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

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

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00132730

Enrollment

604

Registered

2005-08-22

Start date

2004-06-01

Completion date

2005-08-17

Last updated

2018-10-12

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Lung Diseases, Pulmonary Disease, Chronic Obstructive

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.

Interventions

DRUGMK-0873 2.5 mg

DRUGMK-0873 1.25 mg

DRUGMK-0873 0.75 mg

DRUGPlacebo to MK-0873

DRUGUsual Care

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

40 Years to 75 Years

Healthy volunteers

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)

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline in Pre-dose (Trough) Forced Expiratory Volume in 1 Second (FEV1)	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

Measure	Time frame	Description
Change From Baseline in Total Daily Beta-agonist Use	Baseline and Treatment Weeks 8, 10 and 12	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.
Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) Response	Baseline and Treatment Weeks 8 and 12	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.
Transition Dyspnea Index (TDI) Focal Score	Baseline and Treatment Week 12	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.
Change From Baseline in Overall Daytime Symptoms Score	Baseline and Treatment Weeks 8, 10 and 12	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.
Number of Participants With at Least One Chronic Obstructive Pulmonary Disease (COPD) Exacerbation	Baseline through Treatment Week 12	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.
Change From Baseline in Predose (Trough) Forced Vital Capacity (FVC)	Predose at Baseline and Treatment Weeks 8, 10 and 12	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.
Change From Baseline in Shortness of Breath Questionnaire (SOBQ) Response	Baseline and Treatment Weeks 8 and 12	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.

Participant flow

Participants by arm

Arm	Count
MK-0873 0.75 mg Base Study 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)	150
MK-0873 1.25 mg Base Study 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)	148
MK-0873 2.5 mg Base Study 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)	153
Placebo Base Study 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)	153
Total	604

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004	FG005
Period II - 12-week Treatment (Base)	Clinical adverse experience	11	4	9	9	0	0
Period II - 12-week Treatment (Base)	Laboratory adverse experience	1	1	0	0	0	0
Period II - 12-week Treatment (Base)	Other reasons	11	10	9	13	0	0
Period III - Blinded Extension (EXT1)	Clinical adverse experience	0	0	11	1	0	0
Period III - Blinded Extension (EXT1)	Laboratory adverse experience	0	0	0	1	0	0
Period III - Blinded Extension (EXT1)	Other reasons	0	0	14	3	0	0
Period III - Blinded Extension (EXT1)	Site terminated	0	0	57	20	0	0
Period IV - Open-label Extension (EXT2)	Clinical adverse experience	0	0	0	0	3	0
Period IV - Open-label Extension (EXT2)	Laboratory adverse experience	0	0	0	0	1	0
Period IV - Open-label Extension (EXT2)	Other reasons	0	0	0	0	6	0
Period IV - Open-label Extension (EXT2)	Site terminated	0	0	0	0	169	68
Period V - Open-label Extension (EXT2)	Site terminated	0	0	0	0	7	2

Baseline characteristics

Characteristic	MK-0873 0.75 mg Base Study	MK-0873 1.25 mg Base Study	MK-0873 2.5 mg Base Study	Placebo Base Study	Total
Age, Customized	150 participants	148 participants	153 participants	153 participants	604 participants
Sex: Female, Male Female	36 Participants	45 Participants	45 Participants	41 Participants	167 Participants
Sex: Female, Male Male	114 Participants	103 Participants	108 Participants	112 Participants	437 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk	EG007 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —	— / —	— / —	— / —	— / —
other Total, other adverse events	47 / 150	42 / 148	66 / 153	43 / 153	72 / 317	19 / 107	37 / 187	11 / 71
serious Total, serious adverse events	10 / 150	11 / 148	10 / 153	6 / 153	17 / 317	4 / 107	9 / 187	5 / 71

Outcome results

Primary

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.

Time frame: Pre-dose at Baseline and Treatment Weeks 8, 10 and 12

Population: The modified intention-to-treat (ITT) population includes all participants who had a baseline and at least one posttreatment measurement.

Arm	Measure	Value (LEAST_SQUARES_MEAN)
MK-0873 0.75 mg Base Study	Change From Baseline in Pre-dose (Trough) Forced Expiratory Volume in 1 Second (FEV1)	-0.005 liters
MK-0873 1.25 mg Base Study	Change From Baseline in Pre-dose (Trough) Forced Expiratory Volume in 1 Second (FEV1)	-0.037 liters
MK-0873 2.5 mg Base Study	Change From Baseline in Pre-dose (Trough) Forced Expiratory Volume in 1 Second (FEV1)	-0.015 liters
Placebo Base Study	Change From Baseline in Pre-dose (Trough) Forced Expiratory Volume in 1 Second (FEV1)	-0.010 liters

Secondary

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.

Time frame: Baseline and Treatment Weeks 8, 10 and 12