Back to resultsA Study to Evaluate the Pharmacokinetics of Abatacept Converted From Drug Substance by Two Different Processes
Primary Purpose
Rheumatoid Arthritis
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Abatacept
Sponsored by
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis
Eligibility Criteria
Inclusion Criteria:
- Body weight will be between 60 and 100 kg, inclusive.
- Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 24 hours prior to the start of study treatment.
- Women must not be breastfeeding.
- WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with abatacept plus 5 half-lives of abatacept (85 days) plus 30 days (duration of ovulatory cycle) for a total of 115 days post-treatment completion.
- Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with abatacept plus 5 half-lives of abatacept (85 days) plus the duration of spermatogenesis (90 days) for a total of 175 days after the last dose of study treatment. In addition, male participants must be willing to refrain from sperm donation during this time.
Exclusion Criteria:
- Participants who have a present malignancy or previous malignancy within the last 5 years prior to screening (except documented history of cured non-metastatic squamous or basal cell skin carcinoma or cervical carcinoma in situ). Participants who had a screening procedure that is suspicious for malignancy, and in whom the possibility of malignancy cannot be reasonably excluded following additional clinical, laboratory or other diagnostic evaluations.
- Participants with a history of herpes zoster.
- Donation of blood to a blood bank or in a clinical study (except a screening visit or follow-up visit) within 4 weeks of study treatment administration (within 2 weeks of study treatment administration for plasma only).
- Blood transfusion within 4 weeks of study treatment administration.
- Recent (within 6 months of study treatment administration) history of smoking or current smokers. This includes participants using electronic cigarettes or nicotine-containing products such as tobacco for chewing, nicotine patches, nicotine lozenges, or nicotine gum.
- History of allergy to abatacept or related compounds.
Sites / Locations
- Qps-Mra, Llc
- PPD Development, LP
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Treatment A
Treatment B
Arm Description
Participants will receive abatacept at a single dose of 750 mg as IV infusion on Day 1 converted from drug substance by a new process.
Participants will receive abatacept at a single dose 750 mg as IV infusion on Day 1 converted from drug substance by converted from drug substance by the current process.
Outcomes
Primary Outcome Measures
Maximum Observed Serum Concentration (Cmax)
Maximum Observed Serum Concentration
Area Under the Curve AUC(INF)
Area under the serum concentration-time curve from time zero extrapolated to infinity
Secondary Outcome Measures
Time of Maximum Observed Serum Concentration (Tmax)
Time of maximum observed serum concentration
Area Under the Curve AUC(0-T)
Area under the serum concentration-time curve from zero to the last time of the last quantifiable concentration
Area Under the Curve AUC(0-28)
Area under the serum concentration-time curve from time zero to 28 days after dosing
Total Body Clearance (CLT)
Total body clearance
Volume of Distribution at Steady-State (Vss)
Volume of distribution at steady-state
Terminal Phase Elimination Half-life (T-HALF)
Terminal phase elimination half-life in serum
Number of Participants Experiencing Positive Immunogenicity Response to Abatacept
Positive immunogenicity response to Abatacept was defined if one of the following criteria was met:
missing baseline immunogenicity measurement and a positive, post-baseline, laboratory-reported immunogenicity response;
a negative laboratory-reported baseline immunogenicity response and a positive, post-baseline, laboratory-reported response;
a positive, laboratory-reported, baseline immunogenicity response and a positive, post-baseline, laboratory-reported immunogenicity response with a titer value greater than the baseline titer value.
Number of Participants Experiencing Adverse Events
Number of participants experiencing different types of Adverse Events (AEs). Peri-infusional AEs: occurring during the 30 minute study drug infusion period Post-infusional AEs: occurring within 24 hours post drug infusion
Change From Baseline in Blood Pressure
Mean Change from Baseline in systolic and diastolic blood pressure values
Change From Baseline in Heart Rate
Mean Change from Baseline in heart rate values
Change From Baseline in Respiration Rate
Mean Change from Baseline in respiration rate values
Change From Baseline in Body Temperature
Mean Change from Baseline in body temperature values
Change From Baseline in Electrocardiogram (ECG) Parameters
Mean Change from Baseline in ECG parameters, including PR interval, QRS interval, QT interval, and QTC Fridericia
Number of Participants Experiencing Clinically Significant Physical Examination Abnormalities
Number of participants experiencing clinically significant physical examination abnormal findings
Change From Baseline in Laboratory Test Results - Hematology 1
Mean Change from Baseline in laboratory test results - Hematology parameters 1
Change From Baseline in Laboratory Test Results - Hematology 2
Mean Change from Baseline in laboratory test results - Hematology parameters 2
Change From Baseline in Laboratory Test Results - Hematology 3
Mean Change from Baseline in laboratory test results - Hematocrit
Change From Baseline in Laboratory Test Results - Chemistry 1
Mean Change from Baseline in laboratory test results - Chemistry parameters 1
Change From Baseline in Laboratory Test Results - Chemistry 2
Mean Change from Baseline in laboratory test results - Chemistry parameters 2
Change From Baseline in Laboratory Test Results - Chemistry 3
Mean Change from Baseline in laboratory test results - Chemistry parameters 3
Change From Baseline in Laboratory Test Results -Hematology and Chemistry 4
Mean Change from Baseline in laboratory test results - hematology and chemistry parameters 4
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03714022
Brief Title
A Study to Evaluate the Pharmacokinetics of Abatacept Converted From Drug Substance by Two Different Processes
Official Title
A Randomized, Open-Label, Parallel-Group, Single-dose, Biocomparability Study of the Pharmacokinetics of the Abatacept (BMS-188667) Drug Product Converted From Drug Substance of a New Abatacept Drug Substance Process Relative to the Current Abatacept Drug Process in Healthy Participants
Study Type
Interventional
2. Study Status
Record Verification Date
January 2021
Overall Recruitment Status
Completed
Study Start Date
November 9, 2018 (Actual)
Primary Completion Date
April 2, 2019 (Actual)
Study Completion Date
April 2, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bristol-Myers Squibb
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The main objective of this study is to compare the pharmacokinetics (PK) of the abatacept drug product converted from drug substance by a new drug substance process (Treatment A) relative to the current drug substance process (Treatment B) following a single dose (750 mg) intravenous (IV) infusion in healthy participants.
Detailed Description
Participants will be admitted to the clinical facility the day prior to dosing (Day -1) and will be confined until at least 24 hours post-dose. On Day 1, eligible participants will be randomized in a 1:1 ratio to either Treatment A or Treatment B. The randomization will be stratified by weight categories: >= 60 to < 70 kg, >= 70 to < 80 kg, >= 80 to < 90 kg, and >= 90 to <= 100 kg.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
140 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treatment A
Arm Type
Experimental
Arm Description
Participants will receive abatacept at a single dose of 750 mg as IV infusion on Day 1 converted from drug substance by a new process.
Arm Title
Treatment B
Arm Type
Active Comparator
Arm Description
Participants will receive abatacept at a single dose 750 mg as IV infusion on Day 1 converted from drug substance by converted from drug substance by the current process.
Intervention Type
Drug
Intervention Name(s)
Abatacept
Intervention Description
Participants will receive abatacept at a single dose 750 mg as IV infusion.
Primary Outcome Measure Information:
Title
Maximum Observed Serum Concentration (Cmax)
Description
Maximum Observed Serum Concentration
Time Frame
From drug administration to 70 days following drug administration
Title
Area Under the Curve AUC(INF)
Description
Area under the serum concentration-time curve from time zero extrapolated to infinity
Time Frame
From drug administration to 70 days following drug administration
Secondary Outcome Measure Information:
Title
Time of Maximum Observed Serum Concentration (Tmax)
Description
Time of maximum observed serum concentration
Time Frame
From drug administration to 70 days following drug administration
Title
Area Under the Curve AUC(0-T)
Description
Area under the serum concentration-time curve from zero to the last time of the last quantifiable concentration
Time Frame
From drug administration to 70 days following drug administration
Title
Area Under the Curve AUC(0-28)
Description
Area under the serum concentration-time curve from time zero to 28 days after dosing
Time Frame
From drug administration to 70 days following drug administration
Title
Total Body Clearance (CLT)
Description
Total body clearance
Time Frame
From drug administration to 70 days following drug administration
Title
Volume of Distribution at Steady-State (Vss)
Description
Volume of distribution at steady-state
Time Frame
From drug administration to 70 days following drug administration
Title
Terminal Phase Elimination Half-life (T-HALF)
Description
Terminal phase elimination half-life in serum
Time Frame
From drug administration to 70 days following drug administration
Title
Number of Participants Experiencing Positive Immunogenicity Response to Abatacept
Description
Positive immunogenicity response to Abatacept was defined if one of the following criteria was met:
missing baseline immunogenicity measurement and a positive, post-baseline, laboratory-reported immunogenicity response;
a negative laboratory-reported baseline immunogenicity response and a positive, post-baseline, laboratory-reported response;
a positive, laboratory-reported, baseline immunogenicity response and a positive, post-baseline, laboratory-reported immunogenicity response with a titer value greater than the baseline titer value.
Time Frame
From Day 1 (Predose) to Day 71 (Study Discharge), assessed at day 1, day 29, day 57 and day 71
Title
Number of Participants Experiencing Adverse Events
Description
Number of participants experiencing different types of Adverse Events (AEs). Peri-infusional AEs: occurring during the 30 minute study drug infusion period Post-infusional AEs: occurring within 24 hours post drug infusion
Time Frame
From drug administration to 56 days following drug administration
Title
Change From Baseline in Blood Pressure
Description
Mean Change from Baseline in systolic and diastolic blood pressure values
Time Frame
From baseline (last result before start of study medication) to 70 days after start of study medication
Title
Change From Baseline in Heart Rate
Description
Mean Change from Baseline in heart rate values
Time Frame
From baseline (last result before start of study medication) to 70 days after start of study medication
Title
Change From Baseline in Respiration Rate
Description
Mean Change from Baseline in respiration rate values
Time Frame
From baseline (last result before start of study medication) to 70 days after start of study medication
Title
Change From Baseline in Body Temperature
Description
Mean Change from Baseline in body temperature values
Time Frame
From baseline (last result before start of study medication) to 70 days after start of study medication
Title
Change From Baseline in Electrocardiogram (ECG) Parameters
Description
Mean Change from Baseline in ECG parameters, including PR interval, QRS interval, QT interval, and QTC Fridericia
Time Frame
From baseline (last result before start of study medication) to 70 days after start of study medication
Title
Number of Participants Experiencing Clinically Significant Physical Examination Abnormalities
Description
Number of participants experiencing clinically significant physical examination abnormal findings
Time Frame
From the pre-treatment period to 70 days after start of study medication (approximately 100 days)
Title
Change From Baseline in Laboratory Test Results - Hematology 1
Description
Mean Change from Baseline in laboratory test results - Hematology parameters 1
Time Frame
From baseline (last result before start of study medication) to 70 days after start of study medication
Title
Change From Baseline in Laboratory Test Results - Hematology 2
Description
Mean Change from Baseline in laboratory test results - Hematology parameters 2
Time Frame
From baseline (last result before start of study medication) to 70 days after start of study medication
Title
Change From Baseline in Laboratory Test Results - Hematology 3
Description
Mean Change from Baseline in laboratory test results - Hematocrit
Time Frame
From baseline (last result before start of study medication) to 70 days after start of study medication
Title
Change From Baseline in Laboratory Test Results - Chemistry 1
Description
Mean Change from Baseline in laboratory test results - Chemistry parameters 1
Time Frame
From baseline (last result before start of study medication) to 70 days after start of study medication
Title
Change From Baseline in Laboratory Test Results - Chemistry 2
Description
Mean Change from Baseline in laboratory test results - Chemistry parameters 2
Time Frame
From baseline (last result before start of study medication) to 70 days after start of study medication
Title
Change From Baseline in Laboratory Test Results - Chemistry 3
Description
Mean Change from Baseline in laboratory test results - Chemistry parameters 3
Time Frame
From baseline (last result before start of study medication) to 70 days after start of study medication
Title
Change From Baseline in Laboratory Test Results -Hematology and Chemistry 4
Description
Mean Change from Baseline in laboratory test results - hematology and chemistry parameters 4
Time Frame
From baseline (last result before start of study medication) to 70 days after start of study medication
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Body weight will be between 60 and 100 kg, inclusive.
Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 24 hours prior to the start of study treatment.
Women must not be breastfeeding.
WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with abatacept plus 5 half-lives of abatacept (85 days) plus 30 days (duration of ovulatory cycle) for a total of 115 days post-treatment completion.
Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with abatacept plus 5 half-lives of abatacept (85 days) plus the duration of spermatogenesis (90 days) for a total of 175 days after the last dose of study treatment. In addition, male participants must be willing to refrain from sperm donation during this time.
Exclusion Criteria:
Participants who have a present malignancy or previous malignancy within the last 5 years prior to screening (except documented history of cured non-metastatic squamous or basal cell skin carcinoma or cervical carcinoma in situ). Participants who had a screening procedure that is suspicious for malignancy, and in whom the possibility of malignancy cannot be reasonably excluded following additional clinical, laboratory or other diagnostic evaluations.
Participants with a history of herpes zoster.
Donation of blood to a blood bank or in a clinical study (except a screening visit or follow-up visit) within 4 weeks of study treatment administration (within 2 weeks of study treatment administration for plasma only).
Blood transfusion within 4 weeks of study treatment administration.
Recent (within 6 months of study treatment administration) history of smoking or current smokers. This includes participants using electronic cigarettes or nicotine-containing products such as tobacco for chewing, nicotine patches, nicotine lozenges, or nicotine gum.
History of allergy to abatacept or related compounds.
Facility Information:
Facility Name
Qps-Mra, Llc
City
South Miami
State/Province
Florida
ZIP/Postal Code
33143
Country
United States
Facility Name
PPD Development, LP
City
Austin
State/Province
Texas
ZIP/Postal Code
78744
Country
United States
12. IPD Sharing Statement
Links:
URL
https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html
Description
BMS Clinical Trial Information
URL
https://www.bmsstudyconnect.com/s/US/English/USenHome
Description
BMS Clinical Trial Patient Recruiting
URL
https://www.fda.gov/Safety/MedWatch/SafetyInformation/default.htm
Description
FDA Safety Alerts and Recalls
Learn more about this trial
A Study to Evaluate the Pharmacokinetics of Abatacept Converted From Drug Substance by Two Different Processes
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