TransplantationPhase 1NCT00569803
Subcutaneous Pharmacokinetics of Belatacept
A Phase 1 study testing belatacept in people with Transplantation, run by Bristol-Myers Squibb at 1 site in United States.
Trial summary
Pharmacokinetics, Bioavailability, Safety and Immunogenicity of Single Doses of Belatacept Administered Subcutaneously to Healthy Subjects Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Transplantation
- What is being tested?
- belatacept
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 153 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2007to Aug 2008
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Men and women ages 18 to 65 years old
- Subjects must weigh less than or equal to 100 kg
Who cannot join
- Inability to tolerate injections or IV infusions
- autoimmune disorders
- TB
- herpes
- HCV
- HBV
Show all 9Show fewer
- HIV
- bacterial or viral infection
- history of cancer
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Pharmacokinetics, Safety and Immunogenicity of Single Doses of Belatacept Administered Subcutaneously to Healthy Subjects
Pharmacokinetics, Bioavailability, Safety and Immunogenicity of Single Doses of Belatacept Administered Subcutaneously to Healthy Subjects
- Conditions
- Transplantation
- Being tested
- belatacept, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
belataceptDrug
single dose, 116 days
PlaceboDrug
Subcutaneous injection of placebo solution (product ID: 224818-N000- 029)
| Study group | Role | What they receive |
|---|---|---|
| Belatacept 50 mg Subcutaneous Injection | Active comparator | Belatacept 50 mg subcutaneous (SC) injection Receives: Drug: belatacept |
| Belatacept 100 mg Subcutaneous Injection | Active comparator | Belatacept 100 mg SC injection Receives: Drug: belatacept |
| Belatacept 125 mg Subcutaneous Injection | Active comparator | Belatacept 125 mg SC injection Receives: Drug: belatacept |
| Belatacept 150 mg Subcutaneous Injections | Active comparator | 2 SC injections of 75 mg Belatacept Receives: Drug: belatacept |
| Belatacept 200 mg Subcutaneous Injections | Active comparator | 2 SC injections of 100 mg Belatacept Receives: Drug: belatacept |
| Belatacept 250 mg Subcutaneous Injections | Active comparator | 2 SC injections of 125 mg Belatacept Receives: Drug: belatacept |
| Belatacept 125 mg Intravenous Infusion | Active comparator | 125 mg Belatacept intravenous (IV) injection Receives: Drug: belatacept |
| Placebo | Placebo comparator | SC injection of placebo solution Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Observed Serum Concentration (Cmax) of Belatacept
Maximum observed serum concentration (Cmax) values were derived from serum concentration versus time data and reported in micrograms per milliliter (ug/mL).
Measured: 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) of Belatacept
Time of maximum observed serum concentration (Tmax) values were derived from serum concentration versus time data for all participants treated with Belatacept.
Measured: 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
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
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).
Measured: 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
Adjusted Geometric Means of Area Under the Serum Concentration-time Curve From Time Zero Extrapolated to Infinite Time (AUC(INF)) for Belatacept
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)
Measured: 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) of Belatacept
Serum half-life (T-HALF) was determined from serum concentration versus time data and was reported in hours.
Measured: 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) of SC Belatacept
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).
Measured: 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) of IV Belatacept
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)
Measured: 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) for IV Belatacept
Volume of distribution at steady state (VSS) was derived from serum concentration versus time data for all participants treated with IV Belatacept.
Measured: 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) for SC Belatacept
Apparent volume of distribution at steady state (Vss/F) was derived from concentration versus time data for all participants treated with subcutaneous (SC) Belatacept.
Measured: 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
Secondary outcomes (9)
Effect of Number of Injection Sites on Subcutaneous Belatacept Absorption
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.
Measured: 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
Number of Participants With Vital Sign Abnormalities
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.
Measured: 1 day pre-dose, Days 1, 2, 5, 14, 28, 42, 86 and 116
Number of Participants With Injection Site Reactions
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.
Measured: 0.5, 2, 6 and 24 hours post-dose, Days 3, 4, 5, 6, 7, 8, 14, 21 and 116
Number of Participants With Physical Examination Abnormalities
All clinically significant deviations from normal physical examinations were reported.
Measured: Days 1, 2, 5, 14, 28, 42, 86, 116
Number of Participants With Electrocardiogram (ECG) Abnormalities
Participants underwent a 12-lead ECG assessment at Screening (Day 1) and Study Discharge (Day 116). All investigator-assessed ECG abnormalities were reported.
Measured: Days 1 and 116
Number of Participants With Marked Hematology Laboratory Abnormalities
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.
Measured: Day 1 Pre-dose, Days 2, 5, 14, 28, 42, 86, 116
Number of Participants With Marked Serum Chemistry Abnormalities
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).
Measured: Day 1 Pre-dose, Days 2, 5, 14, 28, 42, 86, 116
Number of Participants With Marked Laboratory Abnormalities
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)
Measured: Day 1 Pre-dose, Days 2, 5, 14, 28, 42, 86, 116
Number of Participants With Positive Immunogenicity to Belatacept
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.
Measured: Days 1, 14, 28, 42, 56, 86, 116
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Dec 2007 (estimated)
- Study startDec 2007
- Primary completionAug 2008
- Study completionAug 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for TransplantationStudies of the same condition, open and under way.
- More trials run by Bristol-Myers SquibbThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 153 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bristol-Myers Squibb
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00569803
- Sponsor's protocol ID
- IM103-046
- Status last verified
- Aug 2016
- First submitted
- 30 Nov 2007
- Last updated
- 22 Sep 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No