A Study to Evaluate the Pharmacokinetics of Abatacept Converted From Drug Substance by Two Different Processes
- Registration Number
- NCT03714022
- Lead Sponsor
- Bristol-Myers Squibb
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 140
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Treatment A Abatacept 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. Treatment B Abatacept 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.
- Primary Outcome Measures
Name Time Method Maximum Observed Serum Concentration (Cmax) From drug administration to 70 days following drug administration Maximum Observed Serum Concentration
Area Under the Curve AUC(INF) From drug administration to 70 days following drug administration Area under the serum concentration-time curve from time zero extrapolated to infinity
- Secondary Outcome Measures
Name Time Method Time of Maximum Observed Serum Concentration (Tmax) From drug administration to 70 days following drug administration Time of maximum observed serum concentration
Area Under the Curve AUC(0-T) From drug administration to 70 days following drug administration 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) From drug administration to 70 days following drug administration Area under the serum concentration-time curve from time zero to 28 days after dosing
Total Body Clearance (CLT) From drug administration to 70 days following drug administration Total body clearance
Volume of Distribution at Steady-State (Vss) From drug administration to 70 days following drug administration Volume of distribution at steady-state
Terminal Phase Elimination Half-life (T-HALF) From drug administration to 70 days following drug administration Terminal phase elimination half-life in serum
Number of Participants Experiencing Positive Immunogenicity Response to Abatacept From Day 1 (Predose) to Day 71 (Study Discharge), assessed at day 1, day 29, day 57 and day 71 Positive immunogenicity response to Abatacept was defined if one of the following criteria was met:
1. missing baseline immunogenicity measurement and a positive, post-baseline, laboratory-reported immunogenicity response;
2. a negative laboratory-reported baseline immunogenicity response and a positive, post-baseline, laboratory-reported response;
3. 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 From drug administration to 56 days following drug administration 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 From baseline (last result before start of study medication) to 70 days after start of study medication Mean Change from Baseline in systolic and diastolic blood pressure values
Change From Baseline in Heart Rate From baseline (last result before start of study medication) to 70 days after start of study medication Mean Change from Baseline in heart rate values
Change From Baseline in Respiration Rate From baseline (last result before start of study medication) to 70 days after start of study medication Mean Change from Baseline in respiration rate values
Change From Baseline in Body Temperature From baseline (last result before start of study medication) to 70 days after start of study medication Mean Change from Baseline in body temperature values
Change From Baseline in Electrocardiogram (ECG) Parameters From baseline (last result before start of study medication) to 70 days after start of study medication 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 From the pre-treatment period to 70 days after start of study medication (approximately 100 days) Number of participants experiencing clinically significant physical examination abnormal findings
Change From Baseline in Laboratory Test Results - Hematology 1 From baseline (last result before start of study medication) to 70 days after start of study medication Mean Change from Baseline in laboratory test results - Hematology parameters 1
Change From Baseline in Laboratory Test Results - Hematology 2 From baseline (last result before start of study medication) to 70 days after start of study medication Mean Change from Baseline in laboratory test results - Hematology parameters 2
Change From Baseline in Laboratory Test Results - Hematology 3 From baseline (last result before start of study medication) to 70 days after start of study medication Mean Change from Baseline in laboratory test results - Hematocrit
Change From Baseline in Laboratory Test Results - Chemistry 1 From baseline (last result before start of study medication) to 70 days after start of study medication Mean Change from Baseline in laboratory test results - Chemistry parameters 1
Change From Baseline in Laboratory Test Results - Chemistry 2 From baseline (last result before start of study medication) to 70 days after start of study medication Mean Change from Baseline in laboratory test results - Chemistry parameters 2
Change From Baseline in Laboratory Test Results - Chemistry 3 From baseline (last result before start of study medication) to 70 days after start of study medication Mean Change from Baseline in laboratory test results - Chemistry parameters 3
Change From Baseline in Laboratory Test Results -Hematology and Chemistry 4 From baseline (last result before start of study medication) to 70 days after start of study medication Mean Change from Baseline in laboratory test results - hematology and chemistry parameters 4
Trial Locations
- Locations (2)
Qps-Mra, Llc
🇺🇸South Miami, Florida, United States
PPD Development, LP
🇺🇸Austin, Texas, United States