Pulmonary Disease, Chronic ObstructivePhase 2NCT02130635

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Dose-Response Relationship of Multiple Doses of GSK2269557 Administered as a Dry Powder to Chronic Obstructive Pulmonary Disease (COPD) Patients

A Phase 2 study testing GSK2269557 100 MCG and GSK2269557 500 MCG in people with Pulmonary Disease, Chronic Obstructive, run by GlaxoSmithKline at 2 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 40 to 75 years
Conditions the study is for: Pulmonary Disease, Chronic Obstructive
What is being tested?: GSK2269557 100 MCG and GSK2269557 500 MCG
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 64 participants
Where: 2 sitesGermany
Study dates: 31 Jul 2014to 18 Aug 2015
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 40 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

The subject has a confirmed and established diagnosis of COPD, as defined by the Global Initiative for Chronic Obstructive lung Disease (GOLD) guidelines.
Male or female of non-child bearing potential between 40 and 75 years of age inclusive, at the time of signing the informed consent.
The subject has a post-bronchodilator [400 microgram (mcg) salbutamol] Maximal amount of air FEV1/FVC <0.7 and FEV1 >=40% to <=80% of predicted (Predictions should be according to the European Community of Coal and Steel (ECCS) equations).
Subject is a smoker or an ex-smoker with a smoking history of at least 10 pack years (pack years = (cigarettes per day smoked/20) x number of years smoked)).
The subject is able to produce >100 milligram (mg) of sputum at screening.
Body weight >=45 kilogram (kg) and body mass index (BMI) within the range 17 - 32 kg/square meter (m^2) (inclusive).

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A female subject is eligible to participate if she is of: Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation, hysterectomy, salpingo-oophrectomy or oophrectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 milli-International units (MIU)/millilitre (mL) and estradiol < 40 picogram (pg)/mL (<147 picomole(pmol)/Liter [L]) is confirmatory]. [Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods, if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.]; or has only same-sex partners, when this is her preferred and usual lifestyle.
Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods. This criterion must be followed from the time of the first dose of study medication until the follow-up visit.
Based on averaged QTcF values of triplicate ECGs obtained over a brief recording period (e.g. 5 minutes): QTcF <450 millisecond (msec); or QTcF<480 msec in subjects with right bundle branch block.
Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
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 if the investigator [in consultation with the Glaxosmithkline (GSK) medical monitor if required] documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.

Who cannot join

Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome, asymptomatic gallstones and cholecystectomy).
Subjects who have a past or current medical condition or diseases that are not well controlled and, which as judged by the Investigator, may affect subject safety or influence the outcome of the study. (Note: Patients with adequately treated and well controlled concurrent medical conditions (e.g. hypertension) are permitted to be entered into the study).
Subject has a diagnosis of active tuberculosis, lung cancer, clinically overt bronchiectasis, pulmonary fibrosis, asthma or any other respiratory condition that might, in the opinion of the Investigator, compromise the safety of the subject or affect the interpretation of the results.
History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of >28 units for males or >21 units for females. One unit is equivalent to 8 gram of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
History of sensitivity to any of the study medications, or components (such as lactose) thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
A positive test for Human immunodeficiency virus (HIV) antibody - tested according to local policies.

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The subject has a positive pre-study drug/alcohol screen. A minimum list of drugs that will be screened for include cannabinoids, amphetamines, barbiturates, cocaine and opiates. The detection of drugs (e.g. benzodiazepines, opiates) taken for a legitimate medical purpose would not necessarily be an exclusion to study participation. The detection of alcohol would not be an exclusion at screening but would need to be negative pre-dose and during the study.
A positive pre-study Hepatitis B surface antigen (HBs-Ag) or positive total hepatitis B core antibody (anti-HBc IgM) or positive Hepatitis C antibody result within 3 months of screening.
Pregnant females as determined by positive urine human chorionic gonadotropin (hCG) test at screening or prior to dosing.
Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
Lactating females.
The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
Subject has poorly controlled or unstable COPD, defined as the occurrence of any of the following: Either: acute worsening of COPD (an exacerbation) that is managed by the subject at home requiring treatment with corticosteroids and/or antibiotics in the 4 weeks prior to the screening visit; or more than two exacerbations in the previous 2 months prior to the screening visit that required a course of oral corticosteroids and/or antibiotics, or for which the subject was hospitalised.
Subject has had a respiratory tract infection treated with antibiotics in the 4 weeks prior to first dose.
Subject requires regular treatment with oral corticosteroids or has received oral or parenteral corticosteroids within 4 weeks of screening.
Vulnerable subject (e.g., person kept in detention).
The subject is not able to understand and communicate in German or native language.

Trial locations and contacts

2 sites in 1 country.

Germany2 sites

GSK Investigational Site
Berlin, 14050
GSK Investigational Site
Großhansdorf, Schleswig-Holstein, 22927

Other trials in Germany

About this study

Official title: A Double-Blind (Sponsor Unblind), Placebo Controlled, Randomised, Parallel Group Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Multiple Doses of GSK2269557 Administered as a Dry Powder to COPD Patients and Assessment of Dose Response Using Sputum Biomarkers

This is a randomised, double-blind, placebo controlled, parallel group study to evaluate the safety, tolerability, pharmacokinetics and dose response of multiple doses of GSK2269557 administered as a dry powder in COPD subjects. Pharmacodynamic effects on biomarkers will also be assessed. This study will have two parts. In Part A, subjects will be randomized to active or placebo treatment in a 3:1 ratio and in Part B, to placebo or one of the six doses of active treatment in an equal ratio. A sufficient number of COPD subjects (male and female of non-child bearing potential) will be screened to ensure that approximately 30 subjects are enrolled and at least 20 evaluable subjects are obtained for Part A and approximately 35 subjects will be enrolled for Part B. In both the parts, subjects will receive study treatment once daily for 14 consecutive days. Placebo control will be included for a valid evaluation of adverse events attributable to treatment versus those independent of treatment.

Conditions: Pulmonary Disease, Chronic Obstructive
Being tested: GSK2269557 100 MCG, GSK2269557 500 MCG, PLACEBO
Keywords: PI3Kd, Pharmacodynamics, dry powder inhaler, GSK2269557, safety, COPD subjects
Medical subject headings: Pulmonary Disease, Chronic Obstructive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

GSK2269557 100 MCGDrug
100 mcg of GSK2269557 blended with lactose per blister administered using a dry powder inhaler device
GSK2269557 500 MCGDrug
500 mcg of GSK2269557 blended with lactose per blister administered using a dry powder inhaler device
PLACEBODrug
Lactose administered using a matching dry powder inhaler device

Study groups in NCT02130635
Study group	Role	What they receive
Part A: GSK2269557 1000 MCG	Experimental	Subjects will receive 2 inhalations (2 x GSK2269557 500 mcg = total dose of 1000 mcg GSK2269557) 30 seconds apart, once daily for 14 consecutive days Receives: Drug: GSK2269557 500 MCG
Part A: PLACEBO	Placebo comparator	Subjects will receive 2 inhalations of placebo once daily for 14 consecutive days Receives: Drug: PLACEBO
Part B: GSK2269557 100 MCG	Experimental	Subjects will receive 4 inhalations (1 x GSK2269557 100 mcg and 3 x Placebo = total dose of 100 mcg GSK2269557) 30 seconds apart, once daily for 14 consecutive days Receives: Drug: GSK2269557 100 MCG; Drug: PLACEBO
Part B: GSK2269557 200 MCG	Experimental	Subjects will receive 4 inhalations (2 x GSK2269557 100 mcg and 2 x Placebo = total dose of 200 mcg GSK2269557) 30 seconds apart, once daily for 14 consecutive days Receives: Drug: GSK2269557 100 MCG; Drug: PLACEBO
Part B: GSK2269557 500 MCG	Experimental	Subjects will receive 4 inhalations (1 x GSK2269557 500 mcg and 3 x Placebo = total dose of 500 mcg GSK2269557) 30 seconds apart, once daily for 14 consecutive days, once daily for 14 consecutive days Receives: Drug: GSK2269557 500 MCG; Drug: PLACEBO
Part B: GSK2269557 700 MCG	Experimental	Subjects will receive 4 inhalations (1 x GSK2269557 500 mcg, 2 x GSK2269557 100 mcg and 1 x Placebo = total dose of 700 mcg GSK2269557) 30 seconds apart, once daily for 14 consecutive days Receives: Drug: GSK2269557 100 MCG; Drug: GSK2269557 500 MCG; Drug: PLACEBO
Part B: GSK2269557 1000 MCG	Experimental	Subjects will receive 4 inhalations (2 x GSK2269557 100 mcg and 2 x Placebo = total dose of 1000 mcg GSK2269557) 30 seconds apart, once daily for 14 consecutive days Receives: Drug: GSK2269557 500 MCG; Drug: PLACEBO
Part B: GSK2269557 2000 MCG	Experimental	Subjects will receive 4 inhalations (2 x GSK2269557 100 mcg and 2 x Placebo = total dose of 2000 mcg GSK2269557) 30 seconds apart, once daily for 14 consecutive days Receives: Drug: GSK2269557 500 MCG
Part B: PLACEBO	Placebo comparator	Subjects will receive 4 inhalations of placebo once daily for 14 consecutive days Receives: Drug: PLACEBO

What is being measured

The primary outcome is the main question the study is designed to answer.

Part A: Number of Participants With at Least One Non-serious Adverse Event (AE), Serious Adverse Event (SAE), or Drug-related Adverse Event
An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition, associated with liver injury and impaired liver function defined as alanine aminotransferase >=3 x upper limit of normal (ULN), and total bilirubin >=2 x ULN or international normalized ratio >1.5. AEs were classified as potentially drug-related, based on the investigator's judgment. Refer to the general AE/SAE module for a list of AEs and SAEs.
Measured: From the start of study treatment until follow-up (assessed for approximately 19 days)
Part A: Change From Baseline in Counts of White Blood Cells (WBC), Total Neutrophils (Total Absolute Neutrophil Count [ANC]), Lymphocytes, Monocytes, Eosinophils, Basophils, and Platelets at the Indicated Time Points
Blood samples were collected for measurement for the indicated tests. Baseline is Day 1 pre-dose. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Measured: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Part A: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points
Blood samples were collected for measurement for the indicated tests. Baseline is Day 1 pre-dose. MCHC is one of the red blood cell (RBC) indices. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Measured: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 h post-dose)
Part A: Change From Baseline in Hematocrit at the Indicated Time Points
Blood samples were collected for measurement for the indicated tests. Baseline is Day 1 pre-dose. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Measured: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Part A: Change From Baseline in Counts of RBCs and Reticulocytes at the Indicated Time Points
Blood samples were collected for measurement for the indicated tests. Baseline is Day 1 pre-dose. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Measured: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Part A: Change From Baseline in Mean Corpuscle Hemoglobin (MCH) at the Indicated Time Points
Blood samples were collected for measurement for the indicated tests. Baseline is Day 1 pre-dose. MCH is one of the red blood cell indices. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Measured: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Part A: Change From Baseline in Mean Corpuscle Volume (MCV) at the Indicated Time Points
Blood samples were collected for measurement for the indicated tests. Baseline is Day 1 pre-dose. MCV is one of the RBC indices. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Measured: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Part A: Change From Baseline in Albumin and Total Protein at the Indicated Time Points
Blood samples were collected for measurement for the indicated tests. Baseline is Day 1 pre-dose. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Measured: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Part A: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points
Blood samples were collected for measurement for the indicated tests. Baseline is Day 1 pre-dose. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Measured: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Part A: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points
Blood samples were collected for measurement for the indicated tests. Baseline is Day 1 pre-dose. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Measured: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Part A: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points
Blood samples were collected for measurement for the indicated tests. Baseline is Day 1 pre-dose. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Measured: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Part A: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline
Baseline was the Day 1 pre-dose measurement. Vital signs (SBP, DBP, and HR) were measured at Day 1 (30 minutes [min] and 6 h post-dose), Day 7 (pre-dose), and Day 14 (24 h post-dose). Potential clinical concern range for SBP was <85 millimeters of mercury (mmHg) (low) and >160 mmHg (high), for DBP <45 mmHg (low) and >100 mmHg (high) and for HR <40 bpm and >110 bpm. All measurements were obtained in supine position, after a 5-minute rest. Day 7 assessments could be conducted on Day 7 or Day 8.
Measured: Day 1, Day 7, and Day 14
Part A: Number of Participants With Normal and Abnormal (Clinically Significant or Not Clinically Significant) Findings in 12-lead Electrocardiogram (ECG) at Any Visit Post-Baseline
Baseline was the Day 1 (pre-dose) measurement. Single 12-lead ECGs were obtained using an ECG machine that automatically calculates the HR and measures PR, QRS, QT, and corrected QT intervals. Clinical significance was judged by the investigator. Day 7 assessments could be conducted on Day 7 or Day 8.
Measured: Day 1, Day 7, and Day 14
Part A: Change From Baseline in Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at the Indicated Time Points
Baseline is Day 1 pre-dose. FEV1 and FVC are measures of lung function. FEV1 is defined as the maximal amount of air that can be forcefully exhaled in one second. FVC is defined as the maximum amount of air that can be forcibly blown out after a maximum inspiration. FEV1 and FVC measurements were repeated until three technically acceptable measurements (within 150 milliliters of each other) had been made. Only the best of three measurements were recorded. Baseline was the maximum of the planned pre-dose measurements on Day 1. Change from Baseline at any post-dose time point was calculated as the post-dose value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Measured: Baseline (Day 1 [pre-dose]), Day 1 (1 h post-dose), Day 7 (pre-dose and 1 h post-dose), and Day 14 (24 h post-dose)
Part B: Adjusted Median Response of Cytokine (Interleukin 6 [IL6], Interleukin 8 [IL8], Tumor Necrosis Factor Alpha [TNFalpha]) Concentrations in Induced Sputum, on Day 7 and Day 14
This outcome measure was used to estimate the inhibition levels of various doses of GSK2269557 by analyzing inflammatory cytokines IL6, IL8, and TNF alpha using Bayesian methods of statistical analysis, using non-informative prior distributions for all modeling parameters. Posterior medians (adjusted median response) and 95% credible intervals are reported here as medians and 95% confidence intervals respectively. 95% credible interval is reported as 2-sided 95% confidence in the statistical analyses. Day 7 assessments could be conducted on Day 7 or Day 8.
Measured: Day 7 (pre-dose) and Day 14 (24 h post-dose)

Secondary outcomes (21)

Part A: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose
A 2 mL blood sample for pharmacokinetic (PK) analysis was collected at each of the indicated time point. Only those participants who were available at the indicated time points were analyzed (represented by n=X in the category titles). A value of NA indicates that the geometric mean or 95% confidence interval is not available.
Measured: Day 1 (Pre-dose, 5 min, 30 min, 1, 2, 4 & 6 hours post-dose)
Part B: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose
A 2 mL blood sample for pharmacokinetic (PK) analysis was collected at each of the indicated time point. Concentration measurements were log-transformed. Only those participants who were available at the indicated time points were analyzed (represented by n=X,X in the category titles). A value of NA indicates that the geometric mean or 95% confidence interval is not available.
Measured: Pre-dose, and 5 min, 30 min, 1 h, 2 h, 4 h, and 6 h post-dose on Day 1
Part A: Maximum Observed Plasma Concentration (Cmax) of GSK2269577 on Day 7
Blood samples were collected to determine the plasma concentrations of GSK2269577 immediately after dosing on Day 7. Day 7 sampling could be done on Day 7 or Day 8.
Measured: Day 7 immediately after dosing
Part B: Maximum Observed Plasma Concentration (Cmax) of GSK2269577 on Day 7
Blood samples were collected to determine the plasma concentrations of GSK2269577 immediately after dosing on Day 7. Concentration values were log-transformed. Day 7 sampling could be done on Day 7 or Day 8.
Measured: Day 7 immediately after dosing
Part A: Trough Concentration (Ctau) of GSK2269577 on Day 7 and Day 15
Blood samples were collected to determine the (trough) plasma concentration of GSK2269577 on Day 7 (pre-dose) and Day 15 (24 hours after dosing on Day 14). Day 7 assessments could be done either on Day 7 or on Day 8.
Measured: Day 7 and Day 15
Part B: Trough Concentration (Ctau) of GSK2269577 on Day 7 and Day 15
Blood samples were collected to determine the (trough) plasma concentration of GSK2269577 on Day 7 (pre-dose) and Day 15 (24 hours after dosing on Day 14). Day 7 assessments could be done either on Day 7 or on Day 8.
Measured: Day 7 and Day 15
Part B: Number of Times Rescue Medication Was Used by Participants Daily, During the Treatment Period
Rescue medication was identified from concomitant medication records and the patient diaries which were provided to the participants to record data throughout the treatment period. Only participants who used rescue medication were analyzed. The value NA indicates that the standard deviation could not be calculated as only one participant was analyzed.
Measured: Day 1 to Day 15
Part B: Number of Participants With at Least One Non-serious Adverse Event (AE), Serious Adverse Event (SAE), or Drug-related Adverse Event
An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition, associated with liver injury and impaired liver function defined as alanine aminotransferase >=3 x upper limit of normal (ULN), and total bilirubin >=2 x ULN or international normalized ratio >1.5. AEs were classified as potentially drug-related, based on the investigator's judgment. Refer to the general AE/SAE module for a list of AEs and SAEs.
Measured: From the start of study treatment until follow-up (assessed for approximately 19 days)
Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points
Blood samples were collected for measurement for the indicated tests. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Measured: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Part B: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points
Blood samples were collected for measurement for the indicated tests. MCHC is one of the red blood cell (RBC) indices. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Measured: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Part B: Change From Baseline in Counts of RBCs and Reticulocytes at the Indicated Time Points
Blood samples were collected for measurement for the indicated tests. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Measured: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Part B: Change From Baseline in Hematocrit at the Indicated Time Points
Blood samples were collected for measurement for the indicated tests. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Measured: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Part B: Change From Baseline in Mean Corpuscle Hemoglobin (MCH) at the Indicated Time Points
Blood samples were collected for measurement for the indicated tests. MCH is one of the red blood cell indices. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Measured: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Part B: Change From Baseline in Mean Corpuscle Volume (MCV) at the Indicated Time Points
Blood samples were collected for measurement for the indicated tests. MCV is one of the RBC indices. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Measured: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Part B: Change From Baseline in Albumin and Total Protein at the Indicated Time Points
Blood samples were collected for measurement for the indicated tests. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Measured: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points
Blood samples were collected for measurement for the indicated tests. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Measured: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Part B: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points
Blood samples were collected for measurement for the indicated tests. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Measured: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points
Blood samples were collected for measurement for the indicated tests. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Measured: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Part B: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline
Baseline was the Day 1 pre-dose measurement. Vital signs (SBP, DBP, and HR) were measured at Day 1 (30 minutes [min] and 6 h post-dose), Day 7 (pre-dose), and Day 14 (24 h post-dose). All measurements were obtained in supine position, after a 5-minute rest. Day 7 assessments could be conducted on Day 7 or Day 8.
Measured: Day 1, Day 7, and Day 14
Part B: Number of Participants With Normal and Abnormal (Clinically Significant or Not Clinically Significant) Findings in 12-lead Electrocardiogram (ECG) at Any Visit Post-Baseline
Baseline was the Day 1 (pre-dose) measurement. Single 12-lead ECGs were obtained using an ECG machine that automatically calculates the HR and measures PR, QRS, QT, and corrected QT intervals. Day 7 assessments could be conducted on Day 7 or Day 8.
Measured: Day 1, Day 7, and Day 14
Part B: Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at Screening and Follow-up
FEV1 and FVC are measures of lung function. FEV1 is defined as the maximal amount of air that can be forcefully exhaled in one second. FVC is defined as the maximum amount of air that can be forcibly blown out after a maximum inspiration. FEV1 and FVC measurements were repeated until three technically acceptable measurements (within 150 milliliters of each other) had been made. Only the best of three measurements were recorded.
Measured: Screening (up to 30 days prior to Day 1) and Follow-up (approximately Day 19)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

31 Jul 201418 Aug 2015

First posted5 May 2014 (estimated)
Study start31 Jul 2014
Primary completion18 Aug 2015
Study completion18 Aug 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Pulmonary Disease, Chronic ObstructiveStudies of the same condition, open and under way.
More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 64 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02130635
Sponsor's protocol ID: 115119
Status last verified: Sep 2018
First submitted: 1 May 2014
Last updated: 11 Oct 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: Yes: IPD for this study will be made available via the Clinical Study Data Request site.

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
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Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
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What happens when the study ends?

See locations

Enrolling by invitationObservational study
Firefighter's Longitudinal Airway and Respiratory Exposome/Multiome Study (FLARES)
Anosmia, Chronic Obstructive Pulmonary Disease
RecruitingPhase 3
A Study to Evaluate Axatilimab and Corticosteroids as Initial Treatment for Chronic Graft-Versus-Host Disease
Chronic Graft-versus-host-disease
Not yet recruiting
Impact of Multidisciplinary Care, Structured and Targeted on the COPD Patient's Clinical Pathway.
Chronic Obstructive Pulmonary Disease, Lung Diseases, Obstructive
Not yet recruitingPhase 3
The AIRWARD Study: A Study to Test Whether Verducatib Helps People With Chronic Obstructive Pulmonary Disease
Chronic Obstructive Pulmonary Disease
Not yet recruiting
Evaluating and Promoting Resilience in Adolescents With Tourette Syndrome
Tourette Syndrome, Tic Disorders

All Pulmonary Disease, Chronic Obstructive trials

Study at a glance

From the registry record, last updated by the sponsor on 11 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Double-Blind (Sponsor Unblind), Placebo Controlled, Randomised, Parallel Group Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Multiple Doses of GSK2269557 Administered as a Dry Powder to COPD Patients and Assessment of Dose Response Using Sputum Biomarkers
ClinicalTrials.gov ID: NCT02130635
Acronym / sponsor ID: 115119
Conditions: Pulmonary Disease, Chronic Obstructive
Keywords: PI3Kd, Pharmacodynamics, dry powder inhaler, GSK2269557, safety, COPD subjects
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 64 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Study start: 31 Jul 2014 (actual)
Primary completion: 18 Aug 2015 (actual)
Study completion: 18 Aug 2015 (actual)
First posted: 5 May 2014 (estimated)
Results: Posted 12 Jul 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 9

Arm	Type	Receives
Part A: GSK2269557 1000 MCG	Experimental	Drug: GSK2269557 500 MCGSubjects will receive 2 inhalations (2 x GSK2269557 500 mcg = total dose of 1000 mcg GSK2269557) 30 seconds apart, once daily for 14 consecutive days
Part A: PLACEBO	Placebo comparator	Drug: PLACEBOSubjects will receive 2 inhalations of placebo once daily for 14 consecutive days
Part B: GSK2269557 100 MCG	Experimental	Drug: GSK2269557 100 MCG, Drug: PLACEBOSubjects will receive 4 inhalations (1 x GSK2269557 100 mcg and 3 x Placebo = total dose of 100 mcg GSK2269557) 30 seconds apart, once daily for 14 consecutive days
Part B: GSK2269557 200 MCG	Experimental	Drug: GSK2269557 100 MCG, Drug: PLACEBOSubjects will receive 4 inhalations (2 x GSK2269557 100 mcg and 2 x Placebo = total dose of 200 mcg GSK2269557) 30 seconds apart, once daily for 14 consecutive days
Part B: GSK2269557 500 MCG	Experimental	Drug: GSK2269557 500 MCG, Drug: PLACEBOSubjects will receive 4 inhalations (1 x GSK2269557 500 mcg and 3 x Placebo = total dose of 500 mcg GSK2269557) 30 seconds apart, once daily for 14 consecutive days, once daily for 14 consecutive days
Part B: GSK2269557 700 MCG	Experimental	Drug: GSK2269557 100 MCG, Drug: GSK2269557 500 MCG, Drug: PLACEBOSubjects will receive 4 inhalations (1 x GSK2269557 500 mcg, 2 x GSK2269557 100 mcg and 1 x Placebo = total dose of 700 mcg GSK2269557) 30 seconds apart, once daily for 14 consecutive days
Part B: GSK2269557 1000 MCG	Experimental	Drug: GSK2269557 500 MCG, Drug: PLACEBOSubjects will receive 4 inhalations (2 x GSK2269557 100 mcg and 2 x Placebo = total dose of 1000 mcg GSK2269557) 30 seconds apart, once daily for 14 consecutive days
Part B: GSK2269557 2000 MCG	Experimental	Drug: GSK2269557 500 MCGSubjects will receive 4 inhalations (2 x GSK2269557 100 mcg and 2 x Placebo = total dose of 2000 mcg GSK2269557) 30 seconds apart, once daily for 14 consecutive days
Part B: PLACEBO	Placebo comparator	Drug: PLACEBOSubjects will receive 4 inhalations of placebo once daily for 14 consecutive days

Who may qualify

Ages: 40 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (11 listed)

The subject has a confirmed and established diagnosis of COPD, as defined by the Global Initiative for Chronic Obstructive lung Disease (GOLD) guidelines.
Male or female of non-child bearing potential between 40 and 75 years of age inclusive, at the time of signing the informed consent.
The subject has a post-bronchodilator [400 microgram (mcg) salbutamol] Maximal amount of air FEV1/FVC <0.7 and FEV1 >=40% to <=80% of predicted (Predictions should be according to the European Community of Coal and Steel (ECCS) equations).
Subject is a smoker or an ex-smoker with a smoking history of at least 10 pack years (pack years = (cigarettes per day smoked/20) x number of years smoked)).
The subject is able to produce >100 milligram (mg) of sputum at screening.

Key exclusion criteria (18 listed)

Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome, asymptomatic gallstones and cholecystectomy).
Subjects who have a past or current medical condition or diseases that are not well controlled and, which as judged by the Investigator, may affect subject safety or influence the outcome of the study. (Note: Patients with adequately treated and well controlled concurrent medical conditions (e.g. hypertension) are permitted to be entered into the study).
Subject has a diagnosis of active tuberculosis, lung cancer, clinically overt bronchiectasis, pulmonary fibrosis, asthma or any other respiratory condition that might, in the opinion of the Investigator, compromise the safety of the subject or affect the interpretation of the results.
History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of >28 units for males or >21 units for females. One unit is equivalent to 8 gram of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
History of sensitivity to any of the study medications, or components (such as lactose) thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
GSK2269557 100 MCG100 mcg of GSK2269557 blended with lactose per blister administered using a dry powder inhaler device	Drug	Part B: GSK2269557 100 MCG, Part B: GSK2269557 200 MCG, Part B: GSK2269557 700 MCG
GSK2269557 500 MCG500 mcg of GSK2269557 blended with lactose per blister administered using a dry powder inhaler device	Drug	Part A: GSK2269557 1000 MCG, Part B: GSK2269557 1000 MCG, Part B: GSK2269557 2000 MCG, Part B: GSK2269557 500 MCG, Part B: GSK2269557 700 MCG
PLACEBOLactose administered using a matching dry powder inhaler device	Drug	Part A: PLACEBO, Part B: GSK2269557 100 MCG, Part B: GSK2269557 1000 MCG, Part B: GSK2269557 200 MCG, Part B: GSK2269557 500 MCG, Part B: GSK2269557 700 MCG, Part B: PLACEBO

Primary outcome

Part A: Number of Participants With at Least One Non-serious Adverse Event (AE), Serious Adverse Event (SAE), or Drug-related Adverse Event
Time frame: From the start of study treatment until follow-up (assessed for approximately 19 days)
An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition, associated with liver injury and impaired liver function defined as alanine aminotransferase >=3 x upper limit of normal (ULN), and total bilirubin >=2 x ULN or international normalized ratio >1.5. AEs were classified as potentially drug-related, based on the investigator's judgment. Refer to the general AE/SAE module for a list of AEs and SAEs.
Part A: Change From Baseline in Counts of White Blood Cells (WBC), Total Neutrophils (Total Absolute Neutrophil Count [ANC]), Lymphocytes, Monocytes, Eosinophils, Basophils, and Platelets at the Indicated Time Points
Time frame: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Blood samples were collected for measurement for the indicated tests. Baseline is Day 1 pre-dose. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Part A: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points
Time frame: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 h post-dose)
Blood samples were collected for measurement for the indicated tests. Baseline is Day 1 pre-dose. MCHC is one of the red blood cell (RBC) indices. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Part A: Change From Baseline in Hematocrit at the Indicated Time Points
Time frame: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Blood samples were collected for measurement for the indicated tests. Baseline is Day 1 pre-dose. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Part A: Change From Baseline in Counts of RBCs and Reticulocytes at the Indicated Time Points
Time frame: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Blood samples were collected for measurement for the indicated tests. Baseline is Day 1 pre-dose. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Part A: Change From Baseline in Mean Corpuscle Hemoglobin (MCH) at the Indicated Time Points
Time frame: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Blood samples were collected for measurement for the indicated tests. Baseline is Day 1 pre-dose. MCH is one of the red blood cell indices. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Part A: Change From Baseline in Mean Corpuscle Volume (MCV) at the Indicated Time Points
Time frame: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Blood samples were collected for measurement for the indicated tests. Baseline is Day 1 pre-dose. MCV is one of the RBC indices. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Part A: Change From Baseline in Albumin and Total Protein at the Indicated Time Points
Time frame: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Blood samples were collected for measurement for the indicated tests. Baseline is Day 1 pre-dose. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Part A: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points
Time frame: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Blood samples were collected for measurement for the indicated tests. Baseline is Day 1 pre-dose. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Part A: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points
Time frame: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Blood samples were collected for measurement for the indicated tests. Baseline is Day 1 pre-dose. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Part A: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points
Time frame: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Blood samples were collected for measurement for the indicated tests. Baseline is Day 1 pre-dose. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Part A: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline
Time frame: Day 1, Day 7, and Day 14
Baseline was the Day 1 pre-dose measurement. Vital signs (SBP, DBP, and HR) were measured at Day 1 (30 minutes [min] and 6 h post-dose), Day 7 (pre-dose), and Day 14 (24 h post-dose). Potential clinical concern range for SBP was <85 millimeters of mercury (mmHg) (low) and >160 mmHg (high), for DBP <45 mmHg (low) and >100 mmHg (high) and for HR <40 bpm and >110 bpm. All measurements were obtained in supine position, after a 5-minute rest. Day 7 assessments could be conducted on Day 7 or Day 8.
Part A: Number of Participants With Normal and Abnormal (Clinically Significant or Not Clinically Significant) Findings in 12-lead Electrocardiogram (ECG) at Any Visit Post-Baseline
Time frame: Day 1, Day 7, and Day 14
Baseline was the Day 1 (pre-dose) measurement. Single 12-lead ECGs were obtained using an ECG machine that automatically calculates the HR and measures PR, QRS, QT, and corrected QT intervals. Clinical significance was judged by the investigator. Day 7 assessments could be conducted on Day 7 or Day 8.
Part A: Change From Baseline in Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at the Indicated Time Points
Time frame: Baseline (Day 1 [pre-dose]), Day 1 (1 h post-dose), Day 7 (pre-dose and 1 h post-dose), and Day 14 (24 h post-dose)
Baseline is Day 1 pre-dose. FEV1 and FVC are measures of lung function. FEV1 is defined as the maximal amount of air that can be forcefully exhaled in one second. FVC is defined as the maximum amount of air that can be forcibly blown out after a maximum inspiration. FEV1 and FVC measurements were repeated until three technically acceptable measurements (within 150 milliliters of each other) had been made. Only the best of three measurements were recorded. Baseline was the maximum of the planned pre-dose measurements on Day 1. Change from Baseline at any post-dose time point was calculated as the post-dose value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Part B: Adjusted Median Response of Cytokine (Interleukin 6 [IL6], Interleukin 8 [IL8], Tumor Necrosis Factor Alpha [TNFalpha]) Concentrations in Induced Sputum, on Day 7 and Day 14
Time frame: Day 7 (pre-dose) and Day 14 (24 h post-dose)
This outcome measure was used to estimate the inhibition levels of various doses of GSK2269557 by analyzing inflammatory cytokines IL6, IL8, and TNF alpha using Bayesian methods of statistical analysis, using non-informative prior distributions for all modeling parameters. Posterior medians (adjusted median response) and 95% credible intervals are reported here as medians and 95% confidence intervals respectively. 95% credible interval is reported as 2-sided 95% confidence in the statistical analyses. Day 7 assessments could be conducted on Day 7 or Day 8.

21 secondary outcomes

Part A: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose
Time frame: Day 1 (Pre-dose, 5 min, 30 min, 1, 2, 4 & 6 hours post-dose)
Part B: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose
Time frame: Pre-dose, and 5 min, 30 min, 1 h, 2 h, 4 h, and 6 h post-dose on Day 1
Part A: Maximum Observed Plasma Concentration (Cmax) of GSK2269577 on Day 7
Time frame: Day 7 immediately after dosing
Part B: Maximum Observed Plasma Concentration (Cmax) of GSK2269577 on Day 7
Time frame: Day 7 immediately after dosing
Part A: Trough Concentration (Ctau) of GSK2269577 on Day 7 and Day 15
Time frame: Day 7 and Day 15
Part B: Trough Concentration (Ctau) of GSK2269577 on Day 7 and Day 15
Time frame: Day 7 and Day 15
Part B: Number of Times Rescue Medication Was Used by Participants Daily, During the Treatment Period
Time frame: Day 1 to Day 15
Part B: Number of Participants With at Least One Non-serious Adverse Event (AE), Serious Adverse Event (SAE), or Drug-related Adverse Event
Time frame: From the start of study treatment until follow-up (assessed for approximately 19 days)
Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points
Time frame: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Part B: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points
Time frame: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Part B: Change From Baseline in Counts of RBCs and Reticulocytes at the Indicated Time Points
Time frame: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Part B: Change From Baseline in Hematocrit at the Indicated Time Points
Time frame: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Part B: Change From Baseline in Mean Corpuscle Hemoglobin (MCH) at the Indicated Time Points
Time frame: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Part B: Change From Baseline in Mean Corpuscle Volume (MCV) at the Indicated Time Points
Time frame: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Part B: Change From Baseline in Albumin and Total Protein at the Indicated Time Points
Time frame: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points
Time frame: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Part B: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points
Time frame: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points
Time frame: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Part B: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline
Time frame: Day 1, Day 7, and Day 14
Part B: Number of Participants With Normal and Abnormal (Clinically Significant or Not Clinically Significant) Findings in 12-lead Electrocardiogram (ECG) at Any Visit Post-Baseline
Time frame: Day 1, Day 7, and Day 14
Part B: Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at Screening and Follow-up
Time frame: Screening (up to 30 days prior to Day 1) and Follow-up (approximately Day 19)

Results and safety

Results posted to the registry on 12 Jul 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Part A: Placebo	7	7
Part A: GSK2269577 1000 µg	21	21
Part B: Placebo	0	0
Part B: GSK2269577 100 µg	0	0
Part B: GSK2269577 200 µg	0	0
Part B: GSK2269577 500 µg	0	0
Part B: GSK2269577 700 µg	0	0
Part B: GSK2269577 1000 µg	0	0
Part B: GSK2269577 2000 µg	0	0

Primary outcome: Part A: Number of Participants With at Least One Non-serious Adverse Event (AE), Serious Adverse Event (SAE), or Drug-related Adverse Event

Time frame: From the start of study treatment until follow-up (assessed for approximately 19 days). Number. Unit: Participants

Measure	Part A: Placebo n = 7	Part A: GSK2269577 1000 µg n = 21
At least one AE	2	9
At least one SAE	0	1
At least one drug-related AE	2	6

Population analysed: Safety Population: all participants who received at least one dose of study treatment.

Primary outcome: Part A: Change From Baseline in Counts of White Blood Cells (WBC), Total Neutrophils (Total Absolute Neutrophil Count [ANC]), Lymphocytes, Monocytes, Eosinophils, Basophils, and Platelets at the Indicated Time Points

Time frame: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose). Mean (Standard Deviation). Unit: 10^9 cells per liter (GI/L)

Measure	Part A: Placebo n = 7	Part A: GSK2269577 1000 µg n = 21
WBC; Day 7/Day 8, pre-dose	-0.736 (0.937)	-0.080 (1.387)
WBC; Day 14, 24 h post dose	-0.140 (1.220)	-0.510 (0.947)
Total ANC; Day 7/Day 8, pre-dose	-0.664 (0.624)	-0.363 (1.342)
Total ANC; Day 14, 24 h post dose	-0.153 (0.887)	-0.547 (0.977)
Lymphocytes; Day 7/Day 8, pre-dose	-0.033 (0.321)	0.172 (0.597)
Lymphocytes; Day 14, 24 h post dose	-0.049 (0.197)	0.030 (0.245)
Monocytes; Day 7/Day 8, pre-dose	-0.036 (0.074)	0.046 (0.149)
Monocytes; Day 14, 24 h post dose	0.039 (0.178)	-0.022 (0.116)

Population analysed: Safety Population

Primary outcome: Part A: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points

Time frame: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 h post-dose). Mean (Standard Deviation). Unit: Grams/Liter (g/L)

Measure	Part A: Placebo n = 7	Part A: GSK2269577 1000 µg n = 21
Hemoglobin; Day 7/Day 8, pre-dose	-1.3 (6.63)	1.6 (4.17)
Hemoglobin; Day 14, 24 h post dose	0.3 (6.97)	1.0 (4.12)
MCHC; Day 7/Day 8, pre-dose	-5.3 (7.32)	-2.2 (4.54)
MCHC; Day 14, 24 h post dose	-8.4 (4.39)	-2.4 (6.45)

Population analysed: Safety Population

Primary outcome: Part A: Change From Baseline in Hematocrit at the Indicated Time Points

Time frame: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose). Mean (Standard Deviation). Unit: Ratio

Measure	Part A: Placebo n = 7	Part A: GSK2269577 1000 µg n = 21
Hematocrit; Day 7/Day 8, pre-dose	0.003 (0.023)	0.007 (0.013)
Hematocrit; Day 14, 24 h post dose	0.011 (0.019)	0.006 (0.016)

Population analysed: Safety Population

21 secondary outcomes are reported in the full results.

Adverse events

Time frame: On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occurring from the start of treatment until follow-up (up to approximately 19 days), are reported.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Part A: Placebo	0 of 7 (0%)	2 of 7 (28.6%)	0 of 7
Part A: GSK2269577 1000 µg	1 of 21 (4.8%)	7 of 21 (33.3%)	0 of 21
Part B: Placebo	0 of 5 (0%)	3 of 5 (60%)	0 of 5
Part B: GSK2269577 100 µg	0 of 5 (0%)	3 of 5 (60%)	0 of 5
Part B: GSK2269577 200 µg	0 of 5 (0%)	2 of 5 (40%)	0 of 5
Part B: GSK2269577 500 µg	0 of 5 (0%)	1 of 5 (20%)	0 of 5
Part B: GSK2269577 700 µg	0 of 6 (0%)	3 of 6 (50%)	0 of 6
Part B: GSK2269577 1000 µg	0 of 5 (0%)	4 of 5 (80%)	0 of 5
Part B: GSK2269577 2000 µg	0 of 5 (0%)	2 of 5 (40%)	0 of 5

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 11 Oct 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
IPD for this study will be made available via the Clinical Study Data Request site.Link provided by the sponsor.
Individual participant dataSharing planned: Yes. IPD for this study will be made available via the Clinical Study Data Request site.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

GSK Clinical Trials study director

GlaxoSmithKline

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing GSK2269557 100 MCG and GSK2269557 500 MCG in people with Pulmonary Disease, Chronic Obstructive, run by GlaxoSmithKline at 2 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Jul 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part A: Number of Participants With at Least One Non-serious Adverse Event (AE), Serious Adverse Event (SAE), or Drug-related Adverse Event (time frame: From the start of study treatment until follow-up (assessed for approximately 19 days)). The study lists 15 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02130635.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Oct 2018.