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

Muscular Atrophy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01369511
• Other study ID #: 11671
• Secondary ID: I1Q-MC-JDDE
• Status: Completed
• Phase: Phase 2
• Start date: July 2011
• Est. completion date: February 2014

Study information

• Verified date: May 2018
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 400
• Est. completion date: February 2014
• Est. primary completion date: February 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Atrophy
• Muscular Atrophy

Intervention

Drug:
• LY2495655
Administered subcutaneously
• Placebo
Administered subcutaneously

Locations

Country	Name	City	State
Austria	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Vienna
Austria	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Wiener Neustadt
Belgium	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Genk
Belgium	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Merksem
Canada	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Montreal	Quebec
Canada	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Newmarket	Ontario
Canada	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Quebec
Canada	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Waterloo	Ontario
Denmark	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Ballerup
Estonia	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Tallinn
Estonia	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Tartu
Finland	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Kuopio
Finland	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Oulu
France	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Cahors Cedex 9
France	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Montauban Cedex
Japan	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Fukuoka
Japan	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Hokkaido
Japan	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Hyogo
Japan	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Nagano
Japan	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Osaka
Japan	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Tokyo
Japan	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Wakayama
Spain	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Alcira
Spain	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Barcelona
Spain	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Granada
Spain	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Madrid
Sweden	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Stockholm
Sweden	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Umea
Sweden	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Uppsala
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Altoona	Pennsylvania
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Boston	Massachusetts
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Fort Lauderdale	Florida
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Gainesville	Georgia
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Great Falls	Montana
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Houston	Texas
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Jacksonville	Florida
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Laguna Hills	California
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Lakewood	Colorado
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Memphis	Tennessee
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Orlando	Florida
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Pinellas Park	Florida
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	State College	Pennsylvania
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Tampa	Florida
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Tucson	Arizona
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Wilmington	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Canada,  Denmark,  Estonia,  Finland,  France,  Japan,  Spain,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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