This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Hormonal and Lipid Levels in Male Subjects After a Switch From Carbamazepine to Lacosamide (NCT01375374), a na phase 3 study. The primary outcome is Change in Serum Sex Hormone Binding Globulin (SHBG) From Baseline to Treatment Period End (Comprised of a 4-week Titration Period and an 8-week Maintenance Period).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01375374 |
| Phase | Phase 3 |
| Condition | Epilepsy, Partial |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 11 |
| Arms in the primary outcome | n/a |
| Lead sponsor | UCB Pharma |
| Results posted | Yes |
2. Clinical Question
The study asked whether blood lipid and hormonal parameters changed after male subjects with partial-onset seizures switched from carbamazepine to lacosamide while levetiracetam treatment remained unchanged. The primary question concerned serum sex hormone binding globulin (SHBG), measured from baseline to the end of the treatment period. The registry describes this endpoint as a safety variable assessed for descriptive purposes because enrollment ended before the planned sample size was reached.
Population
Male subjects with partial-onset seizures. The safety set included subjects who received at least 1 dose of lacosamide.
Intervention
Lacosamide replaced carbamazepine as adjunctive treatment to levetiracetam. The registry describes commercial 50 mg and 100 mg lacosamide tablets.
Comparator
There was no separate comparison group. The study was single-group and open-label; the change from baseline served as the reference for the endpoint.
Primary question
How did serum SHBG change between Day 1 (baseline) and Day 84 (treatment period end) after the switch in treatment?
The treatment period comprised a 4-week titration period and an 8-week maintenance period. The registry also lists changes in calculated free androgen index, free thyroxine, and total cholesterol as secondary outcomes. It does not report numerical results for these outcomes or the primary endpoint in the record summarized by the posted information. Accordingly, the study question can be described, but the magnitude and precision of any observed SHBG change cannot be assessed from the registry record.
3. Trial Design
This was a phase 3, multicenter, open-label, single-group study. It enrolled male subjects with partial-onset seizures and examined a treatment switch: carbamazepine was replaced with lacosamide, while levetiracetam remained unchanged. Because there was no parallel control group and treatment was not randomized, the design describes changes over time in the enrolled group rather than a randomized comparison between treatments.
The registry lists enrollment of 11 and a status of terminated. The primary completion date is 2013-03, and the study start is 2011-07. The primary endpoint description states that enrollment ended prematurely before the planned sample size of 28 subjects was achieved. It does not give the reason for termination, so no explanation for why enrollment stopped can be drawn from the registry record.
The primary endpoint was change in serum SHBG from Day 1 to Day 84, after a 4-week titration period and an 8-week maintenance period. The endpoint was specified as a median with full range and expressed in nmol/L. The safety set was defined as all subjects who received at least 1 dose of lacosamide. This definition identifies the population intended for the primary safety assessment, but the registry record does not provide the endpoint’s numerical results.
Open-label means treatment assignment was not masked to participants or study personnel. In a single-group study, changes from baseline may be described, but they cannot by themselves separate a treatment-associated change from other influences over time. The registry does not report a control condition, random assignment, or a detailed statistical analysis plan. The trial’s descriptive intent for the primary safety variable should therefore guide interpretation.
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 1-week Screening Period, a 12-week Treatment Period (comprised of a 4-week Titration Period and an 8-week Maintenance Period), and a Taper/Safety Follow-Up Period 3 to 4 weeks in duration.
Overall Study
| Stage | Lacosamide |
|---|---|
| STARTED | 11 |
| COMPLETED | 10 |
| NOT COMPLETED | 1 |
Reasons for not completing this period:
| Reason | Lacosamide |
|---|---|
| Adverse Event | 1 |
Analysis population for the primary outcome, as defined in the registry: The Analysis Population refers to the Safety Set (SS). The SS consists of all subjects who received at least 1 dose of Lacosamide.
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: The Baseline Analysis Population refers to the Safety Set (SS). The SS consists of all patients who received at least 1 dose of Lacosamide.
| Characteristic | Unit | Lacosamide |
|---|---|---|
| Participants analysed | 11 | |
| Age, Continuous | years | 31.5 (SD 5.9) |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 11 |
| Age, Categorical: >=65 years | Participants | 0 |
| Sex: Female, Male: Female | Participants | 0 |
| Sex: Female, Male: Male | Participants | 11 |
| Race/Ethnicity, Customized: American Indian or Alaska Native | participants | 1 |
| Race/Ethnicity, Customized: Asian | participants | 0 |
| Race/Ethnicity, Customized: Black or African American | participants | 0 |
| Race/Ethnicity, Customized: Native Hawaiin or other Pacific Islander | participants | 0 |
| Race/Ethnicity, Customized: White | participants | 9 |
| Race/Ethnicity, Customized: Other/Mixed | participants | 1 |
| Weight | kilograms | 82.81 (SD 16.25) |
| Height | centimeters | 178.05 (SD 10.14) |
| Body Mass Index | kilogram per square meter | 25.89 (SD 3.01) |
6. Primary Endpoint
The registry lists the primary outcome as Change in Serum Sex Hormone Binding Globulin (SHBG) From Baseline to Treatment Period End (Comprised of a 4-week Titration Period and an 8-week Maintenance Period), measured over From Day 1 (Baseline) to Day 84 (Treatment Period End).
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Full Range |
| Unit | nmol/L |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was change in serum sex hormone binding globulin (SHBG) from baseline to treatment period end. Measurements were taken from Day 1 to Day 84, with the treatment period comprising a 4-week titration period and an 8-week maintenance period. The endpoint was expressed in nmol/L and summarized using the median and full range. The registry states that a negative value indicates an improvement.
SHBG is a blood protein that binds sex hormones. In general, a measured change in SHBG can describe a change in a hormonal parameter during a treatment period; it does not, by itself, establish why that change occurred or what it means for an individual. The registry identifies this measure as a primary safety variable, but does not report numerical values for the baseline measurement, the treatment-period-end measurement, or the change between them. Thus, the direction, size, and spread of the observed change cannot be evaluated from the posted record.
The registry says the endpoint was assessed for descriptive purposes because enrollment terminated before the planned sample size of 28 subjects was achieved. This context matters: a descriptive endpoint can characterize the observations available, but the registry does not present a formal inferential result for SHBG. No confidence interval, p-value, or numerical median change is reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies a clinically specific question: whether serum SHBG changed between baseline and the end of treatment after carbamazepine was replaced by lacosamide while levetiracetam remained unchanged. It also specifies that the SHBG endpoint was summarized by a median and full range. However, the numerical primary outcome is not reported in the registry record. There is therefore no posted median change or range from which to describe the observed direction, magnitude, or variability of the endpoint.
The primary endpoint description notes that a negative value indicates an improvement. That statement explains the registry’s sign convention; it does not establish that a negative change occurred. Without the reported value, the endpoint cannot be classified as positive, negative, or unchanged. Nor can its precision be judged: the registry record does not provide a confidence interval or another numerical measure of uncertainty for the primary result.
The stated enrollment was 11, while the planned sample size was 28 subjects. The record says enrollment ended prematurely and that the primary safety variable was assessed descriptively. This limits what the study can establish, but it does not reveal why the study was terminated or how the planned sample size was selected. Those details are not reported in the registry record.
The design also constrains interpretation. With one open-label group and no separate control group, a before-and-after change would not isolate the effect of switching treatment from other changes occurring over the same period. The registry does not report randomized assignment or masking. Even if numerical before-and-after results were available, they would describe observations in this group rather than provide a randomized estimate of a difference between treatments.
The registry lists three secondary outcomes: calculated free androgen index, free thyroxine, and total cholesterol. It reports four outcome measures overall and no analysis entries. Numerical results for the primary and secondary outcomes are not reported in the registry record. The safety information does include event counts, but those counts should not be treated as a substitute for the missing hormonal and lipid endpoint results.
Any sample-size calculations associated with the posted analysis are planning illustrations, not observed power and not a reconstruction of the trial’s original design. The stated illustration assumptions use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Those assumptions do not match the study’s single-group design. The registry does not report a trial-specific statistical plan that would justify treating such planning figures as a formal analysis of this study.
9. Statistical Methods Explained
The registry identifies the primary endpoint as a change from baseline in serum SHBG and specifies a median and full range as its summary. These are descriptive statistics. The endpoint description also explicitly says it was assessed for descriptive purposes after enrollment ended before the planned sample size of 28 subjects was reached. The registry record contains no numerical primary outcome result or analysis entry, so it does not support a quantitative estimate of the observed change.
What does a median and full range describe?
In general, the median is the middle value when observations are ordered. It describes a central point without relying on the arithmetic mean, which can be more affected by unusually high or low observations. The full range describes the lowest and highest observed values. Together, these summaries can indicate the center and overall spread of a set of observations, but they do not show the detailed shape of the distribution. A range is also sensitive to extreme values and does not, by itself, quantify the precision of an estimated effect.
For this endpoint, the registry’s summary refers to SHBG change in nmol/L. The actual median and full range are not reported in the registry record. Therefore, these general properties of the summaries explain the intended presentation but cannot be used to infer the study’s results. The sign convention—negative values indicate an improvement—is stated in the endpoint description, but no observed change is given to interpret under that convention.
What does descriptive assessment mean?
In general, descriptive analysis organizes and characterizes the observations collected. It can report values, distributions, or counts without making a formal hypothesis test about a treatment effect. The registry specifically says the primary safety variable was assessed descriptively. It does not report a confidence interval, p-value, or formal inferential test for SHBG, and the number of analysis entries in the record is 0.
A confidence interval, in general, is a way to express statistical uncertainty around an estimate. Its width depends on the data and the method used. Because no confidence interval or primary estimate is reported, the precision of the SHBG change cannot be evaluated. This is different from saying that a change was absent: the registry record does not provide the numerical result needed to assess that claim.
How does the study design affect interpretation?
The study used one group and was open-label. In general, a change from baseline in a single group is a within-group description. Without a separate control group, the comparison cannot distinguish a change associated with the treatment switch from other influences that may occur over time. Open-label conduct means treatment was not masked, which can matter for outcomes influenced by awareness of treatment. The registry does not describe whether any safeguards or additional analyses addressed such issues.
The safety set consisted of all subjects who received at least 1 dose of lacosamide. This definition specifies who was included in the intended safety population. The registry does not report how many members of that set had evaluable SHBG measurements at each time point, how missing measurements were handled, or whether any other analysis populations were used. Those details are not reported in the registry record.
How should planning illustrations be read?
In general, sample-size calculations ask how many participants might be needed under stated assumptions to detect an effect with a chosen statistical operating characteristic. The assumptions stated for the planning illustration include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They are not the design of this single-group trial. The planning illustrations are hypothetical and should not be called observed power; they do not establish what the trial could detect from its actual data.
The registry does not report the original sample-size justification, any trial-specific statistical plan, or interim analyses. It states only that the planned sample size was 28 subjects and that enrollment terminated before reaching it. The available information does not explain the choice of that target or the consequences of early termination for any particular estimate.
What can the listed outcomes establish?
The registry identifies the primary SHBG endpoint and three secondary measures: calculated free androgen index, free thyroxine, and total cholesterol. The listed measures can indicate which hormonal and lipid changes the study intended to examine. They do not provide results on their own. Numerical outcome values and analyses are not reported in the registry record, so no direction, magnitude, statistical significance, or comparative effect can be inferred for these measures.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists four outcome measures overall: the primary SHBG change and secondary changes in calculated free androgen index, free thyroxine, and total cholesterol. It reports no analysis entries. The existence of several planned outcomes raises a general multiplicity question: when several outcomes are tested, the chance of at least one apparently unusual result can increase if each is assessed separately. Whether and how that concern was handled in this trial is not reported in the registry record. No adjustment procedure or hierarchy among secondary outcomes is described.
Missing-data handling is also not reported. The registry defines the safety set as all subjects who received at least 1 dose of lacosamide, but it does not state how many had measurements available at baseline and treatment period end for each endpoint. It does not describe imputation, exclusion rules for incomplete measurements, or a sensitivity analysis. The endpoint’s descriptive assessment does not, by itself, indicate how missing observations were treated.
The primary endpoint description says enrollment ended before the planned sample size of 28 subjects was achieved and that the variable was assessed for descriptive purposes. The reason for termination, the sample-size justification, the analysis plan, and any interim analyses are not reported in the registry record. Because numerical results and analysis details are absent, the extent to which missing observations or multiple outcomes affected the reported findings cannot be evaluated.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Lacosamide | 0 | 11 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Lacosamide | 5 of 11 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Lacosamide |
|---|---|---|
| Fatigue | General disorders | 1 of 11 |
| Bronchitis | Infections and infestations | 1 of 11 |
| Influenza | Infections and infestations | 1 of 11 |
| Convulsion | Nervous system disorders | 1 of 11 |
| Disturbance in attention | Nervous system disorders | 1 of 11 |
| Paraesthesia | Nervous system disorders | 1 of 11 |
| Partial seizures | Nervous system disorders | 1 of 11 |
| Tremor | Nervous system disorders | 1 of 11 |
| Aggression | Psychiatric disorders | 1 of 11 |
| Hot flush | Vascular disorders | 1 of 11 |
For the lacosamide group, the registry reports 0 subjects affected by serious adverse events among 11 at risk. It reports 5 subjects affected by other adverse events among 11 at risk. These are event-category counts for the group and safety information in the registry; they are not the SHBG endpoint results and do not describe a comparison with another treatment group.
The record lists no serious adverse event terms. The death count is not reported in the registry record. The serious-event count should be read as the count recorded for this study group, not as proof that serious events are impossible or that the treatment has a particular safety profile beyond these observations. The study was single-group, and the registry does not provide a control group for comparative safety interpretation.
Counts are also not a complete description of event burden. The registry information does not give event-level details for the other adverse events, their timing, severity, duration, or relationship to treatment. It therefore supports a limited description of how many subjects were recorded as affected in the listed categories, but not a broader assessment of the nature or comparative risk of adverse events.
12. What the Result Does, and Does Not, Mean
This record describes a study designed to observe hormonal and lipid parameters after male subjects with partial-onset seizures switched from carbamazepine to lacosamide while continuing levetiracetam. Its primary measure was serum SHBG change from Day 1 to Day 84. The study was terminated, and the registry states that enrollment stopped before the planned sample size of 28 subjects was reached. It also says the primary safety variable was assessed descriptively.
The record does not report the numerical SHBG result, so it cannot show whether the median change was negative, positive, or close to zero, nor how widely individual changes varied. The registry’s statement that a negative value indicates improvement describes the direction convention only. No conclusion about the endpoint’s magnitude or precision can be drawn without the observed value and its distribution.
The design does not provide a randomized treatment comparison. A single-group before-and-after description cannot determine whether any change was caused by the switch rather than by other influences over time. The open-label design and absence of a separate control group further limit comparative interpretation. The record does not report numerical results for the listed secondary hormonal and lipid outcomes either.
The safety counts describe the recorded adverse-event categories in the lacosamide group, but they do not establish comparative safety. The registry reports 0 subjects affected by serious adverse events and 5 affected by other adverse events, each among 11 at risk. The death count is not reported in the registry record, and no serious-event terms are listed.
Thus, the record documents the study question, design, endpoint definitions, and limited safety counts. It does not report the outcome data required to estimate the hormonal or lipid changes, judge their precision, or make a comparative treatment-effect claim.
13. Why This Trial Matters Statistically
The trial illustrates an important distinction between defining an outcome and reporting its result. The registry specifies a focused primary measure—change in serum SHBG from baseline to treatment period end—and gives its unit, summary type, time frame, and sign convention. Yet the numerical result itself is not reported in the registry record. An endpoint definition makes a study question interpretable, but it cannot substitute for the estimate needed to evaluate that question.
The study also shows why design information is essential when reading change-from-baseline results. In a single-group study, baseline provides a reference point, not a concurrent control. Any observed change would describe the participants over time; it would not by itself isolate the contribution of switching from carbamazepine to lacosamide. The open-label design adds further context for interpreting measured outcomes.
Early termination is another relevant feature. The registry states that enrollment ended before the planned sample size of 28 subjects and that the primary safety variable was assessed descriptively. This helps explain why the result was intended as a description, but does not provide the missing numerical outcome or explain why the trial ended. The reason for termination and the sample-size justification are not reported.
Finally, the registry lists several hormonal and lipid outcomes but no analysis entries or numerical results. That makes the distinction between planned measurement and available evidence especially clear. The record can support a careful account of what was intended and how the study was structured, while leaving the substantive outcome question unresolved.
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 primary limitation for interpreting the study is that the registry record does not report numerical results for SHBG, the primary endpoint. Although it specifies a median and full range, no values are given to establish the observed direction, magnitude, spread, or precision of the change. Numerical results for the secondary outcomes—calculated free androgen index, free thyroxine, and total cholesterol—are also not reported.
The study was single-group and open-label, with no separate randomized control group. Consequently, any within-group change would not distinguish treatment-related effects from other changes over time. The registry does not describe masking, random assignment, or a control condition. This limits causal and comparative interpretation even if outcome values were available.
Enrollment was 11, below the planned sample size of 28 subjects, and the registry says the trial was terminated before that target was reached. The reason for termination and the rationale for the target are not reported in the registry record. The primary variable was assessed descriptively, and no analysis entries are listed. A trial-specific statistical plan, interim analyses, multiplicity handling, and inferential results are not reported.
The registry defines the safety set but does not report endpoint-specific measurement availability or missing-data handling. The adverse-event information is limited to category counts; event details and the death count are not reported. These limitations restrict interpretation of both outcome estimates and safety information.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Hormonal and Lipid Levels in Male Subjects After a Switch From Carbamazepine to Lacosamide — NCT01375374.
- Registry record last updated 2017-08-28; status last verified 2017-07.
- Results first posted 2014-11-26.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
NCT01375374 is a phase 3, multicenter, open-label, single-group study in male subjects with partial-onset seizures. It examined a switch from carbamazepine to lacosamide while levetiracetam remained unchanged. Enrollment was 11, and the record lists the study as terminated. The primary completion date was 2013-03.
The primary endpoint was serum SHBG change from Day 1 to Day 84, summarized by median and full range in nmol/L. The treatment period included a 4-week titration period and an 8-week maintenance period. The registry states that the endpoint was assessed descriptively because enrollment ended before the planned sample size of 28 subjects. Numerical primary and secondary outcome results are not reported in the registry record.
The safety set included subjects who received at least 1 dose of lacosamide. The registry reports 0 subjects affected by serious adverse events and 5 affected by other adverse events, among 11 at risk in each category. The death count is not reported in the registry record.