Healthy
Conditions
Keywords
RPH101, RPH-101, Biosimilar, Bevacizumab, Safety
Brief summary
The purpose of this to assess pharmacokinetic bioequivalence between two bevacizumab products, RPH-001 (TRPHARM) and EU sourced Avastin® (Roche), after single IV administration at 5 mg/kg fixed dose.
Interventions
BIOLOGICALRPH001
Avastin® has been approved for treatment of various cancers in many countries of the world including the USA, EU countries, and Turkey. In Turkey, Avastin® is approved with a different trade name, Altuzan®, for treatment of metastatic colorectal cancer.
BIOLOGICALAvastin®
R-Pharm created a biological analog of Avastin®, RPH-001. RPH-001 and Avastin® have similar physicochemical properties, pharmacokinetic profile and affinity to human vascular endothelial growth factor, similar toxicity and efficacy confirmed by preclinical study results.
Sponsors
TRPHARM
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male subjects aged 18 to 55 years inclusive. * Adult healthy male subjects between 18.0 and 30.0 kg/m2 body mass index (inclusive) and body weight ≥ 60 kg and ≤ 100 kg (inclusive).
Exclusion criteria
* Any history or presence of clinically relevant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, metabolic, hematological, neurological, osteomuscular, articular, psychiatric, systemic, ocular, or infectious disease, or signs of acute illness. * Positive result on any of the following tests: hepatitis B surface (HBs Ag) antigen, anti hepatitis C virus (anti-HCV) antibodies, anti-human immunodeficiency virus 1 and 2 antibodies (anti-HIV1 and anti HIV2 Ab). * Positive result on urine drug screen (amphetamines/methamphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, opiates). * Positive alcohol test at screening or baseline visits
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum plasma concentration | Until 100 days after administration | Cmax |
| Area under concentration-time curve from time zero to the last sampling time | Until 100 days after administration | Area Under the Curve - AUC(0-t) |
| Area under concentration-time curve from time zero to infinity | Until 100 days after administration | Area Under the Curve - AUC(0-∞) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Concentration-time profiles | Until 100 days after administration | RPH-001 and Avastin® |
| Time to maximum concentration (Tmax) | Until 100 days after administration | RPH-001 and Avastin® |
| Terminal elimination half-life (t½) | Until 100 days after administration | RPH-001 and Avastin® |
| Terminal elimination rate constant (λz) | Until 100 days after administration | RPH-001 and Avastin® |
| Apparent volume of distribution (Vz) | Until 100 days after administration | RPH-001 and Avastin® |
| Clearance (CL) | Until 100 days after administration | — |
| Volume of distribution at steady state (Vss) | Until 100 days after administration | — |
| Nature, frequency, severity and relationship to study drug of recorded adverse events | Until 100 days after administration | — |
| Physical examination | Until 100 days after administration | — |
| Heart rate | Until 100 days after administration | — |
| Blood Pressure | Until 100 days after administration | — |
| Respiratory rate | Until 100 days after administration | — |
| Oxygen saturation | Until 100 days after administration | — |
| Body temperature | Until 100 days after administration | — |
| ECG | Until 100 days after administration | — |
| Clinical laboratory tests | Until 100 days after administration | — |
| Anti-drug-antibody (ADA) | Until 100 days after administration | — |
| Neutralizing antibody (NAb) | Until 100 days after administration | — |
Outcome results
None listed