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 A Phase 3 Study of Amifampridine Phosphate in Patients With Lambert Eaton Myasthenic Syndrome (LEMS) (NCT01377922), a randomized phase 3 study. The primary outcome is Change From Baseline Quantitative Myasthenia Gravis (QMG) at 14 Days.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01377922 |
| Phase | Phase 3 |
| Condition | Lambert Eaton Myasthenic Syndrome |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 38 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Catalyst Pharmaceuticals, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
Patients with Lambert-Eaton myasthenic syndrome (LEMS) were eligible for this phase 3 study. The registry record lists enrollment of 38 participants. Further eligibility details and characteristics of the enrolled population are not reported in the registry record.
Intervention
Amifampridine phosphate was described at 30-80 mg, given 3-4 times per day, with a maximum single dose of 20 mg (2 x 10 mg tablets), for 2 weeks. The description says dosing was individualized to the patient.
Comparator
The comparator was matching placebo tablets administered 3-4 times a day, matched to the individual patient's tablet count of active treatment at baseline, over 2 weeks.
Primary question
The primary endpoint was change from baseline in the Quantitative Myasthenia Gravis (QMG) score at 14 days. The registry record does not report the outcome values or an estimate of the difference between treatment groups, so the primary efficacy comparison cannot be evaluated from the record.
3. Trial Design
This was a phase 3 randomized, double-blind, parallel study sponsored by Catalyst Pharmaceuticals, Inc. The official title describes a placebo-controlled randomized discontinuation study followed by an open-label extension. The registry lists 38 participants enrolled and a completed status. The study start is recorded as 2011-06 and primary completion as 2016-07.
The intervention descriptions specify a 2-week period for amifampridine phosphate and matching placebo. Active treatment is described as 30-80 mg given 3-4 times per day, with a maximum single dose of 20 mg (2 x 10 mg tablets). Placebo tablets were administered 3-4 times daily to match the individual patient's baseline active-treatment tablet count. Those descriptions give the intended regimens; the registry record does not report adherence, dose changes, or the extent to which participants followed them.
The randomized, double-blind, parallel design identifies the broad comparison structure, but it does not by itself establish the details of treatment assignment, concealment, or analysis. Further information about the randomization procedure and allocation ratio is not reported in the registry record. Equal allocation is an assumption used for a planning illustration, not a documented description of the trial's actual allocation.
The title indicates a discontinuation study and an open-label extension. The registry record does not report enough detail to reconstruct the sequence of study parts, the criteria or procedures for discontinuation, or the extension's treatment and follow-up arrangements. Safety results are labeled for Part 2 and Part 3, but the record does not define those parts in sufficient detail to infer more about their conduct.
The listed secondary outcomes are change from baseline in the Timed 25 Foot Walking Test (T25FW) at 14 days and change in the CGI-I score. Although the registry lists four outcome measures and four analyses, the additional outcome details and results are not reported in the registry record. A phase designation and completed status describe the trial's registration, not the findings of its efficacy analyses.
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: Open-label Run-in (Part 1): titration to the optimal amifampridine dose (well tolerated and resulted in a ≥3 point improvement in QMG score from Screening for patients without previous amifampridine use) for each individual patient. Patients who did not receive amifampridine prior to Run-in and who did not reach the optimal dose were discontinued.
Overall Study
| Stage | Part 2 and Part 3 Placebo | Part 2 and Part 3 Amifampridine Phosphate |
|---|---|---|
| STARTED | 22 | 16 |
| COMPLETED | 21 | 16 |
| NOT COMPLETED | 1 | 0 |
Reasons for not completing this period:
| Reason | Part 2 and Part 3 Placebo | Part 2 and Part 3 Amifampridine Phosphate |
|---|---|---|
| rescue tx after part 2, entered part 4 | 1 | 0 |
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.
| Characteristic | Unit | Part 2 and Part 3 Placebo | Part 2 and Part 3 Amifampridine Phosphate | Total |
|---|---|---|---|---|
| Participants analysed | 22 | 16 | 38 | |
| Age, Continuous | years | 51.5 (SD 17.57) | 51.6 (SD 12.05) | 51.5 (SD 15.30) |
| Sex: Female, Male: Female | Participants | 14 | 9 | 23 |
| Sex: Female, Male: Male | Participants | 8 | 7 | 15 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 3 | 3 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 22 | 12 | 34 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 1 | 1 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): White | Participants | 21 | 13 | 34 |
| Race (NIH/OMB): More than one race | Participants | 0 | 2 | 2 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 1 | 1 | 2 |
| Was the patient taking amifampridine (base or phosphate) immediately prior to enrollment?: Yes | Participants | 7 | 3 | 10 |
| Was the patient taking amifampridine (base or phosphate) immediately prior to enrollment?: No | Participants | 15 | 13 | 28 |
| If yes, number of continuous days of amifampridine exposure immediately prior to enrollment | days | 1287.1 (SD 1525.73) | 2143.3 (SD 3080.16) | 1544.0 (SD 1957.36) |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline Quantitative Myasthenia Gravis (QMG) at 14 Days, measured over Assessment at Baseline and Day 14.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | QMG Score |
| Endpoint classification | Continuous Endpoint |
The primary endpoint was change from baseline in the Quantitative Myasthenia Gravis (QMG) score at 14 days. The QMG is a physician-rated assessment made up of 13 items, including facial strength, swallowing, grip strength, and the duration for which limbs can be maintained in outstretched positions. Each item is scored from 0 (none) to 3 (severe), and the total score ranges from 0 to 39. An increased total score correlates with worsening LEMS symptoms.
A change-from-baseline endpoint describes how a participant's score at follow-up differs from that participant's starting score. Comparing changes between randomized groups can help distinguish changes associated with the assigned study regimens from changes occurring over time in both groups. That is a general explanation of the endpoint's role; the registry record does not report the group results or the method used to compare them.
The QMG offers a structured, clinician-rated way to assess several aspects of strength and function rather than relying on a single task. Its inclusion as the primary endpoint makes it the central efficacy question registered for the study. The score's direction is important for interpretation: higher totals correspond to greater symptom severity. However, without group-specific changes, their variability, and an estimated treatment contrast, no conclusion about the direction or precision of the trial's primary comparison can be drawn from the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies the primary efficacy outcome but does not report its results. In particular, it gives no QMG change estimates by group, no estimate of the between-group contrast, and no confidence interval or p-value for that comparison. As a result, the central statistical question—how the QMG change differed between amifampridine phosphate and placebo over the registered assessment period—cannot be answered from the record.
This absence matters because the endpoint description alone says what was measured, not what happened. Knowing that a measure ranges from 0 to 39 and that increased scores correlate with worsening symptoms does not reveal whether either group changed, how variable those changes were, or how compatible the data are with different treatment effects. The record's completed status likewise does not indicate the direction, magnitude, or statistical precision of an efficacy result.
The registry lists secondary outcomes involving the Timed 25 Foot Walking Test at 14 days and change in CGI-I score. Their numerical results and analysis details are not reported in the registry record. It would therefore be inappropriate to infer secondary findings from the endpoint names or the study's design. The record also lists four outcome measures and four analyses without furnishing the corresponding results needed to interpret them.
The selected safety counts are more informative than the efficacy record in a limited descriptive sense. In the groups labeled Part 2 and Part 3, the serious-event counts are 0 of 22 for placebo and 0 of 16 for amifampridine phosphate. The record separately lists 6 of 21 and 3 of 16 for other adverse events. These counts refer to the listed safety groups and should not be treated as evidence of a difference in risk without fuller information about event definitions, observation periods, and analysis.
Statistical interpretation requires more than a study label, an endpoint definition, or counts without context. Estimates and their uncertainty are needed to understand how much the observed data support a range of possible effects. Because those primary efficacy statistics are not reported in the registry record, neither a claim of benefit nor a claim of no effect is justified by this record. The appropriate reading is that the trial's registered primary question is clear, while its answer is unavailable in the reported results.
9. Statistical Methods Explained
What does the endpoint's summary measure mean?
The primary endpoint is classified as continuous and its stated summary parameter is a mean, with standard deviation as the stated measure of dispersion. In general, a mean gives a central summary of measured values, while a standard deviation describes how spread out participant values are around that mean. These summaries can characterize a group's QMG changes, but they do not on their own describe the uncertainty in a between-group comparison.
A treatment comparison for a continuous outcome commonly focuses on a contrast between groups. In general, an estimate of that contrast conveys the size and direction of the observed difference, while a confidence interval conveys the range of values reasonably compatible with the data under the analysis assumptions. A narrower interval indicates greater precision than a wider interval. These are general statistical explanations; the registry record does not report a QMG contrast, confidence interval, or p-value.
Why does randomization matter?
In general, random assignment aims to make treatment groups comparable with respect to both measured and unmeasured characteristics, on average. A blinded comparison can also reduce some opportunities for expectations to influence treatment, assessment, or reporting. Those design features support a fair comparison when they are implemented as intended, but they do not guarantee that every possible source of bias is eliminated.
The record identifies the study as randomized, double-blind, and parallel. It does not report the sequence-generation procedure, allocation concealment details, who was masked, or whether masking was maintained. It also does not report the actual group sizes for the primary efficacy analysis. The listed enrollment count should not be substituted for analysis-specific denominators.
How should variability and uncertainty be considered?
For a continuous endpoint, variability among participants affects how precisely a group mean or treatment contrast can be estimated. A standard deviation describes participant-level spread; a standard error, when reported, describes the estimated precision of a statistic. A confidence interval combines an estimate and its uncertainty. It helps readers assess whether the data are compatible with effects of differing size and direction, rather than reducing interpretation to a yes-or-no significance label.
These distinctions are general. The record names standard deviation as the dispersion measure for the primary endpoint but does not provide the observed values. It does not report a standard error, confidence interval, or a complete inferential analysis for the primary comparison. No recalculated result can be presented without the underlying group summaries, and no registry efficacy result is available to check against a recalculation.
What do the planning assumptions say?
The registry's sample-size assumptions describe a planning illustration computed from an observed effect, not the trial's own design justification. The illustration uses a two-sided significance level of 0.05, equal allocation between groups, and a normal approximation; its target effect is a stated fraction of the observed effect. For non-time-to-event outcomes, such illustrations are expressed as participants per arm for a specified power level. The actual planning values and observed effect used for the illustration are not reported in the registry record.
Such sample-size illustrations answer a conditional question: under stated assumptions, what sample size would be associated with detecting an effect of the chosen size at a chosen power? They do not state the probability that the trial's result is true, and they are not observed power. When the target effect is tied to an observed effect, the illustration also depends on that estimate, which can itself be uncertain. These are general considerations, not claims about how the sponsor planned or analyzed this trial.
Over-dispersion is a general concern when outcome variation exceeds what a chosen statistical model assumes. If a model understates variability, its uncertainty estimates may be too small and its confidence intervals too narrow. The registry record does not identify a model for the primary analysis or provide data with which to assess over-dispersion. It would therefore be speculative to say whether this issue arose or how it was handled.
What can and cannot be inferred from the safety summaries?
Counts of participants with events are descriptive summaries. In general, an event count should be read alongside its denominator, event definition, observation period, and the way repeat events are handled. A count of participants affected is not the same as a count of all event episodes. Small group counts can also leave substantial uncertainty about the underlying event frequency, even when the observed count is zero.
The registry reports serious events and other adverse events with separate at-risk denominators. It does not report exposure-adjusted rates, event timing, severity detail beyond the serious classification, or inferential comparisons for these counts. The safety information should therefore be read as a limited account of what was recorded for the named groups, not as a complete safety analysis.
More broadly, the registry record does not report the statistical analysis plan, the primary analysis population, missing-data procedures, or interim-analysis arrangements. Those omissions prevent a detailed audit of model choice and analysis conduct. General statistical principles can explain what such methods would address, but they cannot establish which procedures were used in this study.
10. Multiplicity, Missing Data and Analysis Populations
Multiplicity arises when an analysis examines more than one outcome, comparison, or time point. In general, the more statistical tests considered, the greater the chance that at least one result will appear noteworthy by chance if each test is interpreted without accounting for the others. Approaches to multiplicity can define a primary testing sequence, adjust significance thresholds, or emphasize estimation and uncertainty across all outcomes. The registry record does not report a multiplicity strategy, so it is not possible to determine whether or how the listed outcomes and analyses were handled together.
The record identifies the QMG change at 14 days as the primary outcome and lists secondary outcomes for T25FW at 14 days and change in CGI-I score. It also indicates that there are multiple outcome measures and analyses, but does not provide their full results or analysis specifications. The primary endpoint's designation does not establish whether secondary comparisons were confirmatory, exploratory, adjusted, or interpreted under a prespecified hierarchy.
Missing-data handling is also not reported in the registry record. The number of participants with observed primary endpoint data, reasons for missing assessments, and methods used to handle missing values are not reported. In general, missing-data methods rely on assumptions about why measurements are absent; different assumptions can lead to different estimates. Without the missingness information and analysis details, the effect of absent data on the result cannot be assessed.
The analysis populations are not reported in the registry record. It is therefore not possible to determine whether the primary comparison included all randomized participants, only participants who completed a specified treatment period, or another defined group. The registry's enrollment count is not enough to reconstruct these populations or their endpoint denominators. Interim analyses and any associated decision rules are also not reported in the registry record.
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 |
|---|---|---|---|
| Part 2 and Part 3 Placebo | 0 | 22 | 0.0% |
| Part 2 and Part 3 Amifampridine Phosphate | 0 | 16 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Part 2 and Part 3 Placebo | 0 of 22 |
| Part 2 and Part 3 Amifampridine Phosphate | 0 of 16 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Part 2 and Part 3 Placebo | 6 of 21 |
| Part 2 and Part 3 Amifampridine Phosphate | 3 of 16 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Part 2 and Part 3 Placebo | Part 2 and Part 3 Amifampridine Phosphate |
|---|---|---|---|
| Asthenia | General disorders | 2 of 21 | 0 of 16 |
| Fatigue | General disorders | 1 of 21 | 1 of 16 |
| Nasopharyngitis | Infections and infestations | 0 of 21 | 1 of 16 |
| Otitis externa | Infections and infestations | 0 of 21 | 1 of 16 |
| Periodontitis | Infections and infestations | 1 of 21 | 0 of 16 |
| Pulpitis dental | Infections and infestations | 1 of 21 | 0 of 16 |
| Urinary tract infection | Infections and infestations | 0 of 21 | 1 of 16 |
| Muscular weakness | Musculoskeletal and connective tissue disorders | 1 of 21 | 0 of 16 |
| Sensation of heaviness | Musculoskeletal and connective tissue disorders | 1 of 21 | 0 of 16 |
| Blood creatine phosphokinase increased | Investigations | 1 of 21 | 0 of 16 |
The registry lists serious adverse event counts for groups labeled Part 2 and Part 3. For placebo, 0 of 22 participants at risk had a serious adverse event; for amifampridine phosphate, 0 of 16 participants at risk had one. Deaths are listed as 0 in both groups. These are observed counts in the named groups, not proof that the underlying risk is zero.
The separate other-adverse-event counts are 6 of 21 for placebo and 3 of 16 for amifampridine phosphate. The at-risk denominators differ between this category and the serious-event category for the placebo group. These figures should be read with their own denominators rather than assuming a common denominator across categories.
In general, a zero count can occur even when the true event risk is not zero, particularly when the amount of observed information is limited. Counts also do not convey when events occurred, how long participants were followed, whether an event led to treatment changes, or whether participants experienced more than one event. Those details are not reported in the registry record. The figures are descriptive and do not establish a comparative safety effect.
12. What the Result Does, and Does Not, Mean
The trial record establishes a registered comparison of amifampridine phosphate with matching placebo in patients with LEMS, with change in QMG score at 14 days named as the primary endpoint. It also records a phase 3 randomized, double-blind, parallel design and lists safety counts for groups identified as Part 2 and Part 3. These features describe the question and some elements of the study conduct.
The record does not establish what the primary efficacy result was. No group-specific QMG changes, treatment contrast, confidence interval, or p-value are reported. Consequently, it cannot show how large or precise any difference was, or whether the data were compatible with a range of effects. Neither the study's completion nor its phase supplies a substitute for those results.
The limited safety counts likewise do not establish that the treatments had identical risks or that one had a lower risk. They describe the numbers recorded in the specified groups, with different denominators for the serious and other adverse-event categories. Without fuller information about follow-up, exposure, event definitions, and uncertainty, a comparative interpretation would exceed what the registry record supports.
In general, a trial's finding should be interpreted in light of its estimate, uncertainty, analysis population, missing data, and prespecified methods. Here, several of those elements are not reported in the registry record. This does not demonstrate that the study had no result or that no analyses were conducted; it means those results and details cannot be evaluated from the record described. The appropriate conclusion is limited: the registered primary question and broad design are identifiable, while the efficacy answer and important analysis details remain unreported.
13. Why This Trial Matters Statistically
This trial is statistically notable as a randomized, double-blind comparison with a defined continuous primary endpoint and a short assessment timeframe. The QMG score combines physician-rated assessments across several aspects of strength and function, and its direction has a stated clinical interpretation: increased totals correlate with worsening LEMS symptoms. Those details make the endpoint's intended meaning understandable.
At the same time, the record illustrates why a clear endpoint description is not equivalent to a reportable result. To assess an efficacy comparison, readers need the group summaries and an estimate of the contrast, together with information about uncertainty and analysis. Those primary results are not reported in the registry record. Statistical interpretation is therefore constrained regardless of the trial's phase, design label, or completion status.
The listed safety counts also show why denominators and outcome definitions matter. Serious and other adverse events are reported separately, and the at-risk denominators are not identical across those categories. Presenting counts without fuller follow-up and analytic context limits comparisons. This is a general lesson in reading registry results, not evidence of a particular treatment effect in this study.
The registry also names a randomized discontinuation design followed by an open-label extension. Such design language signals that the full study structure may involve more than a straightforward parallel comparison, but the record does not describe the procedures in enough detail to reconstruct them. The statistical value of this trial for readers thus depends not only on its registered question but also on the availability of results and methods that are not reported in the registry record.
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 interpretation is that the registry record does not report the primary QMG outcome results. No group means, standard deviations, treatment contrast, confidence interval, or p-value are available. Without those statistics, the primary comparison's size, direction, and precision cannot be assessed.
Other outcome results are also absent. Although the record names T25FW and CGI-I secondary outcomes and lists four outcome measures and four analyses, it does not provide sufficient results or analysis details to evaluate them. The registry's summary fields therefore do not permit a full account of the efficacy findings.
Information needed to assess analysis conduct is not reported in the registry record. This includes the primary analysis population, endpoint denominators, missing-data procedures, multiplicity approach, and interim-analysis arrangements. Details about random-sequence generation, allocation concealment, maintenance of masking, adherence, and actual dose changes are also not reported. The record does not provide the eligibility criteria or a fuller description of participant characteristics, limiting assessment of who entered the study.
The official title describes a randomized discontinuation study followed by an open-label extension, but the registry does not give enough procedural detail to reconstruct those phases or their relationship to the registered endpoint. Safety summaries are limited to counts and at-risk denominators for named groups; event timing, exposure, severity detail, and comparative analyses are not reported. These limitations restrict interpretation of both efficacy and safety, and they should not be filled by assumptions about the protocol or analysis.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Phase 3 Study of Amifampridine Phosphate in Patients With Lambert Eaton Myasthenic Syndrome (LEMS) — NCT01377922.
- Registry record last updated 2018-01-04; status last verified 2018-01.
- Results first posted 2018-01-04.
- 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
The registry record describes NCT01377922, a phase 3 randomized, double-blind, parallel study of amifampridine phosphate and placebo in patients with Lambert-Eaton myasthenic syndrome. Enrollment is listed as 38, the sponsor as Catalyst Pharmaceuticals, Inc., and study status as completed. The recorded study start is 2011-06 and primary completion is 2016-07.
The primary endpoint was change from baseline in QMG score at 14 days. The record provides the endpoint definition but not its results. It lists secondary outcomes for T25FW and CGI-I, without reporting their results. Safety counts are reported for Part 2 and Part 3 groups, including serious adverse events, other adverse events, and deaths.
Overall, the design and intended primary question can be described, but the registry record does not report the efficacy estimates or key analysis details needed to judge the primary comparison. Its safety figures are limited descriptive counts and do not establish a comparative effect.