Pulmonary Disease, Chronic Obstructive
Conditions
Keywords
Osteoporosis, Bone Mineral Density, Osteopenia, Chronic Obstructive Pulmonary Disease, COPD
Brief summary
This study will last up to 3 years. You will visit the clinic up to 14 times. Certain visits will include lung function tests and scans of your bones. The purpose of this study is to determine the effect of the steroid component of an inhaled product on bone mineral density in patients with Chronic Obstructive Pulmonary Disease (COPD).
Interventions
DRUGSalmeterol 50 mcg BID
Salmeterol xinafoate 50 mcg strength DISKUS inhaler (formulated with lactose), BID in the morning and evening.
DRUGFluticasone Propionate/Salmeterol 250/50 mcg BID
Fluticasone propionate/salmeterol xinafoate combination product 250/50mcg strength DISKUS inhaler (formulated with lactose), BID in the morning and evening.
DEVICEDISKUS inhaler
Each participant received study medication via the DISKUS, for one of two possible treatment groups. Each DISKUS contained 60 doses of study medication. Participants were instructed to administer medication BID (one inhalation in the morning and one inhalation in the evening) approximately 12 hours apart for 156-week treatment period.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Established clinical history of COPD. * Baseline FEV1 \<70% predicted normal, and FEV1/FVC ratio of less than 70%. * Smoking history of at least 10 pack-years, where both current and former smokers will be eligible. * Must have at least one native, evaluable hip.
Exclusion criteria
* History of or evidence for metabolic bone diseases other than osteoporosis or osteopenia.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Bone Mineral Density (BMD) at the Lumbar Spine L1-L4 | Baseline and Week 26, 52, 78, 104, 130, and 156 | BMD, a measure of bone density, reflecting the strength of bones as represented by calcium content. The BMD test detects osteopenia (mild bone loss) and osteoporosis (more severe bone loss, which may cause symptoms). BMD at the lumber spine (L1-L4) was measured via dual energy x-ray absorptiometry (DEXA) (using DEXA equipment) scans at Baseline and every 26 weeks during the study. Acceptable DEXA measurements must be conducted prior to the first dose of randomized study medication. Baseline was defined as the collections taken on Day 1 of treatment period. Change from Baseline was calculated by subtracting the Baseline value from indicated time point value. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in BMD at the Total Hip | Baseline and Week 26, 52, 78, 104, 130, and 156 | BMD, a measure of bone density, reflecting the strength of bones as represented by calcium content. The BMD test detects osteopenia (mild bone loss) and osteoporosis (more severe bone loss, which may cause symptoms).BMD at the total hip was measured via dual energy x-ray absorptiometry (DEXA) (using DEXA equipment) scans at Baseline and every 26 weeks during the study. Acceptable DEXA measurements must be conducted prior to the first dose of randomized study medication. Baseline was defined as the collections taken on day 1 of treatment period. Change from Baseline was calculated by subtracting the Baseline value from indicated time point value. |
Countries
United States
Participant flow
Recruitment details
Total 186 participants, with chronic obstructive pulmonary disease (COPD) were randomized at 31 centers in the United States. Study duration was 14-21 day Single-Blind Run-In period, 156-week treatment period and follow-up phone contact within 2 weeks of treatment stop.
Pre-assignment details
A total of 247 participants were screened for this study, of whom 61 were screen failures and 186 participants were randomized in the study.
Participants by arm
| Arm | Count |
|---|---|
| Salmeterol 50 mcg BID Participants randomized to this arm received salmeterol 50 mcg, formulated with lactose via the DISKUS inhaler one inhalation BID one inhalation in the morning and one inhalation in the evening for 156 Weeks. Each DISKUS contained 60 doses of study medication. Participant were provided with albuterol/salbutamol as relief medication. | 94 |
| Fluticasone Propionate/Salmeterol 250/50 mcg BID Participants randomized to this arm received Fluticasone propionate/salmeterol combination product 250/50 mcg, formulated with lactose via the DISKUS inhaler one inhalation BID, one inhalation in the morning and one inhalation in the evening for 156 Weeks. Each DISKUS contained 60 doses of study medication. Participant were provided with albuterol/salbutamol as relief medication. | 92 |
| Total | 186 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 13 | 15 |
| Overall Study | COPD exacerbation | 1 | 1 |
| Overall Study | Dispensed wrong study drug kit | 1 | 0 |
| Overall Study | Lost to Follow-up | 4 | 2 |
| Overall Study | Non-compliance with Dexa scans | 1 | 0 |
| Overall Study | Overcompliant-PI discretion | 1 | 0 |
| Overall Study | Participant discontinued study drug | 0 | 1 |
| Overall Study | Participant relocated | 0 | 1 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Sponsor terminated study | 2 | 2 |
| Overall Study | Study management | 0 | 1 |
| Overall Study | Use of prohibited medication | 1 | 0 |
| Overall Study | Use of protocol excluded medication | 0 | 1 |
| Overall Study | Withdrawal by participant and physician | 1 | 0 |
| Overall Study | Withdrawal by Subject | 14 | 11 |
Baseline characteristics
| Characteristic | Salmeterol 50 mcg BID | Fluticasone Propionate/Salmeterol 250/50 mcg BID | Total |
|---|---|---|---|
| Age, Continuous | 65.9 Years STANDARD_DEVIATION 9.52 | 65.4 Years STANDARD_DEVIATION 8.36 | 65.6 Years STANDARD_DEVIATION 8.94 |
| Race/Ethnicity, Customized Race American Hispanic | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Black | 1 Participants | 4 Participants | 5 Participants |
| Race/Ethnicity, Customized Race South Asian | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Race White/Caucasian | 92 Participants | 87 Participants | 179 Participants |
| Sex: Female, Male Female | 35 Participants | 37 Participants | 72 Participants |
| Sex: Female, Male Male | 59 Participants | 55 Participants | 114 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 7 / 94 | 5 / 92 |
| other Total, other adverse events | 63 / 94 | 72 / 92 |
| serious Total, serious adverse events | 33 / 94 | 32 / 92 |
Outcome results
Primary
Percent Change From Baseline in Bone Mineral Density (BMD) at the Lumbar Spine L1-L4
BMD, a measure of bone density, reflecting the strength of bones as represented by calcium content. The BMD test detects osteopenia (mild bone loss) and osteoporosis (more severe bone loss, which may cause symptoms). BMD at the lumber spine (L1-L4) was measured via dual energy x-ray absorptiometry (DEXA) (using DEXA equipment) scans at Baseline and every 26 weeks during the study. Acceptable DEXA measurements must be conducted prior to the first dose of randomized study medication. Baseline was defined as the collections taken on Day 1 of treatment period. Change from Baseline was calculated by subtracting the Baseline value from indicated time point value.
Time frame: Baseline and Week 26, 52, 78, 104, 130, and 156
Population: The Safety population - Safety population was defined as all randomized participants who are at least 50% compliant with taking study drug and have a post-Baseline BMD scan. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Salmeterol 50 mcg BID | Percent Change From Baseline in Bone Mineral Density (BMD) at the Lumbar Spine L1-L4 | Week 26 | 0.5 Percent Change | Standard Error 0.33 |
| Salmeterol 50 mcg BID | Percent Change From Baseline in Bone Mineral Density (BMD) at the Lumbar Spine L1-L4 | Week 52 | 0.8 Percent Change | Standard Error 0.39 |
| Salmeterol 50 mcg BID | Percent Change From Baseline in Bone Mineral Density (BMD) at the Lumbar Spine L1-L4 | Week 78 | 1.3 Percent Change | Standard Error 0.52 |
| Salmeterol 50 mcg BID | Percent Change From Baseline in Bone Mineral Density (BMD) at the Lumbar Spine L1-L4 | Week 104 | 0.9 Percent Change | Standard Error 0.55 |
| Salmeterol 50 mcg BID | Percent Change From Baseline in Bone Mineral Density (BMD) at the Lumbar Spine L1-L4 | Week 130 | 0.3 Percent Change | Standard Error 0.66 |
| Salmeterol 50 mcg BID | Percent Change From Baseline in Bone Mineral Density (BMD) at the Lumbar Spine L1-L4 | Week 156 | 0.3 Percent Change | Standard Error 0.68 |
| Fluticasone Propionate/Salmeterol 250/50 mcg BID | Percent Change From Baseline in Bone Mineral Density (BMD) at the Lumbar Spine L1-L4 | Week 130 | 1.0 Percent Change | Standard Error 0.81 |
| Fluticasone Propionate/Salmeterol 250/50 mcg BID | Percent Change From Baseline in Bone Mineral Density (BMD) at the Lumbar Spine L1-L4 | Week 26 | 0.2 Percent Change | Standard Error 0.4 |
| Fluticasone Propionate/Salmeterol 250/50 mcg BID | Percent Change From Baseline in Bone Mineral Density (BMD) at the Lumbar Spine L1-L4 | Week 104 | 0.8 Percent Change | Standard Error 0.71 |
| Fluticasone Propionate/Salmeterol 250/50 mcg BID | Percent Change From Baseline in Bone Mineral Density (BMD) at the Lumbar Spine L1-L4 | Week 52 | 1.3 Percent Change | Standard Error 0.43 |
| Fluticasone Propionate/Salmeterol 250/50 mcg BID | Percent Change From Baseline in Bone Mineral Density (BMD) at the Lumbar Spine L1-L4 | Week 156 | 1.9 Percent Change | Standard Error 0.88 |
| Fluticasone Propionate/Salmeterol 250/50 mcg BID | Percent Change From Baseline in Bone Mineral Density (BMD) at the Lumbar Spine L1-L4 | Week 78 | 1.0 Percent Change | Standard Error 0.64 |
Comparison: The analysis is presented for slope estimate calculated for the percent change from Baseline values at Week 26, 52, 78, 104, 130, and 156.95% CI: [0.06, 1.49]
Secondary
Percent Change From Baseline in BMD at the Total Hip
BMD, a measure of bone density, reflecting the strength of bones as represented by calcium content. The BMD test detects osteopenia (mild bone loss) and osteoporosis (more severe bone loss, which may cause symptoms).BMD at the total hip was measured via dual energy x-ray absorptiometry (DEXA) (using DEXA equipment) scans at Baseline and every 26 weeks during the study. Acceptable DEXA measurements must be conducted prior to the first dose of randomized study medication. Baseline was defined as the collections taken on day 1 of treatment period. Change from Baseline was calculated by subtracting the Baseline value from indicated time point value.
Time frame: Baseline and Week 26, 52, 78, 104, 130, and 156
Population: Safety Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Salmeterol 50 mcg BID | Percent Change From Baseline in BMD at the Total Hip | Week 26 | -0.3 Percent Change | Standard Error 0.28 |
| Salmeterol 50 mcg BID | Percent Change From Baseline in BMD at the Total Hip | Week 52 | -0.5 Percent Change | Standard Error 0.32 |
| Salmeterol 50 mcg BID | Percent Change From Baseline in BMD at the Total Hip | Week 78 | -0.8 Percent Change | Standard Error 0.45 |
| Salmeterol 50 mcg BID | Percent Change From Baseline in BMD at the Total Hip | Week 104 | -1.1 Percent Change | Standard Error 0.46 |
| Salmeterol 50 mcg BID | Percent Change From Baseline in BMD at the Total Hip | Week 130 | -1.7 Percent Change | Standard Error 0.47 |
| Salmeterol 50 mcg BID | Percent Change From Baseline in BMD at the Total Hip | Week 156 | -1.8 Percent Change | Standard Error 0.57 |
| Fluticasone Propionate/Salmeterol 250/50 mcg BID | Percent Change From Baseline in BMD at the Total Hip | Week 130 | -2.7 Percent Change | Standard Error 0.44 |
| Fluticasone Propionate/Salmeterol 250/50 mcg BID | Percent Change From Baseline in BMD at the Total Hip | Week 26 | -0.4 Percent Change | Standard Error 0.31 |
| Fluticasone Propionate/Salmeterol 250/50 mcg BID | Percent Change From Baseline in BMD at the Total Hip | Week 104 | -2.6 Percent Change | Standard Error 0.5 |
| Fluticasone Propionate/Salmeterol 250/50 mcg BID | Percent Change From Baseline in BMD at the Total Hip | Week 52 | -1.4 Percent Change | Standard Error 0.35 |
| Fluticasone Propionate/Salmeterol 250/50 mcg BID | Percent Change From Baseline in BMD at the Total Hip | Week 156 | -2.9 Percent Change | Standard Error 0.46 |
| Fluticasone Propionate/Salmeterol 250/50 mcg BID | Percent Change From Baseline in BMD at the Total Hip | Week 78 | -2.1 Percent Change | Standard Error 0.46 |
Comparison: The analysis is presented for slope estimate calculated for the percent change from Baseline values at Week 26, 52, 78, 104, 130, and 156.95% CI: [-0.78, 0.24]