Study to Compare Exposure of TA Following Administration of Either FX006 or TAcs in Patients With Bilateral Knee OA: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Compare Exposure of TA Following Administration of Either FX006 or TAcs in Patients With Bilateral Knee OA (NCT03378076), a randomized phase 2 study. The primary outcome is Measure the Concentration of Triamcinolone Acetonide (TA) in Blood Plasma.

2. Clinical Question

This is a pharmacokinetic comparison, not a direct assessment of symptom improvement or other clinical benefit. Measuring the concentration of a drug in blood can characterize systemic exposure after a local injection. The stated question focuses on the amount of triamcinolone acetonide measured in plasma over time after treatment was administered to both knees. It does not, by itself, establish how participants’ osteoarthritis symptoms changed or whether one regimen had better clinical outcomes.

The study compares two specified regimens, including different formulations and doses. The registry record describes FX006 as extended-release and TAcs as immediate-release. The total doses were 64 mg and 80 mg, respectively. The record does not describe a separate comparison designed to distinguish formulation effects from dose effects. Therefore, the study question is best understood as a comparison of these regimens as administered, rather than a comparison isolating one component of treatment.

3. Trial Design

The registry identifies NCT03378076 as a randomized, open-label, parallel-group phase 2 study. Its title and description state that it compared systemic exposure of triamcinolone acetonide after administration into both knees. The condition recorded is bilateral knee osteoarthritis, and the study status is completed. Enrollment is listed as 24.

Participants were assigned to one of two treatment groups. The FX006 group received two intra-articular injections of 32 mg, one into each knee, for a total dose of 64 mg. The TAcs group received two intra-articular injections of 40 mg, one into each knee, for a total dose of 80 mg. The registry describes FX006 as extended-release and TAcs as immediate-release. The parallel-group design means the treatment groups were distinct; the record does not describe participants receiving both study regimens in sequence.

Open-label means that the study is identified as having no masking. The record does not report whether laboratory personnel or others involved in measuring or handling concentrations were masked. Randomization is specified, but the method used to generate the allocation sequence, conceal assignments, or manage any stratification is not reported in the registry record.

The recorded study start date is 2017-12-06, and the primary completion date is 2018-03-14. The primary endpoint’s timeframe is 43 days. Its stated analysis population consists of participants who received both injections, completed scheduled sampling, and had sufficient plasma concentration data. The registry record does not report the number in each group who met this definition or the number whose data contributed at each time point.

These details establish the broad comparison and planned endpoint, but not the full conduct of the study. A protocol, detailed schedule of visits, sample-size justification, and detailed statistical analysis plan are not reported in the registry record. The enrollment figure should therefore be read as the listed study enrollment, not as evidence about how that number was selected or how many participants contributed to every endpoint.

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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: All patients who received 2 IA injections (one in each knee) of study drug, completed scheduled sampling, and had sufficient plasma concentration data

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.

6. Primary Endpoint

The registry lists the primary outcome as Measure the Concentration of Triamcinolone Acetonide (TA) in Blood Plasma, measured over 43 days.

The primary endpoint is the concentration of triamcinolone acetonide in blood plasma, measured in pg/mL across time points during a 43-day timeframe. The registry specifies geometric means and 95% confidence intervals as the summary format. Plasma concentrations provide a way to describe systemic exposure following the injections into both knees. They do not directly measure pain, function, or another clinical outcome.

A geometric mean summarizes measurements on a multiplicative scale and is often used for positive concentration data, which can be unevenly distributed. A 95% confidence interval describes the statistical uncertainty around an estimated quantity under the method used to construct it. In general, a narrower interval indicates greater precision than a wider interval, but an interval does not establish clinical importance or prove that two treatments differ.

The endpoint is described by time point rather than as one overall comparison. The registry record does not report the time-point-specific concentration values, confidence limits, or a single summary contrast between groups. It also does not report a threshold for interpreting a concentration difference. Consequently, the endpoint definition explains what was to be measured and how it was to be summarized, but the available record does not establish the magnitude or precision of the observed group differences.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes plasma concentrations at time points using geometric means and 95% confidence intervals. These are descriptive and inferential summaries, respectively: the geometric mean represents a central concentration on a multiplicative scale, while the confidence interval conveys uncertainty about an estimated value. General statistical interpretation depends on the method used to calculate the interval and the data contributing to it. The specific confidence-interval procedure is not reported in the registry record.

Why use a geometric mean?

As a general statistical matter, concentration measurements may be positive and unevenly distributed, with some values substantially higher than others. For data with this kind of right-skew, a geometric mean can be more representative of a typical multiplicative scale than an arithmetic mean. It is commonly related to taking the mean after a logarithmic transformation and then returning to the original scale. That general rationale does not establish which distributional assumptions or transformations were used in this study; those details are not reported in the registry record.

A geometric mean is not the same as an arithmetic average. It also does not describe the full spread of individual measurements. Confidence intervals add information about uncertainty in the estimated summary, but they are not ranges containing a fixed proportion of individual participants’ values. The record names 95% confidence intervals but gives no numerical interval limits for the concentration endpoint, so precision cannot be assessed from the posted endpoint description.

How to read measurements over time

The primary endpoint is expressed across time points during a 43-day timeframe. In general, a sequence of time-specific concentrations can describe how systemic exposure changes over a sampling period. A comparison at one point in time is not interchangeable with a comparison at another point, and a collection of time-specific summaries is not automatically equivalent to a single overall treatment effect. The registry record does not report the concentration values, the individual time points, or a single combined estimate.

Repeated measurements from the same participant are related rather than independent. General methods for longitudinal data can account for that correlation when estimating treatment patterns over time. The record does not identify a longitudinal model or state whether the time-specific summaries were analyzed using a model. It is therefore not possible to infer how within-participant correlation, if any, was handled.

How below-quantification values were treated

The endpoint description specifies rules for concentrations below the limit of quantification, abbreviated BLOQ. A BLOQ result before the first measurable concentration is assigned zero. A BLOQ result after a measurable concentration is treated as missing if it is followed by a value above the lower limit of quantification. A BLOQ result at the end of the collection interval, after the last quantifiable concentration, is set to zero. If two BLOQ values occur in succession after the maximum observed concentration, the profile is considered to have ended at the first BLOQ value, and later concentrations are set to zero for pharmacokinetic calculations.

These rules matter because a value below an assay’s quantification limit is not the same as a measured concentration of zero. General methods for handling such values can affect summaries, especially when many measurements are near or below the limit. The registry record provides the stated handling rules, but does not report how many BLOQ values occurred, how many profiles were affected, or the lower limit of quantification. The impact of these choices on the reported estimates cannot be evaluated without those details and the results.

What the confidence interval can and cannot say

In general, a confidence interval gives a range of values compatible with the observed data under the specified statistical method and its assumptions. A narrower interval indicates a more precise estimate than a wider interval. A confidence interval is not, on its own, a measure of clinical importance, nor does it explain why an estimate differs between treatment groups. The record does not provide the numerical intervals, the method used to calculate them, or a reported interval for a between-group contrast.

Because the endpoint is presented as geometric means by time point, uncertainty around each group’s mean would not necessarily be the same as uncertainty around the difference or ratio between groups. A direct treatment comparison requires a defined contrast and an appropriate estimate of its uncertainty. No such contrast or statistical analysis is reported in the registry record. General statistical principles cannot fill in the missing numerical comparison.

What is not specified

The registry record identifies randomization, open-label masking status, a parallel-group model, the endpoint summaries, and the handling rules for BLOQ measurements. It does not report the statistical model, assumptions, analysis software, significance threshold, sample-size justification, interim analyses, or a detailed analysis plan. The record lists no statistical analyses. These omissions limit assessment of how the endpoint was actually analyzed, whether adjustments were made, and how the estimates should be interpreted beyond their stated descriptive purpose.

10. Multiplicity, Missing Data and Analysis Populations

The primary endpoint is defined across time points, creating more than one possible concentration summary. In general, examining multiple time points can raise a multiplicity question: the more separate comparisons made, the greater the chance that at least one appears notable by chance when each is interpreted as a separate test. A prespecified testing hierarchy, adjustment, or clearly descriptive interpretation can help address this issue. The registry record does not report a multiplicity strategy, a hierarchy of time points, or inferential analyses. It is not possible to determine whether multiplicity adjustments were planned or used.

The record lists two outcome measures and no statistical analyses. The primary endpoint description focuses on plasma concentrations, but numerical results are not reported. The record does not identify a primary time point for a single treatment contrast or state how any secondary outcome would be incorporated into an overall conclusion. No interim analyses are reported in the registry record.

The pharmacokinetic analysis population required receipt of both injections, completion of scheduled sampling, and sufficient plasma concentration data. This criterion makes data completeness part of inclusion in the described analysis population. The number of participants excluded under this definition, the reasons for incomplete sampling, and the number contributing at each time point are not reported in the registry record. The rules for BLOQ observations are specified, but their frequency and impact are not reported.

These details are important because missing concentration measurements can affect both the number of observations and the interpretation of time trends. General methods may use assumptions about why data are missing, but the registry record does not describe such assumptions or any sensitivity analysis. It therefore does not support conclusions about the robustness of the pharmacokinetic findings to missing data or choices made for below-quantification measurements.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry separates serious adverse events, other adverse events, and deaths. In the FX006 32 mg group, 12 participants were at risk for serious events and none were affected; 12 were at risk for other adverse events and 8 were affected; no deaths were recorded. In the TAcs 40 mg group, 12 participants were at risk for serious events and none were affected; 12 were at risk for other adverse events and 5 were affected; no deaths were recorded.

These figures are counts within the registry’s stated groups and at-risk populations. They are descriptive, not estimates of a treatment effect. The record does not list serious-event terms, and the top serious-event terms are empty. It does not provide the individual terms for other adverse events, their timing, severity, duration, or whether investigators considered them related to treatment. The definitions used for the categories are not described in the registry record.

Zero recorded serious events or deaths in these groups does not establish that such events cannot occur. Likewise, the difference in the reported counts for other adverse events cannot be interpreted as a statistically established group difference without an analysis and fuller event information. The registry record reports no such comparison.

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

This study addresses a specific pharmacokinetic question: plasma triamcinolone acetonide concentrations after two injections, one in each knee, of either extended-release FX006 or immediate-release TAcs. The registry identifies the population, treatment regimens, 43-day timeframe, and intended use of geometric means with 95% confidence intervals. These details explain what the primary endpoint was intended to describe.

The endpoint is systemic drug exposure, not a measure of osteoarthritis symptoms or functional outcomes. A concentration comparison can characterize measured drug levels over time, but it does not by itself establish whether participants experienced clinical improvement or whether one regimen was preferable. The record does not report a clinical efficacy comparison.

Numerical primary endpoint estimates and statistical analyses are not reported in the registry record. The direction and size of any concentration differences, their uncertainty, and the statistical evidence for a group contrast are therefore unknown from this record. The safety counts offer limited descriptive information, but no event details or comparative analysis are reported. They cannot establish a safety advantage or disadvantage.

The study’s randomized, parallel-group design identifies an intended comparison between assigned regimens. Its open-label status means masking is not reported as part of the design. Randomization can support a fair comparison when allocation and analysis are appropriately conducted, but the record does not provide enough methodological detail or results to evaluate the full implementation. In particular, the randomization procedure, sample-size justification, analysis plan, and number contributing to the primary endpoint are not reported.

Accordingly, the registry supports a description of the research question and design, but not a conclusion about the observed pharmacokinetic contrast. It also does not establish effects beyond the measured concentrations in this study population. Interpretation of the primary comparison would require the actual concentration estimates, uncertainty measures, analysis details, and participant-level accounting that are not reported in the registry record.

13. Why This Trial Matters Statistically

Pharmacokinetic studies ask how much of a drug is measured in the body over time after administration. That question is distinct from whether a treatment changes symptoms or other clinical outcomes. This trial’s stated endpoint—plasma triamcinolone acetonide concentration—therefore focuses on systemic exposure following injections into both knees, rather than directly evaluating the clinical course of bilateral knee osteoarthritis.

The comparison also illustrates why treatment regimens must be described precisely. The FX006 and TAcs groups differed in formulation and in the stated dose per injection and total dose. The registry record identifies the regimens as administered, but does not describe a design that isolates the contribution of formulation from dose. The relevant comparison is between the two complete regimens recorded, not a clean test of one treatment feature alone.

For statistical interpretation, a time-specific concentration estimate and a group-level treatment contrast are different quantities. Geometric means and confidence intervals can describe concentrations and their precision, but interpreting a difference between groups requires a clearly reported contrast and its uncertainty. The registry record does not report these numerical results or a statistical analysis. This makes the distinction between a planned endpoint and a reported finding especially important.

The study also demonstrates the importance of defining analysis populations and handling measurements below quantification limits. The record specifies eligibility for the pharmacokinetic analysis and rules for BLOQ observations, but does not report how many measurements were affected or how many participants contributed to each summary. Without those data, readers cannot assess the sensitivity of results to incomplete sampling or these processing decisions.

These design and reporting features matter because a well-defined question does not substitute for estimates and analysis. The record permits an understanding of what was intended to be compared, while leaving the quantitative answer unreported.

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 registry record does not report numerical results for the primary concentration endpoint. Although it identifies geometric means, 95% confidence intervals, and a 43-day timeframe, it does not give estimates at any time point or a direct comparison between groups. This prevents assessment of the direction, magnitude, or precision of the pharmacokinetic findings.

The record reports no statistical analyses. A detailed statistical analysis plan, model, method for calculating confidence intervals, significance threshold, and multiplicity strategy are not reported in the registry record. The record also does not report a sample-size justification or interim analyses. Consequently, the basis for enrollment of 24 and the intended inferential approach cannot be assessed.

The primary analysis population requires completed scheduled sampling and sufficient plasma concentration data, but the number meeting this definition is not reported. Group-specific denominators at each time point, the extent and reasons for missing samples, and any sensitivity analyses are also not reported. The endpoint description gives rules for BLOQ values but not their frequency or the assay’s quantification limit.

The study is open-label, and the registry does not report whether any laboratory or analytical personnel were masked. It identifies randomization but does not describe the sequence-generation or allocation-concealment procedures. These omissions make it difficult to evaluate the conduct of allocation and measurement from the registry record alone.

Finally, safety reporting is limited to counts for serious and other adverse events and deaths. Event terms and detail for other adverse events are not reported, and no comparative safety analysis is given. The record therefore supports only a limited descriptive account of safety and does not establish differences between regimens.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study to Compare Exposure of TA Following Administration of Either FX006 or TAcs in Patients With Bilateral Knee OA — NCT03378076.
• Registry record last updated 2024-01-24; status last verified 2024-01.
• Results first posted 2019-05-01.
• 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

NCT03378076 is a completed, randomized, open-label, parallel-group phase 2 study in patients with bilateral knee osteoarthritis. Enrollment is listed as 24. The study compared two injections, one into each knee, of extended-release FX006 32 mg per knee with immediate-release TAcs 40 mg per knee. The stated primary endpoint was plasma triamcinolone acetonide concentration in pg/mL across time points during 43 days, summarized using geometric means and 95% confidence intervals.

The record describes a pharmacokinetic analysis population and rules for handling BLOQ measurements. It reports no statistical analyses and does not give numerical primary endpoint estimates. Safety counts include no serious adverse events or deaths in either group; other adverse events were recorded in both groups. The number contributing to each concentration summary, detailed analysis methods, sample-size justification, and detailed event terms are not reported in the registry record.