Subcutaneous Pharmacokinetics of Belatacept: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Subcutaneous Pharmacokinetics of Belatacept (NCT00569803), a randomized phase 1 study. The primary outcome is Maximum Observed Serum Concentration (Cmax) of Belatacept.

2. Clinical Question

The official title also names safety and immunogenicity as study topics, while the registry lists secondary outcomes concerning absorption, vital signs, injection-site reactions, physical examinations, ECGs and laboratory abnormalities. The posted primary outcome is specifically maximum observed serum concentration, abbreviated Cmax. It was derived from serum concentration measurements over time and reported in micrograms per milliliter.

The record describes a phase 1 study in healthy subjects, with randomized allocation, single masking and a parallel model. Details about who was masked, the allocation procedure and the rationale for the selected dose groups are not reported in the registry record. The question answered by the posted primary results is therefore narrow: it concerns the measured concentration profile after the study doses, not whether belatacept improves a health outcome.

3. Trial Design

This was a completed phase 1 randomized, single-masked, parallel study of single doses of belatacept administered to healthy subjects. The registry lists enrollment of 153. The recorded study start is 2007-12, and primary completion is recorded as 2008-08. The sponsor is Bristol-Myers Squibb. The condition listed is transplantation, but the study title and summary specify healthy subjects.

The treatment groups covered a range of subcutaneous doses and an intravenous dose. Subcutaneous groups received 50 mg, 100 mg or 125 mg as a single injection; the 150 mg, 200 mg and 250 mg groups received two injections, each containing 75 mg, 100 mg or 125 mg respectively. Another group received 125 mg intravenously. A subcutaneous placebo group was also included. These are the assigned study regimens described in the record; further administration details are not reported in the registry record.

For the primary endpoint, the listed group sizes and concentration summaries are 5 participants for each subcutaneous belatacept group and 10 participants for the intravenous group. The primary population is described as all participants treated with belatacept. Adverse-event group counts differ for some groups, so those counts should not be treated as interchangeable with the primary endpoint group sizes. The overall enrollment of 153 is not the number contributing to the posted primary Cmax summaries.

Randomized allocation and a parallel model identify important features of the design, but the allocation ratio, randomization method, and masking procedures are not reported in the registry record. The record also does not describe a formal sample-size justification. Because this is a pharmacokinetic study of single doses, its primary results focus on measured serum concentration rather than on a comparison of longer-term clinical outcomes.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: 153 participants were enrolled, with 106 discontinuing prior to study drug administration because they no longer met study criteria or they withdrew consent. 47 participants met all eligibility criteria and received study medication. 1 subject, who received an incomplete dose due to an injection syringe leak, was replaced.

Only the first 6 of 8 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All participants treated with Belatacept

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Only the first 6 of 9 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Maximum Observed Serum Concentration (Cmax) of Belatacept, measured over 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.

The primary endpoint is maximum observed serum concentration of belatacept, or Cmax. It represents the highest recorded concentration in a participant’s serum during the specified sampling period after dosing. The registry states that Cmax values were derived from serum concentration-versus-time data and reported in ug/mL. Sampling was scheduled immediately before dose and at multiple post-dose times from 0.5 hours through 116 days, including both hours and days after administration.

Cmax is used in pharmacokinetic studies to describe the peak concentration reached after a dose. As a general statistical concept, concentration measurements over time help characterize how a drug appears in the measured compartment after administration; the peak is one feature of that profile. Cmax alone does not describe the entire time course, the duration of exposure, or a clinical outcome. Those questions require other measures and analyses.

The registry reports geometric means and geometric coefficients of variation for the treatment groups. A geometric mean is a summary designed for multiplicative-scale data; the geometric coefficient of variation describes relative spread on that scale. As a general explanation, such summaries can be useful when values vary proportionally rather than by a constant additive amount. The posted endpoint summaries are descriptive; confidence intervals and formal between-group tests for Cmax are not reported in the registry record.

The stated primary population is all participants treated with belatacept. Placebo is not included in the listed primary Cmax results, and no placebo concentration value is reported. Accordingly, these primary results describe measured belatacept concentrations by dose and route rather than a treatment-versus-placebo estimate.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a randomized, single-masked, parallel phase 1 study. In a parallel design, participants are assigned to a study group and the groups receive their respective regimens rather than each participant receiving every regimen in sequence. That is a general description of the design type; the specific allocation method and masking procedures are not reported in the registry record. The registry lists randomized allocation but does not give the allocation ratio.

What does the geometric mean summarize?

The primary outcome is a concentration measure summarized using a geometric mean. As a general statistical explanation, a geometric mean summarizes values on a multiplicative scale, whereas an arithmetic mean summarizes them on an additive scale. This can be a useful way to describe positive measurements whose variation is better understood proportionally. It is not the same as the median, and it should not be interpreted as the concentration of every participant.

The geometric mean Cmax values reported for the belatacept groups are 3.9, 6.2, 8.5, 11.1, 14.5, 14.5 and 42.4 ug/mL. They correspond respectively to the 50 mg, 100 mg, 125 mg, 150 mg, 200 mg and 250 mg subcutaneous groups and the 125 mg intravenous group. The corresponding geometric coefficients of variation are 30.0%, 34.0%, 50.0%, 19.0%, 16.0%, 18.0% and 16.0%. Each primary group summary has a small listed group size: 5 participants in each subcutaneous group and 10 in the intravenous group.

What does the geometric coefficient of variation mean?

As a general concept, a coefficient of variation expresses variability relative to a measure of central tendency, rather than in the original measurement units. The geometric coefficient of variation is associated with variation on a multiplicative scale. It describes dispersion among observations; it is not a confidence interval and does not directly quantify the precision of the geometric mean. The reported values indicate that variability differed across the groups, with the registry listing values from 16.0% to 50.0%.

A confidence interval would be one way to show the range of values reasonably compatible with uncertainty in an estimated group summary under a specified statistical model. No confidence intervals for the primary outcome are reported in the registry record. There are also no reported p-values or formal tests for differences between the dose groups in the primary outcome results. Thus, the numerical summaries support descriptive reading, not a claim that an apparent difference is statistically established.

Why is Cmax used?

As a general pharmacokinetic concept, Cmax captures the peak observed concentration during a defined measurement period. It is one aspect of the concentration-time profile and can be considered alongside other pharmacokinetic measures. The registry describes measurements from immediately before dosing through multiple time points up to 116 days. Cmax is derived from the observed concentration-time data, rather than being a clinical outcome such as symptom change or disease status. The record does not report other primary endpoint estimates in the material described by the posted results.

The listed dose groups also differ in administration route and, for the higher subcutaneous groups, number of injection sites or injections. The record names an outcome concerning the effect of number of injection sites on subcutaneous absorption, but the results of that outcome are not detailed in the registry entries. Any interpretation of those factors beyond the listed regimens is therefore not supported by the registry record.

There are no numerical sample-size planning illustrations reported among the study results. The record does not report the study’s sample-size justification or the intended precision for Cmax. A planning calculation based on an observed effect, when available, would be an illustration for a hypothetical future design and not an observed property of this trial; it would not establish the power of the completed study.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 18 outcome measures, 14 analyses and 9 posted secondary outcomes. The primary endpoint is maximum observed serum concentration. The listed secondary topics include subcutaneous absorption in relation to injection sites and participant counts for vital sign, injection-site, physical examination, ECG and laboratory abnormalities. The registry record does not describe a multiplicity adjustment or specify how statistical testing across outcomes was controlled. In general, testing many outcomes can increase the chance of at least one apparently notable result, so the absence of a reported multiplicity strategy limits interpretation of any inferential findings. No primary endpoint p-values are included in the posted results.

The record identifies the primary outcome population as all participants treated with belatacept. It does not give further eligibility rules for the analysis set, explain how participants with missing measurements were handled, or report imputation methods. The number contributing to each primary group is listed, but reasons for any difference between the overall enrollment and endpoint group sizes are not reported in the registry record. Missing-data assumptions and sensitivity analyses are also not reported in the registry record.

The registry indicates that values were missing or not estimable for a two-arm comparison for another endpoint. This means a comparison could not be reported for that outcome in the registry results; it does not establish why the values were unavailable. The record does not provide enough detail to assess whether missingness was related to treatment, participant characteristics or the measurements themselves.

Although the study is described as randomized, the analysis plan, prespecified statistical methods beyond the endpoint summary, interim analyses and sample-size justification are not reported in the registry record. These omissions matter because they prevent assessment of whether the posted analyses follow a prespecified plan and how uncertainty or multiple comparisons were addressed.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent non-serious adverse event terms

The adverse-event results distinguish serious adverse events from other adverse events. In each listed group, the number of participants reported as affected by serious adverse events is 0: this includes all six subcutaneous belatacept groups, the 125 mg intravenous group, placebo and the aggregate All Belatacept group. These are participant counts in the registry record, not a statement about every possible safety outcome.

For other adverse events, the record lists 2 affected participants among 5 at risk in the 50 mg subcutaneous group; 3 among 5 in each of the 100 mg and 125 mg subcutaneous groups; 4 among 6 in the 150 mg group; 2 among 5 in each of the 200 mg and 250 mg groups; 7 among 10 in the intravenous group; and 1 among 6 in placebo. The aggregate All Belatacept group lists 23 affected among 41 at risk. These counts should be read as the posted group-specific participant figures; they are not a comparison adjusted for differences in group size.

The record does not provide serious adverse event terms, and deaths are not reported in the registry record. The listed counts do not describe event severity beyond the serious/non-serious grouping, event timing, duration or causality. The registry also lists specific safety-related secondary outcomes, but their individual results are not included in the registry record. Consequently, these figures provide a limited count-based account and should not be taken as a complete characterization of safety.

12. What the Result Does, and Does Not, Mean

The primary result is a set of group-level pharmacokinetic summaries after single doses of belatacept in healthy subjects. The subcutaneous geometric mean Cmax values are 3.9 ug/mL, 6.2 ug/mL, 8.5 ug/mL, 11.1 ug/mL, 14.5 ug/mL and 14.5 ug/mL across the listed 50 mg through 250 mg groups. The intravenous 125 mg group has a geometric mean Cmax of 42.4 ug/mL. The reported geometric coefficients of variation range from 16.0% to 50.0%.

These figures describe observed serum concentration summaries in the study groups. They do not establish that any particular regimen produces a clinically meaningful benefit or harm. The trial’s primary endpoint is a concentration measure, not a patient-centered clinical outcome. No comparison with a clinical target, no clinical efficacy endpoint estimate and no formal statistical comparison of the primary endpoint are reported in the registry record.

The study included placebo, but the primary Cmax results are reported for participants treated with belatacept. The displayed concentration summaries therefore do not provide a placebo-adjusted estimate. Likewise, differences between the listed route groups cannot be interpreted as a statistically confirmed route effect because confidence intervals, p-values and a formal comparison are not reported.

Small group sizes and the absence of precision estimates mean that the apparent ordering of group means must be read cautiously. A geometric mean is not an individual participant’s result, and a coefficient of variation is not a measure of certainty about the mean. The posted values also do not reveal the full distribution of concentrations or whether unusual observations influenced a group summary.

The safety counts are similarly limited. Zero participants are listed as affected by serious adverse events in the reported groups, while other adverse events are reported for participants in both belatacept and placebo groups. Those counts alone do not establish comparative risk, and the record does not report deaths. The results should be understood as the registry’s posted, group-level descriptions rather than a comprehensive account of clinical effects.

13. Why This Trial Matters Statistically

This study illustrates a distinction that is central to biostatistics: a trial can be randomized yet its posted primary results may be descriptive rather than a reported hypothesis test. The registry identifies randomized allocation, but the primary Cmax results consist of geometric means and geometric coefficients of variation by belatacept group. Confidence intervals, p-values and a formal contrast are not reported. Randomization is a design feature; it does not by itself supply an estimate of uncertainty or answer every comparison question.

The dose groups also show why pharmacokinetic interpretation benefits from reporting both a measure of central tendency and a measure of variability. The geometric means describe typical concentration levels on a multiplicative scale, while the geometric coefficients of variation describe relative spread. Those summaries are not interchangeable: neither alone shows how precisely the group mean is estimated. Small group sizes make it especially important not to treat differences in point estimates as definitive evidence of group differences.

The design includes multiple subcutaneous dose regimens, an intravenous group and placebo. This creates several possible scientific comparisons, including dose patterns, administration route and safety summaries. The registry lists 18 outcome measures and 14 analyses, but does not report a multiplicity strategy. When numerous outcomes or contrasts are considered, a clearly stated analysis plan helps readers distinguish prespecified questions from exploratory findings.

Finally, the endpoint emphasizes concentration rather than clinical outcome. This is appropriate to the stated pharmacokinetic focus, but it defines the reach of the evidence: Cmax describes a peak serum measurement and is not a direct measure of benefit. The trial therefore provides a useful example of how design, endpoint choice, summary scale, variability and reporting detail jointly determine what can be concluded from posted results.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The primary endpoint results are based on small listed group sizes: 5 participants in each subcutaneous belatacept group and 10 in the intravenous group. The overall enrollment of 153 should not be mistaken for the number contributing to these primary summaries. The registry does not explain the difference between total enrollment and the reported endpoint group sizes, or give reasons for any unavailable observations.

The primary results provide geometric means and geometric coefficients of variation, but no confidence intervals, p-values or formal comparisons. As a result, the precision of the estimates and the statistical uncertainty around differences between groups cannot be assessed from the registry record. The coefficient of variation describes relative dispersion, not precision of the estimated mean.

The primary population is described as all participants treated with belatacept, while placebo has no listed primary Cmax result. This limits direct interpretation of the primary endpoint as a comparison against placebo. The record also does not report a formal analysis comparing subcutaneous and intravenous administration, or a model assessing dose-response patterns.

Details about the randomization procedure, allocation ratio, masking, analysis plan, sample-size justification, missing-data handling and multiplicity are not reported in the registry record. The registry names a secondary outcome concerning injection sites and absorption, but no result for that outcome is included in the registry record. The listed safety counts likewise do not include event terms or detailed timing, and deaths are not reported in the registry record.

Finally, the study concerns single doses in healthy subjects. The record does not provide clinical outcome results that would connect the measured peak concentrations to patient benefit or longer-term safety. These limitations restrict interpretation to the posted pharmacokinetic and count-based summaries.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Subcutaneous Pharmacokinetics of Belatacept — NCT00569803.
• Registry record last updated 2016-09-22; status last verified 2016-08.
• Results first posted 2016-08-15.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

NCT00569803 is a completed, randomized, single-masked, parallel phase 1 study titled “Subcutaneous Pharmacokinetics of Belatacept.” The official title describes pharmacokinetics, safety and immunogenicity of single doses administered subcutaneously to healthy subjects. Enrollment is listed as 153, with a start date of 2007-12 and primary completion in 2008-08. The sponsor is Bristol-Myers Squibb.

The primary endpoint is maximum observed serum concentration of belatacept, summarized using geometric means and geometric coefficients of variation. Posted primary group summaries cover six subcutaneous dose regimens and a 125 mg intravenous group. The study also included subcutaneous placebo and listed secondary safety and absorption outcomes.

The record reports group-level concentration values and adverse-event participant counts. It does not report confidence intervals or formal primary endpoint comparisons. Several analysis details, including the sample-size justification and missing-data methods, are not reported in the registry record.