Healthy Volunteers
Conditions
Keywords
Drug therapy
Brief summary
The purpose of this study is to compare PK of single dose of vedolizumab SC 108 milligram (mg) administered as PFS vs investigational device.
Detailed description
The drug being tested in this study is called vedolizumab SC. The study will assess the PK, and variability of a vedolizumab SC in a PFS vs investigational device. This study will include 2 different device delivery presentations in 2 treatment groups. Participants in each treatment group will be randomized to one of the three administration sites: Abdomen, thigh, or arm. The study will enroll approximately 24 participants, including 4 participants allocated to each administration site within each treatment group. Participants will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups: * Group A: Vedolizumab SC PFS * Group B: Vedolizumab SC Investigational Device All participants will receive a single dose of study drug on Day 1. This single center trial will be conducted in the United States. The overall time to participate in this study is approximately 196 days. Participants will be contacted by telephone on Day 168 after their last dose of study drug for a follow-up assessment which will involve the progressive multifocal leukoencephalopathy (PML) questionnaire survey.
Interventions
DRUGVedolizumab SC
Vedolizumab SC liquid.
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1\. Weighs greater than (\>) 50 kilogram (kg) and less than (\<) 90 kg and has a body mass index (BMI) from 18 to 28 kilogram per square meter (kg/m\^2), inclusive, at the time of informed consent.
Exclusion criteria
1. Has received any investigational or approved biologic or biosimilar within 30 days or 5 half-lives, of Screening, whichever is longer. 2. Has had prior exposure to vedolizumab, or has hypersensitivity to vedolizumab or any of its components. 3. Has had previous exposure to approved or investigational anti-integrins (example, natalizumab, efalizumab, etrolizumab, AMG 181) or anti-mucosal addressin cell adhesion molecule-1 (MAdCAM-1) antibodies or rituximab. 4. Has 1 or more positive responses on the PML subjective symptom checklist at screening or before dosing on Day 1. 5. Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 1 year before the Screening Visit or is unwilling to agree to abstain from alcohol for 7 days before Day -1 throughout confinement and for 48 hours before each clinic visit; and drugs throughout the study. 6. Has evidence of an active infection during the Screening Period. 7. Has received any live vaccinations within 30 days before Screening. 8. Has active or latent tuberculosis (TB) as evidenced by the following: o A diagnostic TB test performed within 30 days of Screening or during the Screening Period that is positive, defined as: 1. Positive QuantiFERON test or 2 successive indeterminate QuantiFERON tests, OR 2. A TB skin test reaction greater than or equal to (\>=) 5 millimeter (mm). NOTE: If participants have received Bacillus Calmette-Guerin (BCG) vaccine then a QuantiFERON TB Gold test should be performed instead of the TB skin test. Note: Participants with documented previously treated TB with a negative QuantiFERON test can be included in the study. 9. Has poor peripheral venous access. 10. Is unable to attend all the study visits or comply with study procedures. 11. Has donated or lost 450 milliliter (mL) or more of his or her blood volume (including serum pheresis), or had a transfusion of any blood product within 45 days before Day 1.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| AUClast: Area Under the Serum Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Vedolizumab SC | Day 1 pre-dose and at multiple time points (up to Day 127) post-dose |
| AUC∞: Area Under the Serum Concentration-time Curve From Time 0 to Infinity for Vedolizumab SC | Day 1 pre-dose and at multiple time points (up to Day 127) post-dose |
| Cmax: Maximum Observed Serum Concentration for Vedolizumab SC | Day 1 pre-dose and at multiple time points (up to Day 127) post-dose |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at 1 investigative site in the United states from 22 February 2018 to 28 August 2018.
Pre-assignment details
Healthy participants were enrolled in one of the two device presentation groups to receive vedolizumab subcutaneous (SC) 108 milligram (mg) using prefilled syringe (PFS) or using an investigational device. Primary objective was to collect data based on two device delivery presentations, not as per administration sites (abdomen, thigh, or arm).
Participants by arm
| Arm | Count |
|---|---|
| Group A: Vedolizumab SC PFS Vedolizumab 108 mg, injection, subcutaneously using a PFS, once on Day 1. | 12 |
| Group B: Vedolizumab SC Investigational Device Vedolizumab 108 mg, injection, subcutaneously using an investigational device, once on Day 1. | 12 |
| Total | 24 |
Baseline characteristics
| Characteristic | Group B: Vedolizumab SC Investigational Device | Total | Group A: Vedolizumab SC PFS |
|---|---|---|---|
| Age, Continuous | 33.6 years STANDARD_DEVIATION 12.52 | 35.4 years STANDARD_DEVIATION 12.89 | 37.2 years STANDARD_DEVIATION 13.55 |
| Body Mass Index (BMI) | 23.603 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.7232 | 24.080 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.9663 | 24.558 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.2381 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 22 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Height | 171.0 centimeter (cm) STANDARD_DEVIATION 7.94 | 170.7 centimeter (cm) STANDARD_DEVIATION 8.88 | 170.4 centimeter (cm) STANDARD_DEVIATION 10.08 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 4 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 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 | 7 Participants | 17 Participants | 10 Participants |
| Region of Enrollment United States | 12 Participants | 24 Participants | 12 Participants |
| Sex: Female, Male Female | 6 Participants | 12 Participants | 6 Participants |
| Sex: Female, Male Male | 6 Participants | 12 Participants | 6 Participants |
| Weight | 69.26 kilogram (kg) STANDARD_DEVIATION 10.637 | 70.30 kilogram (kg) STANDARD_DEVIATION 10.944 | 71.35 kilogram (kg) STANDARD_DEVIATION 11.614 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 9 / 12 | 6 / 12 |
| serious Total, serious adverse events | 1 / 12 | 0 / 12 |
Outcome results
Primary
AUC∞: Area Under the Serum Concentration-time Curve From Time 0 to Infinity for Vedolizumab SC
Time frame: Day 1 pre-dose and at multiple time points (up to Day 127) post-dose
Population: The PK set included all participants who received study drug and had at least 1 measurable serum concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Vedolizumab SC PFS | AUC∞: Area Under the Serum Concentration-time Curve From Time 0 to Infinity for Vedolizumab SC | 446.5 mcg*day/mL | Geometric Coefficient of Variation 36.2 |
| Group B: Vedolizumab SC Investigational Device | AUC∞: Area Under the Serum Concentration-time Curve From Time 0 to Infinity for Vedolizumab SC | 594.0 mcg*day/mL | Geometric Coefficient of Variation 23.6 |
Comparison: Geometric LSMs were calculated by exponentiating the LSMs derived from ANCOVA with weight as a covariate. CIs were calculated using treatment standard errors from the ANCOVA model and t-statistic for error degrees of freedom.90% CI: [1.1147, 1.5807]
Primary
AUClast: Area Under the Serum Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Vedolizumab SC
Time frame: Day 1 pre-dose and at multiple time points (up to Day 127) post-dose
Population: The pharmacokinetic (PK) set included all participants who received study drug and had at least 1 measurable serum concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Vedolizumab SC PFS | AUClast: Area Under the Serum Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Vedolizumab SC | 433.4 microgram*day per milliliter(mcg*day/mL) | Geometric Coefficient of Variation 38.3 |
| Group B: Vedolizumab SC Investigational Device | AUClast: Area Under the Serum Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Vedolizumab SC | 560.3 microgram*day per milliliter(mcg*day/mL) | Geometric Coefficient of Variation 26.3 |
Comparison: Geometric least-squares means (LSMs) were calculated by exponentiating the LSMs derived from analysis of variance (ANCOVA) with weight as a covariate. Confidence intervals (CIs) were calculated using treatment standard errors from the ANCOVA model and t-statistic for error degrees of freedom.90% CI: [1.0786, 1.5486]
Primary
Cmax: Maximum Observed Serum Concentration for Vedolizumab SC
Time frame: Day 1 pre-dose and at multiple time points (up to Day 127) post-dose
Population: The PK set included all participants who received study drug and had at least 1 measurable serum concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Vedolizumab SC PFS | Cmax: Maximum Observed Serum Concentration for Vedolizumab SC | 13.70 microgram per milliliter (mcg/mL) | Geometric Coefficient of Variation 24.2 |
| Group B: Vedolizumab SC Investigational Device | Cmax: Maximum Observed Serum Concentration for Vedolizumab SC | 16.53 microgram per milliliter (mcg/mL) | Geometric Coefficient of Variation 26.9 |
Comparison: Geometric LSMs were calculated by exponentiating the LSMs derived from ANCOVA with weight as a covariate. CIs were calculated using treatment standard errors from the ANCOVA model and t-statistic for error degrees of freedom.90% CI: [1.0394, 1.3804]