An Investigational Drug Study In Patients With COPD (Chronic Obstructive Pulmonary Disease) (MK-0873-005)

Study Overview
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Brief Summary
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This is a study to evaluate the effectiveness and tolerability of a once-daily oral medication (MK-0873) for the treatment of COPD (chronic obstructive pulmonary disease) to determine whether the study drug leads to an improvement in pulmonary (lung) function, as well as symptoms, and quality of life.

Detailed Description
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Following a three-week run-in period (Period I) during which participants received placebo, participants entered into a 12-week double-blind treatment period (Period II) during which they received daily doses of either one of three doses of MK-0873 or placebo. Period I and Period II made up the Base Study. Following the 12-week treatment period in the Base Study, participants were invited to continue in an optional 12-week double-blind extension study (Period III, EXT1). Participants who received any dose of MK-0873 in the Base Study continued on MK-0873 2.5 mg daily in Period III while participants in the placebo arm of the Base Study continued on placebo daily. Following EXT1, participants were invited to continue in an optional open-label second extension study (EXT2) which was to last 80 weeks (Period IV: 28 weeks, Period V: 52 weeks). In EXT2, participants who had been taking MK-0873 2.5 mg in the Base Study were allocated to MK-0873 2.5 mg plus usual care, while participants who had been taking the other two doses of MK-0873 or placebo in the Base Study were allocated to either MK-0873 2.5 mg plus usual care or to usual care alone.

Official Title
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A Double-Blind, Randomized, Placebo-Controlled, Multicenter, Parallel-Group, Dose-Ranging Study of MK-0873 in Patients With COPD

Conditions
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Lung Diseases, Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Drug: MK-0873 2.5 mg
* Drug: MK-0873 1.25 mg
* Drug: MK-0873 0.75 mg
* Drug: Placebo to MK-0873
* Drug: Usual Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females, 40 to 75 years old, with a history consistent with COPD (chronic obstructive pulmonary disease) Lung function tests that meet the requirements of the study Exclusion Criteria: Severe and unstable medical conditions other than COPD (chronic obstructive pulmonary disease) Use of continuous oxygen therapy Cardiac (heart) arrhythmias Other lung disease History of colitis (inflammation of the colon)

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MK-0873 2.5 mg<br>Participants receive placebo tablets once daily for 3 weeks in Period I (Base), MK-0873 2.5 mg tablets once daily for 12 weeks in Period II (Base) and MK-0873 2.5 mg tablets once daily for 12 weeks in Period III (EXT1) | Drug: MK-0873 2.5 mg<br> <br> Drug: Placebo to MK-0873<br> <br> |
| Experimental: MK-0873 1.25 mg<br>Participants receive placebo tablets once daily for 3 weeks in Period I (Base), MK-0873 1.25 mg tablets once daily for 12 weeks in Period II (Base) and MK-0873 2.5 mg tablets once daily for 12 weeks in Period III (EXT1) | Drug: MK-0873 1.25 mg<br> <br> Drug: Placebo to MK-0873<br> <br> |
| Experimental: MK-0873 0.75 mg<br>Participants receive placebo tablets once daily for 3 weeks in Period I (Base), MK-0873 0.75 mg tablets once daily for 12 weeks in Period II (Base) and MK-0873 2.5 mg tablets once daily for 12 weeks in Period III (EXT1) | Drug: MK-0873 0.75 mg<br> <br> Drug: Placebo to MK-0873<br> <br> |
| Placebo Comparator: Placebo<br>Participants receive placebo tablets once daily for 3 weeks in Period I (Base), placebo tablets once daily for 12 weeks in Period II (Base) and placebo tablets once daily for 12 weeks in Period III (EXT1) | Drug: Placebo to MK-0873<br> <br> |
| Experimental: MK-0873 2.5 mg + Usual Care<br>Participants receive MK-0873 2.5 mg tablets once daily plus usual care (inhaled short- or long-acting beta-agonists, inhaled corticosteroids, or short- or long-acting anticholinergics) for 28 weeks during Periods IV and V (EXT2) | Drug: MK-0873 2.5 mg<br> <br> Drug: Usual Care<br> <br> |
| Active Comparator: Usual Care<br>Participants receive usual care (inhaled short- or long-acting beta-agonists, inhaled corticosteroids, or short- or long-acting anticholinergics) for 28 weeks during Periods IV and V (EXT2) | Drug: Usual Care<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Pre-dose (Trough) Forced Expiratory Volume in 1 Second (FEV1) | FEV1 is a measure, in liters, of the amount of air expired in 1 second. Measured values were averaged during the placebo run-in period for baseline and over the last 4 weeks of the 12-week treatment period for on-treatment. For participants who did not have any measurements over the last 4 weeks of the 12-week treatment period, the last available on-treatment measurement was carried forward. | Pre-dose at Baseline and Treatment Weeks 8, 10 and 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Overall Daytime Symptoms Score | On a daily diary card, participants rated their responses to the question Overall, how much of the time did you have symptoms from your lung disease today? (0=none of the time; 5=all of the time). Scores range from 0 to 5, with higher scores indicating more time with symptoms. The overall daytime symptoms score value was the mean daily diary score during the placebo run-in period for baseline and over the last 4 weeks of the 12-week treatment period for on-treatment. | Baseline and Treatment Weeks 8, 10 and 12 | 
| Change From Baseline in Total Daily Beta-agonist Use | The total daily beta-agonist use was measured in puffs per day and was recorded on daily diary cards by participants. It is defined as the sum of beta-agonist use between when participants arose from and went to bed. The total daily beta-agonist use values were the recorded mean during the placebo run-in period for baseline and over the last 4 weeks of the 12-week treatment period for on-treatment. | Baseline and Treatment Weeks 8, 10 and 12 | 
| Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) Response | The SGRQ consists of 76 items in 3 domains: Symptoms (frequency and severity), Activity (activities that cause or are limited by breathlessness) and Impacts (social functioning, psychological disturbances resulting from airways disease). Scores for each domain and a total score are calculated; each questionnaire response has a unique empirically dervied weight. Scores range from 0 to 100, with higher scores indicating poor health. Each domain of the questionnaire is scored separately in 2 steps: 1) The weights for all items with a positive response are summed; 2) The score is calculated by dividing the summed weights by the maximum possible weight for that domain and expressing the results as a percentage. The mean SGRQ scores were calculated during the placebo run-in period for baseline and over the last 4 weeks of the 12-week treatment period for on-treatment. | Baseline and Treatment Weeks 8 and 12 | 
| Transition Dyspnea Index (TDI) Focal Score | The baseline dyspnea index (BDI) was measured at the randomization visit as a 3-domain score with a scale of 0 to 4 in each domain, with a total focal score of 12 indicating no dyspnea limitation and 0 indicating severe dyspnea. After 12 weeks of treatment, the investigator-administered TDI was completed, with a change in each of the 3 domains being rated from -3 (major deterioration) to +3 (major improvement), so that the TDI focal score could range from -9 to +9. A higher TDI focal score indicates improvement. | Baseline and Treatment Week 12 | 
| Change From Baseline in Shortness of Breath Questionnaire (SOBQ) Response | The SOBQ is a validated 24-item measure of dyspnea associated with activities of daily living in patients with moderate to severe chronic lung disease. Twenty-one items ask patients about how frequently they experience shortness of breath (SOB) on a 6-point scale of 0 (never) to 5 (activity given up due to dyspnea) when performing various tasks. Three additional questions about limitations due to SOB, fear of harm from overexertion and fear of SOB are included for a total of 24 items. If patients do not routinely perform the activity indicated in the questionnaire, they are asked to estimate the degree of SOB anticipated. The SOBQ total score is calculated by summing responses across all 24 items. The total score ranges from 0 to 120, with a higher score indicating greater frequency of and limitations due to SOB. The score assessed at the baseline visit was used for the baseline score and the mean score assessed at Treatment Weeks 8 and 12 was used as the on-treatment score. | Baseline and Treatment Weeks 8 and 12 | 
| Number of Participants With at Least One Chronic Obstructive Pulmonary Disease (COPD) Exacerbation | COPD exacerbation is defined as any change in symptoms or functional status that leads to administration (at investigator's discretion) of systemic corticosteroids (above participant's usual dose) and/or antibiotics, or an unscheduled COPD-related hospitalization, emergency room visit, or doctor visit. The number of participants who experienced at least one COPD exacerbation during the 12-week treatment period is reported. | Baseline through Treatment Week 12 | 
| Change From Baseline in Predose (Trough) Forced Vital Capacity (FVC) | FVC is a measure, in liters and using a spirometer, of the amount of air forcibly exhaled from the lungs after taking the deepest breath possible. The values averaged during the placebo run-in period were used for the baseline measurement and the values averaged over Treatment Weeks 8, 10 and 12 were used for the on-treatment measurement. A higher value indicates greater lung exiratory function. | Predose at Baseline and Treatment Weeks 8, 10 and 12 |