A Study in Older Participants Who Have Fallen and Have Muscle Weakness

Study Overview
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Brief Summary
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LY2495655 is an investigational drug being tested for muscle wasting.

Official Title
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A Phase 2 Randomized Study to Investigate the Efficacy and Safety of LY2495655 Versus Placebo in Older Patients Who Have Fallen Recently and Have Muscle Weakness

Conditions
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Muscle Weakness

Intervention / Treatment
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* Biological: LY2495655
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Sustained at least 1 fall within 1 calendar year before study screening. Requires ≥12 seconds to perform a repeated chair stands test or is unable to complete this test at screening. Hand grip strength is ≤37 kilograms (kg) for men (81.4 pounds) or ≤21 kg for women (46.2 pounds) at screening. Can stand up from a chair and walk ≥10 meters without human assistance (gait aids such as cane[s], crutches, or walkers are acceptable) at screening. Able to climb at least 1 step on a staircase without human assistance according to the participant at screening (using handrails is allowed). Have screening clinical laboratory test results within normal reference range for the population, or have results with acceptable deviations that are judged to be not clinically significant by the investigator. Exclusion Criteria: Major lower limb pain or neurologic impairment or vestibular vertigo or visual impairment that could severely confound measures of physical performance. Recent lower limb fracture and/or major lower limb surgery. Planned major surgical procedure within 6 months following study drug dosing. Have had a lower extremity amputation of the foot, leg, and/or thigh. Have a body mass index (BMI) ≥35 kilogram per meter squared (kg/m2). Severe vitamin D deficiency. Underlying muscle disease other than age-associated muscle waste or disuse atrophy. Current use or previous use of any drugs known to influence muscle mass or performance. Have had a recent neurologic injury (<6 months before study drug dosing), such as stroke or spinal cord injury. History of a malignant neoplasm in the 18 months before first study drug dosing. Have a history or presence of unstable cardiovascular or pulmonary comorbidities. Have a positive fecal occult blood (FOB) test at screening, or the participant cannot provide a stool sample for FOB testing before first study drug dosing. Have either severe ongoing liver disease or aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2 times upper limit of normal (ULN), alkaline phosphatase (ALP) >1.5 times ULN, or total bilirubin >1.5 times ULN at screening. Have an estimated creatinine clearance <20 milliliters per minute (mL/minute). Have a history of severe allergic reaction to a monoclonal antibody. Are males with a female partner of childbearing potential who do not agree to use contraception during the treatment period of the study and up to 15 weeks after the last dose of investigational product (study drug). Have known allergies to LY2495655, its constituents, or related compounds. Have severe active psychiatric disease or cognitive impairment as assessed by the Mini-Mental State Examination (MMSE) score <22 (for a participant who went to school up to age 15 years or less) or <24 (for a participant who went to school up to at least age 16), making the participant unlikely to understand the informed consent form or comply with protocol procedures. Exhibit excessive consumption of alcohol or abuse of drugs. Have uncontrolled diabetes mellitus. Have had ocular trauma, ophthalmologic surgery, or eye laser treatment within 6 months before study drug dosing. Have hyponatremia (serum sodium levels <135 millimoles/liter ([mmol/L]) at screening unless a retest shows normonatremia before study drug dosing.

Ages Eligible for Study
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Minimum 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: LY2495655<br>Participants received a 315-milligram (mg) dose of LY2495655, administered subcutaneously (SC), every 4 weeks (Q4W) for 20 weeks. | Biological: LY2495655<br>* Administered SC<br>|
| Placebo Comparator: Placebo<br>Participants received a LY2495655-matching dose of placebo, administered SC, Q4W for 20 weeks. | Drug: Placebo<br>* Administered SC<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to 24 Week Endpoint in Appendicular Lean Body Mass (aLBM) | Change from baseline to 24-week endpoint in aLBM, as measured by dual energy x-ray absorptiometry (DEXA), is presented. Least squares (LS) means were calculated using a mixed model repeated measures (MMRM) with treatment, visit, and treatment-by-visit interaction as fixed effects and baseline aLBM as covariate. | Baseline to 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Stair Climbing (StC) Time | Change from baseline to the 24-week endpoint in StC time is presented. StC time was assessed by measuring the fastest time achieved to climb 4 steps on a 4-step staircase (the test was performed 2 times). LS means were calculated using a MMRM with treatment, visit, and treatment-by-visit interaction as fixed effects and baseline StC score as covariate. | Baseline to 24 weeks | 
| Change From Baseline in Repeated Chair Stands (RCS) Time | Change from baseline to 24-week endpoint in RCS time is presented. In the RCS test, participants were asked to rise from a chair 5 times as fast as possible with their arms folded on their chest. Performance was measured in seconds, as the time from the initial seated position to the final standing position. LS means were calculated using an MMRM with treatment, visit, and treatment-by-visit interaction as fixed effects and baseline RCS time as covariate. | Baseline to 24 weeks | 
| Change From Baseline in Usual Gait Speed (uGS) at 4 Meters | Change from baseline to the 24-week endpoint in uGS is presented. Two attempts to walk a 4-meter distance were made. LS means were calculated using a MMRM with treatment, visit, and treatment-by-visit interaction as fixed effects and baseline uGS as covariate. | Baseline to 24 weeks |