Measurement of Neutrophil Retention in the Lung in Vivo, Using Autologous Labelled Neutrophils, in Healthy Subjects Following Lipopolysaccharide or Saline Challenge and Patients With Chronic Obstructive Pulmonary Disease (COPD)
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Sponsor
- GlaxoSmithKline
- Enrollment
- 46
- Locations
- 1
- Primary Endpoint
- Uptake of labelled neutrophils in the lung as assessed by single-photon emission tomography (SPECT).
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
This is an exploratory study to further develop an imaging platform for the assessment of whole lung neutrophil retention. The primary objective of the study is to quantify and compare neutrophil retention in the lungs of lipopolysaccharide-challenged healthy subjects, saline-challenged healthy subjects and subjects with stable COPD. There will be two treatment groups, one with healthy subjects and the other with subjects with stable COPD. The total duration of this study for healthy subjects will be approximately 1 week, in addition to the screening window of 28 days. The total duration of this study for subjects with COPD will be approximately 1 week for those that complete Visit 1 only, and approximately 2 weeks for those subjects with COPD that return to the unit for Visit 2 7-10 days later, in addition to the screening window of 28 days.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Group 1: Healthy subjects
- •Between 45 and 75 years of age inclusive, at the time of signing the informed consent.
- •Healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring:
- •A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the investigator in consultation with the Medical Monitor if required agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
- •A subject with well-controlled hypertension, non-insulin dependent diabetes or other well controlled medical conditions may be included if the investigator, in consultation with the Medical Monitor if required, agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. Subjects must be stable on their current treatment for at least one month prior to first imaging visit.
- •Current non-smokers who have not used any tobacco products in the 6-month period preceding the screening visit and have a pack history of less than 5 pack years.
- •Pack years = (cigarettes per day smoked/20) x number of years smoked)
- •Body weight \>=50 kilogram (kg) and body mass index (BMI) within the range 19-30 kg/meter (m)\^2 (inclusive).
- •A female subject is eligible to participate if she is not pregnant (as confirmed by a negative human chorionic gonadotrophin (hCG) test), not lactating, and of non reproductive potential defined as:
- •Pre-menopausal females with one of the following: Documented tubal ligation, Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion, Hysterectomy, Documented Bilateral Oophorectomy.
Exclusion Criteria
- •Group 1: healthy subjects
- •Alanine aminotranseferase (ALT) and bilirubin \>1.5xupper limit of normal (ULN) (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
- •Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
- •QT corrected by Frederica's formula (QTcF) \>450 millisecond (msec).
- •History of acute respiratory illnesses within 4 weeks prior to screening.
- •Asthma or history of asthma (including seasonal asthma).
- •Oxygen saturation below 94% on room air.
- •Spirometry FEV1 \<=80% of predicted or FEV1/FVC ratio \<=70% at screening.
- •Ongoing treatment with statins that will be continued during the study or within two weeks of the first imaging visit.
- •History of regular alcohol consumption within 6 months of the study defined as: For United Kingdom sites: an average weekly intake of \>21 units for males or \>14 units for females. One unit is equivalent to 8 gram of alcohol: a half-pint (equivalent to 240 milliliter \[mL\]) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
Outcomes
Primary Outcomes
Uptake of labelled neutrophils in the lung as assessed by single-photon emission tomography (SPECT).
Time Frame: Blood samples will be collected and imaging assessments will be completed after injection of labelled neutrophils at visit 1 (one day) for healthy subjects and visit 1 and 2 (upto two days, 10 days apart) for subjects with COPD.
Uptake of labelled neutrophils in lungs will be assessed to quantify neutrophil retention in the lungs of healthy subjects, lipopolysaccharide -challenged healthy subjects and subjects with stable COPD.
Comparison of neutrophil lung retention between saline-challenged and lipopolysaccharide -challenged healthy subjects.
Time Frame: Blood samples will be collected and imaging assessments will be completed after injection of labelled neutrophils at visit 1 (one day as an outpatient visit).
Comparison of neutrophil lung retention between COPD patients and saline-challenged healthy subjects.
Time Frame: Blood samples will be collected and imaging assessments will be completed after injection of labelled neutrophils at visit 1 (one day) for healthy subjects and visit 1 and 2 (upto two days, 10 days apart) for subjects with COPD.
Comparison of neutrophil lung retention between COPD patients and lipopolysaccharide -challenged healthy subjects.
Time Frame: Blood samples will be collected and imaging assessments will be completed after injection of labelled neutrophils at visit 1 (one day) for healthy subjects and visit 1 and 2 (upto two days, 10 days apart) for subjects with COPD.
Secondary Outcomes
- Uptake of neutrophils in the lung as assessed by SPECT analysis in stable COPD patients scanned on a second visit, 7-10 days after the first visit.(Blood samples will be collected and imaging assessments will be completed after injection of labelled neutrophils at visit 2 (upto two days as outpatient visits, upto 10 days apart) for subjects with COPD.)