Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Scintigraphy Study of PT010 in COPD Patients (RD708/34000)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03906045
Recruitment Status : Completed
First Posted : April 8, 2019
Last Update Posted : February 12, 2021
Sponsor:
Collaborator:
Simbec Research
Information provided by (Responsible Party):
AstraZeneca

Brief Summary:
This study is a single treatment period, single dose gamma scintigraphy study investigating the deposition in the lungs of a Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF-MDI). This study will be investigating how the drug (known as PT010) is distributed in the lungs of Chronic Obstructive Pulmonary Disease (COPD) patients (with moderate to very severe COPD) following a maximal 10 second breath hold. This inhaler is intended to be used in the treatment of COPD, which is a group of diseases which cause lung problems and difficulty breathing. PT010 is a new combination product of 3 marketed drugs called Glycopyrronium, Formoterol Fumarate and Budesonide.

Condition or disease Intervention/treatment Phase
Chronic Obstructive Pulmonary Disease Drug: BGF-MDI Phase 1

Detailed Description:

This will be a single-dose study to assess the pulmonary deposition of Radiolabelled BGF MDI following administration in male and female patients with moderate to severe/very severe COPD. Serious Adverse Events (SAEs) will be recorded from the time of signing of informed consent form to Post-study Follow-up phone call. Non-serious Adverse Events (AEs) will be collected from the first dose on Day 1 to Post-study Follow-up phone call. Study drug will be administered by inhalation.

The study will comprise of a Screening Visit, followed by a single Treatment Period and a Post-study Follow-up phone call. The Treatment Period will be from the afternoon before (Day 1) until 4 hours (h) post dose (Day 1). Patients will arrive at the Clinical Unit on Day 1. Patients will withhold their regular COPD medication in the morning of Day 1 and instead be given short-acting Ventolin Hydrofluoroalkane (HFA) and Atrovent HFA which may be used up to (but not within) 6 h prior to dosing. Investigational Product (IP) will be administered on the afternoon of Day 1 fasted (after a fast of at least 2 h) and patients will be discharged 4 h post dose (Day 1), provided there are no ongoing safety concerns. During the treatment period, patients will also undergo a Krypton-81m (81mKr) gas ventilation imaging scan and a Cobalt-57 (57Co) transmission scan. SAEs will be evaluated from the time of signing the informed consent form and up to the Post-study Follow-up phone call, non-serious AEs will be evaluated from Day 1 following IP dose and up to the Post-study Follow-up phone call. Approximately 20 patients (10 per cohort) will be enrolled for at least 16 to complete the study:

  • Approximately 10 patients with moderate COPD (Forced Expiratory Volume in 1 Second (FEV1) ≥50-<80% of predicted normal), for at least 8 completed patients.
  • Approximately 10 patients with severe/very severe COPD (FEV1 <50% of predicted normal), for at least 8 completed patients.

At the time of dosing, patients will be required to perform 2 inhalations (after priming) under the supervision of an Investigator. Immediately following each inhalation, patients will perform a maximal breath-hold, up to 10 s, prior to exhaling into an exhalation filter. Once the second breath hold and exhalation has been performed, patients will rinse their mouth with water and expel the washings for collection. Patients will then swallow bread and water.

Thereafter, posterior and anterior views of the lungs and stomach, and a lateral head and neck view will be recorded using a gamma camera. All images will be of a maximum of 200 s in duration. Images will also be acquired of the exhalation filter and collected mouth washings. Mass balance calculations will be undertaken to determine the fraction of the emitted dose delivered to the lungs of the patients. The distribution pattern of radiolabel within the lungs will be described in terms of a ratio of radioactive counts in different lung regions, after accounting for differences in regional lung volumes.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 18 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

This will be a single-dose study to assess the pulmonary deposition of Radiolabelled BGF MDI following administration in male and female patients with moderate to severe/very severe COPD. SAEs will be recorded from the time of signing of informed consent form to Post-study Follow-up phone call. Non-serious AEs will be collected from the first dose on Day 1 to Post-study Follow-up phone call. Study drug will be administered by inhalation.

The study will comprise of a Screening Visit, followed by a single Treatment Period and a Post-study Follow-up phone call.

Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I, Single-Dose, Gamma Scintigraphy Study to Assess the Pulmonary Deposition of Technetium-99m Radiolabelled Budesonide, Glycopyrronium and Formoterol Fumarate MDI in Patients With Moderate to Severe/Very Severe COPD.
Actual Study Start Date : April 4, 2019
Actual Primary Completion Date : March 5, 2020
Actual Study Completion Date : March 5, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Nuclear Scans

Arm Intervention/treatment
Experimental: All patients
10 patients with moderate COPD and 10 patients with severe/very severe COPD inhale BGF followed by a breath hold of up to 10 seconds.
Drug: BGF-MDI
Budesonide, Glycopyrronium and Formoterol Fumarate.




Primary Outcome Measures :
  1. The percentage (%) emitted dose of radiolabelled BGF MDI deposited in the lungs following a maximal breath-hold of up to 10 s. [ Time Frame: Day 1 ]
    Percentage of BGF MDI deposited in the lungs.


Secondary Outcome Measures :
  1. Regional airway deposition ratios including the non-normalized parameters O/I and C/P regions and the normalized parameters PI and sC/P of the radiolabelled BGF MDI following a maximal breath-hold of up to 10 s. [ Time Frame: Day 1 ]
    Percentages of BGF MDI deposited in different regions of lungs.


Other Outcome Measures:
  1. The fraction of the dose of radiolabelled BGF MDI deposited in the oropharyngeal and stomach regions (expressed as % emitted dose) following a maximal breath-hold of up to 10 s. [ Time Frame: Day 1 ]
    Percentages of BGF MDI deposited in oropharyngeal and stomach regions.

  2. The fraction of the dose of radiolabelled BGF MDI deposited on the actuator (expressed as % ex-valve dose) and exhalation filter (expressed as % emitted dose) following a maximal breath-hold of up to 10 s. [ Time Frame: Day 1 ]
    Percentages of BGF MDI deposited on the actuator and exhalation filter."

  3. Adverse Events [ Time Frame: Up to 14 days ]
    Number and percentage of patients with at least one treatment emergent adverse events (TEAEs) will be reported. In addition, the number and % of patients reporting TEAEs will be tabulated by maximum intensity and maximum reported causality to investigation product within a patient.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   40 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Main Inclusion Criteria:

  • Males and females at least 40 years of age and no older than 80 years.
  • Patients with diagnosis of COPD as defined by the American Thoracic Society (ATS)/European Respiratory Society (ERS) [1].

    • Post bronchodilator (BD) FEV1 / Forced Vital Capacity (FVC) ratio must be < 0.70.
    • Post BD FEV1 must be < 80% predicted.
  • All patients must be receiving 1 or more inhaled maintenance therapies, including at least 1 long-acting bronchodilator, for the management of their COPD for at least 4 weeks prior to the Screening Visit.
  • Current or former smokers with a history of at least 10 pack-years of cigarette smoking. [Number of pack-years = (number of cigarettes per day/20) x number of years smoked (e.g. 20 cigarettes per day for 10 years or 10 cigarettes per day for 20 years represent 10 pack-years)].

Main Exclusion Criteria:

  • Any significant disease or disorder (e.g. including but not limited to gastrointestinal, hepatic, renal/urinary tract, haematological, neurological, musculoskeletal, endocrine, metabolic, eye, psychiatric which, in the opinion of the Investigator, may either put the patient at risk because of participation in the study, or influence the results of the study.
  • Respiratory:

Current diagnosis of asthma, in the opinion of the Investigator. COPD due to α1-Antitrypsin Deficiency. Sleep apnoea that, in the opinion of the Investigator, is uncontrolled. Other Respiratory Disorders: known active tuberculosis, lung cancer, cystic fibrosis, significant bronchiectasis (high resolution computerised tomography [CT] evidence of bronchiectasis that causes repeated acute exacerbations), immune deficiency disorders, severe neurological disorders affecting control of the upper airway, sarcoidosis, idiopathic interstitial pulmonary fibrosis, primary pulmonary hypertension, or pulmonary thromboembolic disease. Note: allergic rhinitis is not exclusionary.

A moderate or severe exacerbation of COPD ending within 6 weeks prior to dosing (Day 1). The end date of an exacerbation is the last day of treatment with systemic corticosteroids or antibiotics.

Prior pulmonary resection or Lung Volume Reduction Surgery [i.e., lobectomy, bronchoscopic lung volume reduction (endobronchial blockers, airway bypass, endobronchial valves, thermal vapor ablation, biological sealants, and airway implants)].

  • Cardiovascular Patients with significant or unstable ischemic heart disease, arrhythmia, cardiomyopathy, heart failure (including significant cor pulmonale), uncontrolled hypertension as defined by the Investigator, or any other relevant cardiovascular disorder as judged by the Investigator.
  • Current cancer diagnosis requiring treatment.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03906045


Locations
Layout table for location information
United Kingdom
Research Site
Llanelli, United Kingdom, SA14 8QF
Research Site
Merthyr Tydfil, United Kingdom, CF48 4DR
Sponsors and Collaborators
AstraZeneca
Simbec Research
Investigators
Layout table for investigator information
Principal Investigator: Ezanul Wahab Simbec Research
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT03906045    
Other Study ID Numbers: D5980C00020
First Posted: April 8, 2019    Key Record Dates
Last Update Posted: February 12, 2021
Last Verified: February 2021

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AstraZeneca:
COPD
scintigraphy
budesonide
glycopyrronium
formoterol
Additional relevant MeSH terms:
Layout table for MeSH terms
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Lung Diseases
Respiratory Tract Diseases