A Double-Blind, Randomized, Placebo-Controlled, Multicenter, Parallel-Group, Dose-Ranging Study of MK-0873 in Patients With COPD
Overview
- Phase
- Phase 2
- Intervention
- MK-0873 2.5 mg
- Conditions
- Lung Diseases
- Sponsor
- Merck Sharp & Dohme LLC
- Enrollment
- 604
- Primary Endpoint
- Change From Baseline in Pre-dose (Trough) Forced Expiratory Volume in 1 Second (FEV1)
- Status
- Terminated
- Last Updated
- 7 years ago
Overview
Brief Summary
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
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.
Investigators
Eligibility Criteria
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)
Arms & Interventions
MK-0873 2.5 mg
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)
Intervention: MK-0873 2.5 mg
MK-0873 2.5 mg
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)
Intervention: Placebo to MK-0873
MK-0873 1.25 mg
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)
Intervention: MK-0873 1.25 mg
MK-0873 1.25 mg
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)
Intervention: Placebo to MK-0873
MK-0873 0.75 mg
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)
Intervention: MK-0873 0.75 mg
MK-0873 0.75 mg
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)
Intervention: Placebo to MK-0873
Placebo
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)
Intervention: Placebo to MK-0873
MK-0873 2.5 mg + Usual Care
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)
Intervention: MK-0873 2.5 mg
MK-0873 2.5 mg + Usual Care
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)
Intervention: Usual Care
Usual Care
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)
Intervention: Usual Care
Outcomes
Primary Outcomes
Change From Baseline in Pre-dose (Trough) Forced Expiratory Volume in 1 Second (FEV1)
Time Frame: Pre-dose at Baseline and Treatment Weeks 8, 10 and 12
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.
Secondary Outcomes
- Change From Baseline in Total Daily Beta-agonist Use(Baseline and Treatment Weeks 8, 10 and 12)
- Change From Baseline in Overall Daytime Symptoms Score(Baseline and Treatment Weeks 8, 10 and 12)
- Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) Response(Baseline and Treatment Weeks 8 and 12)
- Transition Dyspnea Index (TDI) Focal Score(Baseline and Treatment Week 12)
- Change From Baseline in Shortness of Breath Questionnaire (SOBQ) Response(Baseline and Treatment Weeks 8 and 12)
- Number of Participants With at Least One Chronic Obstructive Pulmonary Disease (COPD) Exacerbation(Baseline through Treatment Week 12)
- Change From Baseline in Predose (Trough) Forced Vital Capacity (FVC)(Predose at Baseline and Treatment Weeks 8, 10 and 12)