Healthy
Conditions
Keywords
Pharmacokinetics
Brief summary
The purpose of this study is to compare the pharmacokinetics, safety and immunogenicity of SB4 and Enbrel (EU sourced Enbrel and US sourced Enbrel) in healthy male subjects.
Detailed description
* Part A: Comparison between SB4 and EU sourced Enbrel * Part B: Comparison between SB4 and US sourced Enbrel * Part C: Comparison between EU sourced Enbrel and US sourced Enbrel
Interventions
BIOLOGICALSB4
SC administration
BIOLOGICALEU sourced Enbrel
SC administration
BIOLOGICALUS sourced Enbrel
SC administration
Sponsors
Samsung Bioepis Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male subjects * Have a body weight between 60 and 94.9 kg and a body mass index between 20.0 and 29.9 kg/m², inclusive.
Exclusion criteria
* history and/or current presence of clinical significant atopic allergy, hypersensitivity or allergic reactions, also including known or suspected clinically relevant drug hypersensitivity to any components of the test and reference IP formulation or comparable drugs. * active or latent Tuberculosis or who have a history of TB. * history of invasive systemic fungal infections or other opportunistic infections * systemic or local infection, a known risk for developing sepsis and/or known active inflammatory process * serious infection associated with hospitalisation and/or which required intravenous antibiotics * history of and/or current cardiac disease * have received live vaccine(s) within 30 days prior to Screening or who will require live vaccine(s) between Screening and the final study visit. * Intake medication with a half-life \> 24 h within 1 month or 10 half-lives of the medication prior to the first administration of IP.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) | 0 to 480 hours post-dose | pre-dose and at 6, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 216, 312 and 480 h post-dose |
| Maximum Serum Concentration (Cmax) | 0 to 480 hours post-dose | pre-dose (0 h) and at 6, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 216, 312 and 480 h post-dose. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) | 0 to 480 hours post-dose | pre-dose and at 6, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 216, 312 and 480 h post-dose |
| Time to Cmax (Tmax) | 0 to 480 hours post-dose | pre-dose and at 6, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 216, 312 and 480 h post-dose |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SB4 and EU Sourced Enbrel in Part A SB4 followed by EU sourced Enbrel
SB4: SC administration
EU sourced Enbrel: SC administration | 23 |
| EU Sourced Enbrel and SB4 in Part A EU sourced Enbrel followed by SB4
SB4: SC administration
EU sourced Enbrel: SC administration | 23 |
| SB4 and US Sourced Enbrel in Part B SB4 followed by US sourced Enbrel
SB4: SC administration
US sourced Enbrel: SC administration | 23 |
| US Sourced Enbrel and SB4 in Part B US sourced Enbrel followed by SB4
SB4: SC administration
US sourced Enbrel: SC administration | 23 |
| EU and US Sourced Enbrel in Part C EU sourced Enbrel followed by US sourced Enbrel
EU sourced Enbrel: SC administration
US sourced Enbrel: SC administration | 23 |
| US and EU Sourced Enbrel in Part C US sourced Enbrel followed by EU sourced Enbrel
EU sourced Enbrel: SC administration
US sourced Enbrel: SC administration | 23 |
| Total | 138 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Period 1 | Adverse Event | 1 | 0 | 0 | 1 | 1 | 1 |
| Period 1 | Other | 0 | 0 | 0 | 0 | 1 | 0 |
| Period 1 | Pathological lab | 0 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Total | SB4 and EU Sourced Enbrel in Part A | EU Sourced Enbrel and SB4 in Part A | SB4 and US Sourced Enbrel in Part B | US Sourced Enbrel and SB4 in Part B | EU and US Sourced Enbrel in Part C | US and EU Sourced Enbrel in Part C |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 40 years STANDARD_DEVIATION 9.8 | 38 years STANDARD_DEVIATION 9.4 | 41 years STANDARD_DEVIATION 10.9 | 38 years STANDARD_DEVIATION 9.7 | 43 years STANDARD_DEVIATION 8.9 | 40 years STANDARD_DEVIATION 10.5 | 41 years STANDARD_DEVIATION 9.4 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 138 Participants | 23 Participants | 23 Participants | 23 Participants | 23 Participants | 23 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 46 | 0 / 46 | 0 / 46 | 0 / 46 | 0 / 46 | 0 / 46 |
| other Total, other adverse events | 18 / 46 | 16 / 46 | 23 / 46 | 20 / 46 | 17 / 46 | 14 / 46 |
| serious Total, serious adverse events | 0 / 46 | 0 / 46 | 0 / 46 | 0 / 46 | 0 / 46 | 0 / 46 |
Outcome results
Primary
Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf)
pre-dose and at 6, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 216, 312 and 480 h post-dose
Time frame: 0 to 480 hours post-dose
Population: Overall number of participans Analyzed equals to number of subjects who contributed to summary statistics.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SB4 in Part A | Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) | 769.069 µg·h/mL | Standard Deviation 243.9039 |
| EU Sourced Enbrel in Part A | Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) | 771.680 µg·h/mL | Standard Deviation 226.2874 |
| SB4 in Part B | Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) | 834.680 µg·h/mL | Standard Deviation 242.7652 |
| US Sourced Enbrel in Part B | Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) | 810.054 µg·h/mL | Standard Deviation 195.977 |
| EU Sourced Enbrel in Part C | Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) | 790.110 µg·h/mL | Standard Deviation 274.2535 |
| US Sourced Enbrel in Part C | Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) | 768.228 µg·h/mL | Standard Deviation 238.1251 |
Primary
Maximum Serum Concentration (Cmax)
pre-dose (0 h) and at 6, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 216, 312 and 480 h post-dose.
Time frame: 0 to 480 hours post-dose
Population: Overall number of participans Analyzed equals to number of subjects who contributed to summary statistics.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SB4 in Part A | Maximum Serum Concentration (Cmax) | 3.607 μg/mL | Standard Deviation 1.4298 |
| EU Sourced Enbrel in Part A | Maximum Serum Concentration (Cmax) | 3.435 μg/mL | Standard Deviation 1.239 |
| SB4 in Part B | Maximum Serum Concentration (Cmax) | 3.869 μg/mL | Standard Deviation 1.3251 |
| US Sourced Enbrel in Part B | Maximum Serum Concentration (Cmax) | 3.613 μg/mL | Standard Deviation 1.0252 |
| EU Sourced Enbrel in Part C | Maximum Serum Concentration (Cmax) | 3.720 μg/mL | Standard Deviation 1.5444 |
| US Sourced Enbrel in Part C | Maximum Serum Concentration (Cmax) | 3.575 μg/mL | Standard Deviation 1.4833 |
Secondary
Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast)
pre-dose and at 6, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 216, 312 and 480 h post-dose
Time frame: 0 to 480 hours post-dose
Population: Overall number of participans Analyzed equals to number of subjects who contributed to summary statistics.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SB4 in Part A | Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) | 728.169 µg·h/mL | Standard Deviation 234.7621 |
| EU Sourced Enbrel in Part A | Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) | 734.015 µg·h/mL | Standard Deviation 220.2722 |
| SB4 in Part B | Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) | 788.773 µg·h/mL | Standard Deviation 232.4636 |
| US Sourced Enbrel in Part B | Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) | 765.187 µg·h/mL | Standard Deviation 184.5046 |
| EU Sourced Enbrel in Part C | Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) | 752.277 µg·h/mL | Standard Deviation 259.2088 |
| US Sourced Enbrel in Part C | Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) | 727.820 µg·h/mL | Standard Deviation 229.8597 |
Secondary
Time to Cmax (Tmax)
pre-dose and at 6, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 216, 312 and 480 h post-dose
Time frame: 0 to 480 hours post-dose
Population: Overall number of participans Analyzed equals to number of subjects who contributed to summary statistics.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SB4 in Part A | Time to Cmax (Tmax) | 75.198 h | Standard Deviation 29.1358 |
| EU Sourced Enbrel in Part A | Time to Cmax (Tmax) | 71.711 h | Standard Deviation 24.7538 |
| SB4 in Part B | Time to Cmax (Tmax) | 75.263 h | Standard Deviation 30.8374 |
| US Sourced Enbrel in Part B | Time to Cmax (Tmax) | 70.385 h | Standard Deviation 22.4972 |
| EU Sourced Enbrel in Part C | Time to Cmax (Tmax) | 70.276 h | Standard Deviation 30.3826 |
| US Sourced Enbrel in Part C | Time to Cmax (Tmax) | 71.150 h | Standard Deviation 29.7904 |