A Study of LY2541546 in Women With Low Bone Mineral Density

• Change from baseline to 12, 24, and 64 weeks in lumbar spine bone mineral density (BMD) [ Time Frame: Baseline, 12 weeks, 24 weeks, 64 weeks ] [ Designated as safety issue: No ]
• Change from baseline to 24, 52 and 64 weeks in proximal femur bone mineral density (BMD) [ Time Frame: Baseline, 24 weeks, 52 weeks, 64 weeks ] [ Designated as safety issue: No ]
• Change from baseline to 52 week endpoint in proximal femur and wrist bone mineral density (BMD) [ Time Frame: Baseline, 52 weeks ] [ Designated as safety issue: No ]
• Change from baseline to 52 week endpoint in Bone-specific alkaline phosphatase (BSAP) [ Time Frame: Baseline, 52 weeks ] [ Designated as safety issue: No ]
• Change from baseline to 52 week endpoint in Serum type I collagen fragment (CTx) [ Time Frame: Baseline, 52 weeks ] [ Designated as safety issue: No ]
• Change from baseline to 52 week endpoint in Osteocalcin [ Time Frame: Baseline, 52 weeks ] [ Designated as safety issue: No ]
• Change from baseline to 52 week endpoint in Serum N-terminal extension propeptide of type I collagen (P1NP) [ Time Frame: Baseline, 52 weeks ] [ Designated as safety issue: No ]

The primary objectives of this study include evaluating the dose response of LY2541546 using bone mineral density (BMD) change from baseline as compared to placebo, and evaluating the overall safety and tolerability of LY2541546 following multiple subcutaneous administrations in postmenopausal (PMP) women with low BMD. Following the last dose of study drug, participant's will be able to participate in a 12 month extension to collect additional safety and efficacy data (no further treatment will be administered during this extension).

• Drug: LY2541546
  Administered subcutaneously
• Drug: Placebo
  Administered subcutaneously

• Experimental: 180 mg LY2541546 given every 4 weeks
  LY2541546 will be administered subcutaneously every 4 weeks with Placebo given every alternate 2 weeks (Patient will receive an injection every 2 weeks) for 52 weeks.
  Interventions:

  • Drug: LY2541546
  • Drug: Placebo
• Experimental: 180 mg LY2541546 given every 2 weeks
  Administered subcutaneously for 52 weeks
  Intervention: Drug: LY2541546
• Experimental: 270 mg LY2541546 given every 2 weeks
  Administered subcutaneously for 52 weeks
  Intervention: Drug: LY2541546
• Placebo Comparator: Placebo given every 2 weeks
  Administered subcutaneously for 52 weeks
  Intervention: Drug: Placebo
• Experimental: 270 mg LY2541546 given every 12 weeks
  LY2541546 will be administered subcutaneously every 12 weeks with Placebo given every 2 weeks when LY2541546 is not administered (Patient will receive an injection every 2 weeks) for 52 weeks.
  Interventions:

  • Drug: LY2541546
  • Drug: Placebo

Inclusion Criteria:

• Ambulatory, postmenopausal women, inclusive.
• Have low bone mineral density (BMD), defined as a T-score, or equivalent BMD absolute value (g/cm2), for the lumbar spine of between -3.5 and -2.0, inclusive.
• Without language barrier, reliable, and willing to make themselves available for the duration of the study and to follow study procedures.
• Willing to take study drug and daily supplements (calcium and Vitamin D).
• Normal laboratory tests or laboratory test results determined not clinically significant by the investigator. Serum phosphate and serum calcium must be within normal limits, and platelet level greater than 100,000 mm3.

Exclusion Criteria:

• Have received treatment with any of the following medications more recently than 3 months prior to screening Androgen, Calcitonin, Estrogen (including over the counter preparations known to have estrogenic activity)*, Progestin (including over the counter preparations known to have progestogenic activity)*, SERMs (Raloxifene, Tamoxifen, Toremifene, Clomiphene), Tibolone
• Have previously used or currently use denosumab, parathyroid hormone (PTH) and/or PTH analogs, strontium ranelate, or parenteral formulations of bisphosphonates.
• Have received treatment with any oral bisphosphonate within the last year
• Have received therapeutic doses of systemic corticosteroids for more than one month during the 6 months prior to screening.
• Have received therapeutic doses of fluorides (20 mg/day) for more than 3 months during the last 3 years, or for more than a total of 2 years, or any within the last 6 months.
• Have severe Vitamin D deficiency defined as 25-hydroxyvitamin D less than <9.2 ng/mL (23nmol/L) at screening. If the serum 25-hydroxy-vitamin D level at screening is less than or equal to 9.2 ng/mL and <20 ng/mL, patients will receive a loading dose of Vitamin D (at a dose of approximately 100,000 IU given orally) prior to enrollment.
• Have any known bone disorder other than low BMD or osteoporosis.
• Have a history of osteoporotic fractures, including known prevalent vertebral fracture or evidence of prevalent vertebral fracture on screening spine X-ray or dual-energy x-ray absorptiometry (DXA), or are considered to be at high risk for fracture.
• Presence of any abnormality (such as artifacts or osteophytes) that would confound DXA evaluation of lumbar vertebrae in the L-1 through L-4 region.
• Have a history of Bell's palsy, other cranial nerve disorders, or have a history of Temporomandibular Joint and Muscle Disorders (TMJDs).
• Have any history of cancer within the previous 5 years, except for excised superficial lesions such as basal cell carcinoma and squamous cell carcinoma of the skin.
• Have history or presence of cardiovascular, respiratory, 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 acute or chronic liver disease ([bilirubin >34 µmol/L or >2.0 mg/dL, alanine transaminase [ALT/SGPT] >100 U/L, or alkaline phosphatase >300 U/L).
• Have impaired kidney function (serum creatinine >135 µmol/L or >2.0 mg/dL).
• Have known allergy to LY2541546, any of diluents or excipients of LY2541546, or significant allergy to any other monoclonal antibody
• History of excessive consumption of alcohol or abuse of drugs within the last year.
• Have poor medical condition or psychiatric risks for treatment with an investigational drug.