to determine the mass balance recovery and generate samples to enable metabolite profiling and structural identification of AZD7594. Each subject will receive a single inhaled 792 µg nominal dose (720 µg delivered dose) of AZD7594 followed by an IV dose of 30 µg \[14C\]AZD7594 containing not more than (NMT) 6.7 kBq (180 nCi) carbon-14 (14C) as a 1 h infusion. The IV dose will be administered approximately 10 min after the inhaled dose. Subjects will remain resident in the clinical unit up to 168 h post dose (up to Day 8).

Conditions

Asthma

Outcome Measures

Primary Outcomes (7)

• AZD7594 excreted (Ae)

  Assessment of total radioactivity by measuring AZD7594 excreted (Ae)

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

• AZD7594 excreted and expressed as a percentage of the administered dose (Fe)

  Assessment of total radioactivity by measuring AZD7594 excreted and expressed as a percentage of the administered dose (Fe)

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

• Cumulative amount of AZD7594 excreted (CumAe)

  Assessment of total radioactivity by measuring the cumulative amount of AZD7594 excreted (CumAe)

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

• Cumulative amount of AZD7594 excreted and expressed as a percentage of the administered dose (CumFe)

  Assessment of total radioactivity by measuring AZD7594 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 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

• 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

Secondary Outcomes (25)

• Determination of routes and rates of elimination of [14C]AZD7594

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

• Determination of the chemical structure of the "major" metabolites of [14C]AZD7594

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

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

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

• Assessment of the IV PK of [14C]AZD7594 and total radioactivity

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

• Assessment of the IV PK of [14C]AZD7594 and total radioactivity

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

Study Arms (1)

Only one study arm

EXPERIMENTAL

\[14C\]AZD7594 Solution for Infusion 5 µg/mL (1.1 kBq/mL) AZD7594 Inhalation Powder, SD3FL Inhaler

Drug: Intravenous Infusion; Drug: Inhaled dose

Interventions

Intravenous Infusion DRUG

30 µg \[14C\]AZD7594 containing 6.7 kBq (180 nCi) carbon-14 (14C) as a 1 hour infusion.

Only one study arm

Inhaled dose DRUG

A single inhalation on one occasion.

Only one study arm

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• 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 or non-pregnant, non-lactating female subjects aged 18 to 55 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 agree to adhere to the contraception requirements defined in Section 9.4 of the protocol.
• Must demonstrate the ability to use the study inhalation device properly.

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 clinically significant 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.
• Subjects with pregnant partners
• 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 or 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.
• 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 AZD7594 or the formulation excipients including lactose. 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.
• Females of childbearing potential who are pregnant or lactating (all female subjects must have a negative urine pregnancy test and screening and admission). A woman is considered of childbearing potential unless she is permanently sterile (hysterectomy, bilateral salpingectomy and bilateral oophorectomy) or is postmenopausal (had no menses for 12 months without an alternative medical cause and a serum follicle stimulating hormone \[FSH\] concentration ≥40 IU/L).
• 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 AZD7594.

Sponsors & Collaborators

• AstraZeneca: lead
• Quotient Sciences: collaborator

Study Sites (1)

Research Site

Ruddington, NG11 6JS, United Kingdom

Location

MeSH Terms

Conditions

Asthma

Interventions

Infusions, Intravenous

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Administration, Intravenous; Drug Administration Routes; Drug Therapy; Therapeutics; Infusions, Parenteral

Study Officials

• Sharan Sidhu, MBChB, BAO, MRCS, MFPM

  Quotient Sciences Limited (indemnified by

  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 18, 2019
• First Posted: June 28, 2019
• Study Start: June 11, 2019
• Primary Completion: July 5, 2019
• Study Completion: July 5, 2019
• Last Updated: July 25, 2019

Record last verified: 2019-07

Locations

GB (1)