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

NCT02053753 | Completed Phase 1 Results

• 1 other identifier: 20120186
• Study Type: interventional
• Target: 146
• Locations: 1 country
• Sites: 2

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

Outcome Measures

Primary Outcomes (2)

• Maximum Observed Drug Concentration (Cmax) of Denosumab

  Serum denosumab concentration-time data were analyzed by non-compartmental methods. Serum concentrations below the LLOQ (20.0 ng/mL) were set to 0 before data analysis.

  Day 1 predose up to day 127

• Area Under the Drug Concentration-time Curve From Time 0 to 18 Weeks Post-dose (AUC0-18 Weeks) of Denosumab

  Serum denosumab concentration-time data were analyzed by non-compartmental methods. Serum concentrations below the LLOQ (20.0 ng/mL) were set to 0 before data analysis.

  Day 1 predose up to day 127

Secondary Outcomes (7)

• Time to Maximum Observed Concentration (Tmax) of Denosumab

  Day 1 predose up to day 127

• Half-life (T1/2) of Denosumab

  Day 1 predose up to day 127

• Area Under the Serum C-telopeptide (CTX1) Percent Inhibition-Time Curve From Time 0 to 18 Weeks Post-dose (AUEC0-18 Weeks)

  Day 1 predose up to day 127

• Maximum Percent Inhibition (Imax) of Serum CTX1

  Day 1 predose up to day 127

• Time to Reach Maximum Percent Inhibition (Tmax) of Serum CTX1

  Day 1 predose up to day 127

Study Arms (2)

Drug Product CP4

EXPERIMENTAL

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

Drug: Denosumab CP4

Drug Product CP2

EXPERIMENTAL

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

Drug: Denosumab CP2

Interventions

Denosumab CP4 DRUG

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

Drug Product CP4

Denosumab CP2 DRUG

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

Also known as: XGEVA®

Drug Product CP2

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Amgen: lead

Study Sites (2)

Research Site

Cypress, California, 90630, United States

Location

Research Site

San Antonio, Texas, 78209, United States

Location

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Interventions

Denosumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 31, 2014
• First Posted: February 4, 2014
• Study Start: February 1, 2014
• Primary Completion: August 1, 2014
• Study Completion: August 1, 2014
• Last Updated: December 29, 2017
• Results First Posted: December 29, 2017

Record last verified: 2017-07

Locations

US (2)