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

Amgen

Status and phase

Completed

Phase 1

Conditions

Healthy Volunteer

Treatments

Drug: Denosumab CP4

Drug: Denosumab CP2

Study type

Interventional

Funder types

Industry

Identifiers

NCT02053753

20120186

Details and patient eligibility

About

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.

Enrollment

146 patients

Sex

All

Ages

18 to 65 years old

Volunteers

Accepts Healthy Volunteers

Inclusion and exclusion 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