A Multiple Dose Study of LY2541546 in Healthy Postmenopausal Women

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: LY2541546 - SC; Drug: Placebo - SC; Drug: LY2541546 - IV; Drug: Placebo - IV

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Daytona Beach, Florida, United States, 32117
      • 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.
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • 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.
  • Indiana
    • Evansville, Indiana, United States, 47710
      • 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.
  • Texas
    • Austin, Texas, United States, 78752
      • 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.
    • Dallas, Texas, United States, 75247
      • 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.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 180 mg LY2541546 SC Q4W; 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; Administered SC; Other Names: Blosozumab; Drug: Placebo - SC; Administered SC
Experimental: 270 mg LY2541546 SC Q2W; 270 mg LY2541546 administered (SC) once every 2 weeks (Q2W) for 8 weeks.	Drug: LY2541546 - SC; Administered SC; Other Names: Blosozumab
Experimental: 270 mg LY2541546 SC Q4W; 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; Administered SC; Other Names: Blosozumab; Drug: Placebo - SC; Administered SC
Experimental: 540 mg LY2541546 IV Q4W; 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; Administered IV; Other Names: Blosozumab; Drug: Placebo - IV; Administered IV
Experimental: 750 mg LY2541546 IV Q2W; 750 mg administered (IV) once every 2 weeks (Q2W) for 8 weeks.	Drug: LY2541546 - IV; Administered IV; Other Names: Blosozumab
Placebo Comparator: Placebo Q2W; Placebo administered IV or SC once every 2 weeks for 8 weeks.	Drug: Placebo - SC; Administered SC; Drug: Placebo - IV; Administered IV

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (Actual): March 1, 2010
• Study Completion (Actual): March 1, 2010

Study Registration Dates

• First Submitted: December 3, 2012
• First Submitted That Met QC Criteria: December 4, 2012
• First Posted (Estimate): December 5, 2012

Study Record Updates

• Last Update Posted (Actual): July 18, 2018
• Last Update Submitted That Met QC Criteria: September 27, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: Volunteers; Postmenopausal females
• Other Study ID Numbers: 13405 (City of Hope Medical Center); I2M-MC-GSDE (Other Identifier: Eli Lilly and Company)