Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01890473
Recruitment Status : Completed
First Posted : July 1, 2013
Results First Posted : November 26, 2015
Last Update Posted : November 26, 2015
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Brief 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.

Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis Drug: Abatacept Phase 1

Detailed Description:
SC=Subcutaneous

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 356 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : July 2013
Actual Primary Completion Date : November 2014
Actual Study Completion Date : November 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Arthritis
Drug Information available for: Abatacept

Arm Intervention/treatment
Experimental: Arm 1: Abatacept (autoinjector)
Abatacept 125 mg/syringe subcutaneously through autoinjector, one dose in 71 days
Drug: Abatacept
Other Names:
  • Orencia
  • BMS-188667

Experimental: Arm 2: Abatacept (prefilled syringe)
Abatacept 125 mg/syringe subcutaneously with prefilled syringe, one dose in 71 days
Drug: Abatacept
Other Names:
  • Orencia
  • BMS-188667




Primary Outcome Measures :
  1. Adjusted Geometric Mean of Maximum Observed Serum Concentration (Cmax) of a Single Dose of Subcutaneous (SC) Abatacept - PK-Evaluable Analysis Population [ Time Frame: Day 1 to Day 71 ]
    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.

  2. 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 [ Time Frame: Day 1 to Day 71 ]
    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.

  3. 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 [ Time Frame: Day 1 to Day 71 ]
    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


Secondary Outcome Measures :
  1. Median of Time to Reach Cmax in Serum (Tmax) of a Single Dose of SC Abatacept - PK-Evaluable Analysis Population [ Time Frame: Day 1 to Day 71 ]
    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).

  2. Mean of Terminal Phase Elimination Half-life in Serum (T-HALF) of a Single Dose of SC Abatacept - PK-Evaluable Analysis Population [ Time Frame: Day 1 to Day 71 ]
    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).

  3. Geometric Mean of Total Body Clearance (CL/F) of a Single Dose of SC Abatacept - PK-Evaluable Analysis Population [ Time Frame: Day 1 to Day 71 ]
    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).

  4. Geometric Mean of Volume of Distribution (V/F) of a Single Dose of Subcutaneous (SC) Abatacept - PK-Evaluable Analysis Population [ Time Frame: Day 1 to Day 71 ]
    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)

  5. Number of Participants Who Had Serious Adverse Events (SAEs), Adverse Events (AEs) That Led to Discontinuation, or Who Died [ Time Frame: Day 1 to 76 days post single dose ]
    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.

  6. Number of Participants With Adverse Events of Special Interest [ Time Frame: Day 1 to 76 days post single dose ]
    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.

  7. Number of Participants With a Positive Immunogenicity Response Relative to Baseline [ Time Frame: Day 57, Day 71 ]
    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.

  8. Number of Participants With Blood Hematology, Chemistry Laboratory Values and Urinalysis Laboratory Values Meeting the Marked Abnormality Criteria [ Time Frame: Day 1 to 76 days post last dose ]
    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 <LLN, use <0.8*preRX or >ULN, or if preRX>ULN, use >1.2*preRX or <LLN; eosinophils (*10^3 cµ/L): if value >0.750*10^3 c/µL; lymphocytes (*10^3 cµ/L): if value <0.750*10^3 c/µL or if value >7.50*10^3 c/µL. Chemistry: blood urea nitrogen (mg/dL): >2*preRX; creatinine (mg/dL): >1.5*preRX; potassium (mEq/L): <0.9*LLN or >1.1*ULN, or if preRX<LLN, use <0.9*preRX or >ULN, or if preRX>ULN, use 1.1*preRX or <LLN; glucose (mg/dL): <65 mg/dL (low) or >220 mg/dL (high). Urine Blood, urine red blood cell (RBC), urine white blood cell (WBC): if missing PreRX use >= 2, or if Value >= 4, or if preRX = 0 or 0.5 then use >= 2, or if preRX = 1 then use >= 3, or if preRX = 2 or 3 then use >= 4.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01890473


  Show 25 Study Locations
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Layout table for investigator information
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb

Additional Information:
Layout table for additonal information
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01890473     History of Changes
Other Study ID Numbers: IM101-366
First Posted: July 1, 2013    Key Record Dates
Results First Posted: November 26, 2015
Last Update Posted: November 26, 2015
Last Verified: October 2015
Additional relevant MeSH terms:
Layout table for MeSH terms
Connective Tissue Diseases
Abatacept
Immunosuppressive Agents
Physiological Effects of Drugs
Antirheumatic Agents
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Autoimmune Diseases
Immune System Diseases
Immunologic Factors