Comparison of Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Bmab 1000 and Prolia® in Normal Healthy Volunteers: DENARIUS: DENosumab Pharmacokinetic equivAlence tRIal in Healthy volUnteerS

Summary: This study is to compare the Pharmacokinetics, Pharmacodynamics, safety, and tolerability of Bmab 1000 and Prolia® in normal healthy volunteers.
clinicaltrials.gov

Acronym: DENARIUS
clinicaltrials.gov

Short title: Comparison of Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Bmab 1000 and Prolia® in Normal Healthy Volunteers: DENARIUS: DENosumab Pharmacokinetic equivAlence tRIal in Healthy volUnteerS
clinicaltrials.gov

Official title: A Randomized, Double-blind, Two-arm, Single-dose, Parallel-Group Study to Compare the Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Bmab 1000 and Prolia® in Normal Healthy Volunteers
clinicaltrials.gov

Control arm: Active comparator
clinicaltrials.gov

Registry reports results: No
clinicaltrials.gov

Listing at source: Listed
clinicaltrials.gov

Recruitment status: Completed
clinicaltrials.gov

Phase: Phase 1
clinicaltrials.gov

Study type: Interventional
clinicaltrials.gov

Completion date: 2023-10-06
clinicaltrials.gov

First posted: 2022-04-12
clinicaltrials.gov

Registry last updated: 2024-04-17
clinicaltrials.gov

Primary completion date: 2023-10-06
clinicaltrials.gov

Start date: 2022-03-09
clinicaltrials.gov

Actual participants: 190
clinicaltrials.gov

Participants: 190
clinicaltrials.gov

Participant count basis: Actual
clinicaltrials.gov

Protocol amendments: 3
clinicaltrials.gov

Randomisation ratio: 1:1
clinicaltrials.gov

Number of sites: 1
clinicaltrials.gov

Data monitoring committee: No
clinicaltrials.gov

Registry sponsor category: Industry
clinicaltrials.gov

Lead sponsor: Biocon Biologics UK Ltd
clinicaltrials.gov

Source registry: ClinicalTrials.gov
clinicaltrials.gov

Registry ID: NCT05323708
clinicaltrials.gov

ClinicalTrials.gov ID: NCT05323708
clinicaltrials.gov

Registry record: Open registry record
clinicaltrials.gov

Allocation: Randomised
Model: Parallel groups
Purpose: Treatment
Masking: Double masking
Masking description: Double-blind (Patient, Investigator)
Masked roles: Participants, Investigators

Sources for study design

clinicaltrials.gov

AUCinf (Area Under the Concentration infinity)
Timeframe: 0 to 36 week
Area under the concentration-time curve from time zero to infinity
AUClast (Area Under the Concentration last)
Timeframe: 0 to 36 week
Area under the concentration-time curve from time zero to last quantifiable concentration
Cmax
Timeframe: 0 to 36 week
Maximum serum concentration

Tmax
Timeframe: 0 to 36 week
Time to reach Cmax
t1/2
Timeframe: 0 to 36 week
Terminal half-life
Kel
Timeframe: 0 to 36 week
Terminal elimination rate constant (kel)
Vd/F
Timeframe: 0 to 36 week
Apparent volume of distribution
Cl/F
Timeframe: 0 to 36 week
Apparent clearance
AUEC of sCTX
Timeframe: 0 to 36 week
Area under the effect curve (AUEC) of serum concentration of C-terminal telopeptide of Type 1 collagen (sCTX)
Emax of sCTX
Timeframe: 0 to 36 week
Maximal inhibitory effect (Emax) of sCTX
Incidence of TEAEs(Treatment Emergent Adverse Events)
Timeframe: 0 to 36 week
Experience at least 1 TEAE
Incidence of SAEs(Serious Adverse Events)
Timeframe: 0 to 36 week
Experience at least 1 SAE
Incidence of ADAs (Anti-Drug Antibodies)
Timeframe: 0 to 36 week
Incidence of ADAs to denosumab
Titer of ADAs
Timeframe: 0 to 36 week
Titer of ADAs to denosumab

Sources for outcomes

clinicaltrials.gov

Sex: All
Age groups: Adults
Minimum age: 28 Years
Maximum age: 55 Years
Healthy volunteers: Yes

Gender: Male or Female
Age: Male subjects: 28-55 years, inclusive at screening; Female subjects: 28-45 years, inclusive at screening.
Weight: For non-Japanese subjects 60.0-95.0 kg, inclusive at screening. For Japanese subjects 55.0-95.0 kg, inclusive at screening.
Body mass index (BMI) between 18.0 and 30.0 kg/m2, inclusive, at screening.
Vital signs showing no clinically relevant deviations according to the Investigator's judgment or their designee's. In the case of subjects > 45 year-old, if a value of SBP above 145 mmHg is confirmed on rechecking the BP after a period of rest, this subject will not be included in the study.
12-lead ECG recording without signs of clinically relevant pathology or showing no clinically relevant deviations as judged by the Investigator or their designee.

Evidence of clinically relevant pathology: Like have a history of and/or current clinically significant gastrointestinal, renal, hepatic, cardiovascular, haematological, pulmonary, neurologic, metabolic, psychiatric disorder, drug or alcohol abuse, or allergic disease excluding mild asymptomatic seasonal allergies. Have a history of malignancy (including lymphoma, leukaemia, and skin cancer).
Unable to follow protocol instructions or not likely to complete the study in the opinion of the Investigator or their designee.
History of relevant drug and/or food allergies (including hypersensitivity to any recombinant protein drug or any of the constituents of denosumab, or latex allergy or hereditary problems of fructose intolerance).
Known history of previous exposure to denosumab.
Have previously been exposed to a monoclonal antibody or fusion protein (other than denosumab) within 270 days (or 5 half-lives whichever is the longest) prior to randomization and/or there is confirmed evidence or clinical suspicion of immunogenicity from previous exposure to a monoclonal antibody or fusion protein.
Prior diagnosis of bone disease, or any condition that will affect bone metabolism such as, but not limited to: osteoporosis, osteogenesis imperfect, 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 < 60 mL/min), Paget's disease of the bone, recent bone fracture (within 6 months), malabsorption syndrome.
Any use of the following bone modifying medications, with no limitation on time since administration: e.g.intravenous bisphosphonates, strontium, fluoride (if administered in treatment of osteoporosis),romosozumab, teriparatide or any parathyroid hormone analogs, calcitonin, and cinacalcet.

Sources for eligibility

clinicaltrials.gov