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 Lisofylline as Continuous Subcutaneous and Intravenous Administration in Subjects With Type 1 Diabetes Mellitus (NCT01603121), a randomized phase 1, phase 2 study. The primary outcome is Safety and Tolerability of Study Drug.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01603121 |
| Phase | Phase 1, Phase 2 |
| Condition | Type 1 Diabetes Mellitus |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | None (open label) |
| Enrollment | 1 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Eastern Virginia Medical School |
| Results posted | Yes |
2. Clinical Question
Population
Subjects with type 1 diabetes mellitus. The registry records enrollment of 1. It does not report further eligibility criteria or a fuller description of the enrolled population.
Intervention
Lisofylline as a continuous subcutaneous infusion at 12mg/kg over 10 hours.
Comparator
Lisofylline as a continuous intravenous infusion at 9 mg/kg over 10 hours. The registry classifies the study as a crossover, but does not report the treatment sequence or other details of the crossover schedule.
Primary question
What safety and tolerability observations occur during and after the study-drug infusion? The registry also identifies bioavailability after subcutaneous versus intravenous infusion and early efficacy as secondary outcomes.
The primary question is descriptive in the available record: it concerns adverse events and findings from physical examinations, electrocardiograms and clinical safety laboratory tests. Follow-up contacts were planned within 5 days after each dosing period and approximately 30 days after the 2nd dosing period. The record does not give numerical results for these assessments, or a statistical comparison of the two routes.
The study is listed as phase 1 and phase 2, randomized, unmasked and crossover. These design labels describe how the study was classified; they do not establish what results were observed or how precisely any route difference was estimated. The registry lists an enrollment of 1, and the record is marked terminated. It does not report why the study was terminated.
3. Trial Design
The registry describes NCT01603121, titled “Lisofylline as Continuous Subcutaneous and Intravenous Administration in Subjects With Type 1 Diabetes Mellitus.” Its official title identifies the work as a safety, tolerability and bioavailability study in subjects with type 1 diabetes mellitus. Eastern Virginia Medical School is listed as sponsor. The study is classified as phase 1 and phase 2, randomized, unmasked and crossover.
The two listed administrations were lisofylline 12mg/kg by continuous subcutaneous infusion over 10 hours and lisofylline 9 mg/kg by continuous intravenous infusion over 10 hours. A crossover design generally aims to compare treatments within participants, rather than only across separate groups. That general design feature does not establish the sequence, spacing, washout, or exact procedures used in this study; those details are not reported in the registry record.
The registry records enrollment of 1, a start of 2012-02, primary completion of 2013-05, and status as terminated. It does not report the reason for termination, whether enrollment reached its intended target, or whether all planned procedures were completed. The record does not give a protocol, a sample-size justification, or details of any interim analyses.
The stated primary outcome is safety and tolerability of the study drug over a timeframe of 1 month. The description says subjects would be monitored for adverse events during and after infusion and would undergo physical examinations, electrocardiograms and clinical safety laboratory tests. The listed secondary outcomes are study-drug bioavailability after subcutaneous and intravenous infusion and evaluation of early efficacy. Although the record identifies three outcome measures, it does not provide numerical outcome results or analyses for those measures.
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.
First Intervention, 10 Hours
| Stage | Lisofylline Subcutaneous First, Then Lisofylline Intravenous | Lisofylline Intravenous First, Then Lisofylline Subcutaneous |
|---|---|---|
| STARTED | 1 | 0 |
| COMPLETED | 1 | 0 |
| NOT COMPLETED | 0 | 0 |
Second Intervention, 10 Hours
| Stage | Lisofylline Subcutaneous First, Then Lisofylline Intravenous | Lisofylline Intravenous First, Then Lisofylline Subcutaneous |
|---|---|---|
| STARTED | 1 | 0 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 1 | 0 |
Reasons for not completing this period:
| Reason | Lisofylline Subcutaneous First, Then Lisofylline Intravenous | Lisofylline Intravenous First, Then Lisofylline Subcutaneous |
|---|---|---|
| Adverse Event | 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.
Population: All subjects enrolled into the study were included in the baseline analysis.
| Characteristic | Unit | All Study Participants |
|---|---|---|
| Participants analysed | 1 | |
| Age, Continuous | years | 44 (SD 0) |
| Sex: Female, Male: Female | Participants | 1 |
| Sex: Female, Male: Male | Participants | 0 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 1 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 0 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 |
| Race (NIH/OMB): White | Participants | 1 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | participants | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Safety and Tolerability of Study Drug, measured over 1 month.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary outcome is titled “Safety and Tolerability of Study Drug,” with a timeframe of 1 month. Its description covers adverse-event monitoring during and after infusion, physical examinations, electrocardiograms and clinical safety laboratory tests. It also describes follow-up contact within 5 days after each dosing period and approximately 30 days after the 2nd dosing period, to review laboratory results and ask about changes in health. An in-person evaluation was to be arranged promptly if needed.
Safety and tolerability outcomes are used to characterize unwanted events and clinical or laboratory findings associated with study-drug administration. They are not, by themselves, a measure of bioavailability or early efficacy; those are listed separately as secondary outcomes. In general, such monitoring can describe the kinds of events observed and when they were assessed. Interpretation depends on knowing which participants were assessed, how events were defined and collected, and whether follow-up was complete.
The registry record does not report a numerical primary-outcome summary, a formal endpoint definition for the assessment findings, or an analysis comparing routes. It also does not report results for the planned examinations, electrocardiograms or laboratory tests. The posted adverse-event counts therefore do not constitute a complete report of every component named in the primary outcome.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The available result information is limited to the adverse-event entries. In the subcutaneous group, the registry lists 1 at risk for serious adverse events and 0 affected; for other adverse events, it lists 1 at risk and 1 affected. In the intravenous group, it lists 1 at risk for serious adverse events and 1 affected; for other adverse events, it lists 1 at risk and 0 affected. These are the counts entered for each group, not a reported statistical comparison between routes.
The record lists syncope and hypotension among the top serious adverse-event terms, each with 100.0%. The available record does not explain the denominator or full event coding context for those percentages. They should therefore be read as registry entries, not as estimates of comparative risk or evidence about which route is safer. Death counts are not reported in the record.
There are no posted analyses for the primary safety and tolerability outcome: the record lists 0 analyses. It gives no statistical estimate, confidence interval or hypothesis test for the route comparison. A confidence interval, in general, describes the range of values compatible with the data and analysis under its assumptions; without a reported estimate and interval, the precision of a route difference cannot be assessed. The record also does not give numerical results for bioavailability or early efficacy.
The registry classifies the study as randomized and crossover, but enrollment is recorded as 1. That context makes broad comparative conclusions especially unsupported by the posted information. Randomization is a method for assigning treatment order or allocation; it does not itself create precision, and a crossover label does not supply missing outcome data or analysis details. The record does not establish whether all intended assessments were completed or how the observations were handled.
The study status is terminated, but the reason is not reported in the registry record. That status alone does not explain the observed event entries, indicate whether the study stopped for safety, or establish whether the planned objectives were met. The posted information supports only a cautious description of the recorded group counts and study design. It does not support a conclusion about the relative safety, tolerability, bioavailability or efficacy of the two administration routes.
9. Statistical Methods Explained
The registry identifies the design as randomized, unmasked and crossover. Each label answers a different design question. Randomization concerns how treatment allocation or sequence is assigned. Masking concerns whether participants or study personnel are kept unaware of the assigned treatment; “NONE” indicates the study is listed as unmasked. A crossover design indicates that treatment comparisons are structured around periods or sequences rather than only parallel groups. These labels do not reveal the detailed implementation. The sequence, washout, period structure, and handling of period or carryover effects are not reported in the registry record.
What does randomization contribute?
In general, randomization helps limit systematic differences in treatment assignment. It does not guarantee that groups or treatment periods will be comparable in every respect, particularly when the recorded enrollment is 1. Nor does randomization substitute for a clearly reported outcome analysis. The record does not describe the randomization method, sequence generation, concealment, or whether the intended allocation was completed.
What does a crossover comparison require?
In general, a crossover analysis must account for the fact that observations from the same participant are related. It may also need to consider treatment period and sequence, and whether effects from an earlier treatment could persist into a later period. Those considerations depend on the protocol and analysis plan. The registry does not report enough detail to determine how these features were addressed, and it provides no numerical route-comparison analysis.
How should safety counts be read?
Adverse-event counts describe the number of people recorded as at risk and the number recorded as affected in each listed group. They are descriptive entries, not a statistical test. In general, a comparison of event counts can be difficult to interpret when the underlying number assessed is small, when follow-up differs, or when participants contribute observations under more than one treatment. Event definitions, event timing and attribution to treatment also matter. The record does not provide enough information to evaluate those details fully.
Serious adverse events and other adverse events are separate categories in the posted entries. The registry lists serious-event terms and percentages, but does not explain the denominator or coding context for the displayed percentages. A percentage alone cannot show how precise an estimate is; that requires its underlying data and appropriate uncertainty measures. No confidence intervals or formal tests are reported.
What do the absent analyses mean?
The registry lists 0 analyses and does not present a numerical result for the primary outcome. This means there is no reported inferential estimate to interpret for safety and tolerability. It does not mean that no events were collected: the registry does include adverse-event counts. Rather, the event entries are not accompanied by a reported analysis linking them to a defined comparative estimand, with uncertainty and an account of the analysis population.
In general, a statistical analysis plan describes the outcomes, estimands, analysis populations, methods and handling of incomplete data. The plan is not reported in the registry record. There is also no reported sample-size justification or interim-analysis plan. Those absences prevent assessment of whether the analysis followed a prespecified approach, whether the design was intended to answer a particular statistical question, or how missing observations were handled.
How do planning illustrations differ from results?
Planning illustrations based on an observed effect are not observed power and are not a substitute for the trial’s own design justification. The stated planning assumptions describe a two-sided significance level of 0.05, equal allocation, a normal approximation, and effects expressed as fractions of an observed effect. However, the registry record does not provide a single reduced comparison for these calculations. It therefore does not support a trial-specific sample-size interpretation or a conclusion about the study’s ability to detect a defined effect.
In general, statistical significance and clinical importance are different ideas. A test addresses compatibility with a specified null model under stated assumptions; it does not by itself establish the size, precision or practical importance of an effect. Here, no test result or effect estimate for the primary outcome is reported, so neither significance nor the magnitude and precision of a route difference can be evaluated from the registry entries.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary safety and tolerability outcome and secondary outcomes for bioavailability and early efficacy. It also records three outcome measures, but does not provide their numerical results or analyses. The multiplicity strategy—how interpretation would account for examining several outcomes or measures—is not reported in the registry record. No adjustment method or hierarchy for interpreting multiple tests is stated.
Missing-data methods and analysis populations are also not reported. The record does not say how many participants contributed data to each outcome, whether assessments were incomplete, how missing laboratory or examination results were handled, or whether any analysis used an intention-to-treat, per-protocol or safety population. With crossover designs, the treatment periods and within-participant data structure can matter; the record does not describe how incomplete periods or treatment sequences were handled.
These omissions limit interpretation of the posted event entries. The at-risk counts are given for each group, but the record does not explain the analysis population or provide a broader account of follow-up completeness. It also does not report a statistical analysis plan, a prespecified multiplicity approach, or interim analyses. Without those details, readers cannot determine whether the listed results represent all planned assessments or how uncertainty and multiple outcomes were intended to be addressed.
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 |
|---|---|---|---|
| Lisofylline Subcutaneous | 0 | 1 | 0.0% |
| Lisofylline Intravenous | 1 | 1 | 100.0% |
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 |
|---|---|
| Lisofylline Subcutaneous | 1 of 1 |
| Lisofylline Intravenous | 0 of 1 |
Most frequent serious adverse event terms
| Event term | Organ system | Lisofylline Subcutaneous | Lisofylline Intravenous |
|---|---|---|---|
| Syncope | General disorders | 0 of 1 | 1 of 1 |
| Hypotension | General disorders | 0 of 1 | 1 of 1 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Lisofylline Subcutaneous | Lisofylline Intravenous |
|---|---|---|---|
| Dizziness | General disorders | 1 of 1 | 0 of 1 |
Serious events with the highest arm-level rate: syncope (100.0%), hypotension (100.0%).
The serious adverse-event entries list 1 at risk and 0 affected for lisofylline subcutaneous, and 1 at risk and 1 affected for lisofylline intravenous. For other adverse events, the corresponding entries are 1 at risk and 1 affected for subcutaneous administration, and 1 at risk and 0 affected for intravenous administration. These counts should be read as registry group entries, not as a complete statistical comparison or a basis for estimating a route effect.
The registry lists syncope and hypotension as top serious-event terms, each with 100.0%. The record does not clarify the denominator, event coding context or relationship between these terms and the group-level affected counts. The listed percentage therefore should not be interpreted as a comparative risk estimate. Deaths are not reported in the registry record.
In general, adverse-event counts are most informative when their definitions, assessment period, denominator and follow-up completeness are clear. The record describes safety monitoring during and after infusion and follow-up contacts within 5 days after each dosing period and approximately 30 days after the 2nd dosing period, but does not report a complete set of outcome results or a statistical analysis. The counts alone cannot establish causation or comparative safety.
12. What the Result Does, and Does Not, Mean
The registry record describes a study designed to examine safety, tolerability and bioavailability after lisofylline administration by two routes in subjects with type 1 diabetes mellitus. It identifies the infusion regimens, a crossover design and planned safety assessments. The posted adverse-event entries provide limited descriptive information: serious and other adverse events are recorded separately for the subcutaneous and intravenous groups.
Those entries do not establish whether one route has a different safety profile from the other. The record gives no comparative estimate, confidence interval or hypothesis test for the primary outcome. It also provides no numerical results for bioavailability or early efficacy. Consequently, the information does not establish the size or precision of any route difference, and it cannot show that the study objectives were achieved.
The record’s enrollment of 1, status of terminated, and absence of reported analyses are important context. The reason for termination, planned sample-size justification, analysis populations and handling of missing data are not reported. The registry information cannot explain why the study ended or whether all planned assessments were completed.
In general, a registry record is a structured account of study design and posted results, not necessarily a full report of the protocol or analysis. Here, the record supports describing the design, planned assessments and entered event counts. It does not support claims that lisofylline is effective or ineffective, that either route is safer, or that the absence of a reported outcome result means no event or effect occurred.
13. Why This Trial Matters Statistically
This study raises statistical issues that are particularly relevant to small crossover trials. A crossover design can compare treatments within the same participant, which in general can account for stable participant characteristics. The benefit depends on complete period data and an analysis that respects the within-participant relationship. The registry classifies the study as crossover but does not report the treatment sequence, period details, washout or analysis method.
The recorded enrollment of 1 and the limited group-level event entries illustrate why descriptive counts should not be mistaken for precise comparative estimates. A numerical difference in recorded counts, without a defined comparative analysis and uncertainty, does not establish a reliable treatment contrast. The registry reports no analysis for the primary outcome, so the precision of any contrast cannot be assessed.
The record also illustrates the distinction between collecting safety information and reporting an analyzable endpoint. The planned monitoring includes adverse events, physical examinations, electrocardiograms and clinical safety laboratory tests, but numerical findings for those assessments are not reported. The listed bioavailability and early-efficacy outcomes likewise have no reported numerical analyses.
Finally, trial status and statistical conclusions answer different questions. “Terminated” describes the status recorded in the registry; it does not explain the reason, establish the quality of collected data, or determine the meaning of the adverse-event entries. Clear reporting of the protocol, analysis populations, missing-data handling, endpoint results and uncertainty would be needed for a fuller statistical interpretation.
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 trial-specific limitation is that the registry records enrollment of 1 and provides no numerical analysis of the primary outcome. The adverse-event counts are sparse descriptive entries and are not accompanied by comparative estimates or measures of uncertainty. The registry does not report results for the physical examinations, electrocardiograms or clinical safety laboratory tests described in the primary-outcome plan.
Important crossover details are absent, including treatment order, timing between periods, washout procedures and the analysis of within-participant observations. The registry also does not report the randomization method, analysis populations, missing-data approach, or a statistical analysis plan. These omissions limit assessment of whether the planned design and analysis were carried out as intended.
The record lists serious-event terms with percentages but does not explain their denominators or coding context. It does not report death counts, numerical bioavailability results, early-efficacy results, or a reason for termination. The stated timeframe and follow-up contacts describe the monitoring plan, but do not establish completeness of follow-up. These limitations mean the posted information cannot support a precise or comprehensive comparison of the two routes.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Lisofylline as Continuous Subcutaneous and Intravenous Administration in Subjects With Type 1 Diabetes Mellitus — NCT01603121.
- Registry record last updated 2016-08-18; status last verified 2016-08.
- Results first posted 2016-08-18.
- 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.
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18. Record Summary
NCT01603121 is a randomized, unmasked crossover study of lisofylline in subjects with type 1 diabetes mellitus, classified as phase 1 and phase 2 and sponsored by Eastern Virginia Medical School. The listed regimens are continuous subcutaneous infusion at 12mg/kg over 10 hours and continuous intravenous infusion at 9 mg/kg over 10 hours. Enrollment is recorded as 1; the study is marked terminated.
The primary outcome is safety and tolerability over 1 month, with adverse-event monitoring, physical examinations, electrocardiograms and clinical safety laboratory tests described. Secondary outcomes concern bioavailability and early efficacy. The posted record includes group-level serious and other adverse-event counts, but lists 0 analyses and does not report numerical primary or secondary outcome analyses. The reason for termination, analysis plan, missing-data methods and detailed crossover procedures are not reported in the registry record.