Clinical trial NCT02053753: Bioequivalence Study of Denosumab CP4 Drug Product and Commercially Available Denosumab CP2 Drug Product
Official title: A Double-Blind, Randomized, Single-Dose, Parallel-Group Study in Healthy Volunteers to Assess the Bioequivalence of a 120 mg Denosumab Subcutaneous Dose When Administered as Denosumab CP4 Drug Product or as Commercially Available Denosumab CP2 Drug Product
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteer
Keywords: denosumab, bioequivalence
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2014-02-04
Enrollment: 146
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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

Primary outcomes:
measure: Maximum Observed Drug Concentration (Cmax) of Denosumab
timeFrame: Day 1 predose up to day 127
measure: Area Under the Drug Concentration-time Curve From Time 0 to 18 Weeks Post-dose (AUC0-18 Weeks) of Denosumab
timeFrame: Day 1 predose up to day 127
Secondary outcomes:
measure: Time to Maximum Observed Concentration (Tmax) of Denosumab
timeFrame: Day 1 predose up to day 127
measure: Half-life (T1/2) of Denosumab
timeFrame: Day 1 predose up to day 127
measure: Area Under the Serum C-telopeptide (CTX1) Percent Inhibition-Time Curve From Time 0 to 18 Weeks Post-dose (AUEC0-18 Weeks)
timeFrame: Day 1 predose up to day 127
measure: Maximum Percent Inhibition (Imax) of Serum CTX1
timeFrame: Day 1 predose up to day 127
measure: Time to Reach Maximum Percent Inhibition (Tmax) of Serum CTX1
timeFrame: Day 1 predose up to day 127
measure: Number of Participants With Adverse Events
timeFrame: From the first dose of denosumab through day 126
measure: Number of Participants Who Developed Anti-denosumab Antibodies
timeFrame: Predose on day 1, and days 29, 67 and 127
Other outcomes:
Locations:
city: Cypress
country: United States
facility: Research Site
state: California
city: San Antonio
country: United States
facility: Research Site
state: Texas
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: