A 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 determine if a single dose of LY2541546 has any side effects on the body and to determine how long and how much LY2541546 stays in the bloodstream of the body.

Official Title
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A Single-Dose, Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LY2541546 in Healthy Postmenopausal Women

Conditions
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Healthy

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


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 Additional Inclusion Criterion for Participants in Open Label Groups: Are currently taking or recently discontinued (not more than 3 months prior to study randomization) alendronate and have taken alendronate for at least 12 of the last 18 months 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 Known allergies to LY2541546, its constituents, or related compounds Persons who have previously participated in this study History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders History of or high risk for adverse outcome from bleeding, for example, transient ischemic attacks, cerebrovascular attacks, and ulcer disease 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 Participants who have an average weekly alcohol intake that exceeds 14 units per week Cigarette consumption of more than 10 cigarettes per day, or are unable or unwilling to refrain from nicotine during Clinical Research Unit (CRU) confinement Additional Exclusion Criterion for Participants in Double Blind Groups Only Have received bisphosphonates during the previous 24 months. Additional Exclusion Criterion for Participants in Open Label Groups Have received intravenous bisphosphonates within the previous 18 months

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 70 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: 7.5 mg LY2541546 - IV<br>Single dose of 7.5 mg LY2541546 administered intravenously (IV) | Drug: LY2541546 - IV<br>* Administered IV<br>* Other names: Blosozumab;|
| Experimental: 25 mg LY2541546 - IV<br>Single dose of 25 mg LY2541546 administered IV | Drug: LY2541546 - IV<br>* Administered IV<br>* Other names: Blosozumab;|
| Experimental: 75 mg LY2541546 - IV<br>Single dose of 75 mg LY2541546 administered IV | Drug: LY2541546 - IV<br>* Administered IV<br>* Other names: Blosozumab;|
| Experimental: 225 mg LY2541546 - IV<br>Single dose of 225 mg LY2541546 administered IV | Drug: LY2541546 - IV<br>* Administered IV<br>* Other names: Blosozumab;|
| Experimental: 750 mg LY2541546 - IV<br>Single dose of 750 mg LY2541546 administered IV | Drug: LY2541546 - IV<br>* Administered IV<br>* Other names: Blosozumab;|
| Experimental: 150 mg LY2541546 - SC<br>Single dose of 150 mg LY2541546 administered subcutaneous (SC) | Drug: LY2541546 - SC<br>* Administered SC<br>|
| Placebo Comparator: Placebo<br>Single dose of placebo administered IV or SC | Drug: Placebo<br>* Administered IV or SC<br>|
| Experimental: 225 mg LY2541546 - IV, OL<br>Single dose of 225 mg LY2541546 administered IV, open label (OL) | Drug: LY2541546 - IV<br>* Administered IV<br>* Other names: Blosozumab;|
| Experimental: 750 mg LY2541546 - IV, OL<br>Single dose of 750 mg LY2541546 administered IV, OL | Drug: LY2541546 - IV<br>* Administered IV<br>* Other names: Blosozumab;|

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 or is considered significant by the investigator for any other reason. | Day 1 through Day 85 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Area Under the Concentration Curve Versus Time Curve From Time Zero to Infinity (AUC0-∞) of LY2541546 |  | Day 1: Predose,30 minutes,45 mintues,1 hour (hr), 1.5 hr, 3 hr, 6 hr, 12 hr Postdose; Day (D) 3,D5 ,D8, D11, D15, D29, D43, D57, D71,D85: anytime | 
| Pharmacodynamics (PD): Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) | A BMD test measures the amount of mineral (such as calcium) in a defined area of bone in grams per square centimeter (g/cm²) and is calculate by dexascan. | Baseline (predose), Day 29 anytime, Day 85 anytime | 
| Pharmacodynamics (PD): Percent 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. Percentage change in P1NP from baseline to post baseline time points was analyzed using the repeated-measures model. | Baseline (predose), Day 29 anytime, Day 85 anytime | 
| Immunogenicity: The Number of Participants With Anti-LY2541546 Antibodies | A validated assay designed to perform in the presence of LY2541546 was used for to assess development of antibodies. | Day 1: Predose, Day 29 anytime, Day 85 anytime | 

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