A Study of LY2495655 in Older Participants Undergoing Elective Total Hip Replacement
Condition: Muscular Atrophy
MeSH terms: Muscular Atrophy; Atrophy
Intervention: LY2495655; Placebo
Intervention description: Administered subcutaneously; Administered subcutaneously
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 400.0
Sex: All
Minimum age: 50 Years
Healthy volunteers: No
Keywords: Disuse Atrophy; Muscle; Strength; Arthroplasty; Hip; Joint Replacement

Summary:

      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).
    

Eligibility criteria:

        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.