Subcutaneous Pharmacokinetics of Belatacept
- Registration Number
- NCT00569803
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
Pharmacokinetics, Bioavailability, Safety and Immunogenicity of Single Doses of Belatacept Administered Subcutaneously to Healthy Subjects
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 153
- Men and women ages 18 to 65 years old
- Subjects must weigh less than or equal to 100 kg
- Inability to tolerate injections or IV infusions
- autoimmune disorders
- TB
- herpes
- HCV
- HBV
- HIV
- bacterial or viral infection
- history of cancer
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Belatacept 50 mg Subcutaneous Injection belatacept Belatacept 50 mg subcutaneous (SC) injection Belatacept 100 mg Subcutaneous Injection belatacept Belatacept 100 mg SC injection Belatacept 125 mg Subcutaneous Injection belatacept Belatacept 125 mg SC injection Belatacept 125 mg Intravenous Infusion belatacept 125 mg Belatacept intravenous (IV) injection Placebo Placebo SC injection of placebo solution Belatacept 200 mg Subcutaneous Injections belatacept 2 SC injections of 100 mg Belatacept Belatacept 250 mg Subcutaneous Injections belatacept 2 SC injections of 125 mg Belatacept Belatacept 150 mg Subcutaneous Injections belatacept 2 SC injections of 75 mg Belatacept
- Primary Outcome Measures
Name Time Method Apparent Total Body Clearance (CLT/F) of SC Belatacept Immediately before dose, 0.5, 2, 6, 12, 24, 36, 48, 60, 72, 84 hours post-dose, Days 5, 6, 7, 8, 14, 21, 28, 35, 42, 56, 86 and 116 Apparent total body clearance (CLT/F) was derived from serum concentration versus time data for all participants who received subcutaneous (SC) Belatacept injections. Units reported in milliliters per hour (mL/h).
Maximum Observed Serum Concentration (Cmax) of Belatacept Immediately before dose, 0.5, 2, 6, 12, 24, 36, 48, 60, 72, 84 hours post-dose, Days 5, 6, 7, 8, 14, 21, 28, 35, 42, 56, 86 and 116 Maximum observed serum concentration (Cmax) values were derived from serum concentration versus time data and reported in micrograms per milliliter (ug/mL).
Adjusted Geometric Means of Area Under the Serum Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUC(0-T)) for Belatacept Immediately before dose, 0.5, 2, 6, 12, 24, 36, 48, 60, 72, 84 hours post-dose, Days 5, 6, 7, 8, 14, 21, 28, 35, 42, 56, 86 and 116 Area under the serum concentration-time curve from time zero to the time of last quantifiable concentration (AUC(0-T)) was derived from serum concentration versus time data. Adjusted geometric means were reported in microgram hours per milliliter (ug\*h/mL).
Time of Maximum Observed Serum Concentration (Tmax) of Belatacept Immediately before dose, 0.5, 2, 6, 12, 24, 36, 48, 60, 72, 84 hours post-dose, Days 5, 6, 7, 8, 14, 21, 28, 35, 42, 56, 86 and 116 Time of maximum observed serum concentration (Tmax) values were derived from serum concentration versus time data for all participants treated with Belatacept.
Adjusted Geometric Means of Area Under the Serum Concentration-time Curve From Time Zero Extrapolated to Infinite Time (AUC(INF)) for Belatacept Immediately before dose, 0.5, 2, 6, 12, 24, 36, 48, 60, 72, 84 hours post-dose, Days 5, 6, 7, 8, 14, 21, 28, 35, 42, 56, 86 and 116 Area under the serum concentration-time curve from time zero extrapolated to infinite time (AUC(INF)) was derived from serum concentration versus time data. Adjusted geometric means were reported in microgram hours per milliliter (ug\*h/mL)
Serum Half-life (T-HALF) of Belatacept Immediately before dose, 0.5, 2, 6, 12, 24, 36, 48, 60, 72, 84 hours post-dose, Days 5, 6, 7, 8, 14, 21, 28, 35, 42, 56, 86 and 116 Serum half-life (T-HALF) was determined from serum concentration versus time data and was reported in hours.
Total Body Clearance (CLT) of IV Belatacept Immediately before dose, 0.5, 2, 6, 12, 24, 36, 48, 60, 72, 84 hours post-dose, Days 5, 6, 7, 8, 14, 21, 28, 35, 42, 56, 86 and 116 Total body clearance (CLT) was derived from serum concentration versus time data for all participants that were treated with IV Belatacept. Units reported in milliliters per hour (mL/h)
Volume of Distribution at Steady State (VSS) for IV Belatacept Immediately before dose, 0.5, 2, 6, 12, 24, 36, 48, 60, 72, 84 hours post-dose, Days 5, 6, 7, 8, 14, 21, 28, 35, 42, 56, 86 and 116 Volume of distribution at steady state (VSS) was derived from serum concentration versus time data for all participants treated with IV Belatacept.
Apparent Volume of Distribution at Steady State (Vss/F) for SC Belatacept Immediately before dose, 0.5, 2, 6, 12, 24, 36, 48, 60, 72, 84 hours post-dose, Days 5, 6, 7, 8, 14, 21, 28, 35, 42, 56, 86 and 116 Apparent volume of distribution at steady state (Vss/F) was derived from concentration versus time data for all participants treated with subcutaneous (SC) Belatacept.
- Secondary Outcome Measures
Name Time Method Effect of Number of Injection Sites on Subcutaneous Belatacept Absorption Immediately before dose, 0.5, 2, 6, 12, 24, 36, 48, 60, 72, 84 hours post-dose, Days 5, 6, 7, 8, 14, 21, 28, 35, 42, 56, 86 and 116 AUC(0-T) and AUC(INF) for Belatacept were derived from serum concentration versus time data to assess the effect of number of injection sites on the subcutaneous absorption of Belatacept. All treatments were dose-normalized to 50mg. Adjusted geometric means reported in microgram hours per milliliter (ug\*h/mL).
AUC(0-T) = Area Under the Serum Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration.
AUC(INF) = Area Under the Serum Concentration-time Curve From Time Zero Extrapolated to Infinite Time.Number of Participants With Vital Sign Abnormalities 1 day pre-dose, Days 1, 2, 5, 14, 28, 42, 86 and 116 Vital signs (body temperature, respiratory rate, seated blood pressure, and heart rate) were recorded at screening. All significant findings were evaluated by the investigator, and all abnormalities were listed.
Number of Participants With Injection Site Reactions 0.5, 2, 6 and 24 hours post-dose, Days 3, 4, 5, 6, 7, 8, 14, 21 and 116 Participants were assessed for erythema, heat, pain, pruritis and swelling at the injection sites and were characterized by the investigator as mild, moderate or severe reactions.
Number of Participants With Physical Examination Abnormalities Days 1, 2, 5, 14, 28, 42, 86, 116 All clinically significant deviations from normal physical examinations were reported.
Number of Participants With Electrocardiogram (ECG) Abnormalities Days 1 and 116 Participants underwent a 12-lead ECG assessment at Screening (Day 1) and Study Discharge (Day 116). All investigator-assessed ECG abnormalities were reported.
Number of Participants With Marked Hematology Laboratory Abnormalities Day 1 Pre-dose, Days 2, 5, 14, 28, 42, 86, 116 LLN=Lower Limit of Normal, ULN=Upper Limit of Normal, Pre-Rx=Value before first dose. Lab values that met the following criteria were marked as abnormalities:
Hemoglobin (grams per deciliter:g/dL): \<0.85\*Pre-Rx. Hematocrit (%): \<0.85\*Pre-Rx. Platelet Count (\*10\^9 cells per liter:c/L): \<0.85\*LLN or \>1.5\*ULN (if Pre-Rx\<LLN, use \<0.85\*Pre-Rx).
Leukocytes (\*10\^3 cells per microliter: c/uL): \<0.9\*LLN, \>1.2\*ULN (if Pre-Rx\<LLN, use \<0.85\*Pre-Rx or \>ULN, if Pre-Rx\>ULN, use \>1.15\*Pre-Rx or \<LLN) Neutrophils+Bands (\*10\^3 c/uL): \<=1.500. Lymphocytes (\*10\^3 c/uL): \<0.750 or \>7.500. Monocytes (\*10\^3 c/uL): \>2.000. Basophils (\*10\^3 c/uL): \>0.400. Eosinophils (\*10\^3 c/uL): \>0.750.Number of Participants With Marked Serum Chemistry Abnormalities Day 1 Pre-dose, Days 2, 5, 14, 28, 42, 86, 116 LLN=Lower Limit of Normal, ULN=Upper Limit of Normal, Pre-Rx=Value before first dose. Lab values that met the following criteria were marked as abnormalities:
Alkaline Phosphatase (units per liter: U/L), Aspartate Aminotransferase (U/L), Alanine Aminotransferase (U/L): \>1.25\*ULN (if Pre-Rx\>ULN, use \>1.25\*Pre-Rx).
Bilirubin (milligrams per deciliter: mg/dL): \>1.1\*ULN (if Pre-Rx\>ULN, use \>1.25\*Pre-Rx).
Blood Urea Nitrogen (mg/dL): \>1.1\*ULN (if Pre-Rx\>ULN, use \>1.2\*Pre-Rx). Creatinine (mg/dL): \>1.33\*Pre-Rx. Sodium (milliequivalents per Liter: mEq/L): \<0.95\*LLN, \>1.05\*ULN (if Pre-Rx\<LLN: \<0.95\*Pre-Rx, \>ULN. If Pre-Rx\>ULN: \>1.05\*Pre-Rx, \<LLN).
Potassium(mEq/L), Chloride (mEq/L), Calcium(mg/dL): \<0.9\*LLN, \>1.1\*ULN (if Pre-Rx\<LLN: \<0.9\*Pre-Rx, \>ULN. If Pre-Rx\>ULN: \>1.1\*Pre-Rx, \<LLN).
Phosphorus (mg/dL): \<0.85\*LLN, \>1.25\*ULN (if Pre-Rx\<LLN, \<0.85\*Pre-Rx, \>ULN. if Pre-Rx\>ULN: \>1.25\*Pre-Rx, \<LLN).Number of Participants With Marked Laboratory Abnormalities Day 1 Pre-dose, Days 2, 5, 14, 28, 42, 86, 116 LLN=Lower Limit of Normal, ULN=Upper Limit of Normal, Pre-Rx=Value before first dose. Lab values that met the following criteria were marked as abnormalities:
Glucose (mg/dL): \<0.8\*LLN, \>1.5\*ULN (if Pre-Rx\<LLN: \<0.8\*Pre-Rx, \>ULN. If Pre-Rx\>ULN: \>2.0\*Pre-Rx, \<LLN).
Protein (grams per deciliter: g/dL): \<0.9\*LLN, \>1.1\*ULN (if Pre-Rx\<LLN: \<0.9\*Pre-Rx, \>ULN. If Pre-Rx\>ULN: \>1.1\*Pre-Rx, \<LLN).
Albumin (g/dL): \<0.9\*LLN (if Pre-Rx\<LLN: \<0.9\*Pre-Rx). Uric Acid (mg.dL): \>1.2\*ULN (if Pre-Rx\>ULN: \>1.25\*Pre-Rx). Lactate Dehydrogenase (U/L): \>1.25\*ULN (if Pre-Rx\>ULN: \>1.5\*Pre-Rx)Number of Participants With Positive Immunogenicity to Belatacept Days 1, 14, 28, 42, 56, 86, 116 The number of participants with positive immunogenicity to Belatacept was reported for each arm. Positive immunogenicity was defined as the presence of a positive antibody response generated against Belatacept.
Trial Locations
- Locations (1)
Ppd Development
🇺🇸Austin, Texas, United States