A Phase 2b Study of Dalfampridine 10mg Extended Release Tablet in Subjects With Chronic Deficits After Ischemic Stroke: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Phase 2b Study of Dalfampridine 10mg Extended Release Tablet in Subjects With Chronic Deficits After Ischemic Stroke (NCT01605825), a randomized phase 2 study. The primary outcome is Safety and Tolerability of Dalfampridine-ER in Subjects With Chronic Deficits After Ischemic Stroke Assessed by Number of Treatment Emergent Adverse Events (TEAEs).

2. Clinical Question

The comparison is framed within a randomized, double-blind, two-period crossover design. Participants were assigned to treatment sequences, so the planned contrast concerns adverse events observed during periods with each treatment. A crossover design can allow observations under both treatments within the same participant, but interpretation depends on the period-specific data and the analysis used to account for the design.

The registry defines a treatment-emergent adverse event as an event that begins, or worsens, on or after double-blind treatment starts and through 7 days after the last dose. Events before treatment and after that window are excluded from the stated primary endpoint. The primary outcome timeframe is up to 36 days.

The posted information gives adverse-event counts by treatment, but does not report a primary endpoint comparison estimate or its uncertainty. It therefore describes observed safety counts without establishing the size or precision of a treatment contrast. The registry record does not report a hypothesis test or an adjusted analysis for the primary outcome.

3. Trial Design

The registry identifies this as a Phase 2 study, while the trial title calls it a Phase 2b study. It is described as randomized, double-blind, placebo-controlled, and crossover. The sponsor is Acorda Therapeutics. The trial status is completed.

The two treatment sequences are placebo/dalfampridine-ER and dalfampridine-ER/placebo. The arm descriptions state that participants were randomized at day 1 to one of two blinded sequences, A or B, in a 2:1 ratio, respectively. The descriptions do not identify which letter corresponds to which listed sequence. The periods are specified as days 1, 8, and 15 for Period 1, and days 22, 29, and 36 for Period 2.

In a crossover study, participants move through treatment periods according to their assigned sequence. This differs from a parallel-group design, in which participants generally remain in one assigned treatment group. A within-participant comparison may account for stable differences between participants, but it also makes period, sequence, and possible carryover effects relevant to interpretation. Those are general design considerations; the registry record does not report how they were addressed in the analysis.

The registry records enrollment of 83. It does not report the number who completed each period, the number contributing data to each treatment-specific safety count, or the handling of participants who discontinued or had incomplete follow-up. The washout arrangements, if any, are not reported in the registry record.

The study description calls the trial multi-center and says it was designed to assess safety and tolerability in subjects with chronic stable sensorimotor deficits after ischemic stroke. The listed intervention sequences and period schedule establish the broad design, but details such as treatment duration per dose, adherence, and site-level procedures 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety population. Number of participants analyzed is number of patients with TEAE's as described in outcome measure description. Excludes pre-treatment and post-treatment adverse events.

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: Safety Population: The Safety Population consists of all randomized subjects who took at least one dose of investigational product.

6. Primary Endpoint

The registry lists the primary outcome as Safety and Tolerability of Dalfampridine-ER in Subjects With Chronic Deficits After Ischemic Stroke Assessed by Number of Treatment Emergent Adverse Events (TEAEs), measured over up to 36 days.

The primary endpoint is the number of participants with treatment-emergent adverse events (TEAEs). The registry defines a TEAE as any adverse event whose onset, or worsening, occurs on or after the start of double-blind treatment and through 7 days after the last dose of double-blind treatment. Events before treatment and after treatment are excluded by the stated definition. The timeframe is up to 36 days.

This endpoint is used to describe tolerability and safety during exposure. Counting participants with at least one event gives a participant-level summary: it indicates whether an event occurred, rather than how many repeated events each participant experienced. The registry also defines mild, moderate, and severe categories in terms of limitation of usual activities, but the posted primary outcome description does not give a treatment comparison across those severity categories.

The safety population description states that the number of participants analyzed is the number of patients with TEAEs, as described in the outcome measure, and excludes pre-treatment and post-treatment adverse events. The registry record does not report a primary endpoint estimate or uncertainty interval. It also does not report how a participant with events in both treatment periods was handled in a treatment-specific comparison.

As a general statistical point, a count of participants with at least one event is useful for communicating how often an event was observed, but it does not capture event duration, recurrence, or severity unless those are analyzed separately. The registry identifies eight outcome measures overall, but the primary outcome details do not reduce the endpoint to a single comparative result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count represent?

The primary outcome uses a count of participants with at least one TEAE. A participant-level count differs from a count of all event episodes: if one participant experiences repeated events, a participant-level summary still counts that participant as having an event. This can make the result easier to interpret as a safety summary, but it does not describe recurrence or total event burden. Those require additional outcomes or analyses, which are not detailed for the primary endpoint in the registry record.

The registry defines the event window relative to double-blind treatment: onset or worsening on or after treatment begins through 7 days after the last dose. Defining a window is important because adverse events outside it are not included in the primary endpoint as described. The stated timeframe is up to 36 days. How follow-up within that window was handled for participants who stopped treatment early is not reported in the registry record.

Why does the crossover design matter?

In a crossover design, treatment sequence and treatment period are distinct. The sequence indicates the order in which treatments are received; the period indicates when a treatment is received. A participant’s outcome under one treatment may be compared with that participant’s outcome under the other, which can reduce the influence of stable differences between people. This is a general feature of crossover comparisons, not a claim about the analysis performed in this trial.

However, treatment periods may differ for reasons other than treatment. General concerns include period effects, sequence effects, and carryover, where effects from an earlier treatment may persist into a later period. The registry lists the sequence options and days for the two periods, but does not report whether there was a washout period or how period, sequence, or carryover were assessed statistically. The registry record does not report a model specification for the crossover analysis.

What can denominators tell readers?

The adverse-event entries include a number at risk for each treatment and counts of participants with events. A denominator gives context for a count, but those entries alone do not explain exposure duration, completeness of observation, or whether each participant contributed to both treatment groups. The record does not state how the treatment-specific denominators relate to period completion or missing observations.

For a paired crossover analysis, the relationship between a participant’s outcomes under the two treatments can matter. Separate treatment totals do not show how many participants had events on both treatments, on only one, or on neither. Without that pairing information and the analysis method, an independent-group comparison would not be justified as a substitute for the trial’s own analysis.

How should uncertainty be understood?

In general, a confidence interval describes a range of values compatible with the data under a specified statistical method and model. A narrow interval indicates greater precision than a wide one, while an interval that includes values representing no difference can indicate that the data do not distinguish a contrast from no difference at the chosen confidence level. These are general explanations; the registry record does not report a confidence interval for the primary comparison.

A hypothesis test and its p-value also depend on the analysis method and assumptions. The registry record lists no analyses for the outcome and does not report a p-value for the primary endpoint. Consequently, no inferential conclusion should be attached to the adverse-event totals alone. The sponsor’s analysis, if reported elsewhere, is not included in the registry record.

What do the planning assumptions mean?

The registry includes a description of a sample-size planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes planning for specified fractions of the observed effect. Such calculations concern hypothetical future-study requirements under stated assumptions; they are not observed power and do not demonstrate that the present trial was adequately powered.

The trial itself is a crossover study, while the planning description refers to equal allocation between two arms. The registry record does not explain how that planning illustration maps to the crossover structure or identify a protocol-based sample-size justification. The planned effect, variance assumptions, and original design calculation are not reported in the registry record. No sample-size illustration can replace the study’s observed estimates and their uncertainty.

More generally, statistical methods should be matched to the design, endpoint, and missingness pattern. The outcome definition, sequence structure, and treatment-specific counts are available, but the registry record does not report the detailed statistical plan, model, multiplicity procedure, interim analyses, or missing-data method. Their absence limits how fully readers can reconstruct the intended inferential analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry identifies eight outcome measures, and it notes that the primary outcome has several categories or time points and is not reduced to one comparison. The number of analyses listed is 0. A multiplicity adjustment, hierarchy among outcomes, or other strategy for controlling false-positive findings is not reported in the registry record. Without that information, the relationship between the primary endpoint and other outcomes cannot be assessed as part of a testing strategy.

The registry’s safety population description specifies participants with TEAEs and excludes pre-treatment and post-treatment events. It does not report how missing observations, incomplete treatment periods, withdrawals, or participants without complete safety follow-up were handled. The number of participants contributing to each treatment-specific analysis is not described beyond the adverse-event denominators.

In general, missingness matters when the probability of an unobserved outcome is related to treatment or safety. Excluding people with incomplete observation can change the composition of the analyzed group; treating missing outcomes as event-free can also misrepresent risk. These are general concerns, not claims about what happened in this trial.

The registry record does not report whether an intention-to-treat principle was used, whether all randomized participants were included in safety analyses, or how crossover-specific incomplete data were treated. It also does not report interim analyses or stopping rules. These omissions limit assessment of potential selection effects and the precision and robustness of the safety comparison.

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 1.3% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: convulsion (2.6%), microcytic anaemia (1.3%), intentional overdose (1.3%), suicide attempt (1.3%), nausea (1.2%).

The registry reports serious adverse events for placebo as 2 participants among 81 at risk, and for dalfampridine-ER as 2 participants among 77 at risk. For other adverse events, it reports 30 participants among 81 at risk for placebo and 42 among 77 at risk for dalfampridine-ER. These figures are descriptive treatment-specific entries, not adjusted comparisons.

The serious-event terms listed include Convulsion, Microcytic anaemia, Intentional overdose, Suicide attempt, Nausea, and Vomiting, with percentages of 2.6%, 1.3%, 1.3%, 1.3%, 1.2%, and 1.2%, respectively. The registry does not report treatment assignment for these term-specific percentages in the listed information, so they should not be attributed to either treatment.

In a crossover study, treatment-specific denominators may reflect observations across periods rather than separate parallel groups. The registry does not explain participant overlap between the treatment entries or how exposure and incomplete follow-up were handled. The counts should therefore be read as reported safety summaries, not as a stand-alone estimate of comparative risk. No deaths are listed for either treatment group.

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

The registry record describes a randomized, double-blind, placebo-controlled crossover study of dalfampridine-ER in subjects with chronic deficits after ischemic stroke. Its primary outcome is a participant count for treatment-emergent adverse events, defined by an explicit treatment-related observation window. The posted adverse-event counts provide a descriptive account for placebo and dalfampridine-ER, including serious and other event counts.

These data do not, on their own, establish whether one treatment has a higher or lower event burden. The record does not provide a primary comparative estimate, confidence interval, or p-value. Counts from a crossover study require attention to the paired nature of participants’ observations and to treatment period and sequence. The posted totals do not reveal the within-participant pattern or the method used to address those features.

The record also does not provide enough information to judge the precision of the primary treatment contrast, the effects of incomplete follow-up, or how the safety summaries relate to the full randomized population. The listed serious-event term percentages are not assigned to treatment groups in the reported information. They should not be treated as comparative rates.

As a general statistical principle, absence of a reported statistical comparison is not evidence that treatments are equivalent, and a difference in raw counts is not by itself evidence of a treatment effect. Interpretation depends on the outcome definition, observation time, analysis population, and design-appropriate analysis. The registry record supports describing the reported safety counts and their definitions, but it does not support a definitive claim about comparative safety or clinical benefit.

This is a safety and tolerability study in a specified population. The registry information does not establish how results would apply to other populations, longer observation periods, or outcomes not reported in the record. It also does not provide medical guidance for individuals.

13. Why This Trial Matters Statistically

This trial is statistically notable for using a crossover design to study safety and tolerability. In such a design, the treatment order and period can affect the interpretation of observed outcomes. Reporting treatment-specific counts is useful, but transparent description of pairing, exposure, period effects, and missing observations is important for understanding a comparative result.

The registry supplies an operational definition of TEAE, including the onset or worsening window and exclusion of pre-treatment and post-treatment events. Clear endpoint definitions matter because they specify which observations enter the outcome and make the scope of a safety summary more interpretable. The severity descriptions also distinguish levels of limitation in usual activities, although the primary outcome listing does not provide a single comparative result across categories or time points.

The record illustrates the difference between a descriptive safety summary and an inferential analysis. Counts can show how many participants were recorded with events in each treatment entry. A comparative conclusion additionally requires an analysis that reflects the randomized crossover structure and quantifies uncertainty. The registry record does not report that primary comparison, its model, or its precision.

The distinction between planning calculations and observed results is also important. Sample-size illustrations based on an observed effect are hypothetical planning tools, not observed power or evidence that an analysis is conclusive. The registry does not report a protocol-based sample-size justification for this crossover design.

For clinical researchers, the record therefore highlights the value of complete reporting: treatment-specific exposure, period-level results, paired outcome patterns, missing-data handling, and design-appropriate estimates with uncertainty. Without those details, readers can describe the reported counts but cannot fully evaluate the strength of a comparative safety inference.

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 registry record does not report a primary treatment-comparison estimate, confidence interval, or p-value. It notes that the primary outcome has several categories or time points and is not reduced to one comparison. As a result, the magnitude and precision of a primary contrast cannot be evaluated from the registry entries.

The crossover design creates specific interpretive needs, but the registry record does not report the statistical model, handling of period or sequence effects, assessment of carryover, or washout arrangements. The arm descriptions give the sequence names and period days but do not identify which sequence corresponds to each lettered assignment.

Although treatment-specific adverse-event counts and denominators are listed, the record does not explain participant overlap between treatment entries, treatment-specific exposure duration, or how incomplete periods and missing follow-up were handled. The safety population description focuses on participants with TEAEs; the relationship between that wording and the treatment-specific denominators is not further clarified.

The listed serious-event terms and percentages are not assigned to a treatment group in the reported information. Their treatment-specific interpretation is therefore limited. The record also does not report a multiplicity strategy, interim analyses, or a protocol-based sample-size justification. These omissions limit reconstruction of the planned statistical analysis and assessment of the robustness of the safety findings.

Finally, the registry record describes a study in subjects with chronic stable sensorimotor deficits after ischemic stroke, with a timeframe of up to 36 days for the primary outcome. It does not establish the relevance of the reported safety summaries to other populations or longer periods of observation.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Phase 2b Study of Dalfampridine 10mg Extended Release Tablet in Subjects With Chronic Deficits After Ischemic Stroke — NCT01605825.
• Registry record last updated 2016-01-22; status last verified 2015-12.
• Results first posted 2014-03-10.
• 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

NCT01605825 is a completed randomized, double-blind, placebo-controlled crossover study sponsored by Acorda Therapeutics. The registry categorizes it as Phase 2; the title calls it Phase 2b. It concerns dalfampridine-ER in subjects with chronic deficits after ischemic stroke and records enrollment of 83.

The two sequences are placebo/dalfampridine-ER and dalfampridine-ER/placebo. Period 1 is specified as days 1, 8, and 15; Period 2 as days 22, 29, and 36. The primary endpoint is the number of participants with treatment-emergent adverse events, with a timeframe of up to 36 days.

The registry reports serious and other adverse-event counts by treatment, but does not report a primary comparative estimate or its uncertainty. Detailed analysis methods, missing-data handling, and crossover-specific modeling are not reported in the registry record.