Trial Outcomes & Findings for Pharmacokinetic Study to Compare the Blood Levels of Abatacept Manufactured at Lonza Biologics to the Blood Levels of Abatacept Manufactured at the Devens, Massachusetts (MA) Facility of Bristol-Myers Squibb (NCT NCT01439204)
NCT ID: NCT01439204
Last Updated: 2014-03-19
Results Overview
Cmax was derived from serum concentration versus time data. Serum samples were analyzed for abatacept by a validated enzyme-linked immunosorbent assay (ELISA) and were obtained at: predose (0 hours), 0.25 hours (h), 0.5, 1, 2, 6, 12, 24, 72, 168, 336, 504, 672, 1008, 1344, and 1688 h post dose (Days 1 to 71). The results were summarized. The lower limit of assay quantitation (LLOQ) was 1.00 nanograms per milliliter (ng/mL). Cmax was measured in micro grams per milliliter (µg/mL).
COMPLETED
PHASE1
223 participants
Days 1 to 71
2014-03-19
Participant Flow
10 October 2011 to 11 Feb 2012. Participants who were randomized to an arm were admitted to a clinical facility the day prior to dosing (Day -1) and confined until 24 hours post the single dose; participants followed to Day 71.
Healthy participants who weighed between 60 and 100 kilograms, inclusive. 223 enrolled; 72 randomized to an arm. Reasons for not being randomized: 24 withdrew consent, 5 poor/non-compliance, 111 no longer met study criteria, 11 other. Participants were age and sex matched between treatment arms.
Participant milestones
| Measure |
750 mg Abatacept From Lonza, NH
A single dose of abatacept 750 mg, manufactured at Lonza, New Hampshire facility, was administered intravenously (IV) using a calibrated, constant rate infusion pump over approximately 30 minutes.
|
750 mg Abatacept From Devens, MA
A single dose of abatacept 750 mg, manufactured at Devens, Massachusetts facility, was administered intravenously (IV) using a calibrated, constant rate infusion pump over approximately 30 minutes.
|
|---|---|---|
|
Overall Study
STARTED
|
36
|
36
|
|
Overall Study
COMPLETED
|
32
|
33
|
|
Overall Study
NOT COMPLETED
|
4
|
3
|
Reasons for withdrawal
| Measure |
750 mg Abatacept From Lonza, NH
A single dose of abatacept 750 mg, manufactured at Lonza, New Hampshire facility, was administered intravenously (IV) using a calibrated, constant rate infusion pump over approximately 30 minutes.
|
750 mg Abatacept From Devens, MA
A single dose of abatacept 750 mg, manufactured at Devens, Massachusetts facility, was administered intravenously (IV) using a calibrated, constant rate infusion pump over approximately 30 minutes.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
|
Overall Study
Lost to Follow-up
|
0
|
2
|
|
Overall Study
No longer meets study criteria
|
1
|
0
|
|
Overall Study
poor/non-compliance
|
3
|
0
|
Baseline Characteristics
Pharmacokinetic Study to Compare the Blood Levels of Abatacept Manufactured at Lonza Biologics to the Blood Levels of Abatacept Manufactured at the Devens, Massachusetts (MA) Facility of Bristol-Myers Squibb
Baseline characteristics by cohort
| Measure |
750 mg Abatacept From Lonza, NH
n=36 Participants
A single dose of abatacept 750 mg, manufactured at Lonza, New Hampshire facility, was administered intravenously (IV) using a calibrated, constant rate infusion pump over approximately 30 minutes.
|
750 mg Abatacept From Devens, MA
n=36 Participants
A single dose of abatacept 750 mg, manufactured at Devens, Massachusetts facility, was administered intravenously (IV) using a calibrated, constant rate infusion pump over approximately 30 minutes.
|
Total
n=72 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
31.6 years
STANDARD_DEVIATION 10.02 • n=93 Participants
|
31.2 years
STANDARD_DEVIATION 8.90 • n=4 Participants
|
31.4 years
STANDARD_DEVIATION 9.41 • n=27 Participants
|
|
Sex: Female, Male
Female
|
22 Participants
n=93 Participants
|
21 Participants
n=4 Participants
|
43 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=93 Participants
|
15 Participants
n=4 Participants
|
29 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
4 Participants
n=93 Participants
|
6 Participants
n=4 Participants
|
10 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
32 Participants
n=93 Participants
|
30 Participants
n=4 Participants
|
62 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Region of Enrollment
United States
|
36 participants
n=93 Participants
|
36 participants
n=4 Participants
|
72 participants
n=27 Participants
|
|
Body Weight
|
78.93 kg
STANDARD_DEVIATION 11.472 • n=93 Participants
|
79.39 kg
STANDARD_DEVIATION 11.057 • n=4 Participants
|
79.16 kg
STANDARD_DEVIATION 11.189 • n=27 Participants
|
PRIMARY outcome
Timeframe: Days 1 to 71Population: Pharmacokinetic (PK) population: all participants who received study drug and had adequate PK profiles. All completers had evaluable PK.
Cmax was derived from serum concentration versus time data. Serum samples were analyzed for abatacept by a validated enzyme-linked immunosorbent assay (ELISA) and were obtained at: predose (0 hours), 0.25 hours (h), 0.5, 1, 2, 6, 12, 24, 72, 168, 336, 504, 672, 1008, 1344, and 1688 h post dose (Days 1 to 71). The results were summarized. The lower limit of assay quantitation (LLOQ) was 1.00 nanograms per milliliter (ng/mL). Cmax was measured in micro grams per milliliter (µg/mL).
Outcome measures
| Measure |
750 mg Abatacept From Lonza, NH
n=32 Participants
A single dose of abatacept 750 mg, manufactured at Lonza, New Hampshire facility, was administered intravenously (IV) using a calibrated, constant rate infusion pump over approximately 30 minutes.
|
750 mg Abatacept From Devens, MA
n=33 Participants
A single dose of abatacept 750 mg, manufactured at Devens, Massachusetts facility, was administered intravenously (IV) using a calibrated, constant rate infusion pump over approximately 30 minutes.
|
|---|---|---|
|
Maximum Observed Concentration (Cmax) of Single Dose Abatacept - Pharmacokinetic Evaluable Population
|
262 µg/mL
Geometric Coefficient of Variation 27
|
255 µg/mL
Geometric Coefficient of Variation 21
|
PRIMARY outcome
Timeframe: Day 1 to Day 71Population: Pharmacokinetic (PK) population: all participants who received study drug and had adequate PK profiles.
Tmax was derived from serum concentration versus time data. Serum samples were analyzed for abatacept by a validated enzyme-linked immunosorbent assay (ELISA) and were obtained at: predose (0 hours), 0.25 hours (h), 0.5, 1, 2, 6, 12, 24, 72, 168, 336, 504, 672, 1008, 1344, and 1688 h post dose (Days 1 to 71). The results were summarized. The lower limit of assay quantitation (LLOQ) was 1.00 nanograms per milliliter (ng/mL). Tmax was measured in hours (h).
Outcome measures
| Measure |
750 mg Abatacept From Lonza, NH
n=32 Participants
A single dose of abatacept 750 mg, manufactured at Lonza, New Hampshire facility, was administered intravenously (IV) using a calibrated, constant rate infusion pump over approximately 30 minutes.
|
750 mg Abatacept From Devens, MA
n=33 Participants
A single dose of abatacept 750 mg, manufactured at Devens, Massachusetts facility, was administered intravenously (IV) using a calibrated, constant rate infusion pump over approximately 30 minutes.
|
|---|---|---|
|
Time to Reach Maximum Concentration (Tmax) of Single Dose Abatacept - Pharmacokinetic Evaluable Population
|
1.00 h
Interval 0.55 to 2.12
|
1.00 h
Interval 1.0 to 6.0
|
PRIMARY outcome
Timeframe: Day 1 to Day 71Population: Pharmacokinetic (PK) population: all participants who received study drug and had adequate PK profiles.
AUC (0 - 28) was derived from serum concentration versus time data. Serum samples were analyzed for abatacept by a validated enzyme-linked immunosorbent assay (ELISA) and were obtained at: predose (0 hours), 0.25 hours (h), 0.5, 1, 2, 6, 12, 24, 72, 168, 336, 504, 672, 1008, 1344, and 1688 h post dose (Days 1 to 71). The results were summarized. The lower limit of assay quantitation (LLOQ) was 1.00 nanograms per milliliter (ng/mL). AUC (0 - 28) was measured in micro grams\*hours per milliliter (µg\*h/mL).
Outcome measures
| Measure |
750 mg Abatacept From Lonza, NH
n=32 Participants
A single dose of abatacept 750 mg, manufactured at Lonza, New Hampshire facility, was administered intravenously (IV) using a calibrated, constant rate infusion pump over approximately 30 minutes.
|
750 mg Abatacept From Devens, MA
n=33 Participants
A single dose of abatacept 750 mg, manufactured at Devens, Massachusetts facility, was administered intravenously (IV) using a calibrated, constant rate infusion pump over approximately 30 minutes.
|
|---|---|---|
|
Area Under the Concentration-time Curve (AUC) From Time Zero to 28 Days [AUC(0-28 Days)] of Single Dose Abatacept - Pharmacokinetic Evaluable Population
|
33195 µg*h/mL
Geometric Coefficient of Variation 26
|
35255 µg*h/mL
Geometric Coefficient of Variation 23
|
PRIMARY outcome
Timeframe: Day 1 to Day 71Population: Pharmacokinetic (PK) population: all participants who received study drug and had adequate PK profiles.
AUC (0 - T) was derived from serum concentration versus time data. Serum samples were analyzed for abatacept by a validated enzyme-linked immunosorbent assay (ELISA) and were obtained at: predose (0 hours), 0.25 hours (h), 0.5, 1, 2, 6, 12, 24, 72, 168, 336, 504, 672, 1008, 1344, and 1688 h post dose (Days 1 to 71). The results were summarized. The lower limit of assay quantitation (LLOQ) was 1.00 nanograms per milliliter (ng/mL). AUC (0 - T) was measured in micro grams\*hour per milliliter (µg\*h/mL).
Outcome measures
| Measure |
750 mg Abatacept From Lonza, NH
n=32 Participants
A single dose of abatacept 750 mg, manufactured at Lonza, New Hampshire facility, was administered intravenously (IV) using a calibrated, constant rate infusion pump over approximately 30 minutes.
|
750 mg Abatacept From Devens, MA
n=33 Participants
A single dose of abatacept 750 mg, manufactured at Devens, Massachusetts facility, was administered intravenously (IV) using a calibrated, constant rate infusion pump over approximately 30 minutes.
|
|---|---|---|
|
Area Under the Concentration-time Curve From Zero to the Last Time of the Last Quantifiable Concentration [AUC(0-T)] of Single Dose Abatacept - Pharmacokinetic Evaluable Population
|
39295 µg*h/mL
Geometric Coefficient of Variation 23
|
41916 µg*h/mL
Geometric Coefficient of Variation 25
|
PRIMARY outcome
Timeframe: Day 1 to Day 71Population: Pharmacokinetic (PK) population: all participants who received study drug and had adequate PK profiles.
AUC (0 - INF) was derived from serum concentration versus time data. Serum samples were analyzed for abatacept by a validated enzyme-linked immunosorbent assay (ELISA) and were obtained at: predose (0 hours), 0.25 hours (h), 0.5, 1, 2, 6, 12, 24, 72, 168, 336, 504, 672, 1008, 1344, and 1688 h post dose (Days 1 to 71). The results were summarized. The lower limit of assay quantitation (LLOQ) was 1.00 nanograms per milliliter (ng/mL). AUC (0 - INF) was measured in µg\*h/mL.
Outcome measures
| Measure |
750 mg Abatacept From Lonza, NH
n=32 Participants
A single dose of abatacept 750 mg, manufactured at Lonza, New Hampshire facility, was administered intravenously (IV) using a calibrated, constant rate infusion pump over approximately 30 minutes.
|
750 mg Abatacept From Devens, MA
n=33 Participants
A single dose of abatacept 750 mg, manufactured at Devens, Massachusetts facility, was administered intravenously (IV) using a calibrated, constant rate infusion pump over approximately 30 minutes.
|
|---|---|---|
|
Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinity [AUC(0 - INF)] of Single Dose Abatacept - Pharmacokinetic Evaluable Population
|
40385 µg*h/mL
Geometric Coefficient of Variation 23
|
43229 µg*h/mL
Geometric Coefficient of Variation 27
|
PRIMARY outcome
Timeframe: Day 1 to Day 71Population: Pharmacokinetic (PK) population: all participants who received study drug and had adequate PK profiles.
T-HALF was derived from serum concentration versus time data. Serum samples were analyzed for abatacept by a validated enzyme-linked immunosorbent assay (ELISA) and were obtained at: predose (0 hours), 0.25 hours (h), 0.5, 1, 2, 6, 12, 24, 72, 168, 336, 504, 672, 1008, 1344, and 1688 h post dose (Days 1 to 71). The results were summarized. The lower limit of assay quantitation (LLOQ) was 1.00 nanograms per milliliter (ng/mL). T-HALF was measured in hours (h).
Outcome measures
| Measure |
750 mg Abatacept From Lonza, NH
n=32 Participants
A single dose of abatacept 750 mg, manufactured at Lonza, New Hampshire facility, was administered intravenously (IV) using a calibrated, constant rate infusion pump over approximately 30 minutes.
|
750 mg Abatacept From Devens, MA
n=33 Participants
A single dose of abatacept 750 mg, manufactured at Devens, Massachusetts facility, was administered intravenously (IV) using a calibrated, constant rate infusion pump over approximately 30 minutes.
|
|---|---|---|
|
Terminal Phase Elimination Half-life (T-HALF) of Single Dose Abatacept - Pharmacokinetic Evaluable Population
|
344 h
Standard Deviation 87.6
|
364 h
Standard Deviation 106
|
PRIMARY outcome
Timeframe: Day 1 to Day 71Population: Pharmacokinetic (PK) population: all participants who received study drug and had adequate PK profiles.
CLT was the volume of abatacept cleared by the system, normalized by baseline body weight. Serum samples were analyzed for abatacept by a validated enzyme-linked immunosorbent assay (ELISA) and were obtained at: predose (0 hours), 0.25 hours (h), 0.5, 1, 2, 6, 12, 24, 72, 168, 336, 504, 672, 1008, 1344, and 1688 h post dose (Days 1 to 71). The results were summarized. The lower limit of assay quantitation (LLOQ) was 1.00 nanograms per milliliter (ng/mL). CLT was measured in milliliters per hours per kilogram of body weight (mL/h/kg).
Outcome measures
| Measure |
750 mg Abatacept From Lonza, NH
n=32 Participants
A single dose of abatacept 750 mg, manufactured at Lonza, New Hampshire facility, was administered intravenously (IV) using a calibrated, constant rate infusion pump over approximately 30 minutes.
|
750 mg Abatacept From Devens, MA
n=33 Participants
A single dose of abatacept 750 mg, manufactured at Devens, Massachusetts facility, was administered intravenously (IV) using a calibrated, constant rate infusion pump over approximately 30 minutes.
|
|---|---|---|
|
Total Body Clearance (CLT) of Single Dose Abatacept - Pharmacokinetic Evaluable Population
|
0.237 mL/h/kg
Geometric Coefficient of Variation 24
|
0.219 mL/h/kg
Geometric Coefficient of Variation 24
|
PRIMARY outcome
Timeframe: Day 1 to Day 71Population: Pharmacokinetic (PK) population: all participants who received study drug and had adequate PK profiles.
Vss was derived from serum concentration versus time data. Serum samples were analyzed for abatacept by a validated enzyme-linked immunosorbent assay (ELISA) and were obtained at: predose (0 hours), 0.25 hours (h), 0.5, 1, 2, 6, 12, 24, 72, 168, 336, 504, 672, 1008, 1344, and 1688 h post dose (Days 1 to 71). The results were summarized. The lower limit of assay quantitation (LLOQ) was 1.00 nanograms per milliliter (ng/mL). Vss was measured in liters per kg body weight (L/kg).
Outcome measures
| Measure |
750 mg Abatacept From Lonza, NH
n=32 Participants
A single dose of abatacept 750 mg, manufactured at Lonza, New Hampshire facility, was administered intravenously (IV) using a calibrated, constant rate infusion pump over approximately 30 minutes.
|
750 mg Abatacept From Devens, MA
n=33 Participants
A single dose of abatacept 750 mg, manufactured at Devens, Massachusetts facility, was administered intravenously (IV) using a calibrated, constant rate infusion pump over approximately 30 minutes.
|
|---|---|---|
|
Volume of Distribution at Steady-state (Vss) of Single Dose Abatacept - Pharmacokinetic Evaluable Population
|
0.088 L/kg
Geometric Coefficient of Variation 33
|
0.083 L/kg
Geometric Coefficient of Variation 22
|
SECONDARY outcome
Timeframe: Days 29, 57, 71Population: Immunogenicity Data Set: All participants with at least 1 postdose visit.
Immunogenicity determination was based on titers of anti-abatacept and anti- cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4-T) antibodies in serum over time. A participant had a positive abatacept-induced immunogenicity if 1 of the following criteria were met: missing baseline measurement and a positive response after baseline; negative baseline response and positive response after baseline; a baseline response and a positive response after baseline that has a titer value strictly greater than the baseline titer value. A validated, sensitive, electrochemiluminescence assay (ECL) method was used to analyze the antibodies in serum. Samples confirmed positive with ECL and with abatacept serum concentrations of less than equal to 1 µg/mL were further analyzed with a validated, in vitro, cell-based bioassay to analyze the sera containing the abatacept neutralizing activity. Samples obtained on Days 29, 57 and 71 post dose of abatacept on Day 1 (baseline).
Outcome measures
| Measure |
750 mg Abatacept From Lonza, NH
n=36 Participants
A single dose of abatacept 750 mg, manufactured at Lonza, New Hampshire facility, was administered intravenously (IV) using a calibrated, constant rate infusion pump over approximately 30 minutes.
|
750 mg Abatacept From Devens, MA
n=36 Participants
A single dose of abatacept 750 mg, manufactured at Devens, Massachusetts facility, was administered intravenously (IV) using a calibrated, constant rate infusion pump over approximately 30 minutes.
|
|---|---|---|
|
Number of Participants With Positive Abatacept-induced Immunogenicity Response
|
4 participants
|
1 participants
|
SECONDARY outcome
Timeframe: Day 2 to Day 71Population: All participants who received study drug (safety population) and had a laboratory assessment were included in the analysis. Day 2 N=36 both arms; Day 15 (Lonza arm N=36; Devens arm N=34; Day 29 (Lonza arm N=34; Devens arm N=33); Day 57 (Lonza arm N=31; Devens arm N=33); Day 71 (Lonza arm N=36; Devens arm N=34).
Blood samples obtained: Days 1, 2, 4, 8, 15, 22, 29, 43, 57 and 71. International Units per liter (U/L); milligram per deciliter (mg/dL); Male(M); Female (F). Reference ranges (low/high) for laboratories for which participants were identified with marked abnormalities during the study: Blood Urea Nitrogen (M/F) 10-20mg/dL ; Creatine Kinase (F) 21-21 U/L,(M) 32-294 U/L; Direct Bilirubin (M/F) 0.1-0.4 mg/dL ; Fasting Glucose (M/F) 70-110 mg/dL; Lactate Dehydrogenase (M/F) 110-209 U/L.
Outcome measures
| Measure |
750 mg Abatacept From Lonza, NH
n=36 Participants
A single dose of abatacept 750 mg, manufactured at Lonza, New Hampshire facility, was administered intravenously (IV) using a calibrated, constant rate infusion pump over approximately 30 minutes.
|
750 mg Abatacept From Devens, MA
n=36 Participants
A single dose of abatacept 750 mg, manufactured at Devens, Massachusetts facility, was administered intravenously (IV) using a calibrated, constant rate infusion pump over approximately 30 minutes.
|
|---|---|---|
|
Number of Participants With Marked Serum Chemistry Abnormalities on Days 2, 15, 29, 57 and 71 - Safety Population
Creatine Kinase (high) Day 2 (N=36)
|
1 participants
|
0 participants
|
|
Number of Participants With Marked Serum Chemistry Abnormalities on Days 2, 15, 29, 57 and 71 - Safety Population
Creatine Kinase (high) Day 15 (N=36,34)
|
1 participants
|
0 participants
|
|
Number of Participants With Marked Serum Chemistry Abnormalities on Days 2, 15, 29, 57 and 71 - Safety Population
Creatine Kinase (high) Day 29 (N=34,33)
|
2 participants
|
1 participants
|
|
Number of Participants With Marked Serum Chemistry Abnormalities on Days 2, 15, 29, 57 and 71 - Safety Population
Creatine Kinase (high) Day 57 (N=31,33)
|
1 participants
|
1 participants
|
|
Number of Participants With Marked Serum Chemistry Abnormalities on Days 2, 15, 29, 57 and 71 - Safety Population
Creatine Kinase (high) Day 71 (N=36,34)
|
1 participants
|
2 participants
|
|
Number of Participants With Marked Serum Chemistry Abnormalities on Days 2, 15, 29, 57 and 71 - Safety Population
Lactate Dehydrogenase (high) Day 2 (N=36)
|
0 participants
|
1 participants
|
|
Number of Participants With Marked Serum Chemistry Abnormalities on Days 2, 15, 29, 57 and 71 - Safety Population
Blood urea nitrogen (high) Day 15 (N=36,34)
|
1 participants
|
0 participants
|
|
Number of Participants With Marked Serum Chemistry Abnormalities on Days 2, 15, 29, 57 and 71 - Safety Population
Blood urea nitrogen (high) Day 29 (N=34)
|
0 participants
|
1 participants
|
|
Number of Participants With Marked Serum Chemistry Abnormalities on Days 2, 15, 29, 57 and 71 - Safety Population
Blood urea nitrogen (high) Day 71 (N=36,34)
|
2 participants
|
0 participants
|
|
Number of Participants With Marked Serum Chemistry Abnormalities on Days 2, 15, 29, 57 and 71 - Safety Population
Bilirubin Direct (high) Day 29 (N=34)
|
0 participants
|
3 participants
|
|
Number of Participants With Marked Serum Chemistry Abnormalities on Days 2, 15, 29, 57 and 71 - Safety Population
Bilirubin Direct (high) Day 71 (N=36,34)
|
0 participants
|
1 participants
|
|
Number of Participants With Marked Serum Chemistry Abnormalities on Days 2, 15, 29, 57 and 71 - Safety Population
Fasting Glucose (high) Day 71 (N=36,34)
|
1 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Day 2 to Day 72Population: All participants who received study drug (safety population) and had a laboratory assessment were included in the analysis. Day 2 N=36 both arms; Day 15 (Lonza arm N=36; Devens arm N=34; Day 29 (Lonza arm N=34; Devens arm N=33); Day 57 (Lonza arm N=31; Devens arm N=33); Day 71 (Lonza arm N=36; Devens arm N=34).
Blood samples obtained: Days 2, 4, 8, 15, 22, 29, 43, 57 and 71. Male(M); Female (F). Reference ranges (low/high) for laboratory parameters for which participants were identified with marked abnormalities during the study: Leukocytes (quantitative White blood cells) (M/F) 4-11\*10\^3/microliters (µL); Neutrophils (absolute)(M/F) 1.4- 8.2\*10\^3/µL.
Outcome measures
| Measure |
750 mg Abatacept From Lonza, NH
n=36 Participants
A single dose of abatacept 750 mg, manufactured at Lonza, New Hampshire facility, was administered intravenously (IV) using a calibrated, constant rate infusion pump over approximately 30 minutes.
|
750 mg Abatacept From Devens, MA
n=36 Participants
A single dose of abatacept 750 mg, manufactured at Devens, Massachusetts facility, was administered intravenously (IV) using a calibrated, constant rate infusion pump over approximately 30 minutes.
|
|---|---|---|
|
Number of Participants With Marked Hematology Abnormalities on Days 2, 15, 29, 57, and 71 - Safety Population
Any marked abnormalities Day 2 (N=36)
|
0 participants
|
0 participants
|
|
Number of Participants With Marked Hematology Abnormalities on Days 2, 15, 29, 57, and 71 - Safety Population
Any marked abnormalities Day 15 (n=36,34)
|
0 participants
|
0 participants
|
|
Number of Participants With Marked Hematology Abnormalities on Days 2, 15, 29, 57, and 71 - Safety Population
Leukocytes (high) Day 29 (N=34,33)
|
0 participants
|
1 participants
|
|
Number of Participants With Marked Hematology Abnormalities on Days 2, 15, 29, 57, and 71 - Safety Population
Leukocytes (high) Day 57 (N=31,33)
|
0 participants
|
1 participants
|
|
Number of Participants With Marked Hematology Abnormalities on Days 2, 15, 29, 57, and 71 - Safety Population
Leukocytes (high) Day 71 (N=36,34)
|
1 participants
|
1 participants
|
|
Number of Participants With Marked Hematology Abnormalities on Days 2, 15, 29, 57, and 71 - Safety Population
Neutrophils (absolute) (high) Day 71 (N=36,34)
|
1 participants
|
1 participants
|
SECONDARY outcome
Timeframe: Day 1 to Day 71Population: All participants who received study drug (safety population) and had systolic assessment were included in the analysis. Days 1 and 2 N=36 both arms; Day 15 (Lonza arm N=36; Devens arm N=34; Day 29 (N=33 in both arms); Day 57 (Lonza arm N=31; Devens arm N=33); Day 71 (Lonza arm N=36; Devens arm N=34).
Blood pressure was obtained while the participant had been quietly seated for at least 5 minutes. Baseline was the 0 hour measurement on Day 1 (day of dosing) or if this value was missing, the last measurement before dosing. Blood pressure was measured in millimeters of mercury (mmHg) on Days 1, 2, 15, 29, 57, and 71.
Outcome measures
| Measure |
750 mg Abatacept From Lonza, NH
n=36 Participants
A single dose of abatacept 750 mg, manufactured at Lonza, New Hampshire facility, was administered intravenously (IV) using a calibrated, constant rate infusion pump over approximately 30 minutes.
|
750 mg Abatacept From Devens, MA
n=36 Participants
A single dose of abatacept 750 mg, manufactured at Devens, Massachusetts facility, was administered intravenously (IV) using a calibrated, constant rate infusion pump over approximately 30 minutes.
|
|---|---|---|
|
Change From Baseline in Systolic Blood Pressure - Safety Population
Day 1 (1 hour post dose) (N=36)
|
-6.3 mmHg
Standard Deviation 9.73
|
-4.5 mmHg
Standard Deviation 9.06
|
|
Change From Baseline in Systolic Blood Pressure - Safety Population
Day 2 (N=36)
|
-3.0 mmHg
Standard Deviation 12.31
|
-1.4 mmHg
Standard Deviation 10.35
|
|
Change From Baseline in Systolic Blood Pressure - Safety Population
Day 15 (N=36,34)
|
-1.1 mmHg
Standard Deviation 12.09
|
0.3 mmHg
Standard Deviation 8.12
|
|
Change From Baseline in Systolic Blood Pressure - Safety Population
Day 29 (N=33)
|
-2.3 mmHg
Standard Deviation 10.94
|
-0.2 mmHg
Standard Deviation 9.65
|
|
Change From Baseline in Systolic Blood Pressure - Safety Population
Day 57 (N=31,33)
|
1.0 mmHg
Standard Deviation 11.96
|
3.4 mmHg
Standard Deviation 9.48
|
|
Change From Baseline in Systolic Blood Pressure - Safety Population
Day 71 (N=36,34)
|
2.2 mmHg
Standard Deviation 12.09
|
2.9 mmHg
Standard Deviation 9.87
|
SECONDARY outcome
Timeframe: Day 1 to Day 71Population: All participants who received study drug (safety population) and had diastolic assessment were included in the analysis. Day 2 N=36 both arms; Day 15 (Lonza arm N=36; Devens arm N=34; Day 29 (N=33 in both arms); Day 57 (Lonza arm N=31; Devens arm N=33); Day 71 (Lonza arm N=36; Devens arm N=34).
Blood pressure was obtained while the participant had been quietly seated for at least 5 minutes. Baseline was the 0 hour measurement on Day 1 (day of dosing) or if this value was missing, the last measurement before dosing. Blood pressure was measured in millimeters of mercury (mmHg) on Days 1, 2, 15, 29, 57, and 71.
Outcome measures
| Measure |
750 mg Abatacept From Lonza, NH
n=36 Participants
A single dose of abatacept 750 mg, manufactured at Lonza, New Hampshire facility, was administered intravenously (IV) using a calibrated, constant rate infusion pump over approximately 30 minutes.
|
750 mg Abatacept From Devens, MA
n=36 Participants
A single dose of abatacept 750 mg, manufactured at Devens, Massachusetts facility, was administered intravenously (IV) using a calibrated, constant rate infusion pump over approximately 30 minutes.
|
|---|---|---|
|
Change From Baseline in Diastolic Blood Pressure on Days 1, 2, 15, 29, 57, and 71 - Safety Population
Day 2 (N=36)
|
-2.3 mmHg
Standard Deviation 8.98
|
-0.6 mmHg
Standard Deviation 6.02
|
|
Change From Baseline in Diastolic Blood Pressure on Days 1, 2, 15, 29, 57, and 71 - Safety Population
Day 1 (1 hour post dose) N=36
|
-4.9 mmHg
Standard Deviation 5.91
|
-4.1 mmHg
Standard Deviation 5.78
|
|
Change From Baseline in Diastolic Blood Pressure on Days 1, 2, 15, 29, 57, and 71 - Safety Population
Day 15 (N=36,34)
|
-1.4 mmHg
Standard Deviation 7.45
|
1.0 mmHg
Standard Deviation 7.29
|
|
Change From Baseline in Diastolic Blood Pressure on Days 1, 2, 15, 29, 57, and 71 - Safety Population
Day 29 (N=33)
|
-1.9 mmHg
Standard Deviation 6.37
|
0.9 mmHg
Standard Deviation 7.08
|
|
Change From Baseline in Diastolic Blood Pressure on Days 1, 2, 15, 29, 57, and 71 - Safety Population
Day 57 (N=31,33)
|
0.4 mmHg
Standard Deviation 7.48
|
3.5 mmHg
Standard Deviation 7.56
|
|
Change From Baseline in Diastolic Blood Pressure on Days 1, 2, 15, 29, 57, and 71 - Safety Population
Day 71 (N=36,34)
|
1.6 mmHg
Standard Deviation 8.59
|
4.0 mmHg
Standard Deviation 5.78
|
SECONDARY outcome
Timeframe: Day 1 to Day 71Population: All participants who received study drug and had at least one ECG value.
12-lead electrocardiograms were performed on a supine participant (5 minutes supine) at baseline (baseline = screening; Days -21 to -2) and at Day 71. QT interval and QTc were measured in mille seconds (msec). A change from baseline QT and QTc (corrected for heart rate by Fridericia formula) greater than (\>) 30 msec or less than (\<) 60 msec were presented, as well as values over 450 and 500 msec. QT interval on ECG image defined as: time from the beginning of the QRS (complex consisting of Q, R and S waves) to the end of the T wave.
Outcome measures
| Measure |
750 mg Abatacept From Lonza, NH
n=36 Participants
A single dose of abatacept 750 mg, manufactured at Lonza, New Hampshire facility, was administered intravenously (IV) using a calibrated, constant rate infusion pump over approximately 30 minutes.
|
750 mg Abatacept From Devens, MA
n=36 Participants
A single dose of abatacept 750 mg, manufactured at Devens, Massachusetts facility, was administered intravenously (IV) using a calibrated, constant rate infusion pump over approximately 30 minutes.
|
|---|---|---|
|
Number of Participants With a Change From Baseline in QT Interval and Corrected (Fridericia) QT Interval (QTcF) - Safety Population
Change from baseline in QT >60 msec
|
0 participants
|
1 participants
|
|
Number of Participants With a Change From Baseline in QT Interval and Corrected (Fridericia) QT Interval (QTcF) - Safety Population
Change from baseline in QT >30 msec < 60 msec
|
5 participants
|
4 participants
|
|
Number of Participants With a Change From Baseline in QT Interval and Corrected (Fridericia) QT Interval (QTcF) - Safety Population
Change from baseline in QTc >60 msec
|
0 participants
|
0 participants
|
|
Number of Participants With a Change From Baseline in QT Interval and Corrected (Fridericia) QT Interval (QTcF) - Safety Population
Change from baseline in QTc >30 msec < 60 msec
|
2 participants
|
2 participants
|
|
Number of Participants With a Change From Baseline in QT Interval and Corrected (Fridericia) QT Interval (QTcF) - Safety Population
QT > 500 msec
|
0 participants
|
0 participants
|
|
Number of Participants With a Change From Baseline in QT Interval and Corrected (Fridericia) QT Interval (QTcF) - Safety Population
QT > 450 msec
|
0 participants
|
1 participants
|
|
Number of Participants With a Change From Baseline in QT Interval and Corrected (Fridericia) QT Interval (QTcF) - Safety Population
QTcF >450 msec
|
0 participants
|
0 participants
|
Adverse Events
750 mg Abatacept From Devens, MA
750 mg Abatacept From Lonza, NH
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
750 mg Abatacept From Devens, MA
n=36 participants at risk
A single dose of abatacept 750 mg, manufactured at Devens, Massachusetts facility, was administered intravenously (IV) using a calibrated, constant rate infusion pump over approximately 30 minutes.
|
750 mg Abatacept From Lonza, NH
n=36 participants at risk
A single dose of abatacept 750 mg, manufactured at Lonza, New Hampshire facility, was administered intravenously (IV) using a calibrated, constant rate infusion pump over approximately 30 minutes.
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
5.6%
2/36 • Day 1 to Day 71
|
2.8%
1/36 • Day 1 to Day 71
|
|
Nervous system disorders
Dizziness
|
5.6%
2/36 • Day 1 to Day 71
|
5.6%
2/36 • Day 1 to Day 71
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
8.3%
3/36 • Day 1 to Day 71
|
5.6%
2/36 • Day 1 to Day 71
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/36 • Day 1 to Day 71
|
5.6%
2/36 • Day 1 to Day 71
|
|
Eye disorders
Vision blurred
|
0.00%
0/36 • Day 1 to Day 71
|
5.6%
2/36 • Day 1 to Day 71
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
5.6%
2/36 • Day 1 to Day 71
|
11.1%
4/36 • Day 1 to Day 71
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
8.3%
3/36 • Day 1 to Day 71
|
0.00%
0/36 • Day 1 to Day 71
|
|
Infections and infestations
Upper respiratory tract infection
|
2.8%
1/36 • Day 1 to Day 71
|
5.6%
2/36 • Day 1 to Day 71
|
|
Nervous system disorders
Headache
|
13.9%
5/36 • Day 1 to Day 71
|
16.7%
6/36 • Day 1 to Day 71
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
0.00%
0/36 • Day 1 to Day 71
|
8.3%
3/36 • Day 1 to Day 71
|
|
Renal and urinary disorders
Dysuria
|
0.00%
0/36 • Day 1 to Day 71
|
5.6%
2/36 • Day 1 to Day 71
|
Additional Information
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