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

NCT ID: NCT02053753

Last Updated: 2017-12-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 146 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-02-28
• Study Completion Date: 2014-08-31

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.

Conditions

Healthy Volunteer

Keywords

denosumab, bioequivalence

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Drug Product CP4

Participants received a single dose of 120 mg denosumab manufactured using the new CP4 process subcutaneously on day 1.

Group Type: EXPERIMENTAL

Denosumab CP4

Intervention Type: DRUG

Denosumab produced by a process referred to as CP4, administered subcutaneously.

Drug Product CP2

Participants received a single dose of 120 mg denosumab manufactured using the current CP2 process subcutaneously on day 1.

Group Type: EXPERIMENTAL

Denosumab CP2

Intervention Type: DRUG

Denosumab produced by a process referred to as CP2, administered subcutaneously.

Interventions

Denosumab CP4

Denosumab produced by a process referred to as CP4, administered subcutaneously.

Intervention Type: DRUG

Denosumab CP2

Denosumab produced by a process referred to as CP2, administered subcutaneously.

Intervention Type: DRUG

Other Intervention Names

XGEVA®

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Amgen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

MD

Role: STUDY_DIRECTOR

Amgen

Locations

Research Site

Cypress, California, United States

Research Site

San Antonio, Texas, United States

Countries

United States

Related Links

http://www.amgentrials.com

AmgenTrials clinical trials website

Other Identifiers

20120186

Identifier Type: -

Identifier Source: org_study_id