Osteoporosis
Conditions
Keywords
osteoporosis
Brief 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).
Interventions
DRUGLY2541546
Administered subcutaneously
DRUGPlacebo
Administered subcutaneously
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
45 Years to 85 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to 52 Week Endpoint in Lumbar Spine Bone Mineral Density (BMD) | Baseline, 52 weeks | Lumbar spine bone mineral density (BMD) measured by dual energy x-ray absorptiometry (DXA). Least squares (LS) mean values were determined using a mixed-effects model repeated-measures (MMRM) analysis of covariance. Factors in the model included treatment, time and the interaction of treatment by time as fixed effects, and baseline lumbar spine BMD as a covariate. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to 24, 52, and 64 Weeks in Proximal Femur Bone Mineral Density (BMD) | Baseline, 24 weeks and 52 weeks and 64 weeks | Femoral neck and total hip bone mineral density (BMD) measured by dual energy x-ray absorptiometry (DXA). Least squares (LS) mean values were determined using a mixed-effects model repeated-measures (MMRM) analysis of covariance. Factors in the model included treatment, time and the interaction of treatment by time as fixed effects, and baseline BMD as a covariate. |
| Change From Baseline to 52 Week Endpoint in Wrist Bone Mineral Density (BMD) | Baseline, 52 weeks | Total radius of the wrist bone mineral density (BMD) measured by dual energy x-ray absorptiometry (DXA). Least squares (LS) mean values were determined using a 1-factor analysis of covariance model with treatment group as the main effect and baseline BMD as a covariate. |
| Change From Baseline to 52 Week Endpoint in Bone-specific Alkaline Phosphatase (BSAP) | Baseline, 52 weeks | — |
| Change From Baseline to 12, 24, and 64 Weeks in Lumbar Spine Bone Mineral Density (BMD) | Baseline, 12 weeks and 24 weeks and 64 weeks | Lumbar spine bone mineral density (BMD) measured by dual energy x-ray absorptiometry (DXA). Least squares (LS) mean values were determined using a mixed-effects model repeated-measures (MMRM) analysis of covariance. Factors in the model included treatment, time and the interaction of treatment by time as fixed effects, and baseline lumbar spine BMD as a covariate |
| Change From Baseline to 52 Week Endpoint in Osteocalcin | Baseline, 52 weeks | — |
| Change From Baseline to 52 Week Endpoint in Serum N-terminal Extension Propeptide of Type I Collagen (P1NP) | Baseline, 52 weeks | — |
| Change From Baseline to 52 Week Endpoint in Serum Type I Collagen Fragment (CTx) | Baseline, 52 weeks | — |
Countries
Denmark, Estonia, Japan, Lithuania, United States
Participant flow
Pre-assignment details
After exposure to study medication for the 52 week treatment phase, participants entered a 12 week non-treatment safety follow-up period with the option of staying in the non-treatment safety follow-up period for an additional 40 weeks (for a total of 52 weeks follow-up for the main study participants only).
Participants by arm
| Arm | Count |
|---|---|
| 180 mg LY2541546 Q4W + Placebo LY2541546 + Placebo: 180 milligrams (mg) LY2541546 administered subcutaneously every 4 weeks (Q4W) for 52 weeks with Placebo administered subcutaneously every alternate 2 weeks from the LY2541546 dose for 52 weeks. | 31 |
| 180 mg LY2541546 Q2W LY2541546: 180 mg administered subcutaneously every 2 weeks (Q2W) for 52 weeks. | 30 |
| 270 mg LY2541546 Q2W LY2541546: 270 mg administered subcutaneously every 2 weeks (Q2W) for 52 weeks. | 30 |
| 270 mg LY2541546 Q12W + Placebo LY2541546 + Placebo: 270 mg LY2541546 administered subcutaneously every 12 weeks (Q12W) with Placebo administered subcutaneously every 2 weeks when LY2541546 is not administered for 52 weeks. | 25 |
| Placebo Q2W Placebo: administered subcutaneously every 2 weeks (Q2W) for 52 weeks. | 37 |
| Total | 153 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| 52 Week Treatment Period | Adverse Event | 0 | 0 | 3 | 2 | 1 |
| 52 Week Treatment Period | Entry Criteria Not Met | 0 | 0 | 1 | 1 | 0 |
| 52 Week Treatment Period | Lost to Follow-up | 1 | 0 | 0 | 0 | 0 |
| 52 Week Treatment Period | Protocol Violation | 0 | 0 | 0 | 0 | 1 |
| 52 Week Treatment Period | Sponsor Decision | 0 | 0 | 0 | 0 | 1 |
| 52 Week Treatment Period | Withdrawal by Subject | 4 | 1 | 1 | 1 | 0 |
| Optional 40 Week Safety Follow-up Period | Adverse Event | 0 | 1 | 0 | 0 | 1 |
| Optional 40 Week Safety Follow-up Period | Lost to Follow-up | 0 | 0 | 0 | 0 | 1 |
| Optional 40 Week Safety Follow-up Period | Sponsor Decision | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | 180 mg LY2541546 Q2W | Total | Placebo Q2W | 180 mg LY2541546 Q4W + Placebo | 270 mg LY2541546 Q12W + Placebo | 270 mg LY2541546 Q2W |
|---|---|---|---|---|---|---|
| Age, Continuous | 64.17 years STANDARD_DEVIATION 8.2 | 65.22 years STANDARD_DEVIATION 8.38 | 65.17 years STANDARD_DEVIATION 8.91 | 66.78 years STANDARD_DEVIATION 8.98 | 63.56 years STANDARD_DEVIATION 8.02 | 66.12 years STANDARD_DEVIATION 7.68 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 27 Participants | 8 Participants | 4 Participants | 9 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants | 115 Participants | 26 Participants | 23 Participants | 16 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 11 Participants | 3 Participants | 4 Participants | 0 Participants | 2 Participants |
| Femoral Neck Bone Mineral Density (Baseline) | 0.66 g/cm^2 STANDARD_DEVIATION 0.15 | 0.66 g/cm^2 STANDARD_DEVIATION 0.14 | 0.66 g/cm^2 STANDARD_DEVIATION 0.17 | 0.66 g/cm^2 STANDARD_DEVIATION 0.15 | 0.63 g/cm^2 STANDARD_DEVIATION 0.11 | 0.69 g/cm^2 STANDARD_DEVIATION 0.11 |
| Lumbar Spine Bone Mineral Density (Baseline) | 0.78 grams/square centimeter (g/cm^2) STANDARD_DEVIATION 0.07 | 0.78 grams/square centimeter (g/cm^2) STANDARD_DEVIATION 0.09 | 0.78 grams/square centimeter (g/cm^2) STANDARD_DEVIATION 0.09 | 0.78 grams/square centimeter (g/cm^2) STANDARD_DEVIATION 0.09 | 0.77 grams/square centimeter (g/cm^2) STANDARD_DEVIATION 0.09 | 0.80 grams/square centimeter (g/cm^2) STANDARD_DEVIATION 0.09 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 13 Participants | 65 Participants | 14 Participants | 14 Participants | 11 Participants | 13 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 17 Participants | 87 Participants | 22 Participants | 17 Participants | 14 Participants | 17 Participants |
| Region of Enrollment Denmark | 4 Participants | 18 Participants | 5 Participants | 6 Participants | 0 Participants | 3 Participants |
| Region of Enrollment Estonia | 3 Participants | 19 Participants | 4 Participants | 4 Participants | 3 Participants | 5 Participants |
| Region of Enrollment Japan | 13 Participants | 65 Participants | 14 Participants | 14 Participants | 11 Participants | 13 Participants |
| Region of Enrollment Lithuania | 4 Participants | 15 Participants | 4 Participants | 3 Participants | 0 Participants | 4 Participants |
| Region of Enrollment United States | 6 Participants | 36 Participants | 10 Participants | 4 Participants | 11 Participants | 5 Participants |
| Sex: Female, Male Female | 30 Participants | 153 Participants | 37 Participants | 31 Participants | 25 Participants | 30 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Total Hip Bone Mineral Density (Baseline) | 0.75 grams/square centimeter STANDARD_DEVIATION 0.13 | 0.75 grams/square centimeter STANDARD_DEVIATION 0.12 | 0.73 grams/square centimeter STANDARD_DEVIATION 0.14 | 0.75 grams/square centimeter STANDARD_DEVIATION 0.11 | 0.73 grams/square centimeter STANDARD_DEVIATION 0.11 | 0.77 grams/square centimeter STANDARD_DEVIATION 0.1 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 30 / 31 | 28 / 30 | 29 / 30 | 21 / 25 | 34 / 37 |
| serious Total, serious adverse events | 4 / 31 | 3 / 30 | 4 / 30 | 1 / 25 | 2 / 37 |
Outcome results
Primary
Change From Baseline to 52 Week Endpoint in Lumbar Spine Bone Mineral Density (BMD)
Lumbar spine bone mineral density (BMD) measured by dual energy x-ray absorptiometry (DXA). Least squares (LS) mean values were determined using a mixed-effects model repeated-measures (MMRM) analysis of covariance. Factors in the model included treatment, time and the interaction of treatment by time as fixed effects, and baseline lumbar spine BMD as a covariate.
Time frame: Baseline, 52 weeks
Population: Participants who received at least one dose of study drug with baseline and at least one post-baseline lumbar spine BMD value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 180 mg LY2541546 Q4W + Placebo | Change From Baseline to 52 Week Endpoint in Lumbar Spine Bone Mineral Density (BMD) | 0.065 g/cm^2 |
| 180 mg LY2541546 Q2W | Change From Baseline to 52 Week Endpoint in Lumbar Spine Bone Mineral Density (BMD) | 0.115 g/cm^2 |
| 270 mg LY2541546 Q2W | Change From Baseline to 52 Week Endpoint in Lumbar Spine Bone Mineral Density (BMD) | 0.142 g/cm^2 |
| 270 mg LY2541546 Q12W + Placebo | Change From Baseline to 52 Week Endpoint in Lumbar Spine Bone Mineral Density (BMD) | 0.054 g/cm^2 |
| Placebo Q2W | Change From Baseline to 52 Week Endpoint in Lumbar Spine Bone Mineral Density (BMD) | -0.011 g/cm^2 |
Secondary
Change From Baseline to 12, 24, and 64 Weeks in Lumbar Spine Bone Mineral Density (BMD)
Lumbar spine bone mineral density (BMD) measured by dual energy x-ray absorptiometry (DXA). Least squares (LS) mean values were determined using a mixed-effects model repeated-measures (MMRM) analysis of covariance. Factors in the model included treatment, time and the interaction of treatment by time as fixed effects, and baseline lumbar spine BMD as a covariate
Time frame: Baseline, 12 weeks and 24 weeks and 64 weeks
Population: Participants who received at least one dose of study drug with baseline and at least one post-baseline lumbar spine BMD value.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| 180 mg LY2541546 Q4W + Placebo | Change From Baseline to 12, 24, and 64 Weeks in Lumbar Spine Bone Mineral Density (BMD) | Week 12 | 0.028 g/cm^2 |
| 180 mg LY2541546 Q4W + Placebo | Change From Baseline to 12, 24, and 64 Weeks in Lumbar Spine Bone Mineral Density (BMD) | Week 64 | 0.046 g/cm^2 |
| 180 mg LY2541546 Q4W + Placebo | Change From Baseline to 12, 24, and 64 Weeks in Lumbar Spine Bone Mineral Density (BMD) | Week 24 | 0.049 g/cm^2 |
| 180 mg LY2541546 Q2W | Change From Baseline to 12, 24, and 64 Weeks in Lumbar Spine Bone Mineral Density (BMD) | Week 24 | 0.083 g/cm^2 |
| 180 mg LY2541546 Q2W | Change From Baseline to 12, 24, and 64 Weeks in Lumbar Spine Bone Mineral Density (BMD) | Week 12 | 0.048 g/cm^2 |
| 180 mg LY2541546 Q2W | Change From Baseline to 12, 24, and 64 Weeks in Lumbar Spine Bone Mineral Density (BMD) | Week 64 | 0.098 g/cm^2 |
| 270 mg LY2541546 Q2W | Change From Baseline to 12, 24, and 64 Weeks in Lumbar Spine Bone Mineral Density (BMD) | Week 24 | 0.098 g/cm^2 |
| 270 mg LY2541546 Q2W | Change From Baseline to 12, 24, and 64 Weeks in Lumbar Spine Bone Mineral Density (BMD) | Week 12 | 0.057 g/cm^2 |
| 270 mg LY2541546 Q2W | Change From Baseline to 12, 24, and 64 Weeks in Lumbar Spine Bone Mineral Density (BMD) | Week 64 | 0.135 g/cm^2 |
| 270 mg LY2541546 Q12W + Placebo | Change From Baseline to 12, 24, and 64 Weeks in Lumbar Spine Bone Mineral Density (BMD) | Week 12 | 0.039 g/cm^2 |
| 270 mg LY2541546 Q12W + Placebo | Change From Baseline to 12, 24, and 64 Weeks in Lumbar Spine Bone Mineral Density (BMD) | Week 64 | 0.046 g/cm^2 |
| 270 mg LY2541546 Q12W + Placebo | Change From Baseline to 12, 24, and 64 Weeks in Lumbar Spine Bone Mineral Density (BMD) | Week 24 | 0.048 g/cm^2 |
| Placebo Q2W | Change From Baseline to 12, 24, and 64 Weeks in Lumbar Spine Bone Mineral Density (BMD) | Week 24 | -0.006 g/cm^2 |
| Placebo Q2W | Change From Baseline to 12, 24, and 64 Weeks in Lumbar Spine Bone Mineral Density (BMD) | Week 12 | -0.007 g/cm^2 |
| Placebo Q2W | Change From Baseline to 12, 24, and 64 Weeks in Lumbar Spine Bone Mineral Density (BMD) | Week 64 | -0.007 g/cm^2 |
Secondary
Change From Baseline to 24, 52, and 64 Weeks in Proximal Femur Bone Mineral Density (BMD)
Femoral neck and total hip bone mineral density (BMD) measured by dual energy x-ray absorptiometry (DXA). Least squares (LS) mean values were determined using a mixed-effects model repeated-measures (MMRM) analysis of covariance. Factors in the model included treatment, time and the interaction of treatment by time as fixed effects, and baseline BMD as a covariate.
Time frame: Baseline, 24 weeks and 52 weeks and 64 weeks
Population: Participants who received at least one dose of study drug with baseline and at least one post-baseline femoral neck or total hip BMD value.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| 180 mg LY2541546 Q4W + Placebo | Change From Baseline to 24, 52, and 64 Weeks in Proximal Femur Bone Mineral Density (BMD) | Femoral Neck BMD Week 24 | 0.010 g/cm^2 |
| 180 mg LY2541546 Q4W + Placebo | Change From Baseline to 24, 52, and 64 Weeks in Proximal Femur Bone Mineral Density (BMD) | Total Hip BMD Week 24 | 0.007 g/cm^2 |
| 180 mg LY2541546 Q4W + Placebo | Change From Baseline to 24, 52, and 64 Weeks in Proximal Femur Bone Mineral Density (BMD) | Femoral Neck BMD Week 52 | 0.018 g/cm^2 |
| 180 mg LY2541546 Q4W + Placebo | Change From Baseline to 24, 52, and 64 Weeks in Proximal Femur Bone Mineral Density (BMD) | Total Hip BMD Week 52 | 0.017 g/cm^2 |
| 180 mg LY2541546 Q4W + Placebo | Change From Baseline to 24, 52, and 64 Weeks in Proximal Femur Bone Mineral Density (BMD) | Femoral Neck BMD Week 64 | 0.016 g/cm^2 |
| 180 mg LY2541546 Q4W + Placebo | Change From Baseline to 24, 52, and 64 Weeks in Proximal Femur Bone Mineral Density (BMD) | Total Hip BMD Week 64 | 0.011 g/cm^2 |
| 180 mg LY2541546 Q2W | Change From Baseline to 24, 52, and 64 Weeks in Proximal Femur Bone Mineral Density (BMD) | Femoral Neck BMD Week 64 | 0.028 g/cm^2 |
| 180 mg LY2541546 Q2W | Change From Baseline to 24, 52, and 64 Weeks in Proximal Femur Bone Mineral Density (BMD) | Total Hip BMD Week 64 | 0.031 g/cm^2 |
| 180 mg LY2541546 Q2W | Change From Baseline to 24, 52, and 64 Weeks in Proximal Femur Bone Mineral Density (BMD) | Femoral Neck BMD Week 24 | 0.017 g/cm^2 |
| 180 mg LY2541546 Q2W | Change From Baseline to 24, 52, and 64 Weeks in Proximal Femur Bone Mineral Density (BMD) | Femoral Neck BMD Week 52 | 0.025 g/cm^2 |
| 180 mg LY2541546 Q2W | Change From Baseline to 24, 52, and 64 Weeks in Proximal Femur Bone Mineral Density (BMD) | Total Hip BMD Week 52 | 0.032 g/cm^2 |
| 180 mg LY2541546 Q2W | Change From Baseline to 24, 52, and 64 Weeks in Proximal Femur Bone Mineral Density (BMD) | Total Hip BMD Week 24 | 0.020 g/cm^2 |
| 270 mg LY2541546 Q2W | Change From Baseline to 24, 52, and 64 Weeks in Proximal Femur Bone Mineral Density (BMD) | Total Hip BMD Week 52 | 0.051 g/cm^2 |
| 270 mg LY2541546 Q2W | Change From Baseline to 24, 52, and 64 Weeks in Proximal Femur Bone Mineral Density (BMD) | Femoral Neck BMD Week 64 | 0.038 g/cm^2 |
| 270 mg LY2541546 Q2W | Change From Baseline to 24, 52, and 64 Weeks in Proximal Femur Bone Mineral Density (BMD) | Femoral Neck BMD Week 24 | 0.026 g/cm^2 |
| 270 mg LY2541546 Q2W | Change From Baseline to 24, 52, and 64 Weeks in Proximal Femur Bone Mineral Density (BMD) | Femoral Neck BMD Week 52 | 0.044 g/cm^2 |
| 270 mg LY2541546 Q2W | Change From Baseline to 24, 52, and 64 Weeks in Proximal Femur Bone Mineral Density (BMD) | Total Hip BMD Week 24 | 0.031 g/cm^2 |
| 270 mg LY2541546 Q2W | Change From Baseline to 24, 52, and 64 Weeks in Proximal Femur Bone Mineral Density (BMD) | Total Hip BMD Week 64 | 0.047 g/cm^2 |
| 270 mg LY2541546 Q12W + Placebo | Change From Baseline to 24, 52, and 64 Weeks in Proximal Femur Bone Mineral Density (BMD) | Total Hip BMD Week 52 | 0.019 g/cm^2 |
| 270 mg LY2541546 Q12W + Placebo | Change From Baseline to 24, 52, and 64 Weeks in Proximal Femur Bone Mineral Density (BMD) | Total Hip BMD Week 24 | 0.015 g/cm^2 |
| 270 mg LY2541546 Q12W + Placebo | Change From Baseline to 24, 52, and 64 Weeks in Proximal Femur Bone Mineral Density (BMD) | Femoral Neck BMD Week 52 | 0.014 g/cm^2 |
| 270 mg LY2541546 Q12W + Placebo | Change From Baseline to 24, 52, and 64 Weeks in Proximal Femur Bone Mineral Density (BMD) | Total Hip BMD Week 64 | 0.021 g/cm^2 |
| 270 mg LY2541546 Q12W + Placebo | Change From Baseline to 24, 52, and 64 Weeks in Proximal Femur Bone Mineral Density (BMD) | Femoral Neck BMD Week 64 | 0.013 g/cm^2 |
| 270 mg LY2541546 Q12W + Placebo | Change From Baseline to 24, 52, and 64 Weeks in Proximal Femur Bone Mineral Density (BMD) | Femoral Neck BMD Week 24 | 0.002 g/cm^2 |
| Placebo Q2W | Change From Baseline to 24, 52, and 64 Weeks in Proximal Femur Bone Mineral Density (BMD) | Femoral Neck BMD Week 64 | 0.002 g/cm^2 |
| Placebo Q2W | Change From Baseline to 24, 52, and 64 Weeks in Proximal Femur Bone Mineral Density (BMD) | Femoral Neck BMD Week 52 | 0.003 g/cm^2 |
| Placebo Q2W | Change From Baseline to 24, 52, and 64 Weeks in Proximal Femur Bone Mineral Density (BMD) | Total Hip BMD Week 24 | -0.007 g/cm^2 |
| Placebo Q2W | Change From Baseline to 24, 52, and 64 Weeks in Proximal Femur Bone Mineral Density (BMD) | Total Hip BMD Week 64 | -0.007 g/cm^2 |
| Placebo Q2W | Change From Baseline to 24, 52, and 64 Weeks in Proximal Femur Bone Mineral Density (BMD) | Total Hip BMD Week 52 | -0.004 g/cm^2 |
| Placebo Q2W | Change From Baseline to 24, 52, and 64 Weeks in Proximal Femur Bone Mineral Density (BMD) | Femoral Neck BMD Week 24 | 0.002 g/cm^2 |
Secondary
Change From Baseline to 52 Week Endpoint in Bone-specific Alkaline Phosphatase (BSAP)
Time frame: Baseline, 52 weeks
Population: Participants who received at least one dose of study drug with baseline and at least one post-baseline bone-specific alkaline phosphatase value.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 180 mg LY2541546 Q4W + Placebo | Change From Baseline to 52 Week Endpoint in Bone-specific Alkaline Phosphatase (BSAP) | -6.000 units/liter |
| 180 mg LY2541546 Q2W | Change From Baseline to 52 Week Endpoint in Bone-specific Alkaline Phosphatase (BSAP) | -2.000 units/liter |
| 270 mg LY2541546 Q2W | Change From Baseline to 52 Week Endpoint in Bone-specific Alkaline Phosphatase (BSAP) | 1.600 units/liter |
| 270 mg LY2541546 Q12W + Placebo | Change From Baseline to 52 Week Endpoint in Bone-specific Alkaline Phosphatase (BSAP) | -3.150 units/liter |
| Placebo Q2W | Change From Baseline to 52 Week Endpoint in Bone-specific Alkaline Phosphatase (BSAP) | -3.900 units/liter |
Secondary
Change From Baseline to 52 Week Endpoint in Osteocalcin
Time frame: Baseline, 52 weeks
Population: Participants who received at least one dose of study drug with baseline and at least one post-baseline osteocalcin value.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 180 mg LY2541546 Q4W + Placebo | Change From Baseline to 52 Week Endpoint in Osteocalcin | -2.087 micrograms/liter |
| 180 mg LY2541546 Q2W | Change From Baseline to 52 Week Endpoint in Osteocalcin | -0.764 micrograms/liter |
| 270 mg LY2541546 Q2W | Change From Baseline to 52 Week Endpoint in Osteocalcin | 0.823 micrograms/liter |
| 270 mg LY2541546 Q12W + Placebo | Change From Baseline to 52 Week Endpoint in Osteocalcin | -3.322 micrograms/liter |
| Placebo Q2W | Change From Baseline to 52 Week Endpoint in Osteocalcin | -2.029 micrograms/liter |
Secondary
Change From Baseline to 52 Week Endpoint in Serum N-terminal Extension Propeptide of Type I Collagen (P1NP)
Time frame: Baseline, 52 weeks
Population: Participants who received at least one dose of study drug with baseline and at least one post-baseline serum N-terminal extension propeptide of type I collagen value.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 180 mg LY2541546 Q4W + Placebo | Change From Baseline to 52 Week Endpoint in Serum N-terminal Extension Propeptide of Type I Collagen (P1NP) | -12.250 nanograms/milliliter |
| 180 mg LY2541546 Q2W | Change From Baseline to 52 Week Endpoint in Serum N-terminal Extension Propeptide of Type I Collagen (P1NP) | -4.200 nanograms/milliliter |
| 270 mg LY2541546 Q2W | Change From Baseline to 52 Week Endpoint in Serum N-terminal Extension Propeptide of Type I Collagen (P1NP) | -1.100 nanograms/milliliter |
| 270 mg LY2541546 Q12W + Placebo | Change From Baseline to 52 Week Endpoint in Serum N-terminal Extension Propeptide of Type I Collagen (P1NP) | -16.050 nanograms/milliliter |
| Placebo Q2W | Change From Baseline to 52 Week Endpoint in Serum N-terminal Extension Propeptide of Type I Collagen (P1NP) | -5.800 nanograms/milliliter |
Secondary
Change From Baseline to 52 Week Endpoint in Serum Type I Collagen Fragment (CTx)
Time frame: Baseline, 52 weeks
Population: Participants who received at least one dose of study drug with baseline and at least one post-baseline serum type I collagen fragment value.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 180 mg LY2541546 Q4W + Placebo | Change From Baseline to 52 Week Endpoint in Serum Type I Collagen Fragment (CTx) | -0.014 nanograms/milliliter |
| 180 mg LY2541546 Q2W | Change From Baseline to 52 Week Endpoint in Serum Type I Collagen Fragment (CTx) | -0.088 nanograms/milliliter |
| 270 mg LY2541546 Q2W | Change From Baseline to 52 Week Endpoint in Serum Type I Collagen Fragment (CTx) | -0.038 nanograms/milliliter |
| 270 mg LY2541546 Q12W + Placebo | Change From Baseline to 52 Week Endpoint in Serum Type I Collagen Fragment (CTx) | -0.022 nanograms/milliliter |
| Placebo Q2W | Change From Baseline to 52 Week Endpoint in Serum Type I Collagen Fragment (CTx) | 0.037 nanograms/milliliter |
Secondary
Change From Baseline to 52 Week Endpoint in Wrist Bone Mineral Density (BMD)
Total radius of the wrist bone mineral density (BMD) measured by dual energy x-ray absorptiometry (DXA). Least squares (LS) mean values were determined using a 1-factor analysis of covariance model with treatment group as the main effect and baseline BMD as a covariate.
Time frame: Baseline, 52 weeks
Population: Participants who received at least one dose of study drug with baseline and at least one post-baseline total radius of the wrist BMD value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 180 mg LY2541546 Q4W + Placebo | Change From Baseline to 52 Week Endpoint in Wrist Bone Mineral Density (BMD) | -0.005 g/cm^2 |
| 180 mg LY2541546 Q2W | Change From Baseline to 52 Week Endpoint in Wrist Bone Mineral Density (BMD) | -0.005 g/cm^2 |
| 270 mg LY2541546 Q2W | Change From Baseline to 52 Week Endpoint in Wrist Bone Mineral Density (BMD) | -0.001 g/cm^2 |
| 270 mg LY2541546 Q12W + Placebo | Change From Baseline to 52 Week Endpoint in Wrist Bone Mineral Density (BMD) | -0.002 g/cm^2 |
| Placebo Q2W | Change From Baseline to 52 Week Endpoint in Wrist Bone Mineral Density (BMD) | -0.005 g/cm^2 |