Sarcopenia
Conditions
Keywords
Sarcopenia (loss of muscle mass)
Brief summary
A study to evaluate the safety, tolerability, and efficacy of MK-0773 in women with sarcopenia (loss of muscle mass).
Interventions
DRUGComparator: MK-0773
MK-0773 50 mg tablets twice daily, 6 month treatment period
DRUGComparator: Placebo
Placebo tablets twice daily, 6 month treatment period
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
65 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient is a woman who is 65 years of age or older * Patient's lean body mass is at least 1 standard deviation below the mean of a healthy young adult population * Patient has difficulty climbing 10 steps or walking outside on level ground for 1/4 mile without resting or Activity Measure for Post Acute Care (AM-PAC)\<66
Exclusion criteria
* Patient has serious neurological, rheumatologic, cardiac, respiratory, kidney, psychiatric conditions * Patient has a history of certain types of cancer
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Participant Lean Body Mass | Baseline, Month 6 | — |
| Change From Baseline in Bilateral Leg Press (BLP) Measurement | Baseline, Month 6 | BLP measurements were obtained with the participant sitting on the BLP exercise machine with flexed hips and knees. The participant held the handgrips with hips flexion and knees bent at a 90 degree angle and feet placed evenly on the footpad with heels placed approximately shoulder width apart. Participants were asked to slowly push the footpad forward, while keeping the knees slightly flexed, and bend back again slowly for one repetition. The BLP procedure measures the maximum amount of weight that the patient can push through his or her full range of motion one time. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Participant Short Physical Performance Battery (SPPB) | Baseline, Month 6 | The Short Physical Performance Battery (SPPB) is an objective assessment tool for evaluating lower extremity functioning in older persons. The SPPB consists of 3 types of physical maneuvers: balance test, speed gait test, and chair stand test. Results from each maneuvers test are scored on a scale of 0 to 4, with an increasing composite score indicating an improved function level. The total maximum score of SPPB is 12. |
| Change From Baseline in Participant Gait Speed | Baseline, Month 6 | — |
| Change From Baseline in Stair Climbing Power | Baseline, Month 6 | Stair-climbing power is an alternate measure of lower extremity muscle strength. Participants were asked to climb a standardized 4-step flight of stairs. The study coordinator timed how long it took the participant to walk up the stairs as quickly as possible. The test starts when the tester says go and ends when both of the patient's feet are flat on the platform area at the top of the staircase. Participants were permitted to use the railing, and/or an assistive device, if needed. Stair climbing power was calculated as = participant weight × gravity constant × height of stairs / time. |
| Change From Baseline in Activity Measure for Post Acute Care (AM-PAC) Physical Movement Score | Baseline, Month 6 | The Activity Measure for Post Acute Care (AM-PAC) measures function in three domains: basic mobility, daily activities, and applied cognitive function. AM-PAC scores in each functional domain have a mean of 50 with a standard deviation of 10 and scores are distributed along a continuum of function. The AM-PAC tracks outcomes as a participant progresses across an episode of care with higher scores indicating an improved level of functioning. |
Participant flow
Recruitment details
Participants were randomized from 28 sites (2 sites in Mexico, 10 sites in South America, 8 sites in Europe, 5 sites in Asia Pacific, and 3 sites in South Africa).
Pre-assignment details
After a 2-week placebo run-in period, patients were randomized in a 1:1 ratio to receive treatment with either oral MK-0773 50 mg twice daily or matching placebo.
Participants by arm
| Arm | Count |
|---|---|
| MK-0773 MK-0773 was administered orally twice daily (BID) at a dose of 50 mg. | 81 |
| Placebo Placebo administered orally twice daily. | 89 |
| Total | 170 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 8 | 7 |
| Overall Study | Lost to Follow-up | 0 | 2 |
| Overall Study | Physician Decision | 0 | 2 |
| Overall Study | Protocol Violation | 2 | 6 |
| Overall Study | Withdrawal by Subject | 1 | 6 |
Baseline characteristics
| Characteristic | MK-0773 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 75.0 years STANDARD_DEVIATION 6.7 | 76.8 years STANDARD_DEVIATION 7.1 | 75.9 years STANDARD_DEVIATION 6.9 |
| Sex: Female, Male Female | 81 Participants | 89 Participants | 170 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 50 / 81 | 52 / 89 |
| serious Total, serious adverse events | 12 / 81 | 9 / 89 |
Outcome results
Primary
Change From Baseline in Bilateral Leg Press (BLP) Measurement
BLP measurements were obtained with the participant sitting on the BLP exercise machine with flexed hips and knees. The participant held the handgrips with hips flexion and knees bent at a 90 degree angle and feet placed evenly on the footpad with heels placed approximately shoulder width apart. Participants were asked to slowly push the footpad forward, while keeping the knees slightly flexed, and bend back again slowly for one repetition. The BLP procedure measures the maximum amount of weight that the patient can push through his or her full range of motion one time.
Time frame: Baseline, Month 6
Population: N = Number of participants with at least one non-missing measurement at the time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MK-0773 | Change From Baseline in Bilateral Leg Press (BLP) Measurement | 17.42 lbs | Standard Deviation 26.04 |
| Placebo | Change From Baseline in Bilateral Leg Press (BLP) Measurement | 15.95 lbs | Standard Deviation 27.84 |
Primary
Change From Baseline in Participant Lean Body Mass
Time frame: Baseline, Month 6
Population: The full analysis set (FAS) included all participants that received at least one dose of the study therapy and had a post-randomization measurement of lean body mass.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MK-0773 | Change From Baseline in Participant Lean Body Mass | 1.26 kg | Standard Deviation 1.09 |
| Placebo | Change From Baseline in Participant Lean Body Mass | 0.29 kg | Standard Deviation 1.29 |
Secondary
Change From Baseline in Activity Measure for Post Acute Care (AM-PAC) Physical Movement Score
The Activity Measure for Post Acute Care (AM-PAC) measures function in three domains: basic mobility, daily activities, and applied cognitive function. AM-PAC scores in each functional domain have a mean of 50 with a standard deviation of 10 and scores are distributed along a continuum of function. The AM-PAC tracks outcomes as a participant progresses across an episode of care with higher scores indicating an improved level of functioning.
Time frame: Baseline, Month 6
Population: N = Number of patient with at least one non-missing measurement at the time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MK-0773 | Change From Baseline in Activity Measure for Post Acute Care (AM-PAC) Physical Movement Score | Baseline | 59.79 Score on a Scale | Standard Deviation 6.29 |
| MK-0773 | Change From Baseline in Activity Measure for Post Acute Care (AM-PAC) Physical Movement Score | Change from Baseline | 2.52 Score on a Scale | Standard Deviation 4.98 |
| Placebo | Change From Baseline in Activity Measure for Post Acute Care (AM-PAC) Physical Movement Score | Baseline | 59.13 Score on a Scale | Standard Deviation 5.28 |
| Placebo | Change From Baseline in Activity Measure for Post Acute Care (AM-PAC) Physical Movement Score | Change from Baseline | 2.38 Score on a Scale | Standard Deviation 4.55 |
Secondary
Change From Baseline in Participant Gait Speed
Time frame: Baseline, Month 6
Population: N = Number of participants with at least one non-missing measurement at the time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MK-0773 | Change From Baseline in Participant Gait Speed | 6.24 cm/sec | Standard Deviation 17.65 |
| Placebo | Change From Baseline in Participant Gait Speed | 8.91 cm/sec | Standard Deviation 15.05 |
Secondary
Change From Baseline in Participant Short Physical Performance Battery (SPPB)
The Short Physical Performance Battery (SPPB) is an objective assessment tool for evaluating lower extremity functioning in older persons. The SPPB consists of 3 types of physical maneuvers: balance test, speed gait test, and chair stand test. Results from each maneuvers test are scored on a scale of 0 to 4, with an increasing composite score indicating an improved function level. The total maximum score of SPPB is 12.
Time frame: Baseline, Month 6
Population: N = Number of participants with at least one non-missing measurement at the time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MK-0773 | Change From Baseline in Participant Short Physical Performance Battery (SPPB) | 0.92 Score on a Scale | Standard Deviation 1.63 |
| Placebo | Change From Baseline in Participant Short Physical Performance Battery (SPPB) | 0.88 Score on a Scale | Standard Deviation 1.6 |
Secondary
Change From Baseline in Stair Climbing Power
Stair-climbing power is an alternate measure of lower extremity muscle strength. Participants were asked to climb a standardized 4-step flight of stairs. The study coordinator timed how long it took the participant to walk up the stairs as quickly as possible. The test starts when the tester says go and ends when both of the patient's feet are flat on the platform area at the top of the staircase. Participants were permitted to use the railing, and/or an assistive device, if needed. Stair climbing power was calculated as = participant weight × gravity constant × height of stairs / time.
Time frame: Baseline, Month 6
Population: The FAS included all participants that received at least one dose of the study therapy and had a post-randomization stair climbing power measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MK-0773 | Change From Baseline in Stair Climbing Power | 19.68 watts | Standard Deviation 23.85 |
| Placebo | Change From Baseline in Stair Climbing Power | 14.98 watts | Standard Deviation 20.71 |