Lamotrigine Extended-Release In Elderly Patients With Epilepsy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Lamotrigine Extended-Release In Elderly Patients With Epilepsy (NCT00516139), a non-randomized phase 3 study. The primary outcome is Number of Participants With Any Serious Adverse Event (SAE) and Any Non-serious Adverse Event.

2. Clinical Question

The registry summary says the study was conducted to determine the safety and tolerability of lamotrigine in elderly patients with epilepsy. The listed primary outcome is a count of participants with adverse events, rather than a comparison of seizure outcomes between treatment groups. Secondary outcome descriptions include seizure-frequency changes, seizure-free status, investigator ratings of seizure severity and overall clinical status, and changes in blood pressure, height and weight. Those descriptions indicate outcomes the record lists, but do not by themselves give their numerical findings.

The central interpretive question is therefore descriptive: what adverse-event counts are recorded among participants who received LTG-XR, and what can those counts tell a reader in the absence of a control group? They characterize the recorded events in this study population and observation period. They do not establish how the counts would compare with an untreated group or another treatment.

3. Trial Design

This was a Phase 3, non-randomized, open-label, single-group study sponsored by GlaxoSmithKline. The study title concerns extended-release lamotrigine in elderly patients with epilepsy. The registry lists 122 participants as enrolled and identifies lamotrigine as the intervention. The arm description is “Open-label lamotrigine.” No separate comparison arm is listed.

The study began in 2007-08, reached primary completion in 2010-07, and is marked completed. The primary outcome observation period starts at baseline, Week 0, and continues until three weeks after the end of treatment, specified as Week 30 or 33. The record does not explain why the two possible end weeks are listed or how they relate to individual participants.

Because allocation is non-randomized and the model is single-group, this is not a randomized controlled comparison. The record itself notes that arms are not a like-for-like control comparison. With no distinct control group, recorded event counts describe the observed participants under the study conditions; they cannot isolate a treatment effect from other explanations through a between-group contrast.

The study is open-label, meaning masking is listed as none. The registry record does not report further information about how outcomes were assessed or whether any assessments used additional safeguards against knowledge of treatment. Enrollment, the safety-population definition, and the denominator shown for adverse events are distinct record details: the safety population includes enrolled participants who took at least one dose, while the adverse-event entries use 121 participants at risk.

The record lists 22 outcome measures and zero analysis entries. It does not report a statistical analysis plan, allocation details beyond the non-randomized designation, or a sample-size justification. These absences limit what can be said about planned analyses and design rationale.

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 4 phases (Ph): 7-week (w) Dose-escalation Ph, 8-w Adjunctive Maintenance (AM) Ph, 13-w Adj. Optimization (AO) Ph or 13-w Conversion/Monotherapy (C/M) Ph, and a 2-5 w Taper/Follow up (T/F) Ph.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety Population: all participants who were enrolled and took at least one dose of study drug

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 Number of Participants With Any Serious Adverse Event (SAE) and Any Non-serious Adverse Event, measured over From Baseline (Week 0) until 3 weeks after the end of treatment (Week 30 or 33).

The primary outcome counts participants with any serious adverse event and any non-serious adverse event. The registry defines an adverse event as an untoward medical occurrence temporally associated with use of a medicinal product, whether or not it is considered related to that product. A serious adverse event is an event that meets at least one listed seriousness criterion: death, a life-threatening event, inpatient hospitalization or its prolongation, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or another important medical event.

The observation window runs from baseline at Week 0 through three weeks after the end of treatment, which is given as Week 30 or 33. In the LTG-XR group, 22 of 121 participants are recorded with a serious adverse event, and 98 of 121 with a non-serious adverse event. These are participant counts for the listed categories; the record does not say that the categories are mutually exclusive. A participant could therefore be represented in both counts, and the counts should not be added to produce a total number of people with any event.

Counting affected participants is a straightforward way to describe how many people experienced an event meeting the registry definitions during the stated period. It does not, by itself, show event timing, duration, severity within each category, or whether an event was judged related to treatment. The primary outcome is useful as a safety summary, but it is not a controlled estimate of risk relative to another treatment.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a participant count. For each listed adverse-event category, the registry records how many participants were at risk and how many were affected. In general, a count answers how many people had a recorded event; it is different from a count of all event episodes, since one person may experience more than one episode. The record does not give episode-level totals. Its entries report 22 participants with a serious adverse event and 98 with a non-serious adverse event, with 121 participants at risk for each category.

In general, a denominator defines the group in which an event count is being described. It is important to keep the denominator attached to the count: the adverse-event entries use 121 participants, while total enrollment is 122. The registry defines the safety population as participants who enrolled and took at least one dose. It does not explain the difference between enrollment and the adverse-event denominator. No further accounting of participants is reported in the registry record.

In general, a confidence interval expresses the uncertainty around an estimate using a range of values compatible with the data and the chosen method. It does not guarantee that the true value lies in the interval, and its interpretation depends on the assumptions of the analysis. No confidence intervals are reported for the primary event counts. The record also contains no comparative estimate or analysis entry from which a measure of precision could be read. Consequently, the counts can be described as posted, but their statistical uncertainty is not quantified in the reported results.

In general, hypothesis tests assess how compatible observed data are with a specified null hypothesis under a statistical model. A p-value is not a measure of the size or clinical importance of an effect. No p-values or hypothesis tests are reported for this primary outcome. More fundamentally, this single-group record does not supply a concurrent control-group comparison for testing a treatment contrast.

In general, randomized allocation can help balance measured and unmeasured prognostic factors between groups, while masking can reduce some forms of expectation or assessment bias. This study is listed as non-randomized, single-group, and unmasked. Those design features mean that the event counts are descriptive of the participants observed, rather than an adjusted or randomized estimate of a treatment effect. The record does not report an adjustment model or other method intended to address confounding.

The sample-size assumptions associated with planning illustrations are not the same as a trial's observed results. In general, a planning illustration can show what sample size might be needed under stated assumptions, but it is not evidence that the study had a particular probability of detecting an effect after the fact. The listed assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect expressed as a stated fraction of the observed effect. The illustrations are defined as participants per arm for outcomes other than time-to-event outcomes, for which the total number of events is used. These assumptions do not establish that this study used such a two-arm design: the registry lists it as a single-group study, and the record does not report its own sample-size justification. Any planning illustration should therefore be read as hypothetical planning, not as observed power or a result of the trial.

In general, over-dispersion occurs when data vary more than a model's assumed distribution allows. It can make standard errors too small if a model fails to account for the extra variation. That issue is relevant to some count-data models, but the primary outcome is reported as participant counts, and no model or over-dispersion assessment is reported in the registry record. No claim about an over-dispersion adjustment can be made.

In general, for binary outcomes, an event and a non-event classification can be analyzed using methods that compare proportions, but the choice depends on the design, estimand, sample structure, and assumptions. The record does not describe a specified inferential method for the primary outcome. No recalculated comparative estimates are available, and no unadjusted re-calculation should be inferred from the two event counts without a defined comparison and analysis plan. The safest statistical reading is descriptive: the record reports how many participants in the listed group were affected over the stated period.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 22 outcome measures, including the primary adverse-event outcome and secondary measures concerning seizure frequency, seizure-free status, investigator assessments, blood pressure, height, and weight. It lists zero analysis entries. The list of outcomes does not explain which results were analyzed together, which were considered confirmatory, or how any multiplicity was handled. A statistical analysis plan is not reported in the registry record.

In general, testing many outcomes can increase the chance of finding an apparently notable result by chance if each is treated as a separate confirmatory test. Approaches to multiplicity depend on the questions and analysis plan. Since no testing results or multiplicity procedure are reported, no conclusion about adjusted or unadjusted testing is possible for this record. The number of listed outcomes alone does not establish that all were formally tested.

Details about missing outcome data, withdrawals, and the handling of incomplete observations are not reported in the registry record. The safety population is defined as enrolled participants who took at least one dose, but the record does not describe how participants with incomplete follow-up contributed to the adverse-event counts. The 121-person denominator and 122-person enrollment count are both listed; the reason they differ is not reported.

The record does not report whether analyses used an intention-to-treat, per-protocol, or other analysis population for outcomes beyond its stated safety-population definition. It also does not provide imputation methods or sensitivity analyses for missing observations. These omissions matter because event ascertainment and outcome summaries can depend on the amount and pattern of follow-up. They limit interpretation of the reported counts, without establishing that any particular data were missing or that a specific method was used.

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: hip fracture (2.5%), ataxia (1.7%), convulsion (1.7%), status epilepticus (1.7%), acute myocardial infarction (0.8%).

The LTG-XR adverse-event entries show 22 of 121 participants with a serious adverse event and 98 of 121 with a non-serious adverse event during the period from baseline at Week 0 to three weeks after treatment ended at Week 30 or 33. The registry's seriousness definition includes specified outcomes such as death, life-threatening events, hospitalization, significant disability, congenital anomaly or birth defect, and other important medical events.

The counts refer to participants, not necessarily to distinct event episodes. The serious and non-serious categories may overlap, and the record does not report a combined number of people with any adverse event. The death count is not reported in the registry record. The named serious-event terms include Hip fracture, 2.5%; Ataxia, 1.7%; Convulsion, 1.7%; Status epilepticus, 1.7%; Acute myocardial infarction, 0.8%; and Balance disorder, 0.8%. The record does not specify the denominator or event counts behind those percentages.

In general, an adverse event's occurrence during a study does not establish that the study treatment caused it. The registry definition explicitly allows events whether or not considered related to the medicinal product. With no control group, these figures describe reported events among participants in the study, not comparative event risk.

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

The posted results describe adverse-event experience recorded in one open-label group of participants receiving LTG-XR. The primary outcome reports 22 participants with a serious adverse event and 98 with a non-serious adverse event among 121 at risk. It also provides a timeframe and definitions that help specify what was counted. These are relevant descriptive details about the study's safety outcome.

The counts do not establish that lamotrigine caused any particular event. The adverse-event definition includes occurrences whether or not they were considered related to the medicinal product, and the registry record does not give an attribution breakdown. The counts also do not show what the event frequency would have been with a different treatment or without study treatment. There is no randomized comparator group, and no comparative estimate, confidence interval, or hypothesis test is reported.

The record lists secondary outcomes related to seizure frequency and other clinical measures, but their numerical results are not reported in the registry record for this analysis. Their presence in the outcome list does not establish the direction, size, or precision of any change. The primary adverse-event counts also cannot answer whether seizure outcomes differed from baseline or from another treatment.

In general, statistical precision concerns how much uncertainty surrounds an estimate, while clinical meaning concerns how an outcome matters in its clinical context. The event counts are presented without interval estimates, so their precision is not quantified. A count alone also does not describe event timing, duration, recurrence, or severity beyond the registry's serious-versus-non-serious classification. No treatment recommendation or claim of comparative benefit follows from these descriptive data.

The appropriate scope of interpretation is therefore limited: these results report participant counts for adverse-event categories in the study group and specified observation period. They do not demonstrate comparative safety, prove causality, or establish effectiveness. Missing statistical and follow-up details further restrict interpretation, but their absence does not justify assuming what the unreported details would have shown.

13. Why This Trial Matters Statistically

This study illustrates an important distinction in clinical-trial interpretation: a recorded event count and a treatment comparison are different kinds of evidence. The registry lists serious and non-serious adverse-event counts for one group, making the results useful as a description of the study population's recorded events during the specified period. But a single-group count does not provide the counterfactual comparison needed to estimate what might have happened under another treatment or no treatment.

The design labels matter for the same reason. Non-randomized allocation, a single-group model, and no masking mean that the record is not a randomized, masked comparison. Those features do not erase the value of descriptive safety reporting, but they do shape the questions the data can answer. The record itself warns that the study is not a like-for-like control comparison.

The gap between total enrollment of 122 and the 121-person adverse-event denominator also highlights why population definitions and denominators need to be read together. The registry defines the safety population by enrollment and receipt of at least one dose, but it does not explain the denominator difference. Likewise, named event terms are listed with percentages without their underlying event counts or denominator. Those details are relevant to evaluating how precisely to interpret safety summaries.

Finally, the registry lists multiple outcomes but no analysis entries. This makes clear that outcome descriptions and numerical analysis results are not interchangeable. Statistical education benefits from distinguishing what a registry says was measured from what it reports as analyzed. In this record, the primary outcome supports a narrow descriptive account; broader claims require information and comparisons that are not reported.

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.

Several limitations specific to this record constrain interpretation. The trial is listed as non-randomized, open-label, and single-group, with no like-for-like control comparison. Therefore the primary event counts cannot isolate an effect attributable to the intervention or establish comparative safety. The record does not report adjustment methods that might address differences in participant characteristics or other influences.

The denominator used for the adverse-event entries is 121, whereas enrollment is 122. Although the safety population is defined as enrolled participants who took at least one dose, the record does not explain the difference in these counts. It also does not report participant flow, withdrawals, completeness of follow-up, or the handling of missing outcome data. The stated follow-up period ends three weeks after treatment at Week 30 or 33; the reason for the two end-week descriptions is not reported.

The serious and non-serious figures are participant counts, but the record does not explain overlap between categories or provide a combined number of participants with any adverse event. It does not report a death count. For the listed serious-event terms, the underlying event counts and the denominator for percentages are not reported. These gaps limit detailed interpretation of the safety summaries.

There are no reported confidence intervals, comparative estimates, hypothesis tests, or analysis entries. The registry lists 22 outcome measures, but a statistical analysis plan, multiplicity approach, and numerical secondary-outcome findings are not reported. The sample-size justification for this trial is also not reported in the registry record. These omissions prevent assessment of the planned inferential framework and precision beyond the posted counts.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Lamotrigine Extended-Release In Elderly Patients With Epilepsy — NCT00516139.
• Registry record last updated 2017-01-18; status last verified 2016-11.
• Results first posted 2012-01-13.
• 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

The completed Phase 3 study, NCT00516139, examined open-label extended-release lamotrigine in elderly patients with epilepsy. It was sponsored by GlaxoSmithKline and is listed as non-randomized, unmasked, and single-group. Enrollment was 122. The study began in 2007-08, and primary completion was in 2010-07.

The primary outcome counted participants with serious and non-serious adverse events from baseline at Week 0 through three weeks after treatment ended at Week 30 or 33. The LTG-XR group records 22 of 121 participants with a serious adverse event and 98 of 121 with a non-serious adverse event. The registry lists 22 outcome measures and zero analysis entries. It does not report a control-group comparison, confidence intervals, a statistical analysis plan, or numerical secondary-outcome results.

These results are descriptive counts from a single study group. The registry record does not establish event causality or comparative safety or effectiveness.