Comparison of Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Bmab 1000 and Prolia® in Normal Healthy Volunteers: DENARIUS: DENosumab Pharmacokinetic equivAlence tRIal in Healthy volUnteerS
- Conditions
- Healthy Volunteers
- Interventions
- Biological: Bmab 1000Biological: Prolia®
- Registration Number
- NCT05323708
- Lead Sponsor
- Biocon Biologics UK Ltd
- Brief Summary
This study is to compare the Pharmacokinetics, Pharmacodynamics, safety, and tolerability of Bmab 1000 and Prolia® in normal healthy volunteers.
- Detailed Description
This study will consist of 2 study periods: Screening period (4 weeks) and Treatment period (Dosing and follow-up).
In this double-blind, 2-arm study, the eligible subjects will be randomized in a 1:1 ratio to receive either Bmab 1000 or Prolia® on Day 1. The interventions (Bmab 1000 or Prolia®) will be administered subcutaneously. End-of-study visit will be at Week 36 post randomization.
The total duration of study participation for a subject will be up to 40 weeks.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 190
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Bmab 1000, A single 60 mg dose of Bmab 1000 administered by subcutaneous injection. Bmab 1000 - Prolia®, A single 60 mg dose of Prolia® administered by subcutaneous injection. Prolia® -
- Primary Outcome Measures
Name Time Method Cmax 0 to 36 week Maximum serum concentration
AUCinf (Area Under the Concentration infinity) 0 to 36 week Area under the concentration-time curve from time zero to infinity
AUClast (Area Under the Concentration last) 0 to 36 week Area under the concentration-time curve from time zero to last quantifiable concentration
- Secondary Outcome Measures
Name Time Method Vd/F 0 to 36 week Apparent volume of distribution
Cl/F 0 to 36 week Apparent clearance
AUEC of sCTX 0 to 36 week Area under the effect curve (AUEC) of serum concentration of C-terminal telopeptide of Type 1 collagen (sCTX)
Incidence of ADAs (Anti-Drug Antibodies) 0 to 36 week Incidence of ADAs to denosumab
Tmax 0 to 36 week Time to reach Cmax
t1/2 0 to 36 week Terminal half-life
Emax of sCTX 0 to 36 week Maximal inhibitory effect (Emax) of sCTX
Kel 0 to 36 week Terminal elimination rate constant (kel)
Incidence of TEAEs(Treatment Emergent Adverse Events) 0 to 36 week Experience at least 1 TEAE
Incidence of SAEs(Serious Adverse Events) 0 to 36 week Experience at least 1 SAE
Titer of ADAs 0 to 36 week Titer of ADAs to denosumab
Trial Locations
- Locations (1)
Biotrial Inc
🇺🇸Newark, New Jersey, United States