A Multiple Dose Study of LY2541546 in Healthy Postmenopausal Women

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and side effects of multiple doses of LY2541546 in postmenopausal women when given subcutaneously (injection just under the skin) and intravenously (directly into a vein). The study will also test how long it takes the study drug to get into the body, how long it takes the body to get rid of it, the overall effect of the study drug on the body, and whether antibodies to the study drug are formed.

Official Title
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A Multiple Dose Study of LY2541546 to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics in Healthy Postmenopausal Women

Conditions
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Healthy

Intervention / Treatment
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* Drug: LY2541546 - SC
* Drug: LY2541546 - IV
* Drug: Placebo - SC
* Drug: Placebo - IV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy postmenopausal females, as determined by medical history and physical examination Body mass index (BMI) at screening between 19.0 and 32.0 kilograms per square meter (kg/m^2), inclusive Acceptable clinical laboratory test results, blood pressure and heart rate Have given written informed consent Exclusion Criteria: Within 30 days of the initial dose of study drug, have received treatment with a drug that has not received regulatory approval for any indication Have received study treatment in any trial of an investigational osteoporosis treatment, including LY2561553 (parathyroid hormone receptor modulator), within 12 weeks of screening or 5 half-lives, whichever is longer Known allergies to LY2541546, its constituents, or related compounds Persons who have previously participated in this study or any other study of LY2541546 History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders History or presence of low platelet count, bleeding issues or family history of bleeding disorders Paget's disease, parathyroid disease, or thyroid disease Fracture of a long bone within 12 weeks of screening Regular use of known drugs of abuse and/or positive findings on urinary drug screening Evidence of human immunodeficiency virus (HIV), hepatitis C, hepatitis B and/or positive for anti-HIV antibodies, hepatitis C antibody, or hepatitis B surface antigen Current use of therapies for osteoporosis or use of hormone replacement therapy (HRT) within the previous 12 months Blood donation within the last month Are unwilling or unable to maintain their normal pattern of alcohol, caffeine, smoking, and exercise from the start to the end of the study or to abide by the clinical research unit restrictions. Note: Average weekly alcohol intake must not exceed 14 units per week Are unable or unwilling to refrain from nicotine usage during Clinical Research Unit (CRU) confinement

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Female

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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 180 mg LY2541546 SC Q4W<br>180 milligram (mg) LY2541546 administered subcutaneous (SC) once every 4 weeks (Q4W) for 8 weeks. Placebo administered SC at Weeks 2 and 6 to maintain the blind. | Drug: LY2541546 - SC<br>* Administered SC<br>* Other names: Blosozumab;Drug: Placebo - SC<br>* Administered SC<br>|
| Experimental: 270 mg LY2541546 SC Q2W<br>270 mg LY2541546 administered (SC) once every 2 weeks (Q2W) for 8 weeks. | Drug: LY2541546 - SC<br>* Administered SC<br>* Other names: Blosozumab;|
| Experimental: 270 mg LY2541546 SC Q4W<br>270 mg LY2541546 administered (SC) once every 4 weeks (Q4W) for 8 weeks. Placebo administered SC at Weeks 2 and 6 to maintain the blind. | Drug: LY2541546 - SC<br>* Administered SC<br>* Other names: Blosozumab;Drug: Placebo - SC<br>* Administered SC<br>|
| Experimental: 540 mg LY2541546 IV Q4W<br>540 mg administered intravenous (IV) once every 4 weeks (Q4W) for 8 weeks. Placebo administered IV at Weeks 2 and 6 to maintain the blind. | Drug: LY2541546 - IV<br>* Administered IV<br>* Other names: Blosozumab;Drug: Placebo - IV<br>* Administered IV<br>|
| Experimental: 750 mg LY2541546 IV Q2W<br>750 mg administered (IV) once every 2 weeks (Q2W) for 8 weeks. | Drug: LY2541546 - IV<br>* Administered IV<br>* Other names: Blosozumab;|
| Placebo Comparator: Placebo Q2W<br>Placebo administered IV or SC once every 2 weeks for 8 weeks. | Drug: Placebo - SC<br>* Administered SC<br>Drug: Placebo - IV<br>* Administered IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | An SAE is any AE from this study that results in one of the following outcomes: death initial or prolonged inpatient hospitalization a life-threatening experience (that is, immediate risk of dying) persistent or significant disability/incapacity congenital anomaly/birth defect is considered significant by the investigator for any other reason | Day 1 through Day 141 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Area Under the Concentration-Time Curve During Dosing Interval at Steady State (AUCss, 0-tau) of LY2541546 | Weekly AUC (AUC[0-tau]) during the first and last dosing interval for each participant receiving LY2541546 is reported. | Day 1 through Day 141 | 
| Pharmacodynamics (PD): Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at Day 85 | A BMD test measures the amount of mineral (such as calcium) in a defined area of bone in grams per square centimeter (g/cm²). The least squares (LS) mean was adjusted for baseline lumbar spine BMD and treatment group. | Predose and Day 85 | 
| Immunogenicity: The Number of Participants With Anti-LY2541546 Antibodies |  | Predose (Day 1) and Postdose (Day 29, 85 and 141) | 
| Pharmacodynamics (PD): Change From Baseline in N-terminal Propeptide of Procollagen Type 1 (P1NP) | N-terminal propeptide of procollagen type 1 (P1NP) is a main bone formation marker. An increase of P1NP in serum reflects elevated anabolic activities of the bone. Change in P1NP from baseline to post baseline time points was analyzed using the repeated-measures model. Least squares (LS) mean was adjusted for baseline P1NP, treatment group, time (i.e. study day), and interaction between treatment group and time. | Predose, through Day 141 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Postmenopausal females, Volunteers