Open-Label Pilot Study of Lisdexamfetamine for Cocaine Dependence: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Open-Label Pilot Study of Lisdexamfetamine for Cocaine Dependence (NCT01486810), a na phase 1, phase 2 study. The primary outcome is Number of Participants Maintained on the Maximum Lisdexamfetamine Daily Dose..

2. Clinical Question

In practical terms, the study sought preliminary information about participants’ ability to reach and remain on the protocol’s maximum dose under open-label conditions. The registry summary describes broader aims of obtaining preliminary data about safety, tolerability, and potential utility, and determining an effective dosage range. Those aims should not be confused with the primary endpoint itself: the endpoint is a count of participants meeting a specified dose-maintenance condition.

Because the study has no concurrent comparator, any observed change during participation would not by itself distinguish an intervention effect from other explanations. The registry record does not report a primary outcome count, an estimate of treatment effect, or an analysis comparing outcomes with a control condition.

3. Trial Design

This is an open-label pilot study listed as Phase 1 and Phase 2. The registry record describes a single-group model, no masking, and no allocation to treatment groups. The sponsor is the New York State Psychiatric Institute. The record lists the study as completed, with a start date of 2011-12 and primary completion of 2013-12.

The record reports 17 participants enrolled. Its primary outcome description states that 16 participants were analyzed because one participant was lost to follow-up without any post-enrollment study data. The brief summary says investigators planned to enroll 12 patients in an eight-week open-label trial. The record’s arm description separately describes titration over two weeks followed by maintenance for four weeks. These are descriptions of the planned study and intervention; the registry does not report a complete account of the timing of each participant’s actual exposure.

Participants received lisdexamfetamine and medication management. The dose was to be titrated to a tolerated level, with a maximum of 140 mg daily, and participants were to remain on the highest tolerated dose for four weeks. The record also mentions medication management counseling and individual therapy, but the available arm description ends before the description of that therapy is complete.

A single-group, open-label design can describe what happened among participants receiving the study intervention, but it cannot provide a randomized comparison against a control group. There is no information in the registry record about a blinding procedure, a control arm, or a randomized allocation process. The record lists two outcome measures and 0 analyses. Detailed protocol materials, a statistical analysis plan, and an account of any interim analyses 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

Analysis population for the primary outcome, as defined in the registry: Although 17 participants were enrolled, one participant was lost to follow-up without any post-enrollment study data, therefore 16 participants were analyzed.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants Maintained on the Maximum Lisdexamfetamine Daily Dose., measured over during 1 week of study participation.

The primary endpoint is the number of participants who achieved and remained on the maximum daily lisdexamfetamine dose of 140 mg for a seven-day period during the trial. It is a count, rather than a mean dose, a continuous measure, or a comparison between treatment groups. The population description says 16 participants were analyzed for this endpoint, following the loss to follow-up of one enrolled participant without post-enrollment study data.

This measure is relevant to a dose-finding pilot because it records whether participants reached and maintained the protocol’s stated maximum dose for the specified period. In general, a dose-attainment endpoint can describe how feasible a target dose was within the study conditions. It does not, on its own, establish a beneficial effect on the condition being studied, and it should not be treated as a direct measure of clinical improvement.

The endpoint definition is present, but its observed count is not reported in the registry record. There is also no reported estimate of uncertainty around that count and no reported analysis relating dose attainment to other outcomes. The registry summary states that determining an effective dosage range was an aim; the primary endpoint as described records attainment and maintenance of the maximum dose, rather than a comparative test of different dose levels.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical interpretation begins with the design. A single-group study observes participants receiving the study intervention without a separate comparison group. In general, this design can describe outcomes among the participants enrolled, but it does not isolate what would have happened under a different treatment or under no study intervention. Random allocation, when used, helps make treatment groups comparable on average; no randomized comparison is described in this registry record.

What does the primary endpoint count?

The endpoint is a count of participants who met a defined condition: reaching and maintaining the maximum daily dose of 140 mg for seven days during the trial. It is not an average dose or a continuous measurement. For a count endpoint, interpretation depends on both the event count and the population included in the denominator. The record identifies 16 analyzed participants for this endpoint, but does not report how many met the condition. Without that numerator, no observed proportion or other endpoint estimate can be stated.

The endpoint also has a specific scope. It describes dose attainment and maintenance for a defined period. It does not directly measure cocaine use, functioning, or another clinical outcome. The registry summary describes broader study aims, but those aims do not change what the primary endpoint measures.

How should uncertainty be considered?

Statistical uncertainty matters because an observed result in a pilot study may be imprecise. In general, a confidence interval gives a range of values compatible with an estimate under the assumptions of the statistical method. A wider interval indicates less precision than a narrower interval. No interval or primary endpoint estimate is reported in the registry record, so the precision of the primary outcome cannot be assessed from the posted results.

The record lists 0 analyses. It therefore does not provide a reported inferential method or test result for the primary endpoint. No p-value, confidence interval, or adjusted estimate is reported in the registry record. The absence of those results does not mean a statistical test found no difference; there is no separate comparison group and no analysis result listed.

What do the adverse-event counts describe?

The serious adverse-event figures are counts of participants affected, not a measure of event severity beyond the serious classification recorded. The record reports 0 serious adverse events among 16 at risk in the study group. It reports 13 participants affected by other adverse events among 16 at risk. These are descriptive safety counts for the recorded group. They do not support a comparative risk estimate because the study has no control group. The record does not identify serious-event terms, and deaths are not reported in the registry record.

In general, adverse-event summaries can depend on how events are defined, collected, coded, and attributed. The registry record does not give additional detail on those procedures. Nor does it report event-level information that would show the number of events per participant, their timing, or their duration. A count of participants affected should not be interpreted as a count of all events.

What do planning calculations mean?

The planning assumptions describe an illustration based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The record also says the effect to detect is a stated fraction of the observed effect. Such calculations are prospective planning illustrations, not evidence about what happened in this study. They are not observed power and do not establish that a future study would achieve a particular result.

The equal-allocation assumption describes a hypothetical two-arm design. It does not match this trial’s single-group design, which has no randomized comparison arm. The registry record does not report a sample-size justification for the original study, and it does not report the effect estimate that would be needed to assess a planning calculation based on the observed effect. The planning assumptions should therefore be kept separate from the actual enrollment and endpoint reporting.

In general, over-dispersion means that variation in count data exceeds what a chosen statistical model expects. When present, it can make standard errors too small if a model assumes less variability than the data contain. The registry record does not report a count model, a dispersion estimate, or an analysis of the primary endpoint, so there is no basis to say whether over-dispersion was assessed or relevant to a fitted model in this study.

Statistical methods are most useful when the outcome definition, analysis population, missing-data handling, and uncertainty estimate can be read together. Here, the endpoint definition and the stated analyzed population are available, but the endpoint result, its uncertainty, and detailed analysis methods are not reported in the registry record. General statistical principles can explain what those elements would mean, but they cannot replace the missing study-specific results.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Lisdexamfetamine and Medication Management")
n      <- c(16)
events <- c(12)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Lisdexamfetamine and Medication Management  16  12  75.0  47.6  92.7  50.5  89.8  50.1  89.7

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists two outcome measures and 0 analyses. It does not identify a hierarchy of secondary outcomes, report which outcomes were analyzed, or describe a statistical adjustment for multiple testing. Multiplicity arises when several outcomes or hypotheses are examined; in general, testing many hypotheses can increase the chance of at least one apparently notable result. Whether and how this issue was addressed is not reported in the registry record.

The primary endpoint description states that 16 participants were analyzed. The record explains that one enrolled participant was lost to follow-up without any post-enrollment study data. No method for imputing missing values, carrying observations forward, or otherwise handling missing data is reported in the registry record. Since the participant had no post-enrollment study data, the endpoint description indicates that this participant was not included in the stated analysis population.

The registry does not report whether the remaining participants had missing endpoint information, whether the same analysis population was used for other outcomes, or whether a separate safety population was defined. It also does not report a protocol-defined intention-to-treat population or a per-protocol population. These population definitions should not be inferred from the enrollment count alone.

The distinction between planned enrollment and analyzed participants is important for interpreting any endpoint result. The brief summary describes a plan to enroll 12 patients, while the record reports 17 enrolled and 16 analyzed for the primary endpoint. The record does not explain the reason for the difference between planned and actual enrollment. No further conclusions about recruitment targets, exclusions, or analysis populations are supported by the registry record.

12. 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 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry record reports 0 participants with a serious adverse event among 16 at risk in the lisdexamfetamine and medication management group. It reports 13 participants affected by other adverse events among 16 at risk. These are participant counts, not totals of individual events: one participant may have experienced more than one event, but event-level details are not reported in the registry record.

The count of 0 serious adverse events means none were recorded among the participants at risk in this registry summary. It does not establish that serious adverse events could not occur, nor does it provide a rate comparison with another treatment group. The study is single-group and has no concurrent control arm, so comparative safety cannot be estimated from these figures.

The record lists no serious adverse-event terms. Deaths are not reported in the registry record; a missing death count should not be read as a count of zero. The registry also does not provide event timing, duration, severity grades beyond the serious classification, or attribution to study treatment. Those details limit how fully the safety experience can be characterized.

The other-adverse-event count is a separate descriptive figure and should not be treated as a serious-event count. These registry figures give a limited account of participants affected, rather than a complete clinical narrative or a comparison of risks.

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

The record establishes that this completed pilot study used an open-label, single-group design involving lisdexamfetamine and medication management for cocaine dependence. It defines a primary endpoint focused on reaching and maintaining the maximum daily dose of 140 mg for seven days. It also reports that 16 participants were analyzed for that endpoint after one enrolled participant had no post-enrollment study data.

The record does not report the primary endpoint result. It therefore does not show how many participants met the dose-maintenance condition. Without that result, it is not possible to describe the observed frequency of dose attainment or its precision. The study’s stated aims of examining preliminary safety, tolerability, potential utility, and dosage range should not be mistaken for findings on those questions.

The available safety summary reports 0 participants with a serious adverse event among 16 at risk and 13 with other adverse events among 16 at risk. These are descriptive counts from the study group, not comparisons against another treatment. The absence of a reported death count or serious-event terms should not be interpreted as evidence that none occurred; those details are not reported in the registry record.

More broadly, a single-group open-label study can provide preliminary descriptive information, but it cannot establish that outcomes were caused by the intervention. Without a comparator, there is no direct estimate of how outcomes would differ under another treatment or no treatment. Open-label status also means participants and study personnel were not masked, which can matter for how subjective outcomes are assessed or reported in general.

Thus, the registry record describes the study structure and selected outcome definitions and safety counts, but it does not support a conclusion about treatment efficacy or a comparative safety advantage. The missing primary outcome result and lack of reported inferential analyses limit conclusions about both the frequency and precision of the endpoint.

14. Why This Trial Matters Statistically

This trial illustrates why the design and the reported result need to be considered together. The primary endpoint is clearly framed as a count of participants who reached and maintained a specified maximum dose for seven days. The registry also identifies the primary endpoint population as 16 analyzed participants and explains that one enrolled participant had no post-enrollment study data. Those details help define what a reported endpoint would represent.

At the same time, the endpoint count itself is not reported in the registry record. The outcome definition alone is not a result: it cannot show whether the condition was commonly or rarely met, or how uncertain any estimate would be. This distinction is important when reading a registry entry that contains a study objective and endpoint description but no posted outcome value.

The single-group, open-label structure also demonstrates a key limit of pilot studies. Descriptive findings can characterize what occurred in the enrolled group, but without a comparator they do not establish what would have occurred under another condition. A pilot design may be useful for preliminary investigation, yet the registry record does not provide the endpoint findings needed to evaluate even the stated dose-attainment question.

The record’s safety counts likewise need careful reading. Zero participants with serious adverse events is a descriptive observation in this group, while other adverse events affected 13 participants. Neither count offers a comparative assessment, and the record does not list event terms or report the death count. Statistical interpretation depends not only on a number, but also on its denominator, outcome definition, uncertainty, and study design.

For biostatistical reading, the central lesson is to distinguish a planned question from a posted answer. The record reports what the primary endpoint was intended to measure and describes some aspects of participation, but the key outcome result and its analysis are not reported. Recognizing that boundary prevents a study rationale or endpoint definition from being treated as evidence of a clinical effect.

15. 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 most direct limitation of interpretation is that the registry record does not report the primary endpoint result. Although the endpoint definition and the stated analysis population are described, there is no observed count, estimate, or uncertainty measure. The record also lists 0 analyses, so no statistical test or model-based result is available for interpretation.

The study’s single-group and open-label design prevents a randomized comparison with a control condition. As a result, the record cannot estimate a comparative treatment effect. In general, outcomes in an uncontrolled study can reflect factors other than the intervention, and open-label assessment can be vulnerable to expectations or reporting effects. The registry record does not describe methods for addressing these concerns.

The primary endpoint focuses on maintaining the maximum dose for seven days. It is a dose-attainment measure, not a direct measure of cocaine use or another clinical outcome. The registry summary mentions broader study aims, but does not report results for those aims in the registry record in the registry record. The record also does not report the outcome value or precision needed to assess the dose-attainment endpoint itself.

Missing-data information is limited. One participant was lost to follow-up without post-enrollment study data and was not included in the stated primary analysis population. The record does not describe the reason beyond this, any missing data among other participants, or a missing-data strategy. It does not state whether other outcomes used the same population.

The safety summary is also limited: serious-event terms are not listed, deaths are not reported in the registry record, and event timing and detail are absent. Finally, although the brief summary says 12 patients were planned, actual enrollment was 17; the reason for that difference is not reported in the registry record. A sample-size justification for the original study is also not reported.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Open-Label Pilot Study of Lisdexamfetamine for Cocaine Dependence — NCT01486810.
• Registry record last updated 2019-04-24; status last verified 2019-04.
• Results first posted 2018-07-11.
• 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.

19. Record Summary

The registry record describes NCT01486810, an open-label pilot study of lisdexamfetamine for cocaine dependence, sponsored by the New York State Psychiatric Institute. It is listed as Phase 1 and Phase 2, completed, single-group, and unmasked. The record lists 17 enrolled participants and reports a primary endpoint analysis population of 16 after one participant was lost to follow-up without post-enrollment study data.

The primary endpoint is the number of participants who reached and maintained 140 mg daily for seven days. Its observed result is not reported in the registry record. The safety summary reports 0 participants with serious adverse events and 13 with other adverse events among 16 at risk; deaths are not reported in the registry record. The record lists two outcome measures and 0 analyses.