Clinical Study of Lamotrigine to Treat Newly Diagnosed Epilepsy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Clinical Study of Lamotrigine to Treat Newly Diagnosed Epilepsy (NCT01431963), a non-randomized phase 3 study. The primary outcome is Number of Participants Who Were Seizure Free in the Maintenance Phase (Across Seizure Types and by Seizure Type Within 6 Months Prior to the Start of the Study).

2. Clinical Question

3. Trial Design

This was a Phase 3, multi-center, uncontrolled, open-label evaluation of lamotrigine monotherapy. It used a single-group model, with non-randomized allocation and no masking. Enrollment was 70. The registry record identifies epilepsy as the condition and GlaxoSmithKline as the sponsor. The study began in 2011-09, reached primary completion in 2013-03, and is listed as completed. The study was conducted in Japan and South Korea.

The study description divides participation into baseline, escalation, maintenance, taper, and post-study examination phases. During escalation, the described oral doses were 25 mg/day for 2 weeks, then 50 mg/day for 2 weeks, and then 100 mg/day for 2 weeks. The maintenance phase was described as 200 mg/day for 24 weeks, with a possible reduction to 100 mg/day for safety concerns. If seizures could not be controlled at 200 mg/day, the dose could be increased gradually up to 400 mg/day. The description says that doses above 200 mg/day could be given in two divided doses.

The study design does not include a randomized or concurrent control group. As a result, the reported outcomes describe participants receiving lamotrigine in this study, rather than a treatment contrast between groups. The registry record does not report details of a formal sample-size justification or the statistical plan used to analyze the outcomes. The registry describes a possible extension for eligible Japanese participants who responded without tolerability issues, but extension-phase results 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.

Before assignment: The study consisted of a 6-week Escalation Phase, a 24-week Maintenance Phase (MP), a \>=2-week Taper Phase, and a post-study examination conducted within 1-4 weeks after the last dose of lamotrigine. In Japan only, the Extension Phase was conducted until either approval for this indication or after 24 months after Last Subject Last Visit in the MP.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set (FAS): all participants in the Safety Population (SP) who provided at least one set of efficacy data after the first dosing of investigational product. The SP is comprised of all participants who had taken at least one dose of investigational product. Only those participants available at the specified time point were analyzed.

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 data were collected in members of the Safety Population, comprised of all participants who had taken at least one dose of investigational product.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants Who Were Seizure Free in the Maintenance Phase (Across Seizure Types and by Seizure Type Within 6 Months Prior to the Start of the Study), measured over Weeks 7 to 30.

The primary endpoint is the number of participants who were seizure free during the maintenance phase, across seizure types and by seizure type within 6 months before study start. A participant counted as seizure free if no seizure was reported during maintenance. The specified timeframe is Weeks 7 to 30. This endpoint is a participant count, not a measure of seizure frequency or time to first seizure.

A seizure-free outcome can describe whether participants experienced any reported seizure during a defined observation period. In this study, examining outcomes by prior seizure type also organizes the result according to the seizure history recorded before study start. The registry description identifies several seizure categories, including partial seizure types and tonic-clonic seizures. These categories are part of the endpoint definition; the registry record does not report the participant counts for them.

The primary endpoint is relevant to the stated study question because it summarizes seizure status during maintenance. However, the endpoint alone does not establish how outcomes would compare with no treatment, another treatment, or a different study setting. The uncontrolled, single-group design has no concurrent comparator. The primary seizure-free count and its statistical precision are not reported in the registry record, so the size and precision of the observed primary outcome cannot be assessed from the registry entry.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study’s main design feature is that it has one treatment group and no randomized comparator. This matters when interpreting any outcome: a single-group count can describe what was observed among participants, but it cannot estimate a randomized difference between treatment strategies. The open-label design also means that masking was absent. General: masking can reduce some influences of expectations on treatment delivery, outcome assessment, or reporting, depending on the outcome and study procedures. The registry record does not report additional steps used to limit those influences.

What does a participant count represent?

The primary outcome is a count of participants who met a binary definition: no reported seizures during maintenance. General: binary outcomes classify each participant into one of two categories for a particular endpoint, such as meeting or not meeting a prespecified criterion. The count is meaningful only alongside its analysis denominator. Here, the registry gives an enrollment total of 70, but it does not report the primary endpoint count or the size of the Full Analysis Set. A rate, confidence interval, or other summary of the primary outcome therefore cannot be established from the registry record.

The registry defines the Safety Population as participants who took at least one dose. It defines the Full Analysis Set as participants in the Safety Population who posted at least one set of efficacy data after the first dose. The Full Analysis Set description ends mid-sentence, so whether further qualifications apply is not reported in the registry record. The distinction between a safety population and an efficacy analysis population is important: safety summaries may include participants based on treatment exposure, while an efficacy analysis may require outcome data. The two denominators need not be the same.

What does a confidence interval add?

General: a confidence interval expresses the statistical uncertainty around an estimate under the assumptions of the analysis. A narrow interval indicates greater precision than a wide interval, while an interval that includes a range of materially different values signals uncertainty about the outcome’s size. A confidence interval does not correct limitations in study design, measurement, or missing data. No confidence interval for the primary seizure-free outcome is reported in the registry record, and the outcome count itself is not reported.

Why does the absence of a control group matter?

General: a controlled comparison evaluates outcomes across groups treated under different assigned conditions. Random assignment can help make groups comparable on average, while a concurrent control group helps distinguish treatment-group outcomes from changes that might also occur without the intervention or under another intervention. This trial is described as non-randomized, uncontrolled, and single group, so it cannot estimate a randomized between-group contrast. The registry record does not report a comparator outcome or an adjusted comparative analysis.

The study’s openness also makes outcome ascertainment worth considering. The primary endpoint depends on reported seizures. General: when an outcome relies on participant report, the completeness and consistency of reporting can affect classification. The registry description defines seizure freedom as no reported seizures during maintenance, but it does not report the method used to collect or verify reports, the assessment schedule, or whether endpoint assessors were independent.

How should the planning assumptions be read?

The planning description specifies a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect expressed as a fraction of the observed effect. It describes participant counts per arm for non-time-to-event outcomes and total event counts for time-to-event outcomes. These are planning assumptions, not features of the original single-group allocation. General: sample-size calculations estimate the amount of information a hypothetical design may need under stated assumptions; they do not measure the probability that a completed study’s result is true, and they are not observed power. The registry record does not report the trial’s own sample-size justification, the observed effect used in the planning illustration, or the resulting planning estimates.

What statistical details remain unavailable?

The registry record lists 3 outcome measures and 5 analyses, but the detailed analysis methods are not reported in the registry record. It does not report the statistical model, covariate adjustment, confidence-interval method, handling of repeated observations, or any interim-analysis plan. These omissions limit the ability to reproduce or evaluate the analysis from the registry entry alone. General: the suitability of an analysis depends on the endpoint structure, data completeness, and assumptions of the chosen method. Without those details and the outcome results, the primary finding’s statistical precision and robustness cannot be assessed.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 3 outcome measures and 5 analyses. The primary outcome is seizure freedom during maintenance across seizure types and by prior seizure type. Secondary outcomes include time to withdrawal or dropout during escalation and maintenance, across seizure types and by seizure type, and time to the first seizure during maintenance, across seizure types and by seizure type. The registry does not explain how the 5 analyses correspond to the outcome measures or whether they were prespecified in a particular hierarchy.

Multiplicity arises when several outcomes or analyses are considered. General: examining multiple endpoints can increase the chance that at least one result appears notable by chance, so an analysis plan may specify which comparisons are primary and whether any adjustment or hierarchical testing is used. Any multiplicity adjustment or strategy is not reported in the registry record. The record also does not report an interim-analysis plan.

The registry defines an efficacy population using post-dose efficacy data and a safety population using receipt of at least one dose. However, the primary analysis population size, the number of participants missing primary endpoint data, and the handling of missing outcome data are not reported in the registry record. It is also not reported whether participants with incomplete maintenance follow-up were excluded, classified in a particular way, or handled using another approach. General: missing-data methods can affect estimates when outcome availability is related to participants’ outcomes or characteristics. Without participant flow and analysis details, the potential influence of missing data cannot be evaluated.

The safety summaries report 65 participants at risk, while enrollment is 70. The reasons for the difference are not reported in the registry record. This prevents a complete assessment of how participants moved from enrollment into each analysis population.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: epilepsy (3.1%), haemorrhoids (1.5%), gastrooesophageal reflux disease (1.5%), intestinal obstruction (1.5%), sick sinus syndrome (1.5%).

The adverse-event summary reports serious adverse events for 8 of the 65 participants at risk and other adverse events for 38 of the 65 participants at risk. These are counts of participants in the registry summary. The record does not report a death count. The serious-event terms listed include Epilepsy at 3.1%, and Haemorrhoids, Gastrooesophageal reflux disease, Intestinal obstruction, Sick sinus syndrome, and Electrocardiogram QT prolonged at 1.5% each.

These summaries should be read as safety observations from a single treatment group. They do not, on their own, establish whether an event was caused by lamotrigine. The registry record does not report comparative safety outcomes, event timing, duration, severity details beyond the serious-event classification, or a causal assessment for each event. It also does not explain the difference between the enrollment total of 70 and the 65 participants at risk in the adverse-event summaries.

General: adverse-event counts describe events observed and recorded under a study’s collection procedures. Interpretation depends on the definitions, observation period, completeness of follow-up, and how events are attributed. The registry record identifies the maintenance schedule but does not give detailed event-collection procedures or the duration of safety follow-up for these summaries. The listed counts and percentages therefore provide only a limited description of reported safety events in this study.

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

The registry record describes an open-label evaluation of lamotrigine monotherapy in a single group of participants with newly diagnosed or recurrent, currently untreated epilepsy. It specifies a maintenance-phase seizure-free endpoint and reports some adverse-event counts. Those details establish what the study set out to observe and identify the design context for interpreting its results.

The primary seizure-free participant count is not reported in the registry record. Nor are the primary analysis denominator, confidence interval, or other measure of precision. As a result, the posted registry information does not quantify the primary endpoint result. It is not possible from this record to describe how many participants met the endpoint or how uncertain that estimate is.

Even if a primary outcome count were available, the uncontrolled single-group design would limit what could be concluded about comparative effects. There is no randomized comparator and no concurrent control group. Outcomes in the study group cannot establish what would have occurred in the same population under another treatment or without the study treatment. The open-label design and reliance on reported seizures are also considerations, while the registry does not describe outcome verification or masking procedures.

The adverse-event figures show that serious and other adverse events were recorded among participants at risk. They do not establish that the treatment caused those events, and the registry summary does not provide a controlled comparison. The event counts should be interpreted with the limited details available about follow-up and event assessment.

Overall, the registry entry supports a description of the trial’s design, planned regimen, endpoint definitions, and recorded safety summaries. It does not provide the numerical primary efficacy result or enough statistical detail to assess its precision, missing-data sensitivity, or comparative meaning. These limits are about what can be inferred from the registry record; they are not a judgment about an unreported result.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of why design features shape the questions a result can answer. The study is identified as Phase 3, but it is also uncontrolled, open-label, non-randomized, and single group. The phase label does not create a comparator or change the limits of a single-group design. Results from such a design can describe observations among participants in the study, but they do not provide a randomized estimate of the difference between treatment strategies.

The endpoint definition also illustrates the importance of specifying both an outcome and its observation period. Seizure freedom is defined as no reported seizures during maintenance, with the timeframe identified as Weeks 7 to 30. This is distinct from the secondary time-to-first-seizure outcome and from time to withdrawal or dropout. Those outcomes address different aspects of participants’ experience and require distinct summaries and analysis methods.

The population definitions matter as well. Enrollment is 70, the safety summaries use 65 participants at risk, and the primary endpoint is assigned to a Full Analysis Set whose size is not reported. Without clear denominators and participant flow, readers cannot determine how much of the enrolled group contributes to each result. The registry’s truncated description of the Full Analysis Set adds uncertainty about any further qualifications.

Finally, the record separates an outcome’s observed value from the precision and analysis choices needed to interpret it. The primary count, uncertainty interval, missing-data approach, and detailed statistical methods are not reported in the registry record. The planning assumptions described for hypothetical sample-size illustrations are not a substitute for those trial results and do not amount to observed power. Together, these features make the registry entry a useful case for distinguishing an endpoint definition from its numerical result and a within-group observation from a comparative treatment effect.

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 main limitation for interpreting efficacy is that the registry record does not report the primary seizure-free participant count. It also does not report the size of the Full Analysis Set or a confidence interval for the endpoint. The primary outcome’s magnitude and precision therefore cannot be assessed from the registry entry.

The design is uncontrolled, open-label, non-randomized, and single group. There is no concurrent comparator, so the study does not estimate a randomized treatment contrast. The endpoint depends on reported seizures, but the registry record does not describe the assessment schedule, reporting procedures, or independent verification. It does not report whether outcome assessment was otherwise protected from knowledge of treatment.

Population accounting is incomplete. Enrollment is 70, while adverse-event summaries use 65 participants at risk. The reason for this difference is not reported in the registry record. The Safety Population and Full Analysis Set are described, but the latter’s definition is truncated and its size is not given. Participant flow, primary endpoint data completeness, withdrawals, and the handling of missing efficacy data are not reported in the registry record.

The registry lists 3 outcome measures and 5 analyses but does not detail their correspondence, the statistical methods, or any multiplicity strategy. The sample-size justification and interim-analysis plan are not reported in the registry record. Safety summaries do not include comparative data or detailed event timing and attribution. The record also describes a possible extension for eligible Japanese participants, but extension results are not reported. These limitations constrain interpretation of both efficacy and safety information available in the registry entry.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Clinical Study of Lamotrigine to Treat Newly Diagnosed Epilepsy — NCT01431963.
• Registry record last updated 2016-10-20; status last verified 2016-08.
• Results first posted 2013-12-03.
• 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

NCT01431963 is a completed Phase 3, multi-center, uncontrolled, open-label study of lamotrigine monotherapy in newly diagnosed or recurrent, currently untreated epilepsy. It was conducted in Japan and South Korea, enrolled 70 participants, and used a non-randomized, single-group design. The registry record gives a study start of 2011-09 and primary completion of 2013-03.

The primary endpoint is the number of participants with no reported seizures during the maintenance phase, with a timeframe of Weeks 7 to 30. The primary result and its precision are not reported in the registry record. Safety summaries list 8 participants with serious adverse events and 38 with other adverse events among 65 at risk. The record does not provide a concurrent comparator or enough analysis detail to support comparative conclusions.