A Study of LY2495655 in Older Participants Undergoing Elective Total Hip Replacement

Study Overview
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Brief Summary
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The primary objective of this study is to test the hypothesis that appendicular lean body mass (aLBM) will increase after 12 weeks of LY2495655 treatment versus placebo in older participants undergoing elective total hip arthroplasty (eTHA).

Official Title
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A Phase 2 Randomized Study to Investigate the Efficacy and Safety of LY2495655 Versus Placebo in Older Patients Undergoing Elective Total Hip Arthroplasty

Conditions
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Muscular Atrophy

Intervention / Treatment
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* Drug: LY2495655
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males with a female partner of childbearing potential should use contraception during the treatment period of the trial and up to 15 weeks after the last dose of investigational product. Females should be of non-child bearing potential. Elective total hip arthroplasty (eTHA) is scheduled. Have a body mass index of <40 kilograms per square meter (kg/m^2) and a weight <136.4 kilograms (kg). Can climb at least 6 stairs with or without holding the handrail (but without human assistance), according to the participant at screening. Can stand up from a chair and walk more than 10 meters without human assistance. Takes at least 12 seconds to perform the Timed Up and Go (TUG) test at screening. Exclusion Criteria: Another inpatient surgical procedure is planned in the 6 months following randomization. Lower extremity amputation. Lower-limb fracture within 6 months prior to screening or any major lower-limb surgery within 3 months prior to randomization. Simultaneous bilateral eTHA. The planned surgical procedure will preclude weight bearing for at least 4 weeks postoperatively (for instance, the planned procedure will involve extensive bone grafting). Partial weight-bearing and weight-bearing as tolerated are acceptable, but non weight-bearing, touch weight-bearing, or feather weight-bearing are exclusive. Underlying muscle disease (for example, polymyositis or muscular dystrophy) or a history of muscle disease other than age-associated muscle waste or disuse atrophy. Recent neurologic injury (<6 months prior to randomization) such as stroke or spinal cord injury, or unstable neurologic disorders that are likely to confound physical performance tests during the course of the study (such as unstable Parkinson disease or hemiplegia). History of positive testing for human immunodeficiency virus (HIV). Current use or previous use of any drugs known to influence muscle mass or performance within 6 months prior to randomization (this includes anabolic steroids, replacement therapy for gonadal deficiency, anti-androgens, luteinizing hormone-releasing hormone [LHRH] agonist and antagonists, growth hormone, Insulin-Like Growth Factor 1 [IGF1], or creatinine supplements) or systemic corticosteroid use for at least 3 months (in the last year) prior to randomization at a daily dose greater than or equal to a 10 mg prednisone equivalent. Severe Vitamin D deficiency defined as 25-hydroxy-vitamin D levels <9.2 nanograms per milliliter (ng/mL) or <23 nanomoles per milliliter (nmol/mL) at screening. History of a malignant neoplasm in the 5 years prior to screening, with the exception of superficial basal cell carcinoma or squamous cell carcinoma of the skin that has been definitively treated. Participants with carcinoma in situ of the uterine cervix treated definitively for more than 1 year prior to screening may enter the study. History of any of the following conditions within 90 days of screening: unstable angina, myocardial infarction, coronary artery bypass graft surgery, or percutaneous coronary intervention (such as, angioplasty or stent placement). Any current supraventricular arrhythmia with an uncontrolled ventricular response (mean heart rate >100 beats per minute [bpm]) at rest despite medical or device therapy, any history of spontaneous or induced sustained ventricular tachycardia (heart rate >100 bpm for 30 seconds) despite medical or device therapy, or any history of resuscitated cardiac arrest or the presence of an automatic internal cardioverter-defibrillator. Any history of congestive heart failure within 6 months of screening. Systolic blood pressure >160 or <90 millimeters of mercury (mmHg) or diastolic blood pressure >100 or <50 mmHg at screening, or malignant hypertension. An abnormality in the locally read 12-lead electrocardiogram (ECG) that in the opinion of the investigator increases the risk of participating in the study. Have either or both of the following: aspartate aminotransferase (AST), alanine aminotransferase (ALT) >2 times the upper limit of normal (ULN), or alkaline phosphatase >1.5 times ULN, or total bilirubin >1.5 times ULN. Known history or presence of severe acute or chronic liver disease. History of significant renal insufficiency, defined as receiving renal dialysis or having an estimated creatinine clearance <30 milliliters per minute (mL/minute) at screening. Current evidence or recent history of significant psychiatric disease such as dementia/Alzheimer's disease, schizophrenia, or bipolar disorder. Are currently enrolled in, or discontinued within the last 30 days (or 5 half-lives whichever is longer) from a clinical trial involving an investigational drug or off-label use of a drug, or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. Regularly uses known drugs of abuse and/or shows positive findings on urinary drug screening (physician prescribed narcotics are allowed). Have a positive fecal occult blood (FOB) test at screening or cannot provide a stool sample for FOB testing prior to randomization. Have uncontrolled diabetes mellitus. Have had ocular trauma, ophthalmologic surgery, or eye laser treatment within 6 months prior to randomization.

Ages Eligible for Study
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Minimum Age: 50 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 |
| --- | --- |
| Placebo Comparator: Placebo<br>Administered subcutaneously every 4 weeks for 12 weeks (administered 4 times) | Drug: Placebo<br>* Administered subcutaneously<br>|
| Experimental: 35 mg LY2495655<br>LY2495655: 35 milligrams (mg) administered subcutaneously every 4 weeks for 12 weeks (administered 4 times) | Drug: LY2495655<br>* Administered subcutaneously<br>|
| Experimental: 105 mg LY2495655<br>LY2495655: 105 mg administered subcutaneously every 4 weeks for 12 weeks (administered 4 times) | Drug: LY2495655<br>* Administered subcutaneously<br>|
| Experimental: 315 mg LY2495655<br>LY2495655: 315 mg administered subcutaneously every 4 weeks for 12 weeks (administered 4 times) | Drug: LY2495655<br>* Administered subcutaneously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Appendicular Lean Body Mass (aLBM) at Week 12 | The percentage change in aLBM of 3 limbs (excluding the operated limb) was measured by dual energy x-ray absorptiometry (DEXA). Least squares (LS) means of the aLBM change from baseline to the 12 week endpoint was adjusted by baseline aLBM values as a covariate and treatment, visit, and the treatment-by-visit interaction were included as fixed effect via a mixed-effects model for repeated measured (MMRM) analysis. | Baseline, 12 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Appendicular Lean Body Mass (aLBM) at Weeks 4, 8, and 16 | The percentage change in aLBM of 3 limbs (excluding the operated limb) was measured by DEXA. LS means of the aLBM change from baseline to the 12 week endpoint was adjusted by baseline aLBM values as a covariate and treatment, visit, and the treatment-by-visit interaction were included as fixed effect via an MMRM analysis. | Baseline, 4 Weeks, 8 Weeks, and 16 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Disuse Atrophy, Muscle, Strength, Arthroplasty, Hip, Joint Replacement