A Study of LY2495655 in Healthy Subjects

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 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 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