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

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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

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Rheumatoid Arthritis
Intervention Drug: Abatacept
Enrollment 356
Recruitment Details  
Pre-assignment Details 356 participants enrolled and 224 randomized. 132 not randomized and reasons for non-randomization: 106 no longer met study criteria, 15 other, 9 withdrew consent, and 2 lost to follow-up.
Arm/Group Title 125 mg Abatacept Via Autoinjector 125 mg Abatacept Via Prefilled Syringe
Hide Arm/Group Description A single dose of 125 mg abatacept was administered subcutaneously (SC) via an autoinjector. A single dose of 125 mg abatacept was administered SC via a Prefilled Syringe (PFS).
Period Title: Overall Study
Started 111 113
Completed 109 113
Not Completed 2 0
Reason Not Completed
Lost to Follow-up             1             0
Poor/non-compliance             1             0
Arm/Group Title 125 mg Abatacept Via Autoinjector 125 mg Abatacept Via Prefilled Syringe Total
Hide Arm/Group Description A single dose of 125 mg abatacept was administered subcutaneously (SC) via an autoinjector. A single dose of 125 mg abatacept was administered SC via a Prefilled Syringe (PFS). Total of all reporting groups
Overall Number of Baseline Participants 111 113 224
Hide Baseline Analysis Population Description
All randomized participants were summarized.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 111 participants 113 participants 224 participants
53.0  (13.34) 56.8  (12.36) 54.9  (12.97)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 111 participants 113 participants 224 participants
Less than (<) 65 90 75 165
Greater than, equal to (>=) 65 21 38 59
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 111 participants 113 participants 224 participants
Female
90
  81.1%
87
  77.0%
177
  79.0%
Male
21
  18.9%
26
  23.0%
47
  21.0%
1.Primary Outcome
Title Adjusted Geometric Mean of Maximum Observed Serum Concentration (Cmax) of a Single Dose of Subcutaneous (SC) Abatacept - PK-Evaluable Analysis Population
Hide Description 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.
Time Frame Day 1 to Day 71
Hide Outcome Measure Data
Hide Analysis Population Description
PK-evaluable analysis population: All randomized and treated participants with adequately evaluable PK parameters were summarized.
Arm/Group Title 125 mg Abatacept Via Autoinjector 125 mg Abatacept Via Prefilled Syringe
Hide Arm/Group Description:
A single dose of 125 mg abatacept was administered subcutaneously (SC) via an autoinjector.
A single dose of 125 mg abatacept was administered SC via a Prefilled Syringe (PFS).
Overall Number of Participants Analyzed 105 111
Geometric Mean (90% Confidence Interval)
Unit of Measure: μg/mL
11.5
(10.6 to 12.4)
12.6
(11.7 to 13.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 125 mg Abatacept Via Autoinjector, 125 mg Abatacept Via Prefilled Syringe
Comments The PK comparability of the two devices was assessed via a linear model for each key PK parameter in log scale (using log (Cmax) without a formal test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter ratio of geometric mean
Estimated Value 0.908
Confidence Interval (2-Sided) 90%
0.815 to 1.01
Estimation Comments [Not Specified]
2.Primary Outcome
Title 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
Hide Description 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.
Time Frame Day 1 to Day 71
Hide Outcome Measure Data
Hide Analysis Population Description
PK-evaluable analysis population: All randomized and treated participants with adequately evaluable PK parameters were summarized.
Arm/Group Title 125 mg Abatacept Via Autoinjector 125 mg Abatacept Via Prefilled Syringe
Hide Arm/Group Description:
A single dose of 125 mg abatacept was administered SC via an autoinjector.
A single dose of 125 mg abatacept was administered SC via a Prefilled Syringe.
Overall Number of Participants Analyzed 105 111
Geometric Mean (90% Confidence Interval)
Unit of Measure: μg*h/mL
4991
(4613 to 5400)
5304
(4913 to 5727)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 125 mg Abatacept Via Autoinjector, 125 mg Abatacept Via Prefilled Syringe
Comments The PK comparability of the two devices was assessed via a linear model for each key PK parameter in log scale, using log (AUC (0-T) without a formal test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter ratio of geometric mean
Estimated Value 0.941
Confidence Interval (2-Sided) 90%
0.843 to 1.05
Estimation Comments [Not Specified]
3.Primary Outcome
Title 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
Hide Description 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
Time Frame Day 1 to Day 71
Hide Outcome Measure Data
Hide Analysis Population Description
PK-evaluable analysis population: All randomized and treated participants with adequately evaluable PK parameters were summarized.
Arm/Group Title 125 mg Abatacept Via Autoinjector 125 mg Abatacept Via Prefilled Syringe
Hide Arm/Group Description:
A single dose of 125 mg abatacept was administered subcutaneously (SC) via an autoinjector.
A single dose of 125 mg abatacept was administered SC via a Prefilled Syringe (PFS).
Overall Number of Participants Analyzed 104 111
Geometric Mean (90% Confidence Interval)
Unit of Measure: μg*h/mL
5308
(4957 to 5684)
5437
(5089 to 5810)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 125 mg Abatacept Via Autoinjector, 125 mg Abatacept Via Prefilled Syringe
Comments The PK comparability of the two devices was assessed via a linear model for each key PK parameter in log scale, using log AUC(INF) without a formal test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter ratio of geometric mean
Estimated Value 0.976
Confidence Interval (2-Sided) 90%
0.888 to 1.07
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Median of Time to Reach Cmax in Serum (Tmax) of a Single Dose of SC Abatacept - PK-Evaluable Analysis Population
Hide Description 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).
Time Frame Day 1 to Day 71
Hide Outcome Measure Data
Hide Analysis Population Description
PK-evaluable analysis population: All randomized and treated participants with adequately evaluable PK parameters were summarized.
Arm/Group Title 125 mg Abatacept Via Autoinjector 125 mg Abatacept Via Prefilled Syringe
Hide Arm/Group Description:
A single dose of 125 mg abatacept was administered SC via an autoinjector.
A single dose of 125 mg abatacept was administered SC via a Prefilled Syringe.
Overall Number of Participants Analyzed 105 111
Median (Full Range)
Unit of Measure: h
96.0
(24 to 337)
96.0
(24 to 336)
5.Secondary Outcome
Title Mean of Terminal Phase Elimination Half-life in Serum (T-HALF) of a Single Dose of SC Abatacept - PK-Evaluable Analysis Population
Hide Description 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).
Time Frame Day 1 to Day 71
Hide Outcome Measure Data
Hide Analysis Population Description
PK-evaluable analysis population: All randomized and treated participants with adequately evaluable PK parameters were summarized.
Arm/Group Title 125 mg Abatacept Via Autoinjector 125 mg Abatacept Via Prefilled Syringe
Hide Arm/Group Description:
A single dose of 125 mg abatacept was administered SC via an autoinjector.
A single dose of 125 mg abatacept was administered SC via a Prefilled Syringe.
Overall Number of Participants Analyzed 104 111
Mean (Standard Deviation)
Unit of Measure: h
285  (89.54) 302  (99.82)
6.Secondary Outcome
Title Geometric Mean of Total Body Clearance (CL/F) of a Single Dose of SC Abatacept - PK-Evaluable Analysis Population
Hide Description 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).
Time Frame Day 1 to Day 71
Hide Outcome Measure Data
Hide Analysis Population Description
PK-evaluable analysis population: All randomized and treated participants with adequately evaluable PK parameters were summarized.
Arm/Group Title 125 mg Abatacept Via Autoinjector 125 mg Abatacept Via Prefilled Syringe
Hide Arm/Group Description:
A single dose of 125 mg abatacept was administered SC via an autoinjector.
A single dose of 125 mg abatacept was administered SC via a Prefilled Syringe.
Overall Number of Participants Analyzed 104 111
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: mL/h/kg
0.31
(52%)
0.30
(62%)
7.Secondary Outcome
Title Geometric Mean of Volume of Distribution (V/F) of a Single Dose of Subcutaneous (SC) Abatacept - PK-Evaluable Analysis Population
Hide Description 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)
Time Frame Day 1 to Day 71
Hide Outcome Measure Data
Hide Analysis Population Description
PK-evaluable analysis population: All randomized and treated participants with adequately evaluable PK parameters were summarized.
Arm/Group Title 125 mg Abatacept Via Autoinjector 125 mg Abatacept Via Prefilled Syringe
Hide Arm/Group Description:
A single dose of 125 mg abatacept was administered SC via an autoinjector.
A single dose of 125 mg abatacept was administered SC via a Prefilled Syringe.
Overall Number of Participants Analyzed 104 111
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: L/kg
0.12
(43%)
0.12
(62%)
8.Secondary Outcome
Title Number of Participants Who Had Serious Adverse Events (SAEs), Adverse Events (AEs) That Led to Discontinuation, or Who Died
Hide Description 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.
Time Frame Day 1 to 76 days post single dose
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants were included in safety analysis.
Arm/Group Title 125 mg Abatacept Via Autoinjector 125 mg Abatacept Via Prefilled Syringe
Hide Arm/Group Description:
A single dose of 125 mg abatacept was administered SC via an autoinjector.
A single dose of 125 mg abatacept was administered SC via a Prefilled Syringe.
Overall Number of Participants Analyzed 111 113
Measure Type: Number
Unit of Measure: participants
Death 0 0
SAE 0 1
Related SAEs 0 0
Discontinued due to AE 0 0
9.Secondary Outcome
Title Number of Participants With Adverse Events of Special Interest
Hide Description 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.
Time Frame Day 1 to 76 days post single dose
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants were included in safety analysis.
Arm/Group Title 125 mg Abatacept Via Autoinjector 125 mg Abatacept Via Prefilled Syringe
Hide Arm/Group Description:
A single dose of 125 mg abatacept was administered subcutaneously (SC) via an autoinjector.
A single dose of 125 mg abatacept was administered SC via a Prefilled Syringe (PFS).
Overall Number of Participants Analyzed 111 113
Measure Type: Number
Unit of Measure: participants
Infections 19 17
Autoimmune Disorders 0 0
Malignancy 0 0
Local site reactions 1 3
AEs within 24 hours of SC injection 10 7
10.Secondary Outcome
Title Number of Participants With a Positive Immunogenicity Response Relative to Baseline
Hide Description 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.
Time Frame Day 57, Day 71
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants with at least one post baseline immunogenicity result reported were included in the immunogenicity analysis. n=number of participants evaluated at the specific time point.
Arm/Group Title 125 mg Abatacept Via Autoinjector 125 mg Abatacept Via Prefilled Syringe
Hide Arm/Group Description:
A single dose of 125 mg abatacept was administered SC via an autoinjector.
A single dose of 125 mg abatacept was administered SC via a Prefilled Syringe.
Overall Number of Participants Analyzed 109 113
Measure Type: Number
Unit of Measure: participants
Day 57 CTLA4, possibly Ig (n=109,111) 10 13
Day 57 Ig and/or junction (n=109,111) 4 5
Day 71 CTLA4, possibly Ig (n=105,112) 23 22
Day 71 Ig and/or junction (n=105,112) 1 5
Overall CTLA4, possibly Ig (n=109,113) 24 24
Overall Ig and/or junction (n=109,113) 4 8
11.Secondary Outcome
Title Number of Participants With Blood Hematology, Chemistry Laboratory Values and Urinalysis Laboratory Values Meeting the Marked Abnormality Criteria
Hide Description 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.
Time Frame Day 1 to 76 days post last dose
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants with laboratory values were included in the safety analysis. n=number of participants evaluated.
Arm/Group Title 125 mg Abatacept Via Autoinjector 125 mg Abatacept Via Prefilled Syringe
Hide Arm/Group Description:
A single dose of 125 mg abatacept was administered SC via an autoinjector.
A single dose of 125 mg abatacept was administered SC via a Prefilled Syringe.
Overall Number of Participants Analyzed 111 113
Measure Type: Number
Unit of Measure: participants
Leukocytes High (n=109, 110) 1 0
Leukocytes Low (n=109, 110) 0 1
Eosinophils High (n=107,107) 1 0
Lymphocytes Low (n=107,107) 2 5
Blood Urea Nitrogen High (n=109,111) 1 0
Creatinine High (n=109,111) 2 0
Potassium Low (n=109,111) 0 1
Glucose High (n=109,110) 2 0
Glucose Low (n=109,110) 3 3
Urine Blood High (n=104,107) 7 1
Urine RBC High (n=28, 26) 5 2
Urine WBC High (n=35, 33) 11 13
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title 125 mg Abatacept Via Autoinjector 125 mg Abatacept Via Prefilled Syringe
Hide Arm/Group Description A single dose of 125 mg abatacept was administered SC via an autoinjector. A single dose of 125 mg abatacept was administered SC via a PFS.
All-Cause Mortality
125 mg Abatacept Via Autoinjector 125 mg Abatacept Via Prefilled Syringe
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
125 mg Abatacept Via Autoinjector 125 mg Abatacept Via Prefilled Syringe
Affected / at Risk (%) Affected / at Risk (%)
Total   0/111 (0.00%)   1/113 (0.88%) 
Musculoskeletal and connective tissue disorders     
Rheumatoid arthritis  1  0/111 (0.00%)  1/113 (0.88%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
125 mg Abatacept Via Autoinjector 125 mg Abatacept Via Prefilled Syringe
Affected / at Risk (%) Affected / at Risk (%)
Total   0/111 (0.00%)   0/113 (0.00%) 
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Results Point of Contact
Name/Title: Bristol-Myers Squibb Study Director
Organization: Bristol-Myers Squibb
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01890473     History of Changes
Other Study ID Numbers: IM101-366
First Submitted: June 27, 2013
First Posted: July 1, 2013
Results First Submitted: October 23, 2015
Results First Posted: November 26, 2015
Last Update Posted: November 26, 2015