Approximately 140 male and female healthy subjects will be randomized (1: 1 ratio) to receive
a 120 mg single dose of denosumab either as a 1. 7 mL single injection of 70 mg/mL denosumab
CP4 (Treatment A) or as a 1. 7 mL single injection of 70 mg/mL denosumab CP2 (Treatment B).
Subjects will be admitted to the research facility on day - 1 and remain in the research
facility through day 2. The subjects will return to the research facility on an outpatient
basis. The PK, PD, and safety assessments will be conducted during the inpatient stay and at
regular intervals during the 18-week treatment period.
Minimum age: 18 Years.
Maximum age: 65 Years.
Gender(s): Both.
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