Bioequivalence Study of Denosumab CP4 Drug Product and Commercially Available Denosumab CP2 Drug Product
Condition: Healthy Volunteer
Intervention: Denosumab CP4; Denosumab CP2
Intervention description: Denosumab produced by a process referred to as CP4, administered subcutaneously.; Denosumab produced by a process referred to as CP2, administered subcutaneously.
Intervention MeSH terms: Denosumab
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 146.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: denosumab, bioequivalence

Summary:

      To evaluate the bioequivalence based on pharmacokinetics (PK) of a single 120 mg subcutaneous
      dose of denosumab administered to healthy volunteers using denosumab CP4 or denosumab CP2
      drug products.
    

Eligibility criteria:

        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