Bioequivalence Study of Denosumab CP4 Drug Product and Commercially Available Denosumab CP2 Drug Product

Key Inclusion:

- Healthy male and female, ages ≥ 18 to ≤ 65 years (inclusive)

- Body weight > 60 to < 100 kg at time of screening

- Clinically acceptable physical exams and laboratory tests (blood hematology, blood
chemistry, urinalysis) and no history or evidence of any clinically significant
medical disorder that would pose a risk to subject safety or interfere with study
evaluations or procedures

- Normal or clinically acceptable electrocardiogram (ECG) (12-lead reporting heart rate
and PR, QRS, QT, and QTc intervals) at screening

- Willing to be confined to the research facility for 2 consecutive nights

- Subject will be available for follow-up assessments

Exclusion Criteria:

Prior diagnosis of bone disease, or any condition that will affect bone metabolism such as,
but not limited to: osteoporosis, osteogenesis imperfecta, hyperparathyroidism,
hyperthyroidism, hypothyroidism, osteomalacia, rheumatoid arthritis, psoriatic arthritis,
ankylosing spondylitis, current flare-up of osteoarthritis and/or gout, active malignancy,
renal disease (defined as glomerular filtration rate [GFR] < 45 mL/min), Paget's disease of
the bone, recent bone fracture (within 6 months), malabsorption syndrome

- Presents with any psychiatric disorder, which may prevent the subject from completing
the study or interfere with the interpretation of the study results

- Significant changes in physical activity during the 6 months before study drug
administration or constant levels of intense physical exercise

- Prior use of any non-Amgen approved medications within 4 weeks or 5-half lives
(whichever time period is longer) of study drug administration and for the duration of
the study. This includes medications such as, but not limited to: bisphosphonates,
fluoride, hormone replacement therapy (ie, estrogen) or selective estrogen receptor
modulator, such as ralaxofene, calcitonin, strontium, parathyroid hormone or
derivatives, supplemental vitamin D [>1000 IU/day], glucocorticosteroids, anabolic
steroids, calcitriol, diuretics, over the counter medications, herbal supplements

- Positive for human immunodeficiency virus (HIV) at screening or known diagnosis of
acquired immune deficiency syndrome (AIDS)

- Positive hepatitis B surface antigen (HepBsAg) (indicative of chronic hepatitis B) or
detectable hepatitis C virus ribonucleic acid (RNA) by polymerase chain reaction (PCR)
at screening (indicative of active hepatitis C - screening is generally done by
hepatitis C antibody [HepCAb], followed by hepatitis C virus RNA by PCR if HepCAb is
positive)

- Known sensitivity to any of the products to be administered during the study

- Prior denosumab administration

- Receiving or has received any investigational drug (or is currently using an
investigational device) within 30 days before receiving study drug, or at least 10
times the respective elimination half-life (whichever period is longer) and for the
duration of the study

- Women with a positive pregnancy test at screening or day-1

- Men and women of reproductive potential who are unwilling to practice a highly
effective method of birth control while on study through 5 months after receiving the
last dose of study drug. Highly effective methods of birth control include sexual
abstinence (men, women); vasectomy; or a condom with spermicide (men) in combination
with either barrier methods, hormonal birth control or intrauterine device (women)

- Women who are lactating/breastfeeding or who plan to breastfeed while on study through
5 half-lives after receiving the dose of study drug

- Women planning to become pregnant while on study through 5 months after receiving the
dose of study drug

- Men with partners who are pregnant or planning to become pregnant while the subject is
on study through 5 months after receiving the last dose of study drug

- Unwilling or unable to limit alcohol consumption throughout the course of the study.
Alcohol is prohibited 24 hours prior to screening, 24 hours prior to check-in on day
-1, and throughout confinement. Alcohol is also limited to no more than 2 drinks per
day during the outpatient period of the study through completion of day 127 (EOS). A
standard drink is equivalent to 12 ounces of regular beer, 8 to 9 ounces of malt
liquor, 5 ounces of wine, or 1.5 ounces of 80 proof distilled spirits

- Positive urine screen for alcohol and/or drugs with a high potential for abuse at
screening or day -1. Rescreening of the subject within 48 hours of a positive result
is permitted

- Any other condition that might reduce the chance of obtaining data required by
protocol or that might compromise the ability to give truly informed consent and/or
comply with study procedures

- Osteonecrosis of the jaw (ONJ) or risk factors for ONJ such as invasive dental
procedures (eg, tooth extraction, dental implants, oral surgery in the past 6 months),
poor oral hygiene, periodontal, and/or pre-existing dental disease

- Recent tooth extraction (within 6 months of screening visit)

- Evidence of hypocalcemia at screening

- Known vitamin D deficiency

- Known intolerance to calcium or vitamin D supplements