A Study to Evaluate the Pharmacokinetics of Abatacept Converted From Drug Substance by Two Different Processes

Rheumatoid Arthritis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03714022
• Other study ID #: IM101-682
• Status: Completed
• Phase: Phase 1
• Start date: November 9, 2018
• Est. completion date: April 2, 2019

Study information

• Verified date: January 2021
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 140
• Est. completion date: April 2, 2019
• Est. primary completion date: April 2, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Abatacept
Participants will receive abatacept at a single dose 750 mg as IV infusion.

Locations

Country	Name	City	State
United States	PPD Development, LP	Austin	Texas
United States	Qps-Mra, Llc	South Miami	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Observed Serum Concentration (Cmax)	Maximum Observed Serum Concentration	From drug administration to 70 days following drug administration
Primary	Area Under the Curve AUC(INF)	Area under the serum concentration-time curve from time zero extrapolated to infinity	From drug administration to 70 days following drug administration
Secondary	Time of Maximum Observed Serum Concentration (Tmax)	Time of maximum observed serum concentration	From drug administration to 70 days following drug administration
Secondary	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	From drug administration to 70 days following drug administration
Secondary	Area Under the Curve AUC(0-28)	Area under the serum concentration-time curve from time zero to 28 days after dosing	From drug administration to 70 days following drug administration
Secondary	Total Body Clearance (CLT)	Total body clearance	From drug administration to 70 days following drug administration
Secondary	Volume of Distribution at Steady-State (Vss)	Volume of distribution at steady-state	From drug administration to 70 days following drug administration
Secondary	Terminal Phase Elimination Half-life (T-HALF)	Terminal phase elimination half-life in serum	From drug administration to 70 days following drug administration
Secondary	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.	From Day 1 (Predose) to Day 71 (Study Discharge), assessed at day 1, day 29, day 57 and day 71
Secondary	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	From drug administration to 56 days following drug administration
Secondary	Change From Baseline in Blood Pressure	Mean Change from Baseline in systolic and diastolic blood pressure values	From baseline (last result before start of study medication) to 70 days after start of study medication
Secondary	Change From Baseline in Heart Rate	Mean Change from Baseline in heart rate values	From baseline (last result before start of study medication) to 70 days after start of study medication
Secondary	Change From Baseline in Respiration Rate	Mean Change from Baseline in respiration rate values	From baseline (last result before start of study medication) to 70 days after start of study medication
Secondary	Change From Baseline in Body Temperature	Mean Change from Baseline in body temperature values	From baseline (last result before start of study medication) to 70 days after start of study medication
Secondary	Change From Baseline in Electrocardiogram (ECG) Parameters	Mean Change from Baseline in ECG parameters, including PR interval, QRS interval, QT interval, and QTC Fridericia	From baseline (last result before start of study medication) to 70 days after start of study medication
Secondary	Number of Participants Experiencing Clinically Significant Physical Examination Abnormalities	Number of participants experiencing clinically significant physical examination abnormal findings	From the pre-treatment period to 70 days after start of study medication (approximately 100 days)
Secondary	Change From Baseline in Laboratory Test Results - Hematology 1	Mean Change from Baseline in laboratory test results - Hematology parameters 1	From baseline (last result before start of study medication) to 70 days after start of study medication
Secondary	Change From Baseline in Laboratory Test Results - Hematology 2	Mean Change from Baseline in laboratory test results - Hematology parameters 2	From baseline (last result before start of study medication) to 70 days after start of study medication
Secondary	Change From Baseline in Laboratory Test Results - Hematology 3	Mean Change from Baseline in laboratory test results - Hematocrit	From baseline (last result before start of study medication) to 70 days after start of study medication
Secondary	Change From Baseline in Laboratory Test Results - Chemistry 1	Mean Change from Baseline in laboratory test results - Chemistry parameters 1	From baseline (last result before start of study medication) to 70 days after start of study medication
Secondary	Change From Baseline in Laboratory Test Results - Chemistry 2	Mean Change from Baseline in laboratory test results - Chemistry parameters 2	From baseline (last result before start of study medication) to 70 days after start of study medication
Secondary	Change From Baseline in Laboratory Test Results - Chemistry 3	Mean Change from Baseline in laboratory test results - Chemistry parameters 3	From baseline (last result before start of study medication) to 70 days after start of study medication
Secondary	Change From Baseline in Laboratory Test Results -Hematology and Chemistry 4	Mean Change from Baseline in laboratory test results - hematology and chemistry parameters 4	From baseline (last result before start of study medication) to 70 days after start of study medication

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