A Pilot Study to Compare the Pharmacokinetics (PK) of Single Subcutaneous (SC) Injections of Vedolizumab Administered in Prefilled Syringe (PFS) Versus (vs) Prefilled Syringe in Needle Safety Device (PFS+NSD) in Healthy Participants
Study Details
Study Description
Brief Summary
The purpose of this study is to compare the PK of single dose of vedolizumab SC 108 milligram (mg) administered as PFS vs investigational device.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 1 |
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 versus an 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 102 participants, including 17 participants allocated to each administration site within each treatment group. Participants will be randomly assigned (per randomization schedule) 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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Active Comparator: Group A: Vedolizumab SC PFS Vedolizumab SC 108 mg, injection, subcutaneously using a PFS, once on Day 1. |
Drug: Vedolizumab SC
Vedolizumab SC liquid.
|
Experimental: Group B: Vedolizumab SC Investigational Device Vedolizumab SC 108 mg, injection, subcutaneously using an investigational device, once on Day 1. |
Drug: Vedolizumab SC
Vedolizumab SC liquid.
|
Outcome Measures
Primary Outcome Measures
- 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]
Eligibility Criteria
Criteria
Inclusion Criteria:
- 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:
-
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.
-
Has 1 or more positive responses on the PML subjective symptom checklist at screening or before dosing on Day 1.
-
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.
-
Has evidence of an active infection during the Screening Period.
-
Has received any live vaccinations within 30 days before Screening.
-
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:
-
Positive QuantiFERON test or 2 successive indeterminate QuantiFERON tests, OR
-
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.
-
Has poor peripheral venous access.
-
Is unable to attend all the study visits or comply with study procedures.
-
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
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Celerion | Tempe | Arizona | United States | 85283 |
Sponsors and Collaborators
- Takeda
Investigators
- Study Director: Medical Director, Takeda
Study Documents (Full-Text)
More Information
Publications
None provided.- VedolizumabSC-1018
- U1111-1205-2298
Study Results
Participant Flow
Recruitment Details | Participants took part in the study at 1 investigative site in the United States from 21 February 2018 to 21 September 2018. |
---|---|
Pre-assignment Detail | 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). |
Arm/Group Title | Group A: Vedolizumab SC PFS | Group B: Vedolizumab SC Investigational Device |
---|---|---|
Arm/Group Description | Vedolizumab SC 108 mg, injection, subcutaneously using a PFS, once on Day 1. | Vedolizumab SC 108 mg, injection, subcutaneously using an investigational device, once on Day 1. |
Period Title: Overall Study | ||
STARTED | 51 | 51 |
COMPLETED | 51 | 50 |
NOT COMPLETED | 0 | 1 |
Baseline Characteristics
Arm/Group Title | Group A: Vedolizumab SC PFS | Group B: Vedolizumab SC Investigational Device | Total |
---|---|---|---|
Arm/Group Description | Vedolizumab SC 108 mg, injection, subcutaneously using a PFS, once on Day 1. | Vedolizumab SC 108 mg, injection, subcutaneously using an investigational device, once on Day 1. | Total of all reporting groups |
Overall Participants | 51 | 51 | 102 |
Age (years) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [years] |
35.9
(12.59)
|
37.0
(11.46)
|
36.5
(11.99)
|
Sex: Female, Male (Count of Participants) | |||
Female |
23
45.1%
|
23
45.1%
|
46
45.1%
|
Male |
28
54.9%
|
28
54.9%
|
56
54.9%
|
Ethnicity (NIH/OMB) (Count of Participants) | |||
Hispanic or Latino |
32
62.7%
|
28
54.9%
|
60
58.8%
|
Not Hispanic or Latino |
19
37.3%
|
23
45.1%
|
42
41.2%
|
Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
Race/Ethnicity, Customized (Count of Participants) | |||
Asian |
1
2%
|
0
0%
|
1
1%
|
Black or African American |
8
15.7%
|
9
17.6%
|
17
16.7%
|
Black/AfricanAmerican,American Indian/AlaskaNative |
1
2%
|
0
0%
|
1
1%
|
White |
36
70.6%
|
41
80.4%
|
77
75.5%
|
White, Black or African American |
3
5.9%
|
1
2%
|
4
3.9%
|
White, Black or African American, Asian |
2
3.9%
|
0
0%
|
2
2%
|
Region of Enrollment (Count of Participants) | |||
United States |
51
100%
|
51
100%
|
102
100%
|
Weight (kilogram (kg)) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [kilogram (kg)] |
67.43
(8.411)
|
71.56
(11.289)
|
69.49
(10.120)
|
Height (centimeter (cm)) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [centimeter (cm)] |
167.0
(8.79)
|
170.0
(11.22)
|
168.5
(10.14)
|
Body mass index (BMI) (kilogram per square meter (kg/m^2)) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [kilogram per square meter (kg/m^2)] |
24.167
(2.5858)
|
24.595
(2.3885)
|
24.381
(2.4861)
|
Outcome Measures
Title | AUClast: Area Under the Serum Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Vedolizumab SC |
---|---|
Description | |
Time Frame | Day 1 pre-dose and at multiple time points (up to Day 127) post-dose |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic (PK) set: Participants received study drug and had at least one measurable serum concentration. Number of participants analyzed includes only those participants who had data available for this measure. It was planned to collect data based on two device delivery presentations, not as per administration sites (abdomen, thigh, or arm). |
Arm/Group Title | Group A: Vedolizumab SC PFS | Group B: Vedolizumab SC Investigational Device |
---|---|---|
Arm/Group Description | Vedolizumab SC 108 mg, injection, subcutaneously using a PFS, once on Day 1. | Vedolizumab SC 108 mg, injection, subcutaneously using an investigational device, once on Day 1. |
Measure Participants | 51 | 50 |
Geometric Mean (Geometric Coefficient of Variation) [microgram*day per milliliter(mcg*day/mL)] |
492.6
(22.5)
|
455.4
(34.4)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Group A: Vedolizumab SC PFS, Group B: Vedolizumab SC Investigational Device |
---|---|---|
Comments | ||
Type of Statistical Test | Equivalence | |
Comments | Geometric least-squares means (LSMs) were calculated by exponentiating the LSMs derived from analysis of variance (ANCOVA) with group, treatment, and injection site as fixed effects and weight as a continuous covariate. Confidence intervals (CIs) were calculated using treatment standard errors from the ANCOVA model and t-statistic for error degrees of freedom. | |
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of Geometric LSMs |
Estimated Value | 0.9807 | |
Confidence Interval |
(2-Sided) 90% 0.9011 to 1.0675 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | AUC∞: Area Under the Serum Concentration-time Curve From Time 0 to Infinity for Vedolizumab SC |
---|---|
Description | |
Time Frame | Day 1 pre-dose and at multiple time points (up to Day 127) post-dose |
Outcome Measure Data
Analysis Population Description |
---|
The PK set: Participants who received study drug and had at least one measurable serum concentration. Number of participants analyzed includes only those participants who had data available for this measure. It was planned to collect data based on two device delivery presentations, not as per administration sites (abdomen, thigh, or arm). |
Arm/Group Title | Group A: Vedolizumab SC PFS | Group B: Vedolizumab SC Investigational Device |
---|---|---|
Arm/Group Description | Vedolizumab SC 108 mg, injection, subcutaneously using a PFS, once on Day 1. | Vedolizumab SC 108 mg, injection, subcutaneously using an investigational device, once on Day 1. |
Measure Participants | 51 | 49 |
Geometric Mean (Geometric Coefficient of Variation) [mcg*day/mL] |
504.4
(22.0)
|
478.4
(30.7)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Group A: Vedolizumab SC PFS, Group B: Vedolizumab SC Investigational Device |
---|---|---|
Comments | ||
Type of Statistical Test | Equivalence | |
Comments | Geometric LSMs were calculated by exponentiating the LSMs derived from ANCOVA with group, treatment, and injection site as fixed effects and weight as a continuous covariate. CIs were calculated using treatment standard errors from the ANCOVA model and t-statistic for error degrees of freedom. | |
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of Geometric LSMs |
Estimated Value | .9981 | |
Confidence Interval |
(2-Sided) 90% 0.9223 to 1.0801 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Cmax: Maximum Observed Serum Concentration for Vedolizumab SC |
---|---|
Description | |
Time Frame | Day 1 pre-dose and at multiple time points (up to Day 127) post-dose |
Outcome Measure Data
Analysis Population Description |
---|
The PK set included all participants who received study drug and had at least one measurable serum concentration. It was planned to collect data based on two device delivery presentations, not as per administration sites (abdomen, thigh, or arm). |
Arm/Group Title | Group A: Vedolizumab SC PFS | Group B: Vedolizumab SC Investigational Device |
---|---|---|
Arm/Group Description | Vedolizumab SC 108 mg, injection, subcutaneously using a PFS, once on Day 1. | Vedolizumab SC 108 mg, injection, subcutaneously using an investigational device, once on Day 1. |
Measure Participants | 51 | 51 |
Geometric Mean (Geometric Coefficient of Variation) [microgram per milliliter (mcg/mL)] |
15.42
(19.9)
|
14.86
(24.4)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Group A: Vedolizumab SC PFS, Group B: Vedolizumab SC Investigational Device |
---|---|---|
Comments | ||
Type of Statistical Test | Equivalence | |
Comments | Geometric LSMs were calculated by exponentiating the LSMs derived from ANCOVA with group, treatment, and injection site as fixed effects and weight as a continuous covariate. CIs were calculated using treatment standard errors from the ANCOVA model and t-statistic for error degrees of freedom. | |
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of Geometric LSMs |
Estimated Value | 1.0038 | |
Confidence Interval |
(2-Sided) 90% 0.9401 to 1.0719 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Adverse Events
Time Frame | Treatment-emergent adverse events are adverse events that started after the administration of the study drug and no more than Day 127 | |||
---|---|---|---|---|
Adverse Event Reporting Description | At each visit the investigator had to assess any occurrence of adverse events. Participants may report AEs occurring at any other time during the study. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. The study was planned to collect data based on two device delivery presentations, not as per administration sites (abdomen, thigh, or arm). | |||
Arm/Group Title | Group A: Vedolizumab SC PFS | Group B: Vedolizumab SC Investigational Device | ||
Arm/Group Description | Vedolizumab SC 108 mg, injection, subcutaneously using a PFS, once on Day 1. | Vedolizumab SC 108 mg, injection, subcutaneously using an investigational device, once on Day 1. | ||
All Cause Mortality |
||||
Group A: Vedolizumab SC PFS | Group B: Vedolizumab SC Investigational Device | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/51 (0%) | 0/51 (0%) | ||
Serious Adverse Events |
||||
Group A: Vedolizumab SC PFS | Group B: Vedolizumab SC Investigational Device | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/51 (0%) | 0/51 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
Group A: Vedolizumab SC PFS | Group B: Vedolizumab SC Investigational Device | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 34/51 (66.7%) | 40/51 (78.4%) | ||
Eye disorders | ||||
Eyelid odema | 0/51 (0%) | 1/51 (2%) | ||
Iridocyclitis | 0/51 (0%) | 1/51 (2%) | ||
Vision blurred | 1/51 (2%) | 1/51 (2%) | ||
Gastrointestinal disorders | ||||
Abdominal pain | 1/51 (2%) | 0/51 (0%) | ||
Aphthous ulcer | 1/51 (2%) | 0/51 (0%) | ||
Diarrhoea | 1/51 (2%) | 0/51 (0%) | ||
Flatulence | 0/51 (0%) | 1/51 (2%) | ||
Nausea | 2/51 (3.9%) | 2/51 (3.9%) | ||
Noninfective gingivitis | 1/51 (2%) | 0/51 (0%) | ||
Toothache | 0/51 (0%) | 1/51 (2%) | ||
Vomiting | 0/51 (0%) | 1/51 (2%) | ||
General disorders | ||||
Chest discomfort | 0/51 (0%) | 1/51 (2%) | ||
Influenza like illness | 1/51 (2%) | 1/51 (2%) | ||
Injection site erythema | 3/51 (5.9%) | 6/51 (11.8%) | ||
Injection site induration | 7/51 (13.7%) | 5/51 (9.8%) | ||
Injection site pain | 27/51 (52.9%) | 27/51 (52.9%) | ||
Thirst | 0/51 (0%) | 1/51 (2%) | ||
Infections and infestations | ||||
Cellulitis | 0/51 (0%) | 1/51 (2%) | ||
Nasopharyngitis | 0/51 (0%) | 3/51 (5.9%) | ||
Oral herpes | 1/51 (2%) | 0/51 (0%) | ||
Urinary tract infection | 0/51 (0%) | 1/51 (2%) | ||
Viral infection | 1/51 (2%) | 1/51 (2%) | ||
Injury, poisoning and procedural complications | ||||
Fall | 0/51 (0%) | 1/51 (2%) | ||
Muscle strain | 1/51 (2%) | 0/51 (0%) | ||
Investigations | ||||
Weight decreased | 0/51 (0%) | 1/51 (2%) | ||
Weight increased | 3/51 (5.9%) | 6/51 (11.8%) | ||
Musculoskeletal and connective tissue disorders | ||||
Arthralgia | 1/51 (2%) | 1/51 (2%) | ||
Back pain | 2/51 (3.9%) | 0/51 (0%) | ||
Myalgia | 1/51 (2%) | 0/51 (0%) | ||
Pain in extremity | 0/51 (0%) | 1/51 (2%) | ||
Nervous system disorders | ||||
Dizziness | 0/51 (0%) | 1/51 (2%) | ||
Headache | 2/51 (3.9%) | 6/51 (11.8%) | ||
Presyncope | 1/51 (2%) | 1/51 (2%) | ||
Somnolence | 1/51 (2%) | 1/51 (2%) | ||
Renal and urinary disorders | ||||
Haematuria | 1/51 (2%) | 1/51 (2%) | ||
Pollakiuria | 0/51 (0%) | 1/51 (2%) | ||
Respiratory, thoracic and mediastinal disorders | ||||
Dysphonia | 1/51 (2%) | 0/51 (0%) | ||
Oropharyngeal pain | 1/51 (2%) | 1/51 (2%) | ||
Productive cough | 1/51 (2%) | 0/51 (0%) | ||
Skin and subcutaneous tissue disorders | ||||
Dermatitis contact | 1/51 (2%) | 0/51 (0%) | ||
Eczema | 0/51 (0%) | 1/51 (2%) | ||
Pruritus | 0/51 (0%) | 1/51 (2%) | ||
Pruritus generalised | 1/51 (2%) | 0/51 (0%) | ||
Rash macular | 0/51 (0%) | 1/51 (2%) | ||
Rash papular | 1/51 (2%) | 1/51 (2%) | ||
Vascular disorders | ||||
Flushing | 1/51 (2%) | 0/51 (0%) |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Research Organization shall not publish any articles or papers nor make any presentations, nor assist any other person in publishing any articles or papers or in making any presentations relating or referring to the Study or any results, data or insights from or any data, information or materials obtained or generated in the performance of its obligations without the prior written consent of Takeda, which consent may be granted or withheld in Takeda's sole discretion.
Results Point of Contact
Name/Title | Medical Director |
---|---|
Organization | Takeda |
Phone | +1-877-825-3327 |
trialdisclosures@takeda.com |
- VedolizumabSC-1018
- U1111-1205-2298