MedPath

GW815SF For Chronic Obstructive Pulmonary Disease (Chronic Bronchitis, Emphysema)

Phase 3
Completed
Conditions
Pulmonary Disease, Chronic Obstructive
Registration Number
NCT00269087
Lead Sponsor
GlaxoSmithKline
Brief Summary

This study evaluates the safety of medicine on COPD (Chronic Obstructive Pulmonary Disease). This study will last up to 56 weeks, and subjects will visit the clinic 16 times. Subjects will be given breathing tests, and will record their breathing symptoms daily on diary cards.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
122
Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Primary Outcome Measures
NameTimeMethod
Number of Participants With Any Adverse Events (AEs) and Serious AEs (SAEs)Up to Week 56

AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE include adverse events that result in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition.

Secondary Outcome Measures
NameTimeMethod
Mean Change From Baseline in Level of Plasma Cortisol 1Baseline and Week 24 and 52

On each assessment day at Week 24 and 52, adrenal cortical function tests were performed between 8:00-10:00 in the morning. Additional measurements were taken at follow up visit, if the measurements made at Week 52 revealed any abnormalities of clinical significance. Blood samples were taken from participants at rest before undergoing spirometry. Baseline value was the measurement taken at the start of run-in or the treatment period. Change from Baseline was any post Baseline value minus value at Baseline.

Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)Baseline and up to Week 56

Systolic and diastolic BP was measured in sitting position. Baseline value was the measurement taken at the start of run-in or the treatment period. Change from Baseline was any post Baseline value minus value at Baseline.

Mean Change From Baseline in WeightBaseline and up to Week 56

Body weight was measured during run-in period, at Week 24 and 52.

Mean Change From Baseline in Forced Vital Capacity (FVC)Baseline and up to Week 52

FVC was the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible measured using spirometer. A participant took rest just before the measurement. At each time of measurement, a participant expired for at least 6 seconds wherever possible. At each time of measurement, at least 3 readings were obtained, and three readings which were obtained in an appropriate manner were stored. Baseline value was the value measured at visit 2. However, when the value at Visit 2 was missing, the value at Visit 1 was used as Baseline. Change from Baseline was any post Baseline value minus Baseline value.

Mean Change From Baseline in Maximal Expiratory Flow Rate at 25% (V25) and 50% (V50) of Vital CapacityBaseline and up to Week 52

V25 and V 50 were measured using spirometer. A participant took rest just before the measurement. At each time of measurement, a participant expired for at least 6 seconds wherever possible. At each time of measurement, at least 3 readings were obtained, and three readings which were obtained in an appropriate manner were stored. Baseline value was the value measured at visit 2. However, when the value at Visit 2 was missing, the value at Visit 1 was used as baseline. Change from Baseline was any post Baseline value minus Baseline value.

Change From Baseline in Symptom Score With Respect to Breathlessness, Cough, Sputum and Nighttime AwakeningsBaseline and up to Week 52

A participant recorded scores on the scale of 0 to 4 for breathlessness and nighttime awakenings, where 0 indicated no symptoms and 4 indicated severe symptoms; on the scale of 0 to 3 for cough and sputum production, where 0 indicated no symptoms and 3 indicated severe symptoms, in the 24 hours prior to each entry in the COPD diary. Baseline was mean value of the consecutive 7 days just before Visit2. Change from Baseline was any post Baseline value minus Baseline value.

Median Time of Observed Maximum Plasma Concentration (Tmax) of FPWithin one hour prior to dosing, 30, 45 minutes, 1, 2, 3, 4, 6, 8 and 12 hours

For analysis of PK parameters for FP, blood samples were taken just before dosing (within one hour prior to dosing), 30, 45 minutes, 1, 2, 3, 4, 6, 8 and 12 hours after dosing to determine plasma drug concentrations. The investigational product was taken in fasting condition just before each blood sampling. Parameters were calculated by a model-independent method with the plasma concentration-time profile data in individual participants.

Median Tmax of SalmeterolWithin one hour prior to dosing, 5, 15, 30, 45 minutes, 1, 2, 3 and 4 hours

For analysis of PK parameters for salmeterol, blood samples were taken just before dosing (within one hour prior to dosing), 5, 15, 30, 45 minutes, 1, 2, 3 and 4 hours after dosing to determine plasma drug concentrations. The investigational product was taken in fasting condition just before each blood sampling. Parameters were calculated by a model-independent method with the plasma concentration-time profile data in individual participants.

Number of Participants With Abnormal (Shift From Baseline) Urinalysis ParametersUp to Week 56

Urinalysis parameters: Urine protein, Glucose and Urobilinogen were presented as shift from Baseline. Only number of participants with urinalysis values more than Baseline values were presented. The plus sign increases with a higher level of glucose and proteins in the urine: 1+: slightly positive, 2+: positive, 3+: high positive and 4+: strongly positive.

Mean Level of Plasma Cortisol 2Up to Week 56

On each assessment day at Week 24, 52 and follow up, adrenal cortical function tests were performed between 8:00-10:00 in the morning. Additional measurements were taken at follow up visit, if the measurements made at Week 52 revealed any abnormalities of clinical significance. Blood samples were taken from participants at rest before undergoing spirometry.

Mean Change From Baseline in Bone Mineral Density (BMD)Baseline and up to Week 56

On each assessment day at Week 52 and follow up, lumber (L1-L4) BMD was determined with a BMD meter by the dual energy X-ray absorption (DEXA) method. Baseline value was the measurement taken during run-in period. Change from Baseline was any value post Baseline minus value at Baseline.

Mean Change From Baseline in Percent of Days Without Use of Rescue MedicationBaseline and up to Week 52

Rescue medication (salbutamol sulfate aerosol provided as an investigational product) was issued to a participant and, when necessary, a spacer at the start of the run-in period. At each time of entry in the Chronic Obstructive Pulmonary Disease (COPD) diary, a participant recorded the number of occasions of rescue medication inhaled in the previous 24 hours in the COPD diary. Baseline was mean value of the consecutive 7 days just before Visit 2. Change from Baseline was any post Baseline value minus Baseline value.

Mean Area Under the Plasma Concentration-time Curve From Zero up to the Last Quantifiable Plasma Concentration [AUC (0-t)] of SalmeterolWithin one hour prior to dosing, 5, 15, 30, 45 minutes, 1, 2, 3 and 4 hours

For analysis of PK parameters for salmeterol, blood samples were taken just before dosing (within one hour prior to dosing), 5, 15, 30, 45 minutes, 1, 2, 3 and 4 hours after dosing to determine plasma drug concentrations. The investigational product was taken in fasting condition just before each blood sampling. Parameters were calculated by a model-independent method with the plasma concentration-time profile data in individual participants.

Number of Participants With Abnormal (Outliers From the Normal Range) Hematology ParametersUp to Week 56

Hematology parameters: Red blood cells (RBC), Hemoglobin (Hb), Hematocrit, Platelet count (PC), White blood cells (WBC), Basophils, Eosinophils, Neutrophils, Lymphocytes and Monocytes were presented as the outliers from the normal range as \> upper limit and \< lower limit. Only number of participants with hematology values outside normal range were presented.

Number of Participants With Abnormal (Clinically Significant) Electrocardiogram (ECG) FindingsUp to Week 56

On each assessment day at Week 24, 52 and follow up 12-lead ECG was performed. Additional measurements were taken at follow up visit, if the measurements made at Week 52 revealed any abnormalities of clinical significance.

Number of Participants With Abnormal (Clinically Significant) Ophthalmological Examinations FindingsUp to Week 56

On each assessment day at Week 24, 52 and follow up, ophthalmological examinations (vision, cornea, lens, intraocular pressure, fundus oculi) were performed to determine the presence or absence of glaucoma and cataract.

Mean Change From Baseline in Peak Expiratory Flow (PEF)Baseline and up to Week 52

PEF was the maximum speed of expiration measured using spirometer. A participant took rest just before the measurement. At each time of measurement, a participant expired for at least 6 seconds wherever possible. At each time of measurement, at least 3 readings were obtained, and three readings which were obtained in an appropriate manner were stored. Baseline value was the value measured at visit 2. However, when the value at Visit 2 was missing, the value at Visit 1 was used as Baseline. Change from Baseline was any post Baseline value minus Baseline value.

Mean Cmax of SalmeterolWithin one hour prior to dosing, 5, 15, 30, 45 minutes, 1, 2, 3 and 4 hours

For analysis of PK parameters for salmeterol, blood samples were taken just before dosing (within one hour prior to dosing), 5, 15, 30, 45 minutes, 1, 2, 3 and 4 hours after dosing to determine plasma drug concentrations. The investigational product was taken in fasting condition just before each blood sampling. Parameters were calculated by a model-independent method with the plasma concentration-time profile data in individual participants.

Mean Area Under the Plasma Concentration-time Curve Over a Dosing Interval [AUC(0-tau)] of FPWithin one hour prior to dosing, 30, 45 minutes, 1, 2, 3, 4, 6, 8 and 12 hours

For analysis of PK parameters for FP, blood samples were taken just before dosing (within one hour prior to dosing), 30, 45 minutes, 1, 2, 3, 4, 6, 8 and 12 hours after dosing to determine plasma drug concentrations. The investigational product was taken in fasting condition just before each blood sampling. Parameters were calculated by a model-independent method with the plasma concentration-time profile data in individual participants.

Number of Participants With Abnormal (Outliers From the Normal Range) Clinical Chemistry ParametersUp to Week 56

Clinical chemistry parameters: Total bilirubin (TB), Alkaline phosphatase (Al-P), Alanine aminotransferase (ALT), Asparate aminotransferase (AST), Gamma-glutamyl transpeptidase (GTP), Lactate dehydrogenase (LDH), Total cholesterol (TC), Glucose, Creatinine, Blood urea nitrogen (BUN), Uric acid (UA), Sodium (Na), Potassium (K), Chloride (Cl) and Calcium (Ca) were presented as the outliers from the normal range as \> upper limit and \< lower limit. Only number of participants with clinical chemistry values outside normal range were presented.

Mean Change From Baseline in Pulse RateBaseline and up to Week 56

Pulse rate was measured in sitting position. Baseline value was the measurement taken at the start of run-in or the treatment period. Change from Baseline was any post Baseline value minus value at Baseline.

Number of Participants With Abnormal Oropharyngeal Examination FindingsUp to Week 56

Oropharyngeal examination was performed in participants with suspected oral infection (candidiasis).

Mean Frequency of Moderate and Severe Chronic Obstructive Pulmonary Disease (COPD) ExacerbationsUp to Week 56

An exacerbation was defined as worsening of the participant's symptoms of cough, sputum production and breathlessness requiring a change in medication. When a moderate or severe COPD exacerbation was observed, details (date of onset, outcome, date of resolution/death, severity, medications provided for treatment, whether the COPD exacerbation required hospitalization, whether the COPD exacerbation required participant withdrawal from the study) were recorded.

Mean Observed Maximum Plasma Concentration (Cmax) of Fluticasone Propionate (FP)Within one hour prior to dosing, 30, 45 minutes, 1, 2, 3, 4, 6, 8 and 12 hours

For analysis of pharmacokinetic (PK) parameters for FP, blood samples were taken just before dosing (within one hour prior to dosing), 30, 45 minutes, 1, 2, 3, 4, 6, 8 and 12 hours after dosing to determine plasma drug concentrations. The investigational product was taken in fasting condition just before each blood sampling. Parameters were calculated by a model-independent method with the plasma concentration-time profile data in individual participants.

Trial Locations

Locations (1)

GSK Investigational Site

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