Trial Outcomes & Findings for Study to Characterize the Pharmacokinetics of a Single Dose of SC Abatacept 125 mg Using the BD Autoinjector or the Prefilled Syringe (NCT NCT01890473)

NCT ID: NCT01890473

Last Updated: 2015-11-26

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 356 participants
• Primary outcome timeframe: Day 1 to Day 71
• Results posted on: 2015-11-26

Participant Flow

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.

Participant milestones

Measure	125 mg Abatacept Via Autoinjector A single dose of 125 mg abatacept was administered subcutaneously (SC) via an autoinjector.	125 mg Abatacept Via Prefilled Syringe A single dose of 125 mg abatacept was administered SC via a Prefilled Syringe (PFS).
Overall Study STARTED	111	113
Overall Study COMPLETED	109	113
Overall Study NOT COMPLETED	2	0

Reasons for withdrawal

Measure	125 mg Abatacept Via Autoinjector A single dose of 125 mg abatacept was administered subcutaneously (SC) via an autoinjector.	125 mg Abatacept Via Prefilled Syringe A single dose of 125 mg abatacept was administered SC via a Prefilled Syringe (PFS).
Overall Study Lost to Follow-up	1	0
Overall Study Poor/non-compliance	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	125 mg Abatacept Via Autoinjector n=111 Participants A single dose of 125 mg abatacept was administered subcutaneously (SC) via an autoinjector.	125 mg Abatacept Via Prefilled Syringe n=113 Participants A single dose of 125 mg abatacept was administered SC via a Prefilled Syringe (PFS).	Total n=224 Participants Total of all reporting groups
Age, Continuous	53.0 years STANDARD_DEVIATION 13.34 • n=5 Participants	56.8 years STANDARD_DEVIATION 12.36 • n=7 Participants	54.9 years STANDARD_DEVIATION 12.97 • n=5 Participants
Age, Customized Less than (<) 65	90 participants n=5 Participants	75 participants n=7 Participants	165 participants n=5 Participants
Age, Customized Greater than, equal to (>=) 65	21 participants n=5 Participants	38 participants n=7 Participants	59 participants n=5 Participants
Sex: Female, Male Female	90 Participants n=5 Participants	87 Participants n=7 Participants	177 Participants n=5 Participants
Sex: Female, Male Male	21 Participants n=5 Participants	26 Participants n=7 Participants	47 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 1 to Day 71

Population: PK-evaluable analysis population: All randomized and treated participants with adequately evaluable PK parameters were summarized.

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.

Outcome measures

Measure	125 mg Abatacept Via Autoinjector n=105 Participants A single dose of 125 mg abatacept was administered subcutaneously (SC) via an autoinjector.	125 mg Abatacept Via Prefilled Syringe n=111 Participants A single dose of 125 mg abatacept was administered SC via a Prefilled Syringe (PFS).
Adjusted Geometric Mean of Maximum Observed Serum Concentration (Cmax) of a Single Dose of Subcutaneous (SC) Abatacept - PK-Evaluable Analysis Population	11.5 μg/mL Interval 10.6 to 12.4	12.6 μg/mL Interval 11.7 to 13.6

PRIMARY outcome

Timeframe: Day 1 to Day 71

Population: PK-evaluable analysis population: All randomized and treated participants with adequately evaluable PK parameters were summarized.

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.

Outcome measures

Measure	125 mg Abatacept Via Autoinjector n=105 Participants A single dose of 125 mg abatacept was administered subcutaneously (SC) via an autoinjector.	125 mg Abatacept Via Prefilled Syringe n=111 Participants A single dose of 125 mg abatacept was administered SC via a Prefilled Syringe (PFS).
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	4991 μg*h/mL Interval 4613.0 to 5400.0	5304 μg*h/mL Interval 4913.0 to 5727.0

PRIMARY outcome

Timeframe: Day 1 to Day 71

Population: PK-evaluable analysis population: All randomized and treated participants with adequately evaluable PK parameters were summarized.

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

Outcome measures

Measure	125 mg Abatacept Via Autoinjector n=104 Participants A single dose of 125 mg abatacept was administered subcutaneously (SC) via an autoinjector.	125 mg Abatacept Via Prefilled Syringe n=111 Participants A single dose of 125 mg abatacept was administered SC via a Prefilled Syringe (PFS).
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	5308 μg*h/mL Interval 4957.0 to 5684.0	5437 μg*h/mL Interval 5089.0 to 5810.0

SECONDARY outcome

Timeframe: Day 1 to Day 71

Population: PK-evaluable analysis population: All randomized and treated participants with adequately evaluable PK parameters were summarized.

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).

Outcome measures

Measure	125 mg Abatacept Via Autoinjector n=105 Participants A single dose of 125 mg abatacept was administered subcutaneously (SC) via an autoinjector.	125 mg Abatacept Via Prefilled Syringe n=111 Participants A single dose of 125 mg abatacept was administered SC via a Prefilled Syringe (PFS).
Median of Time to Reach Cmax in Serum (Tmax) of a Single Dose of SC Abatacept - PK-Evaluable Analysis Population	96.0 h Interval 24.0 to 337.0	96.0 h Interval 24.0 to 336.0

SECONDARY outcome

Timeframe: Day 1 to Day 71

Population: PK-evaluable analysis population: All randomized and treated participants with adequately evaluable PK parameters were summarized.

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).

Outcome measures

Measure	125 mg Abatacept Via Autoinjector n=104 Participants A single dose of 125 mg abatacept was administered subcutaneously (SC) via an autoinjector.	125 mg Abatacept Via Prefilled Syringe n=111 Participants A single dose of 125 mg abatacept was administered SC via a Prefilled Syringe (PFS).
Mean of Terminal Phase Elimination Half-life in Serum (T-HALF) of a Single Dose of SC Abatacept - PK-Evaluable Analysis Population	285 h Standard Deviation 89.54	302 h Standard Deviation 99.82

SECONDARY outcome

Timeframe: Day 1 to Day 71

Population: PK-evaluable analysis population: All randomized and treated participants with adequately evaluable PK parameters were summarized.

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).

Outcome measures

Measure	125 mg Abatacept Via Autoinjector n=104 Participants A single dose of 125 mg abatacept was administered subcutaneously (SC) via an autoinjector.	125 mg Abatacept Via Prefilled Syringe n=111 Participants A single dose of 125 mg abatacept was administered SC via a Prefilled Syringe (PFS).
Geometric Mean of Total Body Clearance (CL/F) of a Single Dose of SC Abatacept - PK-Evaluable Analysis Population	0.31 mL/h/kg Geometric Coefficient of Variation 52	0.30 mL/h/kg Geometric Coefficient of Variation 62

SECONDARY outcome

Timeframe: Day 1 to Day 71

Population: PK-evaluable analysis population: All randomized and treated participants with adequately evaluable PK parameters were summarized.

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)

Outcome measures

Measure	125 mg Abatacept Via Autoinjector n=104 Participants A single dose of 125 mg abatacept was administered subcutaneously (SC) via an autoinjector.	125 mg Abatacept Via Prefilled Syringe n=111 Participants A single dose of 125 mg abatacept was administered SC via a Prefilled Syringe (PFS).
Geometric Mean of Volume of Distribution (V/F) of a Single Dose of Subcutaneous (SC) Abatacept - PK-Evaluable Analysis Population	0.12 L/kg Geometric Coefficient of Variation 43	0.12 L/kg Geometric Coefficient of Variation 62

SECONDARY outcome

Timeframe: Day 1 to 76 days post single dose

Population: All treated participants were included in safety analysis.

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.

Outcome measures

Measure	125 mg Abatacept Via Autoinjector n=111 Participants A single dose of 125 mg abatacept was administered subcutaneously (SC) via an autoinjector.	125 mg Abatacept Via Prefilled Syringe n=113 Participants A single dose of 125 mg abatacept was administered SC via a Prefilled Syringe (PFS).
Number of Participants Who Had Serious Adverse Events (SAEs), Adverse Events (AEs) That Led to Discontinuation, or Who Died Death	0 participants	0 participants
Number of Participants Who Had Serious Adverse Events (SAEs), Adverse Events (AEs) That Led to Discontinuation, or Who Died SAE	0 participants	1 participants
Number of Participants Who Had Serious Adverse Events (SAEs), Adverse Events (AEs) That Led to Discontinuation, or Who Died Related SAEs	0 participants	0 participants
Number of Participants Who Had Serious Adverse Events (SAEs), Adverse Events (AEs) That Led to Discontinuation, or Who Died Discontinued due to AE	0 participants	0 participants

SECONDARY outcome

Timeframe: Day 1 to 76 days post single dose

Population: All treated participants were included in safety analysis.

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.

Outcome measures

Measure	125 mg Abatacept Via Autoinjector n=111 Participants A single dose of 125 mg abatacept was administered subcutaneously (SC) via an autoinjector.	125 mg Abatacept Via Prefilled Syringe n=113 Participants A single dose of 125 mg abatacept was administered SC via a Prefilled Syringe (PFS).
Number of Participants With Adverse Events of Special Interest Infections	19 participants	17 participants
Number of Participants With Adverse Events of Special Interest Autoimmune Disorders	0 participants	0 participants
Number of Participants With Adverse Events of Special Interest Malignancy	0 participants	0 participants
Number of Participants With Adverse Events of Special Interest Local site reactions	1 participants	3 participants
Number of Participants With Adverse Events of Special Interest AEs within 24 hours of SC injection	10 participants	7 participants

SECONDARY outcome

Timeframe: Day 57, Day 71

Population: 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.

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.

Outcome measures

Measure	125 mg Abatacept Via Autoinjector n=109 Participants A single dose of 125 mg abatacept was administered subcutaneously (SC) via an autoinjector.	125 mg Abatacept Via Prefilled Syringe n=113 Participants A single dose of 125 mg abatacept was administered SC via a Prefilled Syringe (PFS).
Number of Participants With a Positive Immunogenicity Response Relative to Baseline Day 71 CTLA4, possibly Ig (n=105,112)	23 participants	22 participants
Number of Participants With a Positive Immunogenicity Response Relative to Baseline Day 57 CTLA4, possibly Ig (n=109,111)	10 participants	13 participants
Number of Participants With a Positive Immunogenicity Response Relative to Baseline Day 57 Ig and/or junction (n=109,111)	4 participants	5 participants
Number of Participants With a Positive Immunogenicity Response Relative to Baseline Day 71 Ig and/or junction (n=105,112)	1 participants	5 participants
Number of Participants With a Positive Immunogenicity Response Relative to Baseline Overall CTLA4, possibly Ig (n=109,113)	24 participants	24 participants
Number of Participants With a Positive Immunogenicity Response Relative to Baseline Overall Ig and/or junction (n=109,113)	4 participants	8 participants

SECONDARY outcome

Timeframe: Day 1 to 76 days post last dose

Population: All treated participants with laboratory values were included in the safety analysis. n=number of participants evaluated.

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.

Outcome measures

Measure	125 mg Abatacept Via Autoinjector n=111 Participants A single dose of 125 mg abatacept was administered subcutaneously (SC) via an autoinjector.	125 mg Abatacept Via Prefilled Syringe n=113 Participants A single dose of 125 mg abatacept was administered SC via a Prefilled Syringe (PFS).
Number of Participants With Blood Hematology, Chemistry Laboratory Values and Urinalysis Laboratory Values Meeting the Marked Abnormality Criteria Leukocytes High (n=109, 110)	1 participants	0 participants
Number of Participants With Blood Hematology, Chemistry Laboratory Values and Urinalysis Laboratory Values Meeting the Marked Abnormality Criteria Leukocytes Low (n=109, 110)	0 participants	1 participants
Number of Participants With Blood Hematology, Chemistry Laboratory Values and Urinalysis Laboratory Values Meeting the Marked Abnormality Criteria Eosinophils High (n=107,107)	1 participants	0 participants
Number of Participants With Blood Hematology, Chemistry Laboratory Values and Urinalysis Laboratory Values Meeting the Marked Abnormality Criteria Lymphocytes Low (n=107,107)	2 participants	5 participants
Number of Participants With Blood Hematology, Chemistry Laboratory Values and Urinalysis Laboratory Values Meeting the Marked Abnormality Criteria Blood Urea Nitrogen High (n=109,111)	1 participants	0 participants
Number of Participants With Blood Hematology, Chemistry Laboratory Values and Urinalysis Laboratory Values Meeting the Marked Abnormality Criteria Urine Blood High (n=104,107)	7 participants	1 participants
Number of Participants With Blood Hematology, Chemistry Laboratory Values and Urinalysis Laboratory Values Meeting the Marked Abnormality Criteria Urine RBC High (n=28, 26)	5 participants	2 participants
Number of Participants With Blood Hematology, Chemistry Laboratory Values and Urinalysis Laboratory Values Meeting the Marked Abnormality Criteria Urine WBC High (n=35, 33)	11 participants	13 participants
Number of Participants With Blood Hematology, Chemistry Laboratory Values and Urinalysis Laboratory Values Meeting the Marked Abnormality Criteria Creatinine High (n=109,111)	2 participants	0 participants
Number of Participants With Blood Hematology, Chemistry Laboratory Values and Urinalysis Laboratory Values Meeting the Marked Abnormality Criteria Potassium Low (n=109,111)	0 participants	1 participants
Number of Participants With Blood Hematology, Chemistry Laboratory Values and Urinalysis Laboratory Values Meeting the Marked Abnormality Criteria Glucose High (n=109,110)	2 participants	0 participants
Number of Participants With Blood Hematology, Chemistry Laboratory Values and Urinalysis Laboratory Values Meeting the Marked Abnormality Criteria Glucose Low (n=109,110)	3 participants	3 participants

Adverse Events

125 mg Abatacept Via Autoinjector

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

125 mg Abatacept Via Prefilled Syringe

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	125 mg Abatacept Via Autoinjector n=111 participants at risk A single dose of 125 mg abatacept was administered SC via an autoinjector.	125 mg Abatacept Via Prefilled Syringe n=113 participants at risk A single dose of 125 mg abatacept was administered SC via a PFS.
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	0.00% 0/111	0.88% 1/113

Other adverse events

Adverse event data not reported

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Email: Clinical.Trials@bms.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER