Study to Characterize the Pharmacokinetics of a Single Dose of SC Abatacept 125 mg Using the BD Autoinjector or the Prefilled Syringe

Rheumatoid Arthritis Clinical Trial

Official title:

Phase Ib, Multicenter, Randomized, Open-Label, Parallel-Group Study to Characterize the Pharmacokinetics of a Single Dose of Abatacept 125 mg Administered Subcutaneously Using the BD Physioject™ Autoinjector or the UltraSafe Passive Needle Guard Prefilled Syringe

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01890473
• Other study ID #: IM101-366
• Status: Completed
• Phase: Phase 1
• First received: June 27, 2013
• Last updated: October 23, 2015
• Start date: July 2013
• Est. completion date: November 2014

Study information

• Verified date: October 2015
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The primary purpose of the protocol is to describe the pharmacokinetics of a single dose of Abatacept 125 mg in Rheumatoid Arthritis patients delivered via the autoinjector device or the approved prefilled syringe.

Description:

SC=Subcutaneous

Recruitment information / eligibility

• Status: Completed
• Enrollment: 356
• Est. completion date: November 2014
• Est. primary completion date: November 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• Subjects =18 years of age

• Diagnosis of Rheumatoid Arthritis confirmed by participant's physician

• Disease activity under control

Key Exclusion Criteria:

• Change in disease-modifying antirheumatic drug (DMARD) therapy within 3 months of enrollment

• Exposure to investigational drug within 4 weeks or 5 half lives whichever is longer

• Current or prior use of Rituximab =6 months

• Current or prior use of the following within 4 weeks or 5 half lives whichever is longer: biologic DMARDS, Tofacitinib, Cyclophosphamide, Mycophenolate Mofetil & d-Penicillamine

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Abatacept

Locations

Country	Name	City	State
Argentina	Local Institution	Cordoba
Argentina	Local Institution	Cordoba
Argentina	Local Institution	Rosario	Santa Fe
Argentina	Local Institution	San Fernando	Buenos Aires
Argentina	Local Institution	San Miguel De Tucuman	Tucuman
Mexico	Local Institution	Yucatan
Peru	Local Institution	Lima
Peru	Local Institution	Lima
South Africa	Local Institution	George	Western Cape
South Africa	Local Institution	Port Elizabeth	Eastern Cape
South Africa	Local Institution	Pretoria	Gauteng
South Africa	Local Institution	Pretoria	Gauteng
United States	Immunoe Int'L Research Ctrs	Centennial	Colorado
United States	Djl Research, Pllc	Charlotte	North Carolina
United States	Community Research	Cincinnati	Ohio
United States	Covance Clinical Research Unit Inc.	Dallas	Texas
United States	Covance Cru Inc	Daytona Beach	Florida
United States	Altoona Center For Clinical Research	Duncansville	Pennsylvania
United States	Rheumatology Associates Of North Alabama, P.C.	Huntsville	Alabama
United States	Physician Research Collaboration, Llc	Lincoln	Nebraska
United States	Wake Research Associates	Raleigh	North Carolina
United States	Pmg Research Of Salisbury	Salisbury	North Carolina
United States	Heartland Research Associates, Llc	Wichita	Kansas
United States	Pmg Research Of Wilmington Llc	Wilmington	North Carolina
United States	Clinical Pharmacology Study Group	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Argentina,  Mexico,  Peru,  South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adjusted Geometric Mean of Maximum Observed Serum Concentration (Cmax) of a Single Dose of Subcutaneous (SC) Abatacept - PK-Evaluable Analysis Population	Serum concentrations of abatacept were analyzed using a validated enzyme-linked immunosorbent assay (ELISA). Cmax was measured in micrograms per milliliter (µg/mL). Blood samples for pharmacokinetic (PK) parameters were collected at Day 1 pre-dose at 0 hour (h), 1, 2, and 8 h post dose, and on subsequent Days, 2 (24 h post dose), 3 (48 h), 5 (96 h), 8 (168 h), 15 (336 h), 29 (672 h) , 43 (1008 h), 57 (1344 h) and 71 (1680 h) following the single administration of abatacept SC.	Day 1 to Day 71	No
Primary	Adjusted Geometric Mean of Area Under the Serum Concentration-time Curve (AUC) From Zero to the Last Time of the Last Quantifiable Concentration (0-T) of a Single Dose of SC Abatacept - PK-Evaluable Analysis Population	Serum concentrations of abatacept were analyzed using ELISA. AUC (0-T) was measured in µg*h/mL. Blood samples were collected at Day 1 pre-dose at 0 h, 1, 2, and 8 h post dose, and on subsequent Days, 2 (24 h post dose), 3 (48 h), 5 (96 h), 8 (168 h), 15 (336 h), 29 (672 h) , 43 (1008 h), 57 (1344 h) and 71 (1680 h) following the single administration of abatacept SC.	Day 1 to Day 71	No
Primary	Adjusted Geometric Mean of Area Under the Serum Concentration-time Curve From Time Zero to Extrapolated to Infinity, AUC (INF), of a Single Dose of SC Abatacept - PK-Evaluable Analysis Population	Serum concentrations of abatacept were analyzed using ELISA. Blood samples were collected at Day 1 pre-dose at 0 hour (h), 1, 2, and 8 h post dose, and on subsequent Days, 2 (24 h post dose), 3 (48 h), 5 (96 h), 8 (168 h), 15 (336 h), 29 (672 h) , 43 (1008 h), 57 (1344 h) and 71 (1680 h) following the single administration of abatacept SC. AUC (INF) was measured in µg*h/mL	Day 1 to Day 71	No
Secondary	Median of Time to Reach Cmax in Serum (Tmax) of a Single Dose of SC Abatacept - PK-Evaluable Analysis Population	Serum concentrations of abatacept were analyzed using ELISA. Blood samples were collected at Day 1 pre-dose at 0 h, 1, 2, and 8 h post dose, and on subsequent Days, 2 (24 h post dose), 3 (48 h), 5 (96 h), 8 (168 h), 15 (336 h), 29 (672 h) , 43 (1008 h), 57 (1344 h) and 71 (1680 h) following the single administration of abatacept SC. Tmax was measured in hours (h).	Day 1 to Day 71	No
Secondary	Mean of Terminal Phase Elimination Half-life in Serum (T-HALF) of a Single Dose of SC Abatacept - PK-Evaluable Analysis Population	Serum concentrations of abatacept were analyzed using ELISA. Blood samples were collected at Day 1 pre-dose at 0 h, 1, 2, and 8 h post dose, and on subsequent Days, 2 (24 h post dose), 3 (48 h), 5 (96 h), 8 (168 h), 15 (336 h), 29 (672 h) , 43 (1008 h), 57 (1344 h) and 71 (1680 h) following the single administration of abatacept SC. T-HALF was measured in hours (h).	Day 1 to Day 71	No
Secondary	Geometric Mean of Total Body Clearance (CL/F) of a Single Dose of SC Abatacept - PK-Evaluable Analysis Population	Serum concentrations of abatacept were analyzed using ELISA. Blood samples were collected at Day 1 pre-dose at 0 h, 1, 2, and 8 h post dose, and on subsequent Days, 2 (24 h post dose), 3 (48 h), 5 (96 h), 8 (168 h), 15 (336 h), 29 (672 h) , 43 (1008 h), 57 (1344 h) and 71 (1680 h) following the single administration of abatacept SC. CL/F was measured in milliliters per hour per kilogram body weight (mL/h/kg).	Day 1 to Day 71	No
Secondary	Geometric Mean of Volume of Distribution (V/F) of a Single Dose of Subcutaneous (SC) Abatacept - PK-Evaluable Analysis Population	Serum concentrations of abatacept were analyzed using ELISA. Blood samples were collected at Day 1 pre-dose at 0 h, 1, 2, and 8 h post dose, and on subsequent Days, 2 (24 h post dose), 3 (48 h), 5 (96 h), 8 (168 h), 15 (336 h), 29 (672 h) , 43 (1008 h), 57 (1344 h) and 71 (1680 h) following the single administration of abatacept SC. V/F was measured in liters per kilogram body weight (L/kg)	Day 1 to Day 71	No
Secondary	Number of Participants Who Had Serious Adverse Events (SAEs), Adverse Events (AEs) That Led to Discontinuation, or Who Died	AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug. Includes data Day 1 up to 76 days (71 days + 5 day window) post the single dose of study drug.	Day 1 to 76 days post single dose	Yes
Secondary	Number of Participants With Adverse Events of Special Interest	Prospectively identified events of special interest which were a subset of all AEs, and were either SAEs or non-serious AEs, included the following categories: Infections, Autoimmune Disorders, Malignancy, local site reactions, any AE occurring within 24 hours of SC injection. AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.	Day 1 to 76 days post single dose	Yes
Secondary	Number of Participants With a Positive Immunogenicity Response Relative to Baseline	Blood samples were screened at baseline, Day 57 and Day 71 for the presence of drug-specific antibodies using Electrochemiluminescence (ECL). A positive immunogenicity response relative to baseline for Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4) and 'possibly immunoglobulin (Ig)', and 'Ig and/or Junction Region', respectively, was defined as: A missing baseline immunogenicity measurement and a positive analytical laboratory reported immunogenicity response post-baseline; A negative baseline immunogenicity response and a positive analytical laboratory reported immunogenicity response post-baseline; A positive baseline immunogenicity response and a positive analytical laboratory reported immunogenicity response post-baseline that has a titer value strictly greater than the baseline titer value. Baseline=Pre-dose value.	Day 57, Day 71	No
Secondary	Number of Participants With Blood Hematology, Chemistry Laboratory Values and Urinalysis Laboratory Values Meeting the Marked Abnormality Criteria	Marked abnormality criteria: lower limit of normal (LLN); upper limit of normal (ULN); pretreatment (preRX); cells per microliter (cµ/L); milligram per deciliter (mg/dL); milliequivalent (mEq): Hematology: leukocytes (*10^3 c/µL): <0.75*LLN or >1.25*ULN, or if preRX	Day 1 to 76 days post last dose	Yes

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