A Study of LY2541546 in Women With Low Bone Mineral Density
Condition: Osteoporosis
MeSH terms: Osteoporosis; Bone Diseases, Metabolic
Intervention: LY2541546; Placebo
Intervention description: Administered subcutaneously; Administered subcutaneously
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 154.0
Sex: Female
Minimum age: 45 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: osteoporosis

Summary:

      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,
      participants 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).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Ambulatory, postmenopausal women, inclusive.

          -  Have low bone mineral density (BMD), defined as a T-score or equivalent BMD absolute
             value (grams/square centimeter [g/cm^2]) 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 cubic millimeters (mm^3).

        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), selective estrogen receptor
             modulators (SERMs) (Raloxifene, Tamoxifen, Toremifene, Clomiphene), or 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 milligrams per 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
             nanograms per milliliter (ng/mL) [23 nanomoles per liter (nmol/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, participants will receive a loading dose of Vitamin D (at a dose of
             approximately 100,000 international units (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 micromoles per liter (µmol/L) or
             >2.0 milligrams per deciliter (mg/dL), alanine transaminase [ALT/SGPT] >100 units per
             liter (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.