A Multiple Dose Study of LY2541546 in Healthy Postmenopausal Women

Phase 1

Completed

Conditions: Healthy

Interventions: Drug: LY2541546 - SC
Drug: LY2541546 - IV
Drug: Placebo - SC
Drug: Placebo - IV

Registration Number: NCT01742091

Lead Sponsor: Eli Lilly and Company

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 59

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
180 mg LY2541546 SC Q4W	LY2541546 - SC	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.
180 mg LY2541546 SC Q4W	Placebo - SC	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.
270 mg LY2541546 SC Q2W	LY2541546 - SC	270 mg LY2541546 administered (SC) once every 2 weeks (Q2W) for 8 weeks.
270 mg LY2541546 SC Q4W	LY2541546 - SC	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.
270 mg LY2541546 SC Q4W	Placebo - SC	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.
540 mg LY2541546 IV Q4W	LY2541546 - IV	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.
540 mg LY2541546 IV Q4W	Placebo - IV	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.
750 mg LY2541546 IV Q2W	LY2541546 - IV	750 mg administered (IV) once every 2 weeks (Q2W) for 8 weeks.
Placebo Q2W	Placebo - SC	Placebo administered IV or SC once every 2 weeks for 8 weeks.
Placebo Q2W	Placebo - IV	Placebo administered IV or SC once every 2 weeks for 8 weeks.

Primary Outcome Measures

Name	Time	Method
Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration	Day 1 through Day 141	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

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics (PK): Area Under the Concentration-Time Curve During Dosing Interval at Steady State (AUCss, 0-tau) of LY2541546	Day 1 through Day 141	Weekly AUC (AUC\[0-tau\]) during the first and last dosing interval for each participant receiving LY2541546 is reported.
Pharmacodynamics (PD): Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at Day 85	Predose and 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.
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)	Predose, through Day 141	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.

Trial Locations

Locations (1): For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
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Dallas, Texas, United States