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

Lilly

Status and phase: Completed; Phase 2

Conditions: Muscular Atrophy

Treatments: Drug: Placebo; Drug: LY2495655

Study type: Interventional

Funder types: Industry

Identifiers

NCT01369511

11671

I1Q-MC-JDDE (Other Identifier)

Details and patient eligibility

About

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).

Enrollment: 400 patients

Sex: All

Ages: 50+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

400 participants in 4 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Administered subcutaneously every 4 weeks for 12 weeks (administered 4 times)

Treatment:

Drug: Placebo

35 mg LY2495655

Experimental group

Description:

LY2495655: 35 milligrams (mg) administered subcutaneously every 4 weeks for 12 weeks (administered 4 times)

Treatment:

Drug: LY2495655

105 mg LY2495655

Experimental group

Description:

LY2495655: 105 mg administered subcutaneously every 4 weeks for 12 weeks (administered 4 times)

Treatment:

Drug: LY2495655

315 mg LY2495655

Experimental group

Description:

LY2495655: 315 mg administered subcutaneously every 4 weeks for 12 weeks (administered 4 times)

Treatment:

Drug: LY2495655