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Subcutaneous Pharmacokinetics of Belatacept

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00569803
First received: November 30, 2007
Last updated: August 16, 2016
Last verified: August 2016
  Purpose
Pharmacokinetics, Bioavailability, Safety and Immunogenicity of Single Doses of Belatacept Administered Subcutaneously to Healthy Subjects

Condition Intervention Phase
Transplantation
Drug: belatacept
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Supportive Care
Official Title: Pharmacokinetics, Safety and Immunogenicity of Single Doses of Belatacept Administered Subcutaneously to Healthy Subjects

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Maximum Observed Serum Concentration (Cmax) of Belatacept [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Maximum observed serum concentration (Cmax) values were derived from serum concentration versus time data and reported in micrograms per milliliter (ug/mL).

  • Time of Maximum Observed Serum Concentration (Tmax) of Belatacept [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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 to the Time of Last Quantifiable Concentration (AUC(0-T)) for Belatacept [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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).

  • Adjusted Geometric Means of Area Under the Serum Concentration-time Curve From Time Zero Extrapolated to Infinite Time (AUC(INF)) for Belatacept [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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 [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Serum half-life (T-HALF) was determined from serum concentration versus time data and was reported in hours.

  • Apparent Total Body Clearance (CLT/F) of SC Belatacept [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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).

  • Total Body Clearance (CLT) of IV Belatacept [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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 [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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 [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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:
  • Effect of Number of Injection Sites on Subcutaneous Belatacept Absorption [ Time Frame: 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 ] [ Designated as safety issue: No ]

    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 [ Time Frame: 1 day pre-dose, Days 1, 2, 5, 14, 28, 42, 86 and 116 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 0.5, 2, 6 and 24 hours post-dose, Days 3, 4, 5, 6, 7, 8, 14, 21 and 116 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Days 1, 2, 5, 14, 28, 42, 86, 116 ] [ Designated as safety issue: Yes ]
    All clinically significant deviations from normal physical examinations were reported.

  • Number of Participants With Electrocardiogram (ECG) Abnormalities [ Time Frame: Days 1 and 116 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Day 1 Pre-dose, Days 2, 5, 14, 28, 42, 86, 116 ] [ Designated as safety issue: Yes ]

    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 [ Time Frame: Day 1 Pre-dose, Days 2, 5, 14, 28, 42, 86, 116 ] [ Designated as safety issue: Yes ]

    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 [ Time Frame: Day 1 Pre-dose, Days 2, 5, 14, 28, 42, 86, 116 ] [ Designated as safety issue: Yes ]

    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 [ Time Frame: Days 1, 14, 28, 42, 56, 86, 116 ] [ Designated as safety issue: No ]
    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.


Enrollment: 153
Study Start Date: December 2007
Study Completion Date: August 2008
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Belatacept 50 mg Subcutaneous Injection
Belatacept 50 mg subcutaneous (SC) injection
Drug: belatacept
single dose, 116 days
Active Comparator: Belatacept 100 mg Subcutaneous Injection
Belatacept 100 mg SC injection
Drug: belatacept
single dose, 116 days
Active Comparator: Belatacept 125 mg Subcutaneous Injection
Belatacept 125 mg SC injection
Drug: belatacept
single dose, 116 days
Active Comparator: Belatacept 150 mg Subcutaneous Injections
2 SC injections of 75 mg Belatacept
Drug: belatacept
single dose, 116 days
Active Comparator: Belatacept 200 mg Subcutaneous Injections
2 SC injections of 100 mg Belatacept
Drug: belatacept
single dose, 116 days
Active Comparator: Belatacept 250 mg Subcutaneous Injections
2 SC injections of 125 mg Belatacept
Drug: belatacept
single dose, 116 days
Active Comparator: Belatacept 125 mg Intravenous Infusion
125 mg Belatacept intravenous (IV) injection
Drug: belatacept
single dose, 116 days
Placebo Comparator: Placebo
SC injection of placebo solution
Drug: Placebo
Subcutaneous injection of placebo solution (product ID: 224818-N000- 029)

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Men and women ages 18 to 65 years old
  • Subjects must weigh less than or equal to 100 kg

Exclusion Criteria:

  • Inability to tolerate injections or IV infusions
  • autoimmune disorders
  • TB
  • herpes
  • HCV
  • HBV
  • HIV
  • bacterial or viral infection
  • history of cancer
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00569803

Locations
United States, Texas
Ppd Development
Austin, Texas, United States, 78744
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00569803     History of Changes
Other Study ID Numbers: IM103-046 
Study First Received: November 30, 2007
Results First Received: July 5, 2016
Last Updated: August 16, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Abatacept
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents

ClinicalTrials.gov processed this record on December 07, 2016