A Study to Assess Drug Absorption of Fixed Dose Combinations of Budesonide, Glycopyrronium, and Formoterol

NCT04600505 | Completed Phase 1 Results FDA Drug

• 1 other identifier: D5985C00001
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

Brief Summary

The study will evaluate bioavailability, pharmacokinetics, safety, and tolerability of budesonide, glycopyrronium and formoterol (BGF) metered dose inhaler (MDI) formulated with 3 different propellants: Propellant 1 (Treatment A \[test\]), Propellant 2 (Treatment B \[test\]) and Hydrofluoroalkane (HFA) (Treatment C \[reference\]).

Conditions

Chronic Obstructive Pulmonary Disease (COPD)

Keywords

Budesonide; Glycopyrronium; Formoterol; Hydrofluoroalkane; Metered dose inhaler

Outcome Measures

Primary Outcomes (3)

• Maximum Observed Concentration (Cmax) of BGF MDI

  Evaluation of the relative bioavailability between the test formulations and the reference formulation for fixed dose combinations (FDCs) of BGF when delivered as BGF MDI with 3 different propellants by Cmax.

  Pre-dose and 2, 5, 10, 20, 30, and 45 minutes post-dose and 1, 2, 4, 8, 12 and 24 hours post-dose

• Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinity (AUCinf) of BGF MDI

  Evaluation of the relative bioavailability between the test formulations and the reference formulation for FDCs of BGF when delivered as BGF MDI with 3 different propellants by AUCinf.

  Pre-dose and 2, 5, 10, 20, 30, and 45 minutes post-dose and 1, 2, 4, 8, 12 and 24 hours post-dose

• Area Under the Plasma Concentration- Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) of BGF MDI

  Evaluation of the relative bioavailability between the test formulations and the reference formulation for FDCs of BGF when delivered as BGF MDI with 3 different propellants by AUClast.

  Pre-dose and 2, 5, 10, 20, 30, and 45 minutes post-dose and 1, 2, 4, 8, 12 and 24 hours post-dose

Secondary Outcomes (5)

• Time to Reach Maximum Observed Concentration (Tmax) of BGF MDI

  Pre-dose and 2, 5, 10, 20, 30, and 45 minutes post-dose and 1, 2, 4, 8, 12 and 24 hours post-dose

• Terminal Elimination Half-life (t½λz) of BGF MDI

  Pre-dose and 2, 5, 10, 20, 30, and 45 minutes post-dose and 1, 2, 4, 8, 12 and 24 hours post-dose

• Apparent Total Body Clearance of Drug After Extravascular Administration (CL/F) of BGF MDI

  Pre-dose and 2, 5, 10, 20, 30, and 45 minutes post-dose and 1, 2, 4, 8, 12 and 24 hours post-dose

• Apparent Volume of Distribution During the Terminal Phase After Extravascular Administration (Vz/F) of BGF MDI

  Pre-dose and 2, 5, 10, 20, 30, and 45 minutes post-dose and 1, 2, 4, 8, 12 and 24 hours post-dose

• Number of Participants With Serious Adverse Events (SAE) and Non-serious Adverse Events

  Screening, Day -1 until Follow-up visit, up to 53 days

Study Arms (6)

Treatment Sequence ABC

EXPERIMENTAL

Participants will be randomized to one of the 6 different treatment sequences. Each participant will receive 3 single-dose treatments of BGF MDI (Treatment A; Treatment B; Treatment C) in 3 treatment periods, with first dose on Day -1 for all treatment periods.

Drug: Treatment A; Drug: Treatment B; Drug: Treatment C

Treatment Sequence BCA

EXPERIMENTAL

Participants will be randomized to one of the 6 different treatment sequences. Each participant will receive 3 single-dose treatments of BGF MDI (Treatment B; Treatment C; Treatment A) in 3 treatment periods, with first dose on Day -1 for all treatment periods.

Drug: Treatment A; Drug: Treatment B; Drug: Treatment C

Treatment Sequence CAB

EXPERIMENTAL

Participants will be randomized to one of the 6 different treatment sequences. Each participant will receive 3 single-dose treatments of BGF MDI (Treatment C; Treatment A; Treatment B) in 3 treatment periods, with first dose on Day -1 for all treatment periods.

Drug: Treatment A; Drug: Treatment B; Drug: Treatment C

Treatment Sequence ACB

EXPERIMENTAL

Participants will be randomized to one of the 6 different treatment sequences. Each participant will receive 3 single-dose treatments of BGF MDI (Treatment A; Treatment C; Treatment B) in 3 treatment periods, with first dose on Day -1 for all treatment periods.

Drug: Treatment A; Drug: Treatment B; Drug: Treatment C

Treatment Sequence BAC

EXPERIMENTAL

Participants will be randomized to one of the 6 different treatment sequences. Each participant will receive 3 single-dose treatments of BGF MDI (Treatment B; Treatment A; Treatment C) in 3 treatment periods, with first dose on Day -1 for all treatment periods.

Drug: Treatment A; Drug: Treatment B; Drug: Treatment C

Treatment Sequence CBA

EXPERIMENTAL

Participants will be randomized to one of the 6 different treatment sequences. Each participant will receive 3 single-dose treatments of BGF MDI (Treatment C; Treatment B; Treatment A) in 3 treatment periods, with first dose on Day -1 for all treatment periods.

Drug: Treatment A; Drug: Treatment B; Drug: Treatment C

Interventions

Treatment A DRUG

Participants will receive 2 inhalations of BGF MDI with propellant 1.

Also known as: BGF MDI Propellant 1

Treatment Sequence ABC; Treatment Sequence ACB; Treatment Sequence BAC; Treatment Sequence BCA; Treatment Sequence CAB; Treatment Sequence CBA

Treatment B DRUG

Participants will receive 2 inhalations of BGF MDI with propellant 2.

Also known as: BGF MDI Propellant 2

Treatment Sequence ABC; Treatment Sequence ACB; Treatment Sequence BAC; Treatment Sequence BCA; Treatment Sequence CAB; Treatment Sequence CBA

Treatment C DRUG

Participants will receive 2 inhalations of BGF MDI with HFA propellant.

Also known as: BGF MDI HFA

Treatment Sequence ABC; Treatment Sequence ACB; Treatment Sequence BAC; Treatment Sequence BCA; Treatment Sequence CAB; Treatment Sequence CBA

Eligibility Criteria

• Age: 18 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.
• Non-smoking male participants with suitable veins for cannulation or repeated venipuncture.
• Participants must agree to follow the reproductive restrictions.
• Have a body mass index between 18 and 30 kg/m\^2 and weigh at least 50 kg and no more than 100 kg.
• Participants must have a forced expiratory volume in one second ≥ 80% of the predicted value regarding age, height, and ethnicity at the screening visit.

You may not qualify if:

• History or current evidence of a clinically significant (CS) disease or disorder (including but not limited to cardiovascular, hepatic, renal, hematological, neurological, endocrine, gastrointestinal, or pulmonary).
• 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 CS illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of investigational medicinal product (IMP).
• Narrow angle glaucoma not adequately treated. All medications approved for control of intraocular pressures are allowed, including topical ophthalmic non-selective β-blockers.
• Symptomatic prostatic hypertrophy or bladder neck obstruction/urinary retention that, in the opinion of the principal investigator (PI), is CS.
• Any cancer except squamous cell and basal cell carcinomas of the skin are allowed in the study.
• Any CS abnormalities in clinical chemistry, hematology, or urinalysis results, at screening and/or admission to the Clinical Unit:
• Systolic blood pressure (BP) \< 90 mmHg or \> 140 mmHg.
• Diastolic BP \< 50 mmHg or \> 90 mmHg.
• Heart rate \< 45 or \> 85 bpm.
• Any CS abnormal findings in vital signs, after 5 minutes supine rest, at screening and/or Day -1 of each Treatment Period, as judged by the PI.
• Any clinically important abnormalities in rhythm, conduction or morphology of the resting electrocardiogram (ECG) and any clinically important abnormalities in the 12-lead ECG as considered by the PI.
• Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody, and human immunodeficiency virus antibody.
• Known or suspected history of drug abuse.
• Participant has a positive reverse transcription polymerase chain reaction test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prior to randomization.

Sponsors & Collaborators

• AstraZeneca: lead
• Parexel: collaborator

Study Sites (1)

Research Site

Glendale, California, 91206, United States

Location

Related Publications (1)

• Aurivillius M, Bednarczyk A, Kokot M, Madriaga J, Mei J, Collison K, Surujbally R, Archbell J, Joshi V, Gillen M. Relative bioavailability of budesonide/glycopyrrolate/formoterol fumarate triple therapy delivered using next generation propellants with low global warming potential. Pulm Pharmacol Ther. 2023 Dec;83:102245. doi: 10.1016/j.pupt.2023.102245. Epub 2023 Aug 20.

  PMID: 37607661 DERIVED

Related Links

• CSR Synopsis
• CSP \& SAP

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Global Clinical Head
• Organization: AstraZeneca Clinical Study Information Center

information.center@astrazeneca.com

1-877-240-9479

Study Officials

• David Han, Dr.

  PAREXEL Early Phase Clinical Unit-Los Angeles

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: This is a single blind study with regard to BGF MDI treatment, administered with 3 different propellants (Treatment A, B or C), in which the participants will remain blinded.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 19, 2020
• First Posted: October 23, 2020
• Study Start: October 19, 2020
• Primary Completion: May 17, 2021
• Study Completion: May 17, 2021
• Last Updated: January 23, 2023
• Results First Posted: January 23, 2023

Record last verified: 2022-04

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 refer 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 de-identified 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

US (1)