Peripheral Vascular Diseases
Conditions
Brief summary
A 12-Week Efficacy Study in participants with Peripheral Arterial Disease. the primary hypothesis is that MK-0736 7 mg administered once daily for 12 weeks will result in a decrease in lower extremity atherosclerotic plaque macrophage content when compared to placebo (an approximate decrease of up to 30% is expected).
Interventions
DRUGMK-0736
MK-0736; 7mg once daily, orally at approximately the same time each morning for 12 weeks.
DRUGComparator: placebo (unspecified)
Matching Placebo once daily, orally at approximately the same time each morning for 12 weeks.
Sponsors
FoxHollow Technologies
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Participants with peripheral arterial disease * Participants must be 18 to 85 years of age * Females must be postmenopausal or sterile
Exclusion criteria
* Participans with hepatic, HIV, endocrine, connective tissue, psychiatric disorders or uncontrolled hypertension
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Cluster of Differentiation 68 (CD68) | Baseline and Week 12 | CD68 is a heavily glycosylated transmembrane protein resident to macrophage lysosomes, and is the standard immunohistochemical (IHC) marker for macrophages in human tissues. CD68 protein content as a measure of macrophage number is the most often reported marker in clinical studies of plaque instability. Blood samples were taken to determine the level of CD69 present at baseline (predose Day 1) and again after 12 weeks of study drug administration in participants with peripheral arterial disease of the lower extremity who are scheduled for excision of an atherosclerotic plaque. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Messenger Ribonucleic Acid (mRNA) | Baseline and Week 12 | mRNA is a biomarker associated with the inflammatory response. Blood samples were taken to determine the level of mRNA present at baseline (predose Day 1) and again after 12 weeks of study drug administration in participants with peripheral arterial disease of the lower extremity who are scheduled for excision of an atherosclerotic plaque. |
| Number of Participants Who Were Discontinued From the Study Due to an Adverse Event (AE) | up to 14 weeks | An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the study drug. Any worsening of a preexisting condition which is temporally associated with the use of the study drug is also an AE. The percentage of participants who were discontinued from the study due to an AE was summarized. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MK-0736 Participants will be orally administered 7 mg of MK-0736 once daily for 12 weeks | 8 |
| Placebo Participants will be orally administered placebo once daily for 12 weeks. | 6 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Other | 0 | 3 |
| Overall Study | Study Terminated | 2 | 1 |
Baseline characteristics
| Characteristic | MK-0736 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 67.6 years STANDARD_DEVIATION 7.4 | 70.8 years STANDARD_DEVIATION 8.6 | 69.0 years STANDARD_DEVIATION 7.82 |
| Sex: Female, Male Female | 5 Participants | 2 Participants | 7 Participants |
| Sex: Female, Male Male | 3 Participants | 4 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 8 | 4 / 6 |
| serious Total, serious adverse events | 1 / 8 | 1 / 6 |
Outcome results
Primary
Change From Baseline in Cluster of Differentiation 68 (CD68)
CD68 is a heavily glycosylated transmembrane protein resident to macrophage lysosomes, and is the standard immunohistochemical (IHC) marker for macrophages in human tissues. CD68 protein content as a measure of macrophage number is the most often reported marker in clinical studies of plaque instability. Blood samples were taken to determine the level of CD69 present at baseline (predose Day 1) and again after 12 weeks of study drug administration in participants with peripheral arterial disease of the lower extremity who are scheduled for excision of an atherosclerotic plaque.
Time frame: Baseline and Week 12
Population: Study terminated early. Planned analyses was not performed.
Secondary
Change From Baseline in Messenger Ribonucleic Acid (mRNA)
mRNA is a biomarker associated with the inflammatory response. Blood samples were taken to determine the level of mRNA present at baseline (predose Day 1) and again after 12 weeks of study drug administration in participants with peripheral arterial disease of the lower extremity who are scheduled for excision of an atherosclerotic plaque.
Time frame: Baseline and Week 12
Population: Study terminated early. Planned analyses was not performed.
Secondary
Number of Participants Who Were Discontinued From the Study Due to an Adverse Event (AE)
An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the study drug. Any worsening of a preexisting condition which is temporally associated with the use of the study drug is also an AE. The percentage of participants who were discontinued from the study due to an AE was summarized.
Time frame: up to 14 weeks
Population: All enrolled participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK-0736 | Number of Participants Who Were Discontinued From the Study Due to an Adverse Event (AE) | 0 Particpants |
| Placebo | Number of Participants Who Were Discontinued From the Study Due to an Adverse Event (AE) | 1 Particpants |