Healthy Participants
Conditions
Keywords
Adalimumab, Pharmacokinetic
Brief summary
A Single-Center, Randomized, Single-Blind, Single-Dose, Parallel-Group Trial to Assess the Pharmacokinetic Similarity Between CHS-1420 40 mg/0.4 mL and HUMIRA® (Adalimumab) 40 mg/0.4 mL in Healthy Chinese Adult Participants under Fasting Conditions
Interventions
Sponsors
Nanjing King-Friend Biochemical Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Able to provide signed Informed Consent Form before the trial, and fully understand the trial content, process and possible adverse drug reactions (ADRs) 2. Able to complete the trial in compliance with the protocol 3. Participants (including males) willing to adopt effective contraceptive methods and with no pregnancy plan from 14 days before screening to 6 months after the last scheduled visit 4. Males and females between 18 and 55 years old, inclusive 5. At least 50 kg for participants, with a Body Mass Index(BMI)=Weight/ Height2 (kg/m2) between 19.0-26.0 kg/m2, inclusive 6. No history of chro nic or serious cardiac, hepatic, renal, digestive tract,nervous system, hematologic, respiratory, dermatological, mental and metabolic disorders, etc.
Exclusion criteria
1. With ≥ 5 cigarettes per day on average within 3 months before screening, or not able to quit smoking during the trial 2. Allergic constitution, or allergic to the drug components and its analogues; history of allergic reaction to a biological medication 3. A history of alcohol abuse (alcohol consumption of more than 14 units per week : 1 unit of alcohol = 285 mL beer, or 25 mL spirits, or 100 mL wine) 4. Blood donation or massive blood loss (\> 400 mL) within 3 months before investigational products dosing; Or any blood donation plan from screening until 3 months after administration 5. History of any major surgery within the past year, or history of any surgery within the past 6 months; or any elective medical procedures, including dental procedures 6. Any history of organ transplantation 7. Medical history of tuberculosis (or suspected tuberculosis), or with a positive tuberculosis test result 8. Medical history of heart failure or other cardiac disorders which may lead to heart failure, e.g. coronary heart disease, hypertension, senile degenerative valvular disease, rheumatic valvular heart disease, dilated cardiomyopathy, acute severe myocarditis 9. Medical history of immune system disorders (e.g. systemic lupus erythematosus, multiple sclerosis, etc.), or positive results of antinuclear antibody tests 10. Medical history of recurrent or chronic infections (including transverse myelitis, optic neuritis, other demyelinating disorders, etc.), or a history of an opportunistic infection within the past year due to bacterial, mycobacterial, invasive fungal, viral, parasitic, or other opportunistic pathogens 11. History of seizure attack 12. Medication history of TNF-α blockers e.g. Adalimumab or its analogues 13. Any medication of monoclonal antibodies within the past year before investigational products dosing 14. Any usage history of prescription medicines or OTCs (especially antibiotics), or Chinese herbal medicine or health supplementary within 30 days before investigational products dosing 15. Any vaccination within 3 months before investigational products dosing, or any plan for vaccination within 3 months after investigational products administration 16. Consumption of any special diets or food items (such as grapefruit), or strenuous exercise engagement, or other factors in the opinion of investigators affecting drug absorption, distribution, metabolism and excretion within 7 days before investigational products dosing 17. Participation in other drug clinical trials within 3 months before investigational products dosing 18. Any clinically significant abnormality findings, as judged by a clinical physican, such as physical examination, vital signs, electrocardiogram and laboratory tests, as well as Chest X-ray 19. Positive results of hepatitis B surface antigen, hepatitis C antibody, and HIV antibody or syphilis 20. Consumption of chocolate or any food/beverage containing caffeine or rich in xanthine within 48 h before investigational products dosing 21. Consumption of any products containing alcohol within 48 h before investigational products dosing, or a positive result of the alcohol breath test 22. A positive result of the drug abuse test, or a history of drug abuse in the past 5 years, or intake of any narcotic drugs within 3 months prior to the trial 23. A positive result of the pregnancy test, or in lactation during screening or the test period for female participants 24. Not tolerable on venipuncture, or a history of fainting on acupuncture and/or blood 25. Special requirements and unable to follow the unified diet 26. Unable to participate in this trial for participants' own reasons 27. Other conditions in which participants are not suitable for the trial determined by investigators
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Areas Under the Serum Concentration Versus Time Curve Extrapolated to Infinity (AUC0-∞) | 0 to 1536 hours post-dose | pre-dose (0 h) and at 2, 4, 8, 12,24,36,48,60,72,96,120,144,168,216,288,360,528,696,864,1032,1200,1368,1536h post-dose |
| The Maximum Serum Drug Concentration (Cmax) | 0 to 1536 hours post-dose | pre-dose (0 h) and at 2, 4, 8, 12,24,36,48,60,72,96,120,144,168,216,288,360,528,696,864,1032,1200,1368,1536h post-dose |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Areas Under the Serum Concentration Versus Time Curve Calculated to the Last Measurable Observation (AUC0-t) | 0 to 1536 hours post-dose | pre-dose (0 h) and at 2, 4, 8, 12,24,36,48,60,72,96,120,144,168,216,288,360,528,696,864,1032,1200,1368,1536h post-dose |
| Areas Under the Serum Concentration Versus Time Curve Calculated to 65 Days Postdose(AUC0-65days) | 0 to 1536 hours post-dose | pre-dose (0 h) and at 2, 4, 8, 12,24,36,48,60,72,96,120,144,168,216,288,360,528,696,864,1032,1200,1368,1536h post-dose |
| The Time to Maximum Serum Concentration(Tmax) | 0 to 1536 hours post-dose | pre-dose (0 h) and at 2, 4, 8, 12,24,36,48,60,72,96,120,144,168,216,288,360,528,696,864,1032,1200,1368,1536h post-dose |
| The Elimination Half-life (t1/2) | 0 to 1536 hours post-dose | pre-dose (0 h) and at 2, 4, 8, 12,24,36,48,60,72,96,120,144,168,216,288,360,528,696,864,1032,1200,1368,1536h post-dose |
| Elimination Rate Constant (Kel) | 0 to 1536 hours post-dose | pre-dose (0 h) and at 2, 4, 8, 12,24,36,48,60,72,96,120,144,168,216,288,360,528,696,864,1032,1200,1368,1536h post-dose |
| Volumeof Distribution (Vd/F) | 0 to 1536 hours post-dose | pre-dose (0 h) and at 2, 4, 8, 12,24,36,48,60,72,96,120,144,168,216,288,360,528,696,864,1032,1200,1368,1536h post-dose |
| Clearance(CL/F) | 0 to 1536 hours post-dose | pre-dose (0 h) and at 2, 4, 8, 12,24,36,48,60,72,96,120,144,168,216,288,360,528,696,864,1032,1200,1368,1536h post-dose |
| Immunogenicity Estimands | Day1 to Day 65 | Presence of anti-adalimumab antibodies |
| Safety Estimands | Day1 to Day 65 | Frequency of Adverse Events |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CHS-1420 CHS-1420(adalimumab) at a dose of 40 mg, administered as a single subcutaneous injection, which will be performed on day 1 | 119 |
| HUMIRA® Humira (adalimumab) at a dose of 40 mg, administered as a single subcutaneous injection, which will be performed on day 1. | 119 |
| Total | 238 |
Baseline characteristics
| Characteristic | CHS-1420 | HUMIRA® | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 119 Participants | 119 Participants | 238 Participants |
| BMI | 23.33 kg/m^2 STANDARD_DEVIATION 1.437 | 23.25 kg/m^2 STANDARD_DEVIATION 1.689 | 23.29 kg/m^2 STANDARD_DEVIATION 1.565 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 119 Participants | 119 Participants | 238 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 44 Participants | 44 Participants | 88 Participants |
| Sex: Female, Male Male | 75 Participants | 75 Participants | 150 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 119 | 0 / 119 |
| other Total, other adverse events | 59 / 119 | 69 / 119 |
| serious Total, serious adverse events | 0 / 119 | 0 / 119 |
Outcome results
Primary
PK Endpoints
Areas under the serum concentration versus time curve extrapolated to infinity (AUC0-∞).
Time frame: Day1 to Day 65
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CHS-1420 | PK Endpoints | 2321566.8 h·ng/mL | Standard Deviation 995890.41 |
| HUMIRA® | PK Endpoints | 2358855.5 h·ng/mL | Standard Deviation 1038026.7 |
Primary
PK Endpoints
The maximum serum drug concentration (Cmax)
Time frame: Day1 to Day 65
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CHS-1420 | PK Endpoints | 3602.38 ng/mL | Standard Deviation 1145.963 |
| HUMIRA® | PK Endpoints | 3620.75 ng/mL | Standard Deviation 1489.729 |
Secondary
Immunogenicity Estimands
Presence of anti-adalimumab antibodies
Time frame: Day1 to Day 65
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CHS-1420 | Immunogenicity Estimands | ADA positive participants at 0h | 1 Participants |
| CHS-1420 | Immunogenicity Estimands | No Anit-Drug Antibody Confirmed Positive Results | 9 Participants |
| CHS-1420 | Immunogenicity Estimands | baseline negative ADA participants with at least one post dose positive ADA result | 109 Participants |
| HUMIRA® | Immunogenicity Estimands | ADA positive participants at 0h | 4 Participants |
| HUMIRA® | Immunogenicity Estimands | No Anit-Drug Antibody Confirmed Positive Results | 14 Participants |
| HUMIRA® | Immunogenicity Estimands | baseline negative ADA participants with at least one post dose positive ADA result | 100 Participants |
Secondary
PK Endpoints
The time to maximum serum concentration(Tmax)
Time frame: Day1 to Day 65
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CHS-1420 | PK Endpoints | 168.000 h |
| HUMIRA® | PK Endpoints | 156.000 h |
Secondary
PK Endpoints
Elimination rate constant (Kel)
Time frame: Day1 to Day 65
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CHS-1420 | PK Endpoints | 0.0053 1/h | Standard Deviation 0.0034 |
| HUMIRA® | PK Endpoints | 0.0050 1/h | Standard Deviation 0.0034 |
Secondary
PK Endpoints
Volumeof distribution (Vd/F)
Time frame: Day1 to Day 65
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CHS-1420 | PK Endpoints | 5489.1 mL | Standard Deviation 3152.11 |
| HUMIRA® | PK Endpoints | 5687.4 mL | Standard Deviation 3240.04 |
Secondary
PK Endpoints
Clearance(CL/F)
Time frame: Day1 to Day 65
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CHS-1420 | PK Endpoints | 20.6798 mL/h | Standard Deviation 8.8808 |
| HUMIRA® | PK Endpoints | 20.9731 mL/h | Standard Deviation 10.7637 |
Secondary
PK Endpoints
The elimination half-life (t1/2)
Time frame: Day1 to Day 65
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CHS-1420 | PK Endpoints | 240.698 h | Standard Deviation 219.3439 |
| HUMIRA® | PK Endpoints | 238.869 h | Standard Deviation 186.2289 |
Secondary
PK Endpoints
Areas under the serum concentration versus time curve calculated to the last measurable observation (AUC0-t)
Time frame: Day1 to Day 65
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CHS-1420 | PK Endpoints | 2153350.8 h·ng/mL | Standard Deviation 808597.63 |
| HUMIRA® | PK Endpoints | 2191368.0 h·ng/mL | Standard Deviation 884277.79 |
Secondary
PK Endpoints
Areas under the serum concentration versus time curve calculated to 65 days postdose(AUC0-65days)
Time frame: Day1 to Day 65
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CHS-1420 | PK Endpoints | 2154968.6 h·ng/mL | Standard Deviation 807292.73 |
| HUMIRA® | PK Endpoints | 2192846.0 h·ng/mL | Standard Deviation 883361.98 |
Secondary
Safety Estimands
Frequency of Adverse Events
Time frame: Day1 to Day 65
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CHS-1420 | Safety Estimands | 59 Participants |
| HUMIRA® | Safety Estimands | 69 Participants |