Comparing the Extent to Which Romosozumab (AMG 785) is Made Available in the Body When Administered as a Single SC Injection or as 2 SC Injections

A Phase 1, Open-label, Randomized, Parallel Group Study to Evaluate the Relative Bioavailability of Romosozumab (AMG 785) 210 mg Administered as a Single SC Injection or 2 SC Injections in Healthy Participants

The primary objective of this trial is to evaluate the relative bioavailability of romosozumab administered as a single 2.34 mL subcutaneous (SC) injection from a prefilled syringe (PFS) or 2 x 1.17 mL SC injections from PFS in healthy participants.

Inclusion Criteria:

• Healthy adults, male or female, 18 to 60 years of age.
• Able and willing to provide written informed consent before any study procedures.
• Body weight between 45.0 kg and 95.0 kg (inclusive).
• Women must not be able to become pregnant (for example, postmenopausal or permanently sterile, as defined by the protocol).
• Men who can father a child must agree to use the required contraception during the study and for 3 months after the study drug dose.
• Willing and able to take daily calcium (500 to 2,000 mg elemental calcium) and vitamin D (at least 400 IU) supplements from Day 1 through the end of the study.

Exclusion Criteria:

• Any clinically significant medical condition or abnormal finding that, in the opinion of the study doctor, could make participation unsafe or interfere with the study or its results.
• Clinically significant abnormalities on medical history, physical examination, vital signs, electrocardiogram (ECG), or laboratory tests, including suspected Gilbert syndrome.
• History or current signs or symptoms of significant cardiovascular disease, including heart attack, heart failure, congenital heart disease, cardiomyopathy, valve disease, angina, coronary revascularization, stroke, transient ischemic attack, or peripheral revascularization.
• Clinically significant abnormal heart rhythm or conduction disorder, including clinically significant ECG abnormalities.
• QT interval corrected for heart rate (QTcF) greater than 450 milliseconds for men or greater than 470 milliseconds for women, or a history of long QT syndrome.
• Second- or third-degree atrioventricular (AV) block.
• Systolic blood pressure greater than 140 millimeters of mercury (mmHg) or less than 90 mmHg, diastolic blood pressure greater than 90 mmHg or less than 50 mmHg, or pulse rate greater than 100 beats per minute or less than 40 beats per minute at screening or check-in.
• Deep vein thrombosis or pulmonary embolism within 3 months before screening.
• History of osteoporosis, vertebral fracture, or a fragility fracture of the wrist, upper arm, hip, or pelvis after 50 years of age.
• History of metabolic bone disease, including conditions such as Paget disease, osteomalacia, osteogenesis imperfecta, osteopetrosis, sclerosteosis, ankylosing spondylitis, rheumatoid arthritis, Cushing disease, hyperprolactinemia, or malabsorption syndrome.
• History of osteonecrosis of the jaw.
• Bone fracture within 6 months before screening.
• Vitamin D level below 20 nanograms per milliliter (ng/mL) at screening (participants may be treated and retested before enrollment).
• Current hyperparathyroidism or hypoparathyroidism.
• Kidney function below study requirements (estimated glomerular filtration rate less than 60 mL/min/1.73 m^2).
• Low or high blood calcium levels that do not meet study requirements.
• Liver blood test results (alanine aminotransferase [ALT] or aspartate aminotransferase [AST]) above the normal range.
• History of hyperthyroidism or hypothyroidism unless on stable treatment for at least 6 months with normal thyroid function tests.
• History of hearing loss caused by excessive bone growth compressing the eighth cranial nerve.
• Positive test for human immunodeficiency virus (HIV).
• Active hepatitis B or hepatitis C infection.
• Cancer within the past 5 years, except non-melanoma skin cancer or cervical or breast ductal carcinoma in situ.
• History of solid organ or bone marrow transplantation.
• History of allergy or hypersensitivity to romosozumab, its ingredients, other biologic medicines, or medicines derived from mammalian cells.
• Previous use of medications affecting bone metabolism that are not allowed by the protocol, including:
• Any intravenous or oral bisphosphonate.
• Fluoride for osteoporosis within 24 months before screening.
• Denosumab or cathepsin K inhibitors within 18 months before screening.
• Parathyroid hormone or strontium within 12 months before screening.
• Calcitonin, selective estrogen receptor modulators, or tibolone within 3 months before screening.
• Systemic corticosteroids (5 mg or more prednisone equivalent daily for more than 10 days) within 3 months before screening.
• Use of prescription or over-the-counter medications within 30 days or 5 half-lives (whichever is longer) before check-in, unless approved by the study doctor. Acetaminophen up to 2 g/day is permitted. Stable hormone replacement therapy is allowed if unchanged for at least 3 months before dosing and throughout the study.
• Use of herbal medicines, vitamins (other than study-required calcium and vitamin D), or dietary supplements within 30 days before enrollment unless approved by the study doctor.
• Currently participating in another clinical study, receiving another investigational treatment, or participation in another investigational drug or device study within the previous 90 days or 5 half-lives (whichever is longer).
• Previous participation in this study or previous exposure to a sclerostin antibody.
• History of alcohol abuse or regular alcohol intake greater than 14 units per week within the year before check-in.
• Alcohol use within 48 hours before check-in or unwillingness to comply with study alcohol restrictions.
• Positive alcohol test at check-in.
• Positive drug screen for illicit drugs, including cannabis, at screening or check-in.
• History of illicit drug use within 6 months before screening.
• Unwilling to avoid illicit drug use, including cannabis, throughout the study.
• Smoking more than 10 cigarettes per day or equivalent nicotine use within 1 month before check-in, or unwillingness to comply with study tobacco restrictions.
• Consumption of foods or drinks containing poppy seeds within 7 days before check-in.
• Positive pregnancy test at screening or check-in.
• Pregnant, breastfeeding, or planning to breastfeed during the study or within 3 months after receiving the study drug.
• Receipt of blood products within 2 months before check-in.
• Blood donation within 3 months before screening, plasma donation within 2 weeks before screening, or platelet donation within 6 weeks before screening.
• Poor veins that would make repeated blood sampling difficult.
• Any other reason that, in the opinion of the study doctor, would make participation unsafe or inappropriate.