A Study of LY2495655 in Healthy Subjects

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and tolerability of single and multiple doses of LY2495655 administered subcutaneously and intravenously in Japanese subjects.

Official Title
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A Single- and Multiple-Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LY2495655 in Japanese Subjects

Conditions
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Healthy Volunteer

Intervention / Treatment
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* Drug: LY2495655
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Single dose cohort Overtly healthy males or females, as determined by medical history and physical examination Between the ages of 24 and 50 years Multiple dose cohorts Sedentary males and females with stable medical problems, if any, that, in the investigator's opinion, will not place the subject at increased risk by participating in the study and will not interfere with interpretation of the data Between the ages of 50 and 85 years Score <600 Metabolic Equivalent Tasks (METs) per week based on International Physical Activity Questionnaire (IPAQ) All subjects Male subjects: agree to use a reliable method of birth control Female subjects: women not of child-bearing potential due to surgical sterilization (at least 6 weeks post-surgical bilateral oophorectomy with or without hysterectomy or tubal ligation) confirmed by medical history, or menopause Up to third generation Japanese, that is defined as all of the subject's biological grandparents are of exclusive Japanese descent and have been born in Japan Are ambulatory and able to perform a stair climb test Have clinical laboratory tests within normal reference range for the population or investigator site, or results with acceptable deviations that are judged to be not clinically significant by the investigator Have venous access sufficient to allow for blood sampling and/or administration of investigational product for intravenous administration Exclusion Criteria: Single dose cohort Intend to use over the counter or prescription medication within 14 days prior to dosing through 2 months after dosing except for thyroid replacement hormones or non-absorbed topical preparations per investigator instructions Abnormal supine blood pressure defined as diastolic blood pressure > 90 millimeters of mercury (mmHg) and/or systolic blood pressure >140 mmHg Multiple dose cohort If taking medications, subjects who have not been stable for at least 3 months, or the time required to produce stable effects of the drug Abnormal supine blood pressure defined as >100 mmHg and/or systolic blood pressure >160 mmHg All subjects Have known allergies to LY2495655, related compounds or any components of the formulation Have a history or presence of cardiovascular, respiratory (including moderate to severe restrictive lung disease and obstructive disease, chronic bronchitis, and those with symptomatic asthma), hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of constituting a risk when taking the study medication or of interfering with the interpretation of data Have a history of seizures or convulsions, excluding febrile convulsions in childhood Subjects with underlying muscle disease or a history of muscle disease (for example, polymyositis or rhabdomyolysis) Evidence or recent history of significant active psychiatric disease such as schizophrenia, depression, or bipolar disorder Recent immobilization or major trauma to the legs within 6 months Knee or hip replacement or lower extremity amputation Participate in, or have participated within 3 months of study drug administration, a regular resistance training program or plan to participate in an exercise program during the study Actively working in a physically demanding profession Have contraindications for the Magnetic Resonance Imaging (MRI) scan Tattoos on the right leg if the tattoos are at least 20 years old and may have iron-containing pigments Electrocardiogram (ECG) considered outside the normal limits for the study population by the investigator and relevant for interpretation or indicating cardiac disease Clinically significant abnormality in neurologic or neurocognitive examinations at screening

Ages Eligible for Study
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Minimum Age: 24 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single IV dose LY2495655<br>Single 70 milligram (mg) dose LY2495655 administered intravenously (IV) | Drug: LY2495655<br>* administered intravenously or subcutaneously<br>|
| Experimental: Multiple SC dose 17.5 mg LY2495655<br>17.5 mg of LY2495655 administered subcutaneously (SC) every 2 weeks for 8 weeks (total of 5 doses) | Drug: LY2495655<br>* administered intravenously or subcutaneously<br>|
| Experimental: Multiple SC dose 140 mg LY2495655<br>140 mg of LY2495655 administered subcutaneously (SC) every 2 weeks for 8 weeks (total 5 doses) | Drug: LY2495655<br>* administered intravenously or subcutaneously<br>|
| Experimental: Multiple SC dose 420 mg LY2495655<br>420 mg dose of LY2495655 administered subcutaneously (SC) every 2 weeks for 8 weeks (total 5 doses) | Drug: LY2495655<br>* administered intravenously or subcutaneously<br>|
| Placebo Comparator: Single IV dose placebo<br>Single Placebo dose administered intravenously (IV) | Drug: Placebo<br>* administered intravenously or subcutaneously<br>|
| Placebo Comparator: Multiple SC dose placebo<br>Placebo dose administered subcutaneously (SC) every 2 weeks for 8 weeks (total of 5 doses) | Drug: Placebo<br>* administered intravenously or subcutaneously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Clinically Significant Effects | Clinically significant effects are defined as treatment emergent adverse events (TEAEs) which in the opinion of the investigator are thought to be possibly related to study drug. A summary of serious and all other non-serious adverse events (whether or not related to study drug) is located in the Reported Adverse Events module. | Baseline to study completion (up to 135 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics, Maximum Concentration (Cmax) |  | Single Dose:Day 1:Predose,10 minutes before end,2,6,12,24,48,192,360,528,696,1032,1368and2040 hours(hrs)Postdose;Multiple Dose:Day 1:Predose,24,48,96,168,264,360,528,696,1032hrs Postdose; Day57:Predose,24,48,96,168,336,672and1680hrs Postdose | 
| Pharmacokinetics, Area Under the Concentration Versus Time Curve (AUC) | Area under the concentration curve (AUC) time zero to infinity (0-inf) was calculated for single dose administration and AUCtau (AUCτ) at steady state was calculated for multiple dose administration. | Single Dose:Day 1:Predose,10 minutes before end,2,6,12,24,48,192,360,528,696,1032,1368and2040 hours(hrs)Postdose;Multiple Dose:Day 1:Predose,24,48,96,168,264,360,528,696,1032hrs Postdose; Day57:Predose,24,48,96,168,336,672and1680hrs Postdose | 
| Pharmacokinetics, Time of Maximum Observed Drug Concentration (Tmax) |  | Single Dose:Day 1:Predose,10 minutes before end,2,6,12,24,48,192,360,528,696,1032,1368and2040 hours(hrs)Postdose;Multiple Dose:Day 1:Predose,24,48,96,168,264,360,528,696,1032hrs Postdose; Day57:Predose,24,48,96,168,336,672and1680hrs Postdose | 
| Percentage Change in Thigh Muscle Volume | Thigh muscle volume was determined by Magnetic Resonance Imaging (MRI) scan of the right leg thigh muscle. Percentage change in thigh muscle volume=(time point value-baseline value)*100. Change from baseline for muscle volume was analyzed using mixed model repeated measures (MMRM) model with fixed effects of treatment, time and treatment*time interaction and a random effect of subject where baseline values were included as a covariate. | Baseline, Day 22 for a single dose arm/ baseline, Days 22 and 71 for multiple dose arms |