A Scintigraphy Study of PT010 in COPD Patients
A Scintigraphy Study of PT010 in COPD Patients
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.
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.
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.