A First-in-human Study Evaluating Romosozumab (AMG 785) in Healthy Men and Postmenopausal Women

A Randomized, Double-blind, Placebo-controlled, Ascending Single-dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 785 in Healthy Men and Postmenopausal Women

The primary objective of this study is to assess the safety and tolerability of romosozumab following single dose subcutaneous (SC) or intravenous (IV) administration in healthy men and postmenopausal women.

Inclusion Criteria:

• Healthy males or female between 45 to 59 years of age, inclusive
• Postmenopausal females defined as 12 continuous months of spontaneous amenorrhea confirmed by a serum follicle-stimulating hormone (FSH) result > 40mIU/mL, or 6 weeks postsurgical bilateral oophorectomy (with or without hysterectomy)
• Males must agree to use a condom during sexual intercourse with female partners who are of reproductive potential and to have their female partners use an additional effective means of contraception or to abstain from sexual intercourse for the duration of the study
• Has no history or evidence of a clinically significant disorder, condition or disease that would pose a risk to subject safety or interfere with the study evaluation, procedures or completion

Exclusion Criteria:

• Diagnosed with any condition that will affect bone metabolism
• Administration of the following medications within 6 months before study drug administration:
• Hormone replacement therapy [Infrequent use of estrogen vaginal creams (< 3 times per week) is allowed.]
• Calcitonin
• Parathyroid hormone (or any derivative)
• Supplemental Vitamin D > 1,000 IU/day
• Glucocorticosteroids (inhaled or topical corticosteroids administered more than 2 weeks before the enrollment date are allowed)
• Anabolic steroids
• Calcitriol, and available analogues
• Administration of the following medications within 12 months before study drug administration:
• Bisphosphonates
• Fluoride for osteoporosis
• Administration of herbal medications within 2 weeks or 5 half-lives (whichever is longer) before study drug administration
• Greatly differing levels of physical activity or constant levels of intense physical exercise during the 6 months before study drug administration
• Routine alcohol intake of > 2 drinks per day, on average, within 6 months of study drug administration
• Known sensitivity to mammalian-derived drug preparations
• Known to be hepatitis B surface antigen, hepatitis C virus, or human immunodeficiency virus (HIV) positive, or a known diagnosis of acquired immunodeficiency syndrome (AIDS)
• Any organic or psychiatric disorder which may pose a risk to subject safety and may prevent the subject from completing the study or interfere with the interpretation of the study results
• Unavailable for follow-up assessment or any concerns for subject's compliance with the protocol procedures
• Any other condition that might reduce the chance of obtaining data required by the protocol or that might compromise the ability to give truly informed consent
• Has a history of drug or alcohol abuse with the last 12 months and/or a positive urine test result at screening or admission
• Has any clinically significant abnormality during the screening physical examination, electrocardiogram (ECG), or laboratory evaluation
• Has participated in another clinical study within 4 weeks of screening or within 5 times the half-life of the investigational agent in the other clinical study, if known
• Weight ≥ 98 kilograms (216 pounds) and/or height ≥ 78 inches
• Has donated or lost 400 milliliters or more of blood or plasma within 8 weeks of study drug administration