Levetiracetam Versus Oxcarbazepine as Monotherapy to Evaluate Efficacy and Safety in Subjects With Newly or Recently Diagnosed Partial Epilepsy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Levetiracetam Versus Oxcarbazepine as Monotherapy to Evaluate Efficacy and Safety in Subjects With Newly or Recently Diagnosed Partial Epilepsy (NCT01498822), a randomized phase 4 study. The primary outcome is Percentage of Subjects With a Treatment Failure.

2. Clinical Question

3. Trial Design

The registry record describes a randomized, multicenter, open-label, parallel-group phase 4 study comparing levetiracetam with oxcarbazepine as monotherapy. Masking was listed as none. Both treatments were administered twice a day. The record gives an enrollment of 353 and identifies epilepsy as the condition under study. The study status is completed; the recorded start was 2011-06 and primary completion was 2014-07.

The main analysis reported for treatment failure used the Per Protocol Set. Its stated criteria include receipt of at least one partial dose of study medication, return of at least one post-Baseline seizure diary, and absence of important protocol deviations. The record also says that subjects who discontinued before Week 50 for a reason other than treatment failure were treated in a particular way, but that part of the population definition is cut off. The complete handling of those subjects is therefore not reported in the registry record. Seizure-freedom outcomes were reported for the Full Analysis Set.

The primary outcome covered Week 0, defined as the first dose, through Week 50. The secondary seizure-freedom measures covered a 48-week treatment period, with their listed timeframe running from Week 2 to Week 50. The registry lists four outcome measures and one analysis. It does not report the original sample-size justification, the planned statistical analysis details beyond the posted analysis, or whether interim analyses were planned.

The parallel-group comparison allows each treatment group’s observed outcome to be described separately and then compared. Because the study was open-label, participants and study personnel were not masked to treatment assignment. The registry record does not report whether outcome assessment was blinded or describe procedures intended to limit the effects of knowledge of treatment assignment.

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: Participant Flow refers to the Randomized Set, consisting of all subjects who were randomized in this study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Per Protocol Set (PPS) consisted of all subjects who received at least 1 (partial) dose of study mediaction, returned at least 1 post-Baseline seizure diary and had no important protocol deviations. Subjects who discontinued the study before Week 50 for any reason other than treatment failure were excluded from the PPS.

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.

Population: Baseline Characteristics refer to the Randomized Set, consisting of all subjects who were randomized in this study.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Subjects With a Treatment Failure, measured over Week 0 (First Dose) to Week 50.

The primary endpoint was the percentage of subjects with a treatment failure between the first dose and Week 50. A subject could meet the endpoint through dropout due to a related intolerable adverse event, lack of efficacy, or the need to add another antiepileptic drug. The definition also included a need for a one-step down-titration. The endpoint therefore combines events that may arise for different reasons rather than measuring a single event type.

A treatment-failure outcome can capture whether the assigned monotherapy was continued under the trial’s stated criteria over the follow-up period. Including lack of efficacy, tolerability-related dropout, addition of another drug, and dose reduction makes the endpoint relevant to treatment continuation as defined by the protocol. At the same time, the combined outcome does not show which component drove the group results. Component-specific treatment-failure counts are not reported in the registry record.

The posted result is a percentage, so it describes the share of subjects in the analyzed set who met the endpoint. The primary analysis population was the Per Protocol Set, rather than all enrolled subjects. Its stated eligibility rules require treatment exposure, a returned post-Baseline seizure diary, and no important protocol deviations. That restriction is important when interpreting the result: it describes the recorded outcome in that defined analysis set, and should not be silently treated as an all-enrolled-subjects estimate.

7. Results Posted in the Registry

• Per Protocol Set (OXC Treated Subjects): 23.4% (30/128) versus 12.7% (15/118) on control; risk difference 10.7 percentage points (95% CI 1.2 to 20.2), risk ratio 1.84 (1.05–3.25); unadjusted two-proportion z-test p = 0.030.

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.

Percentage of Subjects Who Achieved Seizure Freedom for 24 Consecutive Weeks During the 48 Weeks Treatment Period at Any Time

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Full Analysis Set (OXC Treated Subjects): 58.5% (100/171) versus 53.8% (93/173) on control; risk difference 4.7 percentage points (95% CI -5.8 to 15.2), risk ratio 1.09 (0.90–1.31); unadjusted two-proportion z-test p = 0.378.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Full Analysis Set (OXC Treated Subjects) and the control. The interval gives the range of effects that remain compatible with the data.

Percentage of Subjects Who Achieved Seizure Freedom During the 48 Weeks Treatment Period

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Full Analysis Set (OXC Treated Subjects): 40.9% (70/171) versus 34.7% (60/173) on control; risk difference 6.3 percentage points (95% CI -4.0 to 16.5), risk ratio 1.18 (0.90–1.55); unadjusted two-proportion z-test p = 0.232.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Full Analysis Set (OXC Treated Subjects) and the control. The interval gives the range of effects that remain compatible with the data.

The posted secondary seizure-freedom outcomes both have observed percentages that are numerically higher in the oxcarbazepine group than in the levetiracetam group. In the recalculated comparisons, both confidence intervals include zero, and neither unadjusted p-value is below 0.05. The estimates are therefore less decisive than their point estimates alone might suggest: the uncertainty is compatible with no group difference as well as with differences in either direction.

These outcomes provide a different perspective from the primary treatment-failure measure. Seizure freedom is not the same endpoint as treatment failure, which combines several reasons for treatment discontinuation or adjustment. The secondary results should not be used to infer which component of treatment failure accounts for the primary comparison. They also use the Full Analysis Set, whereas the primary outcome uses the Per Protocol Set, so their estimates do not arise from identical analysis populations.

The secondary outcomes are unadjusted in the posted recalculations. When multiple outcomes are examined, the chance of seeing an apparently notable result across the set can increase unless the analysis plan accounts for multiplicity. The registry record does not report a multiplicity strategy or a hierarchy for interpreting these outcomes. For that reason, the secondary findings carry less confirmatory weight than a clearly prespecified primary test with a reported analysis plan. They are best read as supportive descriptions of the posted data, alongside their confidence intervals and population definitions, rather than as independent proof that one treatment is superior or equivalent.

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

• Time to the First Seizure Defined as the Time From the First Dose of Medication to the Occurrence of the First Seizure During the 48 Weeks Treatment Period
• Percentage of Subjects Who Achieved Seizure Freedom for 24 Consecutive Weeks During the 48 Weeks Treatment Period at Any Time
• Percentage of Subjects Who Achieved Seizure Freedom During the 48 Weeks Treatment Period

9. Statistical Interpretation

10. Statistical Methods Explained

What does the percentage measure?

For a binary outcome, each subject is classified according to whether the event occurred or did not occur under the outcome definition. The reported percentage is the proportion with the event in the specified analysis population. Here, treatment failure is the binary primary outcome, while the secondary outcomes classify whether seizure freedom was achieved under their respective definitions. A percentage does not indicate when an event occurred, and it does not describe the reasons for each treatment failure unless those components are reported separately.

What is a risk difference?

A risk difference compares the event proportions between groups by subtracting one group’s proportion from the other’s. Its sign depends on the order of subtraction. The posted recalculation defines the primary contrast with oxcarbazepine relative to levetiracetam, so a positive estimate corresponds to a higher event proportion in the oxcarbazepine group. The sponsor’s reported absolute difference uses the opposite direction, producing a negative estimate for the same ordering of group outcomes. Comparing signs without checking the contrast direction can therefore be misleading. The magnitude and interval must be read with the stated group order in mind.

What does the confidence interval convey?

A confidence interval describes the uncertainty around an estimated group contrast under the statistical method used. A relatively narrow interval indicates greater precision than a wider interval, while an interval spanning values on both sides of zero is compatible with contrasts in either direction under that method. For the primary recalculation, the interval is entirely above zero under the oxcarbazepine-minus-levetiracetam ordering. The secondary recalculated intervals include zero. A confidence interval is not a range containing a fixed proportion of individual outcomes, and it does not address sources of bias or limitations in the study design.

How should a p-value be read?

A p-value measures how incompatible the observed data are with a specified null hypothesis under the statistical model and assumptions used. It is not the probability that the null hypothesis is true, nor does it quantify the size or clinical importance of an effect. The posted p-values for the recalculations are unadjusted. Without a reported multiplicity plan, the primary and secondary p-values should not be interpreted as though each were the sole planned test. The sponsor’s reported analysis has no p-value in the registry record.

Why distinguish the sponsor’s analysis from the recalculation?

The sponsor’s analysis is the reported analysis in the registry record and is described as using Wald methodology. The recalculated contrasts are simple, unadjusted comparisons based on the posted group summary statistics. They do not replace the sponsor’s analysis or reproduce unreported adjustments, modeling choices, or protocol rules. The record marks no discrepancy between the reported and recalculated analysis. Even so, the methods and contrast directions need to be kept distinct when interpreting the two presentations.

Why does the analysis population matter?

The primary result is based on the Per Protocol Set, whose listed criteria include treatment exposure, a returned post-Baseline seizure diary, and no important protocol deviations. A per-protocol analysis describes outcomes among subjects meeting those criteria; it is not automatically equivalent to an analysis of everyone randomized. The registry record’s population definition is incomplete, so the full handling of discontinuations and other exclusions is not reported in the registry record. The secondary seizure-freedom outcomes are based on the Full Analysis Set. Estimates from the two populations are not direct like-for-like comparisons because membership differs by definition.

Why do open-label and composite outcomes need care?

In an open-label study, treatment assignment is not masked. Knowledge of assignment can potentially affect participant behavior, care decisions, reporting, or assessment, depending on the outcome and study procedures. The registry record does not say whether assessors were blinded or provide further safeguards. Treatment failure also combines several qualifying events, including tolerability-related dropout, lack of efficacy, addition of another antiepileptic drug, and dose reduction. A group contrast in the composite cannot identify which component accounts for the observed difference unless component results are reported.

What does over-dispersion mean in general?

Over-dispersion occurs when observed variability is greater than a statistical model expects. It is a concern for some count or rate analyses, because underestimated variability can make intervals too narrow and tests appear more decisive than warranted. These posted outcomes are percentages for binary measures, and no dispersion estimate is given. The registry record does not report an over-dispersion adjustment or a need for one. This general concept should not be mistaken for a method reported for this trial.

What can the posted analysis establish?

The posted analysis gives group-specific percentages and a recalculated unadjusted contrast with an interval for the primary outcome, plus seizure-freedom summaries and a sponsor-reported absolute difference. Those statistics describe observed outcomes under the stated definitions and analysis populations. They do not, on their own, resolve potential effects of missing data, multiplicity, open-label conduct, or incomplete population definitions. Details of the original statistical plan, including the prespecified primary contrast and any adjustment strategy, are not reported in the registry record.

11. Confidence Intervals and Precision

The primary recalculated risk difference is 0.107, with a 95% confidence interval from 0.012 to 0.202. With oxcarbazepine minus levetiracetam as the contrast, the interval lies above zero. Its width reflects uncertainty in the estimated difference; the interval does not by itself address bias, the choice of analysis population, or the practical importance of the endpoint. The reported percentages are based on 118.0 subjects in the levetiracetam Per Protocol Set and 128.0 subjects in the oxcarbazepine Per Protocol Set.

The sponsor’s reported absolute difference is -10.7, with a 95% confidence interval from -20.2 to -1.2. The negative direction corresponds to the opposite group ordering from the recalculated contrast. The registry identifies the sponsor method as Wald methodology. The registry does not give a sponsor p-value or the non-inferiority margin, so the interval alone cannot establish how the sponsor’s formal decision criteria were applied.

For the secondary seizure-freedom outcomes, the recalculated confidence intervals include zero. That means the intervals do not rule out a zero risk difference under the stated calculation; they also include contrasts in either direction. This is different from evidence that the groups are exactly equivalent. The estimates have finite precision, and the registry record does not report equivalence margins for these outcomes.

Confidence intervals express sampling uncertainty under their assumptions. They do not account for every uncertainty that may matter, including unreported missing-data methods, analysis choices, outcome assessment procedures, or multiplicity. The primary and secondary analyses also use different analysis populations and outcome definitions. Precision should therefore be judged alongside those design and reporting limitations, rather than by interval width alone.

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 figures are participants per arm for 80% power and participants per arm for 90% power. They are not total event counts. The registry’s planning illustration uses a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. It considers detecting the stated fraction of the observed effect. The original trial’s own sample-size assumptions and justification are not reported in the registry record.

The 80% power column gives the modeled number of participants per arm for a future study to have an 80% chance of detecting the specified effect under those planning assumptions, if that effect and the assumptions are correct. The 90% column uses a higher target chance of detection and therefore calls for more participants per arm for the same effect. These are planning illustrations based on the observed contrast, not evidence that the completed trial had a particular probability of detecting its true effect.

The rows represent planning for 100%, 75%, or 50% of the observed effect. A smaller target effect is harder to distinguish from random variation, so the illustration requires more participants per arm as the assumed effect becomes smaller. The figures can help show how study size depends on the effect chosen for planning, but they do not establish that the observed effect is the effect a future study should expect.

This is not observed power. Observed power is not a substitute for reading the estimate and its confidence interval, and these planning calculations should not be used to reinterpret the trial’s result as proof of success or failure. The calculation method is a simplified illustration; the registry record does not report that these assumptions were used to design the trial.

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, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.127; treatment proportion p₁ = 0.234; average p̄ = 0.181.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.5442 = 1.0666.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.5389 = 0.4535.
4. n = (1.0666 + 0.4535)² / (0.1073)² = 200.9, rounded up to 201 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
p0 <- 0.127118644067797                          # control proportion
p1 <- 0.234375                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^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 (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(1498822)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 201 (80% power), 269 (90% power)
 75% of observed effect: n per arm = 337 (80% power), 451 (90% power)
 50% of observed effect: n per arm = 710 (80% power), 950 (90% power)
power.prop.test: 200.9 
Simulated power at n = 201 per arm: 0.806 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-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

The sponsor’s own analysis reports an absolute difference of -10.7, with a 95% confidence interval from -20.2 to -1.2, using Wald methodology. The analysis is classified in the registry record as non-inferiority or equivalence. No p-value is posted for this analysis, and the non-inferiority or equivalence margin and detailed decision rule are not reported in the registry record.

The simple recalculation reports the risk difference in the opposite direction, with oxcarbazepine relative to levetiracetam. Its estimate is 0.107 and its 95% confidence interval is 0.012 to 0.202; the unadjusted p-value is 0.03. Reversing the group order reverses the sign, so the two estimates point in the same observed direction when their contrast definitions are taken into account. The registry record marks no discrepancy between the reported and recalculated results.

The recalculation is not a replacement for the sponsor’s analysis. It is an unadjusted re-analysis from posted summary statistics and may not reproduce aspects of a prespecified analysis that are not available in the record. The sponsor’s result remains the trial’s reported analysis, but the missing margin and decision details prevent independent evaluation of a formal non-inferiority conclusion from the registry information alone.

15. Multiplicity, Missing Data and Analysis Populations

The registry record lists one analysis and four outcome measures, including the primary treatment-failure measure and posted secondary outcomes. It does not report whether the study’s original statistical plan specified a hierarchy among outcomes, adjusted for multiple testing, or treated the secondary outcomes as exploratory. The recalculated p-values are unadjusted. Without a reported strategy for multiplicity, a p-value should be interpreted as applying to its individual comparison rather than as a family-wise conclusion across all outcomes.

The primary result is reported for the Per Protocol Set, while the secondary seizure-freedom measures use the Full Analysis Set. The primary population criteria include receipt of at least one partial dose, a returned post-Baseline seizure diary, and no important protocol deviations. The description of how subjects who stopped before Week 50 for reasons other than treatment failure were handled is truncated. The complete population definition is not reported in the registry record.

The record does not report the missing-data strategy for the primary or secondary outcomes, the number of missing outcome observations, or sensitivity analyses addressing missingness. It also does not provide a full account of exclusions from each analysis population or a complete flow from randomization through analysis. These omissions limit assessment of how robust the posted percentages are to missing observations and population selection.

The study is open-label, and the registry record does not say whether outcome assessors were blinded. It does not report interim analyses, stopping rules, the original sample-size justification, or the complete prespecified statistical analysis plan. These details should not be inferred from the posted results. They are relevant to judging how the analysis was planned and how much inferential weight to place on an unadjusted comparison.

16. 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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: convulsion (2.9%), cardiac arrest (1.1%), abdominal pain (0.6%), diarrhoea (0.6%), chest discomfort (0.6%).

The registry lists serious adverse events for 15 subjects among 173 at risk in the levetiracetam group and 15 subjects among 174 at risk in the oxcarbazepine group. These are group-level counts and at-risk denominators as recorded; they are not a comparison adjusted for follow-up time or differences in exposure. The record lists convulsion at 2.9% among the serious adverse-event terms, followed by cardiac arrest at 1.1%, and abdominal pain, diarrhoea, chest discomfort, and fibula fracture at 0.6% each.

Serious adverse events are not the same as all adverse events, and these summaries do not establish whether an event was caused by treatment. The registry also reports other adverse events in 67 subjects among 173 at risk for levetiracetam and 93 among 174 at risk for oxcarbazepine. Death counts are not reported in the registry record. The posted summaries do not give event timing, severity details beyond the serious-event classification, or a complete account of individual event histories. These figures should be read as descriptive safety reporting, not as a stand-alone estimate of comparative safety.

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

The primary outcome shows a higher observed treatment-failure percentage in the oxcarbazepine Per Protocol Set than in the levetiracetam Per Protocol Set. The recalculated unadjusted risk difference and its confidence interval indicate the direction and uncertainty of that comparison under the stated contrast. The sponsor’s reported estimate expresses the same group ordering in the opposite direction. Those results describe the endpoint as defined in the registry record; they do not identify which treatment-failure component accounts for the difference.

The result does not by itself establish that either treatment is clinically preferable. The registry record labels the sponsor analysis as non-inferiority or equivalence, but does not report the margin or decision criteria. The posted interval cannot be evaluated against an unreported margin. The simple recalculation is also not a substitute for a complete prespecified analysis plan.

The secondary seizure-freedom findings have uncertainty intervals that include zero in the recalculations. They do not establish that the treatments have identical outcomes, and they do not overturn or explain the primary composite result. Their interpretation is further limited by unadjusted testing and use of a different analysis population.

More broadly, the posted numbers apply to the recorded analysis populations and timeframes. The trial was open-label, the primary population description is incomplete, and missing-data handling and multiplicity procedures are not reported in the registry record. These limitations affect how confidently the estimates can be generalized or interpreted. Statistical evidence from this trial should be distinguished from a medical recommendation; treatment decisions are outside the scope of these results.

18. Why This Trial Matters Statistically

This trial illustrates why the endpoint definition and analysis population matter as much as the headline percentage. Treatment failure is a composite: dropout for specified tolerability or efficacy reasons, addition of another antiepileptic drug, and a need for dose reduction all contribute. A difference in the composite can be statistically described without revealing which component drove it. Component-specific reporting would be needed to distinguish those pathways.

The study also demonstrates the importance of contrast direction. The recalculation presents oxcarbazepine relative to levetiracetam, whereas the sponsor reports the absolute difference in the reverse direction. The point estimates have different signs but describe the same ordering of the observed group percentages. Clear labeling prevents a sign from being mistaken for a contradictory result.

The contrast between the primary and secondary results is also instructive. The primary endpoint is treatment failure in the Per Protocol Set, while the seizure-freedom outcomes are in the Full Analysis Set and have confidence intervals that include zero. Outcomes with related clinical context are not interchangeable statistical measures, and a finding on one does not automatically determine the others.

Finally, a sponsor-reported non-inferiority or equivalence analysis cannot be fully assessed without its margin and decision criteria. The registry’s sample-size illustrations are based on observed effects and stated planning assumptions, not the original trial design. Together, these features show why estimates, uncertainty, analysis populations, and missing protocol details should be read together rather than reducing a trial to a single p-value.

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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

The study was open-label, with no masking listed. Knowledge of assignment may matter for behavior, reporting, or decisions that contribute to a composite endpoint. The registry record does not report whether outcome assessment was blinded or describe measures to address potential influence from treatment knowledge.

The primary result is based on the Per Protocol Set rather than the Full Analysis Set used for the posted secondary outcomes. The registry record’s description of the Per Protocol Set is incomplete, including the handling of subjects who discontinued before Week 50 for reasons other than treatment failure. Missing-data methods, sensitivity analyses, and the number of missing observations are not reported in the registry record.

Treatment failure combines several types of events, and component results are not posted. The composite can therefore indicate a difference in overall failure without showing whether the result reflects tolerability, lack of efficacy, treatment addition, or down-titration. The study’s sponsor analysis is classified as non-inferiority or equivalence, but its margin and full decision criteria are not reported, limiting assessment of that formal claim.

The registry record does not report the original sample-size justification, complete statistical analysis plan, multiplicity handling, or interim-analysis procedures. The planning illustrations use the observed effect and specified simplified assumptions; they should not be mistaken for the basis of the trial’s design. Safety summaries are descriptive and do not provide event timing or a complete account of individual outcomes. These reporting gaps limit independent assessment of the robustness and scope of the posted findings.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Levetiracetam Versus Oxcarbazepine as Monotherapy to Evaluate Efficacy and Safety in Subjects With Newly or Recently Diagnosed Partial Epilepsy — NCT01498822.
• Registry record last updated 2015-08-20; status last verified 2015-07.
• Results first posted 2015-08-20.
• 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

NCT01498822 is a completed randomized, open-label, parallel-group phase 4 study comparing twice-daily levetiracetam monotherapy with twice-daily oxcarbazepine monotherapy in subjects with newly or recently diagnosed partial epilepsy. The registry records enrollment of 353, a start of 2011-06, and primary completion in 2014-07.

The primary outcome was treatment failure through Week 50, analyzed in the Per Protocol Set. The posted group percentages were 12.7% for levetiracetam and 23.4% for oxcarbazepine. The sponsor reported an absolute difference with a 95% confidence interval and Wald methodology; the registry classifies the analysis as non-inferiority or equivalence, but does not report the margin. Recalculated unadjusted comparisons and secondary seizure-freedom outcomes provide additional descriptive context. Important details, including the complete analysis plan and missing-data procedures, are not reported in the registry record.