A Study to Assess the Pulmonary Distribution of Budesonide, Glycopyrronium and Formoterol Fumarate

NCT03740373 | Completed Phase 1

• 1 other identifier: D5980C00007
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a 2 treatment period, single dose crossover, gamma scintigraphy study investigating the deposition in the lungs of a Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler. This study will be investigating how the drug (known as PT010) is distributed in the lungs following a 10 second or 3 second breath hold. The study will involve the following visits: 1 screening visits, 2 treatment visits, each separated by around 7 days (each with 1 overnight stay; from the evening before dosing until a minimum of 4 hours post-dose on the morning of Day 1) and a post-study follow up phone call. The study population will be 10 healthy males, aged between 28 and 50 years of age.

Conditions

Pulmonary Disease, Chronic Obstructive

Outcome Measures

Primary Outcomes (1)

• Percentage lung deposition following 10 s breath hold

  The percentage (%) emitted dose of radiolabelled BGF MDI deposited in the lungs following 10 s breath hold.

  Day 1 (of either Treatment Period 1 or 2)

Secondary Outcomes (7)

• Percentage lung deposition following 3 s breath hold

  Day 1 (of either Treatment Period 1 or 2)

• Regional airway deposition following 10 s breath hold

  Day 1 (of either Treatment Period 1 or 2)

• Oropharyngeal and stomach deposition following 10 s breath hold

  Day 1 (of either Treatment Period 1 or 2)

• Actuator and exhalation filter deposition following 10 s breath hold

  Day 1 (of either Treatment Period 1 or 2)

• Regional airway deposition following 3 s breath hold

  Day 1 (of either Treatment Period 1 or 2)

Other Outcomes (9)

• Number of TEAEs

  Day 1 to Follow-up (Day 7-14 post-dose)

• Number of subjects reporting at least 1 Treatment Emergent Adverse Event

  Day 1 to Follow-up (Day 7-14 post-dose)

• Number of subjects reporting at least 1 serious Treatment Emergent Adverse Event

  Day 1 to follow-up (Day 7-14 post dose)

Study Arms (2)

Treatment Sequence 1

EXPERIMENTAL

Subjects will receive BGF MDI with 10 s breath hold during Treatment Period 1 and BGF MDI with 3 s breath hold during Treatment Period 2

Drug: BGF MDI (budesonide, glycopyrronium and formoterol fumarate) with 10 s breath hold; Drug: BGF MDI ((budesonide, glycopyrronium and formoterol fumarate) with 3 s breath hold

Treatment Sequence 2

EXPERIMENTAL

Subjects will receive BGF MDI with 3 s breath hold during Treatment Period 1 and BGF MDI with 10 s breath hold during Treatment Period 2

Drug: BGF MDI (budesonide, glycopyrronium and formoterol fumarate) with 10 s breath hold; Drug: BGF MDI ((budesonide, glycopyrronium and formoterol fumarate) with 3 s breath hold

Interventions

BGF MDI (budesonide, glycopyrronium and formoterol fumarate) with 10 s breath hold DRUG

Participants will receive a single dose of BGF MDI; the dose will be administered with a 10 s breath-hold.

Also known as: PT010 with 10 s breath hold

Treatment Sequence 1; Treatment Sequence 2

BGF MDI ((budesonide, glycopyrronium and formoterol fumarate) with 3 s breath hold DRUG

Participants will receive a single dose of BGF MDI; the dose will be administered with a 3 s breath-hold.

Also known as: PT010 with 3 s breath hold

Treatment Sequence 1; Treatment Sequence 2

Eligibility Criteria

• Age: 28 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy males between 28 and 50 years of age inclusive;
• Male subject willing to wear a condom and whose partner of child bearing potential uses a highly effective method of contraception (e.g. partner use of intrauterine device (IUD)) or an effective method of contraception, i.e., established method of contraception + condom, if applicable (unless anatomically sterile or where abstaining from sexual intercourse is in line with the preferred and usual lifestyle of the subject) from first dose until 3 months after last dose of IMP;
• Subjects who have a body weight ≥50 kg at the Screening Visit and Subjects with a body mass index (BMI) of 18-30; BMI = body weight (kg) / \[height (m)\]2.
• Subject with no clinically significant history of previous allergy / sensitivity to Budesonide, Glycopyrronium and Formoterol Fumarate or any of the excipients contained within the IMP;
• Subject with no clinically significant abnormal serum biochemistry, haematology and urine examination values within 28 days before the first dose of IMP;
• Subject with a negative urinary drugs of abuse screen, determined within 28 days before the first dose of IMP (N.B. a positive alcohol result may be repeated at Investigator's discretion);
• Subject with negative human immunodeficiency virus (HIV) and hepatitis B surface antigen (Hep B) and hepatitis C virus antibody (Hep C) results;
• Subject with no clinically significant abnormalities in 12-lead electrocardiogram (ECG) determined within 28 days before first dose of IMP;
• Subject with no clinically significant abnormalities in vital signs (e.g., blood pressure/pulse, respiration rate, oral temperature) determined within 28 days before first dose of IMP (Supine BP \<140/90 mmHg or resting HR\<100 beats per minute);
• Subject must be available to complete the study (including all follow up contact);
• Subject must satisfy a medical examiner about their fitness to participate in the study;
• Subject must provide written informed consent to participate in the study.

You may not qualify if:

• Subjects with clinically significant neurologic, cardiovascular, hepatic, renal, endocrinologic, pulmonary, haematological, psychiatric, or other medical illness that would interfere with participation in this study;
• Subjects with a history of ECG abnormalities including PR\>220 msec; QRS complex \>120 msec; QT Corrected Using Fridericia's Formula (QTcF) \>450 ms; or any significant morphological changes other than non-specific T wave changes;
• A history of additional risk factors for Torsades de Pointes (e.g., heart failure, family history of Long QT Syndrome);
• Subjects who have cancer that has not been in complete remission for at least 5 years;
• Subjects with a FEV1 \< 80% of predicted value and/or a FEV1/FVC ratio \< 0.7 at screening. Subjects must be able to perform reliable, reproducible pulmonary function test manoeuvres per American Thoracic Society / European Respiratory Society (ATS/ERS) guidelines;
• Subjects with symptomatic prostatic hypertrophy / prostrate resection within 6 months of screening / bladder neck obstruction or urinary retention that is clinically significant in the opinion of the Investigator;
• Subjects with a family history of glaucoma or a diagnosis of glaucoma;
• History of substance-related disorders (with the exception of caffeine-related and nicotine-related disorders) as defined in the Diagnostic and Statistical Manual of Mental Disorders (DSM), fourth edition, text revision within 1 year of Screening;
• History of smoking or the use of nicotine containing products or electronic cigarettes within 3 months of Screening by self-reporting;
• A positive alcohol or urine drug screen including cotinine for drugs of abuse at the Screening Visit or at the beginning of each treatment period;
• Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements within 28 days or 5 half-lives (whichever is longer) prior to the first dose of IMP, unless in the opinion of the Investigator and Sponsor's Responsible Physician the medication will not interfere with the study procedures or compromise subject safety. Paracetamol will be permitted at doses of ≤4 grams/day;
• Subjects with a history of an allergic reaction or hypersensitivity to the study drugs, or who develop allergic reaction or hypersensitivity to any component of the formulation(s) used in this study including 99mTc;
• Subjects with a chronic medical condition that requires ongoing treatment with medication;
• Subjects with a history of major surgery within 4 weeks or minor surgery within 2 weeks of drug administration;
• Subjects with any flu-like syndrome or other respiratory infections within 2 weeks of drug administration;

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

Pentrebach, CF48 4DR, United Kingdom

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Budesonide; Glycopyrrolate; Formoterol Fumarate; Breath Holding

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Quaternary Ammonium Compounds; Amines; Organic Chemicals; Onium Compounds; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Ethanolamines; Amino Alcohols; Alcohols; Respiration; Respiratory Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena

Study Officials

• Samuel Israel

  Simbec Research

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: August 3, 2018
• First Posted: November 14, 2018
• Study Start: September 4, 2018
• Primary Completion: October 11, 2018
• Study Completion: October 11, 2018
• Last Updated: November 14, 2018

Record last verified: 2018-11

Locations

GB (1)