Clinical trial NCT03714022: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Rheumatoid Arthritis
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2018-10-22
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Maximum Observed Serum Concentration (Cmax)
timeFrame: From drug administration to 70 days following drug administration
measure: Area Under the Curve AUC(INF)
timeFrame: From drug administration to 70 days following drug administration
Secondary outcomes:
measure: Time of Maximum Observed Serum Concentration (Tmax)
timeFrame: From drug administration to 70 days following drug administration
measure: Area Under the Curve AUC(0-T)
timeFrame: From drug administration to 70 days following drug administration
measure: Area Under the Curve AUC(0-28)
timeFrame: From drug administration to 70 days following drug administration
measure: Total Body Clearance (CLT)
timeFrame: From drug administration to 70 days following drug administration
measure: Volume of Distribution at Steady-State (Vss)
timeFrame: From drug administration to 70 days following drug administration
measure: Terminal Phase Elimination Half-life (T-HALF)
timeFrame: From drug administration to 70 days following drug administration
measure: Number of Participants Experiencing Positive Immunogenicity Response to Abatacept
timeFrame: From Day 1 (Predose) to Day 71 (Study Discharge), assessed at day 1, day 29, day 57 and day 71
measure: Number of Participants Experiencing Adverse Events
timeFrame: From drug administration to 56 days following drug administration
measure: Change From Baseline in Blood Pressure
timeFrame: From baseline (last result before start of study medication) to 70 days after start of study medication
measure: Change From Baseline in Heart Rate
timeFrame: From baseline (last result before start of study medication) to 70 days after start of study medication
measure: Change From Baseline in Respiration Rate
timeFrame: From baseline (last result before start of study medication) to 70 days after start of study medication
measure: Change From Baseline in Body Temperature
timeFrame: From baseline (last result before start of study medication) to 70 days after start of study medication
measure: Change From Baseline in Electrocardiogram (ECG) Parameters
timeFrame: From baseline (last result before start of study medication) to 70 days after start of study medication
measure: Number of Participants Experiencing Clinically Significant Physical Examination Abnormalities
timeFrame: From the pre-treatment period to 70 days after start of study medication (approximately 100 days)
measure: Change From Baseline in Laboratory Test Results - Hematology 1
timeFrame: From baseline (last result before start of study medication) to 70 days after start of study medication
measure: Change From Baseline in Laboratory Test Results - Hematology 2
timeFrame: From baseline (last result before start of study medication) to 70 days after start of study medication
measure: Change From Baseline in Laboratory Test Results - Hematology 3
timeFrame: From baseline (last result before start of study medication) to 70 days after start of study medication
measure: Change From Baseline in Laboratory Test Results - Chemistry 1
timeFrame: From baseline (last result before start of study medication) to 70 days after start of study medication
measure: Change From Baseline in Laboratory Test Results - Chemistry 2
timeFrame: From baseline (last result before start of study medication) to 70 days after start of study medication
measure: Change From Baseline in Laboratory Test Results - Chemistry 3
timeFrame: From baseline (last result before start of study medication) to 70 days after start of study medication
measure: Change From Baseline in Laboratory Test Results -Hematology and Chemistry 4
timeFrame: From baseline (last result before start of study medication) to 70 days after start of study medication
Other outcomes:
Locations:
city: South Miami
country: United States
facility: Qps-Mra, Llc
state: Florida
city: Austin
country: United States
facility: PPD Development, LP
state: Texas
Study officials:
References: