Healthy
Conditions
Keywords
Postmenopausal females, Volunteers
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.
Interventions
DRUGLY2541546 - SC
Administered SC
DRUGLY2541546 - IV
Administered IV
DRUGPlacebo - SC
Administered SC
DRUGPlacebo - IV
Administered IV
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
45 Years to 80 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 9 |
| 270 mg LY2541546 SC Q2W 270 mg LY2541546 administered (SC) once every 2 weeks (Q2W) for 8 weeks. | 11 |
| 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. | 10 |
| 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. | 9 |
| 750 mg LY2541546 IV Q2W 750 mg administered (IV) once every 2 weeks (Q2W) for 8 weeks. | 8 |
| Placebo Q2W Placebo administered IV or SC once every 2 weeks for 8 weeks. | 12 |
| Total | 59 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | 180 mg LY2541546 SC Q4W | 270 mg LY2541546 SC Q2W | 270 mg LY2541546 SC Q4W | 540 mg LY2541546 IV Q4W | 750 mg LY2541546 IV Q2W | Placebo Q2W | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 58 years STANDARD_DEVIATION 5.1 | 57 years STANDARD_DEVIATION 5.5 | 56 years STANDARD_DEVIATION 7.5 | 57 years STANDARD_DEVIATION 8.3 | 66 years STANDARD_DEVIATION 8.8 | 62 years STANDARD_DEVIATION 10.5 | 59 years STANDARD_DEVIATION 8.3 |
| Race/Ethnicity, Customized Asian | 0 participants | 4 participants | 0 participants | 0 participants | 4 participants | 4 participants | 12 participants |
| Race/Ethnicity, Customized Black or African American | 0 participants | 0 participants | 1 participants | 1 participants | 0 participants | 0 participants | 2 participants |
| Race/Ethnicity, Customized White | 9 participants | 7 participants | 9 participants | 8 participants | 4 participants | 8 participants | 45 participants |
| Region of Enrollment United States | 9 participants | 11 participants | 10 participants | 9 participants | 8 participants | 12 participants | 59 participants |
| Sex: Female, Male Female | 9 Participants | 11 Participants | 10 Participants | 9 Participants | 8 Participants | 12 Participants | 59 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 7 / 9 | 11 / 11 | 7 / 10 | 5 / 9 | 7 / 8 | 9 / 12 |
| serious Total, serious adverse events | 0 / 9 | 0 / 11 | 0 / 10 | 0 / 9 | 1 / 8 | 0 / 12 |
Outcome results
Primary
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
Time frame: Day 1 through Day 141
Population: All participants who received study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 180 mg LY2541546 SC Q4W | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 participants |
| 270 mg LY2541546 SC Q2W | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 participants |
| 270 mg LY2541546 SC Q4W | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 participants |
| 540 mg LY2541546 IV Q4W | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 participants |
| 750 mg LY2541546 IV Q2W | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 participants |
| Placebo Q2W | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 participants |
Secondary
Immunogenicity: The Number of Participants With Anti-LY2541546 Antibodies
Time frame: Predose (Day 1) and Postdose (Day 29, 85 and 141)
Population: All participants who received study drug and had evaluable antibody results at the analyzed time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 180 mg LY2541546 SC Q4W | Immunogenicity: The Number of Participants With Anti-LY2541546 Antibodies | Day 1 | 0 participants |
| 180 mg LY2541546 SC Q4W | Immunogenicity: The Number of Participants With Anti-LY2541546 Antibodies | Day 29 | 1 participants |
| 180 mg LY2541546 SC Q4W | Immunogenicity: The Number of Participants With Anti-LY2541546 Antibodies | Day 85 | 3 participants |
| 180 mg LY2541546 SC Q4W | Immunogenicity: The Number of Participants With Anti-LY2541546 Antibodies | Day 141 | 3 participants |
| 270 mg LY2541546 SC Q2W | Immunogenicity: The Number of Participants With Anti-LY2541546 Antibodies | Day 29 | 0 participants |
| 270 mg LY2541546 SC Q2W | Immunogenicity: The Number of Participants With Anti-LY2541546 Antibodies | Day 1 | 0 participants |
| 270 mg LY2541546 SC Q2W | Immunogenicity: The Number of Participants With Anti-LY2541546 Antibodies | Day 141 | 2 participants |
| 270 mg LY2541546 SC Q2W | Immunogenicity: The Number of Participants With Anti-LY2541546 Antibodies | Day 85 | 2 participants |
| 270 mg LY2541546 SC Q4W | Immunogenicity: The Number of Participants With Anti-LY2541546 Antibodies | Day 1 | 0 participants |
| 270 mg LY2541546 SC Q4W | Immunogenicity: The Number of Participants With Anti-LY2541546 Antibodies | Day 29 | 1 participants |
| 270 mg LY2541546 SC Q4W | Immunogenicity: The Number of Participants With Anti-LY2541546 Antibodies | Day 85 | 4 participants |
| 270 mg LY2541546 SC Q4W | Immunogenicity: The Number of Participants With Anti-LY2541546 Antibodies | Day 141 | 2 participants |
| 540 mg LY2541546 IV Q4W | Immunogenicity: The Number of Participants With Anti-LY2541546 Antibodies | Day 1 | 0 participants |
| 540 mg LY2541546 IV Q4W | Immunogenicity: The Number of Participants With Anti-LY2541546 Antibodies | Day 29 | 0 participants |
| 540 mg LY2541546 IV Q4W | Immunogenicity: The Number of Participants With Anti-LY2541546 Antibodies | Day 141 | 1 participants |
| 540 mg LY2541546 IV Q4W | Immunogenicity: The Number of Participants With Anti-LY2541546 Antibodies | Day 85 | 0 participants |
| 750 mg LY2541546 IV Q2W | Immunogenicity: The Number of Participants With Anti-LY2541546 Antibodies | Day 85 | 0 participants |
| 750 mg LY2541546 IV Q2W | Immunogenicity: The Number of Participants With Anti-LY2541546 Antibodies | Day 1 | 1 participants |
| 750 mg LY2541546 IV Q2W | Immunogenicity: The Number of Participants With Anti-LY2541546 Antibodies | Day 29 | 0 participants |
| 750 mg LY2541546 IV Q2W | Immunogenicity: The Number of Participants With Anti-LY2541546 Antibodies | Day 141 | 5 participants |
| Placebo Q2W | Immunogenicity: The Number of Participants With Anti-LY2541546 Antibodies | Day 29 | 0 participants |
| Placebo Q2W | Immunogenicity: The Number of Participants With Anti-LY2541546 Antibodies | Day 85 | 0 participants |
| Placebo Q2W | Immunogenicity: The Number of Participants With Anti-LY2541546 Antibodies | Day 141 | 0 participants |
| Placebo Q2W | Immunogenicity: The Number of Participants With Anti-LY2541546 Antibodies | Day 1 | 0 participants |
Secondary
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.
Time frame: Predose and Day 85
Population: All participants who received study drug and had evaluable BMD results at the analyzed time points.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 180 mg LY2541546 SC Q4W | Pharmacodynamics (PD): Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at Day 85 | 0.02 gram per square centimeter (g/cm^2) |
| 270 mg LY2541546 SC Q2W | Pharmacodynamics (PD): Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at Day 85 | 0.05 gram per square centimeter (g/cm^2) |
| 270 mg LY2541546 SC Q4W | Pharmacodynamics (PD): Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at Day 85 | 0.03 gram per square centimeter (g/cm^2) |
| 540 mg LY2541546 IV Q4W | Pharmacodynamics (PD): Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at Day 85 | 0.05 gram per square centimeter (g/cm^2) |
| 750 mg LY2541546 IV Q2W | Pharmacodynamics (PD): Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at Day 85 | 0.06 gram per square centimeter (g/cm^2) |
| Placebo Q2W | Pharmacodynamics (PD): Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at Day 85 | 0.00 gram per square centimeter (g/cm^2) |
Secondary
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.
Time frame: Predose, through Day 141
Population: All participants who received study drug and had evaluable P1NP results at the analyzed time points.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| 180 mg LY2541546 SC Q4W | Pharmacodynamics (PD): Change From Baseline in N-terminal Propeptide of Procollagen Type 1 (P1NP) | Day 85 | 1.69 microgram per liter (ug/L) |
| 180 mg LY2541546 SC Q4W | Pharmacodynamics (PD): Change From Baseline in N-terminal Propeptide of Procollagen Type 1 (P1NP) | Day 29 | 20.36 microgram per liter (ug/L) |
| 270 mg LY2541546 SC Q2W | Pharmacodynamics (PD): Change From Baseline in N-terminal Propeptide of Procollagen Type 1 (P1NP) | Day 85 | 24.19 microgram per liter (ug/L) |
| 270 mg LY2541546 SC Q2W | Pharmacodynamics (PD): Change From Baseline in N-terminal Propeptide of Procollagen Type 1 (P1NP) | Day 29 | 121.68 microgram per liter (ug/L) |
| 270 mg LY2541546 SC Q4W | Pharmacodynamics (PD): Change From Baseline in N-terminal Propeptide of Procollagen Type 1 (P1NP) | Day 85 | 9.66 microgram per liter (ug/L) |
| 270 mg LY2541546 SC Q4W | Pharmacodynamics (PD): Change From Baseline in N-terminal Propeptide of Procollagen Type 1 (P1NP) | Day 29 | 42.60 microgram per liter (ug/L) |
| 540 mg LY2541546 IV Q4W | Pharmacodynamics (PD): Change From Baseline in N-terminal Propeptide of Procollagen Type 1 (P1NP) | Day 85 | 52.44 microgram per liter (ug/L) |
| 540 mg LY2541546 IV Q4W | Pharmacodynamics (PD): Change From Baseline in N-terminal Propeptide of Procollagen Type 1 (P1NP) | Day 29 | 124.47 microgram per liter (ug/L) |
| 750 mg LY2541546 IV Q2W | Pharmacodynamics (PD): Change From Baseline in N-terminal Propeptide of Procollagen Type 1 (P1NP) | Day 29 | 134.93 microgram per liter (ug/L) |
| 750 mg LY2541546 IV Q2W | Pharmacodynamics (PD): Change From Baseline in N-terminal Propeptide of Procollagen Type 1 (P1NP) | Day 85 | 91.06 microgram per liter (ug/L) |
| Placebo Q2W | Pharmacodynamics (PD): Change From Baseline in N-terminal Propeptide of Procollagen Type 1 (P1NP) | Day 85 | 4.20 microgram per liter (ug/L) |
| Placebo Q2W | Pharmacodynamics (PD): Change From Baseline in N-terminal Propeptide of Procollagen Type 1 (P1NP) | Day 29 | 1.36 microgram per liter (ug/L) |
Secondary
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.
Time frame: Day 1 through Day 141
Population: All participants who received study drug and had sufficient evaluable results for PK analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 180 mg LY2541546 SC Q4W | Pharmacokinetics (PK): Area Under the Concentration-Time Curve During Dosing Interval at Steady State (AUCss, 0-tau) of LY2541546 | First Dose | 6.77 nanomole x hour per mililiter (nmol*h/mL | Standard Deviation 2 |
| 180 mg LY2541546 SC Q4W | Pharmacokinetics (PK): Area Under the Concentration-Time Curve During Dosing Interval at Steady State (AUCss, 0-tau) of LY2541546 | Last Dose | 6.85 nanomole x hour per mililiter (nmol*h/mL | Standard Deviation 2.09 |
| 270 mg LY2541546 SC Q2W | Pharmacokinetics (PK): Area Under the Concentration-Time Curve During Dosing Interval at Steady State (AUCss, 0-tau) of LY2541546 | First Dose | 18.5 nanomole x hour per mililiter (nmol*h/mL | Standard Deviation 5.27 |
| 270 mg LY2541546 SC Q2W | Pharmacokinetics (PK): Area Under the Concentration-Time Curve During Dosing Interval at Steady State (AUCss, 0-tau) of LY2541546 | Last Dose | 38.4 nanomole x hour per mililiter (nmol*h/mL | Standard Deviation 13.3 |
| 270 mg LY2541546 SC Q4W | Pharmacokinetics (PK): Area Under the Concentration-Time Curve During Dosing Interval at Steady State (AUCss, 0-tau) of LY2541546 | First Dose | 13.9 nanomole x hour per mililiter (nmol*h/mL | Standard Deviation 4.73 |
| 270 mg LY2541546 SC Q4W | Pharmacokinetics (PK): Area Under the Concentration-Time Curve During Dosing Interval at Steady State (AUCss, 0-tau) of LY2541546 | Last Dose | 14.7 nanomole x hour per mililiter (nmol*h/mL | Standard Deviation 5.45 |
| 540 mg LY2541546 IV Q4W | Pharmacokinetics (PK): Area Under the Concentration-Time Curve During Dosing Interval at Steady State (AUCss, 0-tau) of LY2541546 | Last Dose | 68.9 nanomole x hour per mililiter (nmol*h/mL | Standard Deviation 11.4 |
| 540 mg LY2541546 IV Q4W | Pharmacokinetics (PK): Area Under the Concentration-Time Curve During Dosing Interval at Steady State (AUCss, 0-tau) of LY2541546 | First Dose | 61.2 nanomole x hour per mililiter (nmol*h/mL | Standard Deviation 7.23 |
| 750 mg LY2541546 IV Q2W | Pharmacokinetics (PK): Area Under the Concentration-Time Curve During Dosing Interval at Steady State (AUCss, 0-tau) of LY2541546 | First Dose | 167 nanomole x hour per mililiter (nmol*h/mL | Standard Deviation 11.9 |
| 750 mg LY2541546 IV Q2W | Pharmacokinetics (PK): Area Under the Concentration-Time Curve During Dosing Interval at Steady State (AUCss, 0-tau) of LY2541546 | Last Dose | 332 nanomole x hour per mililiter (nmol*h/mL | Standard Deviation 54.6 |