Phase 1
N=146
Bioequivalence Study of Denosumab CP4 Drug Product and Commercially Available Denosumab CP2 Drug Product
Healthy Volunteer
Bottom Line
View on ClinicalTrials.gov: NCT02053753 ↗Enrolled (actual)
146
Serious AEs
0.7%
Results posted
Dec 2017
Primary outcome: Primary: Maximum Observed Drug Concentration (Cmax) of Denosumab — 12.7; 11.8 μg/mL
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- Denosumab CP4 (Drug); Denosumab CP2 (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Amgen
- Primary completion
- Aug 2014
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Maximum Observed Drug Concentration (Cmax) of Denosumab |
12.7; 11.8 | — |
| PRIMARY Area Under the Drug Concentration-time Curve From Time 0 to 18 Weeks Post-dose (AUC0-18 Weeks) of Denosumab |
579; 555 | — |
| SECONDARY Time to Maximum Observed Concentration (Tmax) of Denosumab |
6.9; 7.0 | — |
| SECONDARY Half-life (T1/2) of Denosumab |
23.9; 22.4 | — |
| SECONDARY Area Under the Serum C-telopeptide (CTX1) Percent Inhibition-Time Curve From Time 0 to 18 Weeks Post-dose (AUEC0-18 Weeks) |
8380; 8190 | — |
| SECONDARY Maximum Percent Inhibition (Imax) of Serum CTX1 |
69.8; 70.3 | — |
| SECONDARY Time to Reach Maximum Percent Inhibition (Tmax) of Serum CTX1 |
3.01; 3.96 | — |
| SECONDARY Number of Participants With Adverse Events |
26; 24; 0; 1; 0; 0 | — |
| SECONDARY Number of Participants Who Developed Anti-denosumab Antibodies |
0; 0 | — |
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 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
Data sourced from ClinicalTrials.gov (NCT02053753). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.