Asthma, Chronic Obstructive Pulmonary Disease
Conditions
Keywords
Asthma, Chronic Obstructive pulmonary Disease, Pharmacokinetics, Healthy volunteers
Brief summary
An open-label, single dose Pharmacokinetic (PK) comparability study to demonstrate comparable drug exposure following Subcutaneous benralizumab administration by using accessorized pre-filled syringe (APFS) or autoinjector (AI) devices.
Detailed description
A study of descriptive comparison of benralizumab PK by weight and injection site. This study will be a multicenter, randomized, open-label, parallel group Phase 1 study designed to compare benralizumab PK exposure in healthy subjects following single subcutaneous (SC) administration of fixed 30 mg dose of benralizumab by using APFS and single-use AI. Eligible subjects will be healthy subjects aged 18 to 55 years, with a body weight of 55 to 100 kg and a body mass index of 18 to 29.9 kg/m2 . A total of 180 subjects will be randomized. Randomization will be stratified by weight group (55 to 69.9 kg, 70 to 84.9 kg and 85 to 100 kg), and within each of the 3 weight groups, subjects will be randomized 1:1:1:1:1:1 to 1 of the 6 combinations of treatment (APFS or AI) with injection site (upper arm, abdomen or thigh), presented in Table 1. This study will be performed at 2 study centers.
Interventions
BIOLOGICALBenralizumab
A humanized, afucosylated, monoclonal antibody (mAb) that binds specifically to the human IL-5 receptor alpha subunit (IL-5Rα) on the target cell.
Sponsors
Parexel
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male and/or female subjects of non-child-bearing potential aged 18 to 55 years (inclusive) with suitable veins for cannulation or repeated venipuncture. * Females must be non pregnant,non lactating and non-child-bearing potential, confirmed at screening * Sexually active male willingness to use contraception * Body mass index (BMI) between 18 and 29.9 kg/m2 inclusive and weigh at least 55 kg and no more than 100 kg inclusive.
Exclusion criteria
* History of any clinically significant disease, severe allergy/anaphylaxis to any biologic therapy, Guillain-Barré syndrome, smoking and alcohol or drug abuse * Diagnosis of helminth parasitic infection and acute upper or lower respiratory infections * Disorders related to cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, hematological, psychiatric, or major physical impairment * Alanine aminotransferase/aspartate aminotransferase level ≥1.5 times the upper limit of normal * White blood cell count and neutrophils \< lower limit of normal * Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of Investigational medicinal product (IMP) * Positive result for serum hepatitis B surface antigen or anti-Hemoglobin C (anti-HBc) antibody, hepatitis C antibody, and human immunodeficiency virus (HIV) antibody. * Intake of new chemical entity (not been approved for marketing) within 3 months of the first administration of investigational product * Plasma donation within 1 month of screening or any blood donation/loss more than 500 mL during the 3 months prior to screening * Receipt of immunoglobulin or blood products within 30 days prior to the date informed consent * Receipt of any marketed (e.g., omalizumab, mepolizumab etc.) or investigational biologic within 4 months or 5 half-lives prior to the date informed consent * Receipt of live attenuated vaccines 30 days prior to randomization on Day 1 * Current malignancy, or history of malignancy except (basal cell carcinoma, localized squamous cell carcinoma of the skin or in situ carcinoma of the cervix) * Use of drugs with enzyme-inducing properties such as St John's Wort within 3 weeks prior to the first administration of IMP. * Use of antacids, analgesics (except paracetamol/acetaminophen), herbal remedies, mega-dose vitamins (20 to 600 times the recommended daily dose) and minerals during the 2 weeks prior to the first administration of IMP or longer * Previous receipt of received benralizumab * Any ongoing or recent minor medical complaints * Vulnerable subjects, e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve From Zero to Infinity (AUCinf) | At Pre-dose (Day 1) and at Days 2, 4, 5, 6, 8, 15, 29, 43 and 57 | To compare the AUCinf following single SC administration of Benralizumab by using APFS or AI devices |
| Area Under the Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) | At Pre-dose (Day 1) and at Days 2, 4, 5, 6, 8, 15, 29, 43 and 57 | To compare the AUClast following single SC administration of Benralizumab by using APFS or AI devices |
| Maximum Observed Concentration (Cmax) | At Pre-dose (Day 1) and at Days 2, 4, 5, 6, 8, 15, 29, 43 and 57 | To compare the Cmax following single SC administration of Benralizumab by using APFS or AI devices |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Apparent Volume of Distribution Based on the Terminal Phase (Vz/F) | At Pre-dose (Day 1) and at Days 2, 4, 5, 6, 8, 15, 29, 43 and 57 | To evaluate the Vz/F of Benralizumab administered to various anatomical injection sites and in subjects with different body weight ranges. |
| Time When Maximum Concentration is Observed (Tmax) | At Pre-dose (Day 1) and at Days 2, 4, 5, 6, 8, 15, 29, 43 and 57 | To evaluate the Tmax of Benralizumab administered to various injection sites and in subjects with different body weight ranges |
| Antidrug Antibody (ADA) Status | At predose (Day 1), Days 29 and 57 | To evaluate the immunogenicity of Benralizumab |
| Number of Participants With Adverse Events | At predose and 2 h postdose (Day 1), Days 2, 4, 5, 6, 8, 15, 29, 43 and 57 | To evaluate safety and tolerability of Benralizumab |
| Terminal Half-life (t½) | At Pre-dose (Day 1) and at Days 2, 4, 5, 6, 8, 15, 29, 43 and 57 | To evaluate the t½ of Benralizumab administered to various anatomical injection sites and in subjects with different body weight ranges. |
| Apparent Extravascular Clearance (CL/F) | At Pre-dose (Day 1) and at Days 2, 4, 5, 6, 8, 15, 29, 43 and 57 | To evaluate the CL/F of Benralizumab administered to various anatomical injection sites and in subjects with different body weight ranges. |
Countries
Germany
Participant flow
Recruitment details
Subjects who met all the inclusion and none of the exclusion criteria were enrolled at PAREXEL Early Phase Clinical Unit in Berlin and London.
Pre-assignment details
Subjects attended a Screening Visit within 28 days before receiving their first dose of Benralizumab. All subjects underwent inclusion exclusion criteria assessment and all eligible subjects signed the informed consent before undergoing any study-related procedures.
Participants by arm
| Arm | Count |
|---|---|
| Benralizumab 30mg Autoinjector (AI) All randomized subjects received 30mg Benralizumab by AI under fasted conditions. | 90 |
| Benralizumab 30mg Accessorized Pre-filled Syringe (AFPS) All randomized subjects received 30mg Benralizumab by APFS under fasted conditions. | 90 |
| Total | 180 |
Baseline characteristics
| Characteristic | Benralizumab 30mg Accessorized Pre-filled Syringe (AFPS) | Total | Benralizumab 30mg Autoinjector (AI) |
|---|---|---|---|
| Age, Continuous | 41.1 Years STANDARD_DEVIATION 11.1 | 40.9 Years STANDARD_DEVIATION 10.9 | 40.8 Years STANDARD_DEVIATION 10.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 3 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 88 Participants | 177 Participants | 89 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 10 Participants | 5 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 | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) White | 80 Participants | 163 Participants | 83 Participants |
| Sex: Female, Male Female | 16 Participants | 33 Participants | 17 Participants |
| Sex: Female, Male Male | 74 Participants | 147 Participants | 73 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 90 | 0 / 90 |
| other Total, other adverse events | 50 / 90 | 46 / 90 |
| serious Total, serious adverse events | 0 / 90 | 0 / 90 |
Outcome results
Primary
Area Under the Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast)
To compare the AUClast following single SC administration of Benralizumab by using APFS or AI devices
Time frame: At Pre-dose (Day 1) and at Days 2, 4, 5, 6, 8, 15, 29, 43 and 57
Population: The PK analysis set consisted of all subjects who received benralizumab for whom PK blood samples were assumed not to be affected by factors such as protocol violations (e.g., disallowed medications or incomplete dose administration) and who had at least one post dose quantifiable serum PK observation.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Benralizumab 30mg AI | Area Under the Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) | 60560 day·ng/mL | Geometric Coefficient of Variation 27.3 |
| Benralizumab 30mg AFPS | Area Under the Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) | 65230 day·ng/mL | Geometric Coefficient of Variation 29.2 |
90% CI: [87.41, 98.58]ANOVA
Primary
Area Under the Concentration-time Curve From Zero to Infinity (AUCinf)
To compare the AUCinf following single SC administration of Benralizumab by using APFS or AI devices
Time frame: At Pre-dose (Day 1) and at Days 2, 4, 5, 6, 8, 15, 29, 43 and 57
Population: The PK analysis set consisted of all subjects who received benralizumab for whom PK blood samples were assumed not to be affected by factors such as protocol violations (e.g., disallowed medications or incomplete dose administration) and who had at least one post dose quantifiable serum PK observation.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Benralizumab 30mg AI | Area Under the Concentration-time Curve From Zero to Infinity (AUCinf) | 72210 day·ng/mL | Geometric Coefficient of Variation 29.7 |
| Benralizumab 30mg AFPS | Area Under the Concentration-time Curve From Zero to Infinity (AUCinf) | 76220 day·ng/mL | Geometric Coefficient of Variation 32.1 |
90% CI: [88.16, 101.21]ANOVA
Primary
Maximum Observed Concentration (Cmax)
To compare the Cmax following single SC administration of Benralizumab by using APFS or AI devices
Time frame: At Pre-dose (Day 1) and at Days 2, 4, 5, 6, 8, 15, 29, 43 and 57
Population: The PK analysis set consisted of all subjects who received benralizumab for whom PK blood samples were assumed not to be affected by factors such as protocol violations (e.g., disallowed medications or incomplete dose administration) and who had at least one post dose quantifiable serum PK observation.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Benralizumab 30mg AI | Maximum Observed Concentration (Cmax) | 2096 ng/mL | Geometric Coefficient of Variation 32.7 |
| Benralizumab 30mg AFPS | Maximum Observed Concentration (Cmax) | 2269 ng/mL | Geometric Coefficient of Variation 35.4 |
90% CI: [86.34, 98.75]ANOVA
Secondary
Antidrug Antibody (ADA) Status
To evaluate the immunogenicity of Benralizumab
Time frame: At predose (Day 1), Days 29 and 57
Population: Safety set consisted of all subjects who received at least 1 dose of Benralizumab were included in the safety analysis for the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Benralizumab 30mg AI | Antidrug Antibody (ADA) Status | ADA prevalence (positive at any visit) | 2 Participants |
| Benralizumab 30mg AI | Antidrug Antibody (ADA) Status | ADA incidence | 0 Participants |
| Benralizumab 30mg AFPS | Antidrug Antibody (ADA) Status | ADA prevalence (positive at any visit) | 6 Participants |
| Benralizumab 30mg AFPS | Antidrug Antibody (ADA) Status | ADA incidence | 3 Participants |
Secondary
Apparent Extravascular Clearance (CL/F)
To evaluate the CL/F of Benralizumab administered to various anatomical injection sites and in subjects with different body weight ranges.
Time frame: At Pre-dose (Day 1) and at Days 2, 4, 5, 6, 8, 15, 29, 43 and 57
Population: The PK analysis set consisted of all the subjects as defined for above endpoint. For Benralizumab 30mg AI, two subjects and for Benralizumab 30mg AFPS, three subjects were excluded from the PK analysis set.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Benralizumab 30mg AI | Apparent Extravascular Clearance (CL/F) | Abdomen 70.0 to 84.9 kg | 462.9 mL/day | Geometric Coefficient of Variation 29.5 |
| Benralizumab 30mg AI | Apparent Extravascular Clearance (CL/F) | Thigh 85.0 to 100.0 kg | 378.2 mL/day | Geometric Coefficient of Variation 26.8 |
| Benralizumab 30mg AI | Apparent Extravascular Clearance (CL/F) | Thigh 55.0 to 69.9 kg | 350.1 mL/day | Geometric Coefficient of Variation 32.6 |
| Benralizumab 30mg AI | Apparent Extravascular Clearance (CL/F) | Upper arm 55.0 to 69.9 kg | 345.8 mL/day | Geometric Coefficient of Variation 24.7 |
| Benralizumab 30mg AI | Apparent Extravascular Clearance (CL/F) | Abdomen 85.0 to 100.0 kg | 504.6 mL/day | Geometric Coefficient of Variation 18.3 |
| Benralizumab 30mg AI | Apparent Extravascular Clearance (CL/F) | Upper arm 70.0 to 84.9 kg | 429.4 mL/day | Geometric Coefficient of Variation 19.5 |
| Benralizumab 30mg AI | Apparent Extravascular Clearance (CL/F) | Thigh 70.0 to 84.9 kg | 393.7 mL/day | Geometric Coefficient of Variation 29.6 |
| Benralizumab 30mg AI | Apparent Extravascular Clearance (CL/F) | Upper arm 85.0 to 100.0 kg | 532.6 mL/day | Geometric Coefficient of Variation 21.7 |
| Benralizumab 30mg AI | Apparent Extravascular Clearance (CL/F) | Abdomen 55.0 to 69.9 kg | 388.8 mL/day | Geometric Coefficient of Variation 34.3 |
| Benralizumab 30mg AFPS | Apparent Extravascular Clearance (CL/F) | Upper arm 85.0 to 100.0 kg | 471.6 mL/day | Geometric Coefficient of Variation 20.3 |
| Benralizumab 30mg AFPS | Apparent Extravascular Clearance (CL/F) | Abdomen 55.0 to 69.9 kg | 388.9 mL/day | Geometric Coefficient of Variation 43.8 |
| Benralizumab 30mg AFPS | Apparent Extravascular Clearance (CL/F) | Abdomen 70.0 to 84.9 kg | 508.9 mL/day | Geometric Coefficient of Variation 33.2 |
| Benralizumab 30mg AFPS | Apparent Extravascular Clearance (CL/F) | Abdomen 85.0 to 100.0 kg | 402.7 mL/day | Geometric Coefficient of Variation 30.4 |
| Benralizumab 30mg AFPS | Apparent Extravascular Clearance (CL/F) | Thigh 55.0 to 69.9 kg | 281.1 mL/day | Geometric Coefficient of Variation 16.8 |
| Benralizumab 30mg AFPS | Apparent Extravascular Clearance (CL/F) | Thigh 70.0 to 84.9 kg | 325.9 mL/day | Geometric Coefficient of Variation 18.2 |
| Benralizumab 30mg AFPS | Apparent Extravascular Clearance (CL/F) | Thigh 85.0 to 100.0 kg | 406.0 mL/day | Geometric Coefficient of Variation 22.9 |
| Benralizumab 30mg AFPS | Apparent Extravascular Clearance (CL/F) | Upper arm 55.0 to 69.9 kg | 455.2 mL/day | Geometric Coefficient of Variation 29.8 |
| Benralizumab 30mg AFPS | Apparent Extravascular Clearance (CL/F) | Upper arm 70.0 to 84.9 kg | 366.1 mL/day | Geometric Coefficient of Variation 27 |
Secondary
Apparent Volume of Distribution Based on the Terminal Phase (Vz/F)
To evaluate the Vz/F of Benralizumab administered to various anatomical injection sites and in subjects with different body weight ranges.
Time frame: At Pre-dose (Day 1) and at Days 2, 4, 5, 6, 8, 15, 29, 43 and 57
Population: The PK analysis set consisted of all the subjects as defined for above endpoint. For Benralizumab 30mg AI, two subjects and for Benralizumab 30mg AFPS, three subjects were excluded from the PK analysis set.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Benralizumab 30mg AI | Apparent Volume of Distribution Based on the Terminal Phase (Vz/F) | Abdomen 70.0 to 84.9 kg | 13.50 Liters | Geometric Coefficient of Variation 30.4 |
| Benralizumab 30mg AI | Apparent Volume of Distribution Based on the Terminal Phase (Vz/F) | Thigh 85.0 to 100.0 kg | 10.38 Liters | Geometric Coefficient of Variation 20.2 |
| Benralizumab 30mg AI | Apparent Volume of Distribution Based on the Terminal Phase (Vz/F) | Thigh 55.0 to 69.9 kg | 9.386 Liters | Geometric Coefficient of Variation 18.2 |
| Benralizumab 30mg AI | Apparent Volume of Distribution Based on the Terminal Phase (Vz/F) | Upper arm 55.0 to 69.9 kg | 11.21 Liters | Geometric Coefficient of Variation 21.2 |
| Benralizumab 30mg AI | Apparent Volume of Distribution Based on the Terminal Phase (Vz/F) | Abdomen 85.0 to 100.0 kg | 14.26 Liters | Geometric Coefficient of Variation 25 |
| Benralizumab 30mg AI | Apparent Volume of Distribution Based on the Terminal Phase (Vz/F) | Upper arm 70.0 to 84.9 kg | 12.72 Liters | Geometric Coefficient of Variation 23.6 |
| Benralizumab 30mg AI | Apparent Volume of Distribution Based on the Terminal Phase (Vz/F) | Thigh 70.0 to 84.9 kg | 11.32 Liters | Geometric Coefficient of Variation 23.5 |
| Benralizumab 30mg AI | Apparent Volume of Distribution Based on the Terminal Phase (Vz/F) | Upper arm 85.0 to 100.0 kg | 14.61 Liters | Geometric Coefficient of Variation 23 |
| Benralizumab 30mg AI | Apparent Volume of Distribution Based on the Terminal Phase (Vz/F) | Abdomen 55.0 to 69.9 kg | 10.56 Liters | Geometric Coefficient of Variation 28 |
| Benralizumab 30mg AFPS | Apparent Volume of Distribution Based on the Terminal Phase (Vz/F) | Upper arm 85.0 to 100.0 kg | 13.21 Liters | Geometric Coefficient of Variation 32.9 |
| Benralizumab 30mg AFPS | Apparent Volume of Distribution Based on the Terminal Phase (Vz/F) | Abdomen 55.0 to 69.9 kg | 11.30 Liters | Geometric Coefficient of Variation 28.4 |
| Benralizumab 30mg AFPS | Apparent Volume of Distribution Based on the Terminal Phase (Vz/F) | Abdomen 70.0 to 84.9 kg | 12.79 Liters | Geometric Coefficient of Variation 25.5 |
| Benralizumab 30mg AFPS | Apparent Volume of Distribution Based on the Terminal Phase (Vz/F) | Abdomen 85.0 to 100.0 kg | 12.22 Liters | Geometric Coefficient of Variation 15.8 |
| Benralizumab 30mg AFPS | Apparent Volume of Distribution Based on the Terminal Phase (Vz/F) | Thigh 55.0 to 69.9 kg | 7.999 Liters | Geometric Coefficient of Variation 15.5 |
| Benralizumab 30mg AFPS | Apparent Volume of Distribution Based on the Terminal Phase (Vz/F) | Thigh 70.0 to 84.9 kg | 8.596 Liters | Geometric Coefficient of Variation 13.5 |
| Benralizumab 30mg AFPS | Apparent Volume of Distribution Based on the Terminal Phase (Vz/F) | Thigh 85.0 to 100.0 kg | 10.13 Liters | Geometric Coefficient of Variation 21 |
| Benralizumab 30mg AFPS | Apparent Volume of Distribution Based on the Terminal Phase (Vz/F) | Upper arm 55.0 to 69.9 kg | 11.36 Liters | Geometric Coefficient of Variation 17.7 |
| Benralizumab 30mg AFPS | Apparent Volume of Distribution Based on the Terminal Phase (Vz/F) | Upper arm 70.0 to 84.9 kg | 10.65 Liters | Geometric Coefficient of Variation 18.7 |
Secondary
Number of Participants With Adverse Events
To evaluate safety and tolerability of Benralizumab
Time frame: At predose and 2 h postdose (Day 1), Days 2, 4, 5, 6, 8, 15, 29, 43 and 57
Population: Safety set consisted of all subjects who received at least 1 dose of Benralizumab were included in the safety analysis for the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Benralizumab 30mg AI | Number of Participants With Adverse Events | Any AE leading to discontinuation | 0 Participants |
| Benralizumab 30mg AI | Number of Participants With Adverse Events | Any AE | 50 Participants |
| Benralizumab 30mg AI | Number of Participants With Adverse Events | Death | 0 Participants |
| Benralizumab 30mg AI | Number of Participants With Adverse Events | Any SAE | 0 Participants |
| Benralizumab 30mg AFPS | Number of Participants With Adverse Events | Any SAE | 0 Participants |
| Benralizumab 30mg AFPS | Number of Participants With Adverse Events | Death | 0 Participants |
| Benralizumab 30mg AFPS | Number of Participants With Adverse Events | Any AE leading to discontinuation | 0 Participants |
| Benralizumab 30mg AFPS | Number of Participants With Adverse Events | Any AE | 46 Participants |
Secondary
Terminal Half-life (t½)
To evaluate the t½ of Benralizumab administered to various anatomical injection sites and in subjects with different body weight ranges.
Time frame: At Pre-dose (Day 1) and at Days 2, 4, 5, 6, 8, 15, 29, 43 and 57
Population: The PK analysis set consisted of all the subjects as defined for above endpoint. For Benralizumab 30mg AI, two subjects and for Benralizumab 30mg AFPS, three subjects were excluded from the PK analysis set.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Benralizumab 30mg AI | Terminal Half-life (t½) | Abdomen 85.0 to 100.0 kg | 19.59 Days | Geometric Coefficient of Variation 19.9 |
| Benralizumab 30mg AI | Terminal Half-life (t½) | Upper arm 85.0 to 100.0 kg | 19.01 Days | Geometric Coefficient of Variation 26.9 |
| Benralizumab 30mg AI | Terminal Half-life (t½) | Abdomen 55.0 to 69.9 kg | 18.83 Days | Geometric Coefficient of Variation 24.9 |
| Benralizumab 30mg AI | Terminal Half-life (t½) | Abdomen 70.0 to 84.9 kg | 20.22 Days | Geometric Coefficient of Variation 21 |
| Benralizumab 30mg AI | Terminal Half-life (t½) | Thigh 55.0 to 69.9 kg | 18.58 Days | Geometric Coefficient of Variation 20.6 |
| Benralizumab 30mg AI | Terminal Half-life (t½) | Thigh 70.0 to 84.9 kg | 19.93 Days | Geometric Coefficient of Variation 23.4 |
| Benralizumab 30mg AI | Terminal Half-life (t½) | Thigh 85.0 to 100.0 kg | 19.02 Days | Geometric Coefficient of Variation 19.9 |
| Benralizumab 30mg AI | Terminal Half-life (t½) | Upper arm 55.0 to 69.9 kg | 22.46 Days | Geometric Coefficient of Variation 13.6 |
| Benralizumab 30mg AI | Terminal Half-life (t½) | Upper arm 70.0 to 84.9 kg | 20.54 Days | Geometric Coefficient of Variation 14 |
| Benralizumab 30mg AFPS | Terminal Half-life (t½) | Upper arm 55.0 to 69.9 kg | 17.30 Days | Geometric Coefficient of Variation 26.9 |
| Benralizumab 30mg AFPS | Terminal Half-life (t½) | Thigh 70.0 to 84.9 kg | 18.28 Days | Geometric Coefficient of Variation 17.9 |
| Benralizumab 30mg AFPS | Terminal Half-life (t½) | Upper arm 85.0 to 100.0 kg | 19.42 Days | Geometric Coefficient of Variation 26.3 |
| Benralizumab 30mg AFPS | Terminal Half-life (t½) | Abdomen 55.0 to 69.9 kg | 20.15 Days | Geometric Coefficient of Variation 21.8 |
| Benralizumab 30mg AFPS | Terminal Half-life (t½) | Thigh 85.0 to 100.0 kg | 17.30 Days | Geometric Coefficient of Variation 11.5 |
| Benralizumab 30mg AFPS | Terminal Half-life (t½) | Abdomen 70.0 to 84.9 kg | 17.43 Days | Geometric Coefficient of Variation 21.7 |
| Benralizumab 30mg AFPS | Terminal Half-life (t½) | Abdomen 85.0 to 100.0 kg | 21.04 Days | Geometric Coefficient of Variation 21.7 |
| Benralizumab 30mg AFPS | Terminal Half-life (t½) | Upper arm 70.0 to 84.9 kg | 20.16 Days | Geometric Coefficient of Variation 25.3 |
| Benralizumab 30mg AFPS | Terminal Half-life (t½) | Thigh 55.0 to 69.9 kg | 19.72 Days | Geometric Coefficient of Variation 21.4 |
Secondary
Time When Maximum Concentration is Observed (Tmax)
To evaluate the Tmax of Benralizumab administered to various injection sites and in subjects with different body weight ranges
Time frame: At Pre-dose (Day 1) and at Days 2, 4, 5, 6, 8, 15, 29, 43 and 57
Population: The PK analysis set consisted of all subjects who received benralizumab for whom PK blood samples were assumed not to be affected by factors such as protocol violations (e.g., disallowed medications or incomplete dose administration) and who had at least one post dose quantifiable serum PK observation.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Benralizumab 30mg AI | Time When Maximum Concentration is Observed (Tmax) | Abdomen 70.0 to 84.9 kg | 6.98 Days |
| Benralizumab 30mg AI | Time When Maximum Concentration is Observed (Tmax) | Thigh 85.0 to 100.0 kg | 4.59 Days |
| Benralizumab 30mg AI | Time When Maximum Concentration is Observed (Tmax) | Thigh 55.0 to 69.9 kg | 4.00 Days |
| Benralizumab 30mg AI | Time When Maximum Concentration is Observed (Tmax) | Upper arm 55.0 to 69.9 kg | 6.97 Days |
| Benralizumab 30mg AI | Time When Maximum Concentration is Observed (Tmax) | Abdomen 85.0 to 100.0 kg | 5.06 Days |
| Benralizumab 30mg AI | Time When Maximum Concentration is Observed (Tmax) | Upper arm 70.0 to 84.9 kg | 7.00 Days |
| Benralizumab 30mg AI | Time When Maximum Concentration is Observed (Tmax) | Thigh 70.0 to 84.9 kg | 4.05 Days |
| Benralizumab 30mg AI | Time When Maximum Concentration is Observed (Tmax) | Upper arm 85.0 to 100.0 kg | 7.00 Days |
| Benralizumab 30mg AI | Time When Maximum Concentration is Observed (Tmax) | Abdomen 55.0 to 69.9 kg | 4.59 Days |
| Benralizumab 30mg AFPS | Time When Maximum Concentration is Observed (Tmax) | Upper arm 85.0 to 100.0 kg | 6.97 Days |
| Benralizumab 30mg AFPS | Time When Maximum Concentration is Observed (Tmax) | Abdomen 55.0 to 69.9 kg | 6.06 Days |
| Benralizumab 30mg AFPS | Time When Maximum Concentration is Observed (Tmax) | Abdomen 70.0 to 84.9 kg | 5.98 Days |
| Benralizumab 30mg AFPS | Time When Maximum Concentration is Observed (Tmax) | Abdomen 85.0 to 100.0 kg | 6.96 Days |
| Benralizumab 30mg AFPS | Time When Maximum Concentration is Observed (Tmax) | Thigh 55.0 to 69.9 kg | 4.52 Days |
| Benralizumab 30mg AFPS | Time When Maximum Concentration is Observed (Tmax) | Thigh 70.0 to 84.9 kg | 3.52 Days |
| Benralizumab 30mg AFPS | Time When Maximum Concentration is Observed (Tmax) | Thigh 85.0 to 100.0 kg | 4.03 Days |
| Benralizumab 30mg AFPS | Time When Maximum Concentration is Observed (Tmax) | Upper arm 55.0 to 69.9 kg | 4.96 Days |
| Benralizumab 30mg AFPS | Time When Maximum Concentration is Observed (Tmax) | Upper arm 70.0 to 84.9 kg | 5.02 Days |