Bioequivalence of Two Formulations of Levothyroxine Sodium 200 Micrograms (mcg) Under Tablet Form: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Bioequivalence of Two Formulations of Levothyroxine Sodium 200 Micrograms (mcg) Under Tablet Form (NCT04037748), a randomized phase 1 study. The primary outcome is Baseline Corrected Maximum Observed Plasma Concentration (Cmax[Adj]) of Levothyroxine Sodium.

2. Clinical Question

3. Trial Design

This was a phase 1, randomized, open-label, two-period crossover study in healthy subjects. In a crossover design, each participant receives both study treatments in separate periods, so comparisons can use within-participant information as well as the treatment order. The registry describes two sequences: Puran T4® followed by Eutirox®, and Eutirox® followed by Puran T4®. Each administration was a single oral 600 mcg dose under fasting conditions.

The registry reports enrollment of 72 participants and a completed study. Its recorded start date is 2019-06-25, and its primary completion date is 2019-09-11. Masking was none, so the study was open-label. The treatment-period wash-out description is incomplete for the Puran-first sequence. The Eutirox-first sequence description specifies a wash-out period of 70 days. Whether this same interval applied to both sequences is not fully documented in the registry record.

The primary pharmacokinetic analysis set is defined as participants who completed both periods and had valid pharmacokinetic parameters in both. The endpoint summaries report 55 participants for each treatment. The registry does not explain the difference between total enrollment and the endpoint analysis counts, or provide a participant flow account in the registry record for this explanation.

Randomization determines the treatment sequence; it does not mean participants were masked. The crossover structure can help account for stable differences between people because each participant receives both formulations. However, an appropriate analysis must also consider the paired nature of the observations, treatment period, and sequence. The exact sponsor analysis method and the handling of period or sequence effects are not reported in the registry record.

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.

Treatment Period 1

Reasons for not completing this period:

Treatment Period 2

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Pharmacokinetic (PK) analysis set included all participants who completed both periods and had valid PK parameters in both.

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 Baseline Corrected Maximum Observed Plasma Concentration (Cmax[Adj]) of Levothyroxine Sodium, measured over Pre-dose, 24, 36, 48 and 72 hours post-dose.

The primary endpoint was baseline-corrected maximum observed plasma concentration, or Cmax[Adj], of levothyroxine sodium. Cmax is the highest observed concentration in a participant’s plasma concentration-time profile. The registry states that the value was obtained from the plasma concentration-time curve and adjusted by basal-level correction. The listed measurement times were pre-dose and 24, 36, 48, and 72 hours post-dose. The unit was nanograms per milliliter.

In general, maximum concentration is used in pharmacokinetic comparisons as a measure related to the peak level reached after dosing. It can inform comparison of the rate and magnitude of absorption, while area under the concentration-time curve is generally used to describe overall exposure. Those are complementary aspects of a concentration-time profile, not interchangeable outcomes.

Baseline correction is intended, in general, to account for concentrations present before a dose when interpreting post-dose measurements. The registry does not report the specific correction procedure, so the precise calculation cannot be reconstructed from the record. The primary analysis set consisted of participants completing both periods with valid pharmacokinetic parameters in both. The reported means were 67.26 ng/mL for Puran T4® and 60.55 ng/mL for Eutirox®.

7. Results Posted in the Registry

• Eutirox®: mean 60.55 versus 67.26 on control; difference -6.71 (95% CI -13.02 to -0.39), standardized effect d = -0.40; z-test p = 0.037.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Area Under the Plasma Concentration-time Curve From Time Zero to 72 Hours (AUC 0-72) of Levothyroxine Sodium

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Eutirox®: mean 7,005 versus 7,205 on control; difference -200.11 (95% CI -667.11 to 266.89), standardized effect d = -0.16; z-test p = 0.401.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Eutirox® and the control. The interval gives the range of effects that remain compatible with the data.

Maximum Observed Plasma Concentration (Cmax) of Levothyroxine Sodium

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Eutirox®: mean 122.89 versus 130.07 on control; difference -7.17 (95% CI -15.56 to 1.22), standardized effect d = -0.32; z-test p = 0.094.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Eutirox® and the control. The interval gives the range of effects that remain compatible with the data.

The posted secondary endpoints cover both overall exposure and peak concentration, alongside time to maximum concentration. Across the reported results, the sponsor analyses are expressed as geometric least-squares mean ratios and are labeled as equivalence analyses. Their confidence intervals are relatively close to their corresponding ratio estimates, but the registry does not report the equivalence margins needed to independently assess each equivalence claim. The arithmetic summary-based comparisons are separate analyses and should not be substituted for the sponsor’s reported approach.

These measures complement the primary baseline-corrected Cmax[Adj] result. In general, area under the concentration-time curve describes overall exposure, while maximum concentration describes the peak and time to maximum concentration characterizes when that peak is observed. Looking across these dimensions helps distinguish different features of a concentration-time profile. Similar direction or pattern across endpoints can provide context, but it does not make the endpoints interchangeable or prove that every aspect of exposure is equivalent.

Secondary results generally carry less evidential weight than a designated primary result, especially when many outcomes are examined. Testing multiple outcomes increases the chance of at least one apparently notable result arising by chance if each is interpreted independently. The registry does not report a multiplicity adjustment or a hierarchy for interpreting secondary outcomes. Consequently, unadjusted secondary findings are best treated as supportive or exploratory rather than as independent confirmation of the primary analysis. The overall pattern can inform interpretation, but it cannot supply missing equivalence margins or analysis details.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Time to Reach Maximum Plasma Concentration (Tmax) of Levothyroxine Sodium
• Area Under the Plasma Concentration-time Curve From Time Zero to 72 Hours (AUC 0-72) of Levothyroxine Sodium
• Maximum Observed Plasma Concentration (Cmax) of Levothyroxine Sodium

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: it is a measured plasma concentration, summarized as a mean and standard deviation. A mean describes the central value of a group’s observations, while a standard deviation describes how spread out individual observations are around that mean. These summaries describe the observed data; they do not alone establish whether the treatments meet an equivalence criterion.

What does the mean difference represent?

The recalculated comparison subtracts the Puran T4® mean from the Eutirox® mean. The estimate is -6.706 ng/mL. A negative value therefore indicates that the reported arithmetic mean was lower in the Eutirox® summary. This is a simple, unadjusted calculation from posted group summaries. It is not the sponsor’s geometric least-squares ratio analysis and does not incorporate the individual paired observations that arise in a crossover trial.

A confidence interval expresses uncertainty about an estimated quantity under the assumptions of the analysis. The 95% interval for the recalculated mean difference extends from -13.02 to -0.388 ng/mL. It gives a range of values compatible with this particular unadjusted estimation procedure; it does not account for information that is unavailable in the group summaries, such as the within-participant correlation. A p-value of 0.037 is reported for this unadjusted comparison. It is not a probability that a treatment is equivalent, nor a measure of the size or practical importance of a difference.

Why is the sponsor result on another scale?

The sponsor analysis is reported as a geometric least-squares mean ratio, with a value of 90.8 and a 90% confidence interval from 86.3 to 95.6. A ratio compares quantities proportionally rather than by their absolute difference. A geometric least-squares mean is typically associated with analysis on a transformed scale and adjustment through a statistical model, but the precise transformation, model, and covariates are not reported in the registry record. The sponsor’s value should therefore be described as reported, without attempting to recreate its derivation from the arithmetic means.

For an equivalence analysis, the estimate and confidence interval are generally assessed against prespecified lower and upper equivalence bounds. The registry labels the analysis as equivalence, but the bounds and the rationale for their selection are not reported in the registry record. The confidence interval alone, without those bounds and full methods, is insufficient to independently verify the equivalence decision.

How does crossover allocation affect interpretation?

In a crossover study, a participant receives both treatments, and the randomized sequence determines which is received first. This design can reduce the influence of stable differences among participants when treatment comparisons are made within the same person. It also creates dependencies between observations: results from the two treatment periods for one participant are not independent in the same way as results from two unrelated groups.

That structure makes the analysis method important. A crossover analysis may need to account for treatment, period, sequence, and within-participant variation. The registry defines the primary pharmacokinetic analysis set but does not report the sponsor’s detailed model or explain how period and sequence were handled. The recalculation from group means and standard deviations cannot recover those features. It is useful as a transparent summary-based comparison, but it is not a substitute for the trial’s own analysis.

Why can over-dispersion matter?

In general, over-dispersion means that observed variability is greater than a statistical model expects. It can make standard errors too small and intervals too narrow if a model does not accommodate the extra variability. The posted primary summaries include standard deviations of 19.65 for Puran T4® and 13.61 for Eutirox®. The registry does not report an over-dispersion assessment or a model-based response to one. For a continuous pharmacokinetic outcome, the issue is better framed as whether the selected model adequately represents the outcome distribution and participant-level variation; no such diagnostic information is reported in the registry record.

The general distinction between statistical significance and equivalence is central. A test of a difference asks whether evidence is inconsistent with a zero difference under its assumptions. An equivalence assessment asks whether the uncertainty is sufficiently contained within prespecified acceptable bounds. These are different questions and can rely on different scales and confidence levels. The unadjusted p-value and mean-difference interval do not replace the sponsor’s reported ratio analysis.

11. Confidence Intervals and Precision

Precision describes how narrowly an estimate is determined by the observed data and the analysis assumptions. For the primary endpoint, the recalculated mean difference is -6.706 ng/mL, and the associated 95% confidence interval ranges from -13.02 to -0.388 ng/mL. The interval is the uncertainty range for that unadjusted difference estimate. It is not a range containing a specified proportion of individual participant values, and it does not represent the probability that the true value lies in the interval.

The sponsor’s reported primary result is on a ratio scale: 90.8, with a 90% confidence interval from 86.3 to 95.6. Its confidence level differs from that of the recalculated mean-difference interval, and the two intervals refer to different estimands. A ratio interval is not an absolute concentration difference. Both results should be read in their own terms rather than compared by the apparent width of their endpoints.

The interval for the recalculated difference excludes zero, while the sponsor’s interval must be interpreted relative to the equivalence bounds. Those bounds are not reported in the registry record. A narrow-looking interval does not automatically establish equivalence; the location of the interval relative to the prespecified bounds is essential. The registry’s equivalence designation is reported, but the posted information does not include enough detail to independently check the criterion.

These intervals also depend on how observations are analyzed. The recalculation uses posted group summaries and does not recover the within-participant covariance of the crossover data. The sponsor analysis may use a model that does, but its method is not reported in the registry record. Thus the precision statements describe the reported analyses and should not be interpreted as complete reconstructions of the participant-level uncertainty.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning illustration gives participants per arm for 80% power and participants per arm for 90% power. These are not total event counts: this is a continuous-outcome illustration, and the figures refer to participants in each of two equally allocated arms. The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The target effect is set to the stated fraction of the observed effect. The trial’s own original sample-size assumptions are not reported in the registry record.

For the primary endpoint, planning for 100% of the observed effect gives 100 participants per arm for 80% power and 134 participants per arm for 90% power. Planning for 75% of the observed effect gives 178 participants per arm for 80% power and 238 participants per arm for 90% power. Planning for 50% of the observed effect gives 399 participants per arm for 80% power and 535 participants per arm for 90% power.

In general, the 80% power column describes a hypothetical design intended to have an 80% chance of detecting the chosen effect under the stated assumptions, if that effect is real. The 90% column uses a higher target chance under the same kind of assumptions. Smaller effects are harder to distinguish from random variation, so planning for a smaller fraction of the observed effect requires more participants. These figures are planning illustrations based on the observed effect, not observed power and not evidence about the trial’s original design.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -6.706; pooled standard deviation σ = 16.904.
2. n = 2 × (1.96 + 0.842)² × 16.904² / -6.706² = 99.7, rounded up to 100 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -6.706                      # observed difference in means
sigma <- 16.904316253549                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(4037748)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 100 (80% power), 134 (90% power)
 75% of observed effect: n per arm = 178 (80% power), 238 (90% power)
 50% of observed effect: n per arm = 399 (80% power), 535 (90% power)
power.t.test: 100.7 
Simulated power at n = 100 per arm: 0.794 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

For the primary endpoint, the registry reports the sponsor’s analysis as a geometric least-squares mean ratio of 90.8, with a 90% confidence interval from 86.3 to 95.6. The analysis is classified in the registry as equivalence. The unadjusted recalculation instead gives an arithmetic mean difference of -6.706 ng/mL, with a 95% confidence interval from -13.02 to -0.388 ng/mL and an unadjusted p-value of 0.037.

These results are not competing estimates of exactly the same quantity: one is a ratio and the other is an absolute difference. The calculations also differ in confidence level and potentially in their treatment of the crossover structure. The recalculation relies on posted summary statistics and cannot reproduce a participant-level model. The registry record does not report the sponsor’s full method, including the model details or equivalence margins.

There is no reported discrepancy flag for this endpoint. Even so, for the trial’s stated equivalence question, the sponsor’s own analysis takes precedence over the simple summary-statistic recalculation. That does not make the recalculation a substitute for missing methods or margins; it remains a separate, unadjusted descriptive comparison. The sponsor’s equivalence designation should be reported as such, while noting that its prespecified decision bounds are not reported in the registry record.

15. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary pharmacokinetic endpoint and several secondary outcomes, including exposure, peak concentration, and time to maximum concentration measures. When multiple outcomes are examined, the chance of encountering an apparently notable result by chance can increase. Statistical approaches may control this multiplicity, for example through a prespecified testing sequence or adjustment of significance levels. Whether such a strategy was planned or used is not reported in the registry record. The reported secondary p-values are unadjusted recalculations, so they should not be treated as multiplicity-controlled evidence.

The primary population is described as participants who completed both periods and had valid pharmacokinetic parameters in both. The endpoint summaries report 55 participants per formulation, whereas enrollment was 72. The record does not explain participant disposition, reasons for exclusion from the primary analysis set, or whether missing observations were imputed. The missing-data procedures are not reported in the registry record.

In a crossover trial, missing data in either period can affect whether a participant contributes to a within-person treatment comparison. The record’s requirement for valid parameters in both periods makes the analysis population definition clear at a high level, but not the detailed handling of incomplete profiles or invalid measurements. Sensitivity analyses evaluating the impact of missing or excluded data are not reported in the registry record.

The registry also does not report the sponsor’s detailed statistical plan, model specification, period and sequence handling, or equivalence margins. These omissions limit independent appraisal of both the primary equivalence analysis and secondary outcomes. They do not establish that the trial lacked such methods; they mean those details are not reported in the registry record.

16. 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 reports serious adverse events for 72 participants at risk in each treatment group, with zero serious events in the Puran T4 group and zero in the Eutirox® group. It reports zero deaths in both groups. These are the posted serious-event counts; they should be distinguished from non-serious adverse events.

The record lists other, non-serious adverse events among 2 participants in the Puran T4 group and 5 participants in the Eutirox® group, each with 72 participants at risk. Those counts are separate from the serious-event figures and do not change the reported serious-event count. No serious adverse-event terms are listed among the top serious terms.

Zero reported serious events in these groups means none were recorded in the registry results for the stated groups and risk counts. It does not establish that an event could not occur, and the study is not described as a broad or long-term safety assessment. The registry does not provide event-level descriptions or further context for the other adverse events in the registry record for this explanation. These counts are descriptive and should not be interpreted as a treatment recommendation.

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

The registry reports a randomized crossover comparison of two levothyroxine sodium formulations in healthy subjects, with a primary focus on baseline-corrected maximum plasma concentration. The sponsor’s primary analysis is labeled as an equivalence analysis and reports a geometric least-squares mean ratio of 90.8, with a 90% confidence interval from 86.3 to 95.6. That is the result to cite when describing the sponsor’s analysis of the stated equivalence question.

The summary-based recalculation answers a different statistical question. It compares arithmetic means and estimates an unadjusted difference of -6.706 ng/mL, with a 95% confidence interval from -13.02 to -0.388 ng/mL. The interval and p-value describe that unadjusted comparison; neither alone determines equivalence. Equivalence requires interpretation against prespecified bounds, which are not reported in the registry record.

The results concern pharmacokinetic measurements after single doses under fasting conditions in healthy participants. They do not, by themselves, establish how the formulations compare in other populations, dosing circumstances, or clinical outcomes. The primary analysis set is limited to participants who completed both periods and had valid pharmacokinetic parameters in both. The record does not explain why the analysis count is smaller than enrollment, and it does not report detailed missing-data procedures.

As a general statistical distinction, an absence of a statistically significant difference is not the same as evidence of equivalence. Conversely, a statistically distinguishable difference in an unadjusted arithmetic comparison does not by itself negate an equivalence analysis conducted on another scale with prespecified bounds. Here, the sponsor’s equivalence label is recorded, but independent assessment is limited by the absence of those bounds and full method details.

The findings therefore describe the posted pharmacokinetic results and the analyses reported in the registry. They do not establish treatment benefit, clinical effectiveness, or a recommendation about use. Such conclusions would require evidence and context beyond these pharmacokinetic comparisons.

18. Why This Trial Matters Statistically

This study illustrates why the estimand and analysis scale matter in bioequivalence reporting. An arithmetic mean difference and a geometric least-squares mean ratio answer related but distinct questions. The difference is expressed in concentration units, whereas a ratio expresses proportional comparison. Their estimates and confidence intervals cannot be directly compared as if they were alternative presentations of the same statistic.

It also demonstrates why equivalence is not the same as a conventional test for a difference. An equivalence analysis requires predefined acceptable bounds, and interpretation depends on how the confidence interval relates to those bounds. The registry labels the sponsor result as equivalence, but does not report the bounds. The label can be described faithfully; the decision criterion cannot be independently checked from the registry record.

The crossover structure adds an important design issue. Because participants received both formulations in randomized order, their observations are related. A re-calculation from group-level summaries cannot recover the participant-level pairing or fully reproduce a crossover model. This makes a clear distinction between sponsor analyses and simple unadjusted recalculations essential.

Finally, the distinction between enrollment and the primary analysis set, as well as the absence of reported multiplicity and missing-data procedures, shows how registry transparency affects statistical appraisal. Readers can identify the measured outcomes and posted results, but cannot fully evaluate every assumption behind the sponsor analysis. These are general lessons in interpreting trial statistics, not claims about unreported procedures in this study.

19. 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 does not report the equivalence margins for the primary or secondary sponsor analyses. Without the margins, the equivalence-labeled results cannot be independently checked against the decision criteria. The sponsor’s detailed statistical method is also not reported, including the model specification and how the crossover’s treatment periods, sequence, and within-participant correlation were handled.

The primary summaries include 55 participants per formulation, while enrollment was 72. The record defines the pharmacokinetic analysis set as participants completing both periods with valid parameters in both, but does not provide a participant flow explanation or reasons for non-inclusion. Missing-data handling and sensitivity analyses are not reported in the registry record.

The treatment-period description is incomplete for the Puran-first sequence: its wash-out sentence ends before giving an interval. The Eutirox-first sequence description specifies a wash-out period of 70 days. The available record therefore does not fully establish whether the same interval was described for both sequences. Details of the baseline correction procedure are also not reported.

Multiplicity procedures for the secondary outcomes are not reported. The summary-based recalculations cannot recreate paired crossover analyses and should be viewed as unadjusted comparisons, not as replacements for the sponsor’s analysis. Finally, the study was conducted in healthy subjects with single-dose fasting administration, so the posted pharmacokinetic results have a defined population and dosing context. Broader interpretation is limited to what those conditions support.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Bioequivalence of Two Formulations of Levothyroxine Sodium 200 Micrograms (mcg) Under Tablet Form — NCT04037748.
• Registry record last updated 2020-09-29; status last verified 2020-08.
• Results first posted 2020-09-29.
• 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.

23. Record Summary

The registry describes a completed phase 1, randomized, open-label crossover study in healthy subjects, with enrollment of 72. Participants received single oral doses of Puran T4® and Eutirox® in randomized sequence under fasting conditions. The primary endpoint was baseline-corrected maximum observed plasma concentration of levothyroxine sodium, with the primary pharmacokinetic analysis set defined by completion of both periods and valid parameters in both.

The sponsor reports a geometric least-squares mean ratio of 90.8 for the primary endpoint, with a 90% confidence interval from 86.3 to 95.6, and classifies the analysis as equivalence. An unadjusted summary-based re-calculation estimates an arithmetic mean difference of -6.706 ng/mL, with a 95% confidence interval from -13.02 to -0.388 ng/mL. Equivalence margins and full sponsor methods are not reported in the registry record, limiting independent evaluation of the equivalence criterion.

The registry also reports secondary pharmacokinetic outcomes and adverse-event counts. The primary analysis set includes 55 participants per formulation; the record does not explain the difference from enrollment. Serious adverse events and deaths were reported as zero in both treatment groups.