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 Fentanyl Pectin Nasal Spray (FNPS) for Exercise-Induced Breakthrough Dyspnea (NCT01832402), a randomized phase 2 study. The primary outcome is Dyspnea Numeric Rating Scale.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01832402 |
| Phase | Phase 2 |
| Condition | Advanced Cancers |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 35 |
| Arms in the primary outcome | n/a |
| Lead sponsor | M.D. Anderson Cancer Center |
| Results posted | Yes |
2. Clinical Question
Population
People with advanced cancers who had been treated or were being treated for cancer, according to the study summary. The registry record does not report further eligibility details or a more specific description of the analyzed population.
Intervention
Fentanyl pectin nasal spray (FPNS), administered intranasally. The intervention description gives a dose equivalent to 15-25% of the morphine equivalent daily dose and describes administration before later 6-minute walk tests.
Comparator
Placebo nasal spray. The study summary describes placebo as a spray that looks like the study drug but is not designed to treat an illness.
Primary question
The study aimed to assess dyspnea intensity “now” using a numeric rating scale during a single visit involving 6-minute walk tests. The primary outcome description concerns mean differences between the first and second tests and between the first and third tests. Results for those comparisons are not reported in the registry record.
3. Trial Design
This was a phase 2, randomized, double-masked, parallel-group study sponsored by M.D. Anderson Cancer Center. The registry record lists an enrollment of 35 and a completed status. It gives the study start as 2013-06-11 and primary completion as 2019-11-25. These record details describe the study’s registration and timeline; they do not establish how many participants contributed data to any particular outcome.
The study compared fentanyl pectin nasal spray with placebo nasal spray in people with advanced cancers. The summary describes the research aim as learning whether fentanyl nasal spray could help control shortness of breath in patients treated or being treated for cancer. Fentanyl is described as commonly used for cancer pain; the study’s purpose was to examine its relationship to breathlessness in the study setting, not to report a conclusion about treatment benefit.
The intervention descriptions place the sprays within a sequence of 6-minute walk tests. For the FPNS arm, the registered description specifies a dose equivalent to 15-25% of the morphine equivalent daily dose, administered intranasally before the second walk test, with the same dose repeated before the third and final test. The placebo description likewise places placebo before the second and third tests. Some wording in the arm descriptions is incomplete, so details beyond the stated schedule are not reported in the registry record.
Walk tests, questionnaires, and mental ability tests are listed among the interventions. The primary outcome concerns a dyspnea numeric rating scale; secondary outcomes are the Dyspnea Borg Scale and walk distance at 6 minutes. The registry record does not report the randomization procedure, allocation concealment, masking procedures, or the detailed analysis plan.
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
| Stage | Intervention Group (Fentanyl Pectin Nasal Spray) | Controlled Group (Placebo) |
|---|---|---|
| STARTED | 19 | 16 |
| Received Allocated Medication | 12 | 12 |
| Completed Study With Correct Dose | 10 | 9 |
| Completed Study With Incorrect Dose | 2 | 3 |
| COMPLETED | 12 | 12 |
| NOT COMPLETED | 7 | 4 |
Reasons for not completing this period:
| Reason | Intervention Group (Fentanyl Pectin Nasal Spray) | Controlled Group (Placebo) |
|---|---|---|
| Lost to Follow-up | 2 | 0 |
| Withdrawal by Subject | 3 | 3 |
| Declining Performance status | 2 | 1 |
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: Intention to treat analysis participants data
| Characteristic | Unit | Intervention Group (Fentanyl Pectin Nasal Spray) | Controlled Group (Placebo) | Total |
|---|---|---|---|---|
| Participants analysed | 12 | 12 | 24 | |
| Age, Continuous | Years | 51.5 (44.7 to 58.3) | 53.3 (45.0 to 61.6) | 52.4 (47.5 to 57.4) |
| Sex: Female, Male: Female | Participants | 9 | 4 | 13 |
| Sex: Female, Male: Male | Participants | 3 | 8 | 11 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 1 | 2 | 3 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 11 | 10 | 21 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| 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 | 3 | 2 | 5 |
| Race (NIH/OMB): White | Participants | 9 | 10 | 19 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Region of Enrollment: United States | participants | 12 | 12 | 24 |
| Education: High School or less | Participants | 4 | 2 | 6 |
| Education: College | Participants | 8 | 7 | 15 |
| Education: Advanced Degree | Participants | 0 | 3 | 3 |
| Cancer Type: GastroIntestinal Cancer | Participants | 2 | 4 | 6 |
| Cancer Type: Breast Cancer | Participants | 3 | 2 | 5 |
| Cancer Type: Lung Cancer | Participants | 1 | 2 | 3 |
| Cancer Type: Genitourinary Cancer | Participants | 2 | 0 | 2 |
| Cancer Type: Gynecologic Cancer | Participants | 2 | 0 | 2 |
| Cancer Type: Hematologic | Participants | 0 | 2 | 2 |
| Cancer Type: Others | Participants | 2 | 2 | 4 |
| Cancer Stage: Metastatic Stage | Participants | 8 | 10 | 18 |
| Cancer Stage: Localized/Locally advanced | Participants | 4 | 2 | 6 |
| Comorbidity: Asthma | Participants | 5 | 0 | 5 |
| Comorbidity: COPD | Participants | 2 | 2 | 4 |
| Comorbidity: Heart Failure | Participants | 1 | 0 | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Dyspnea Numeric Rating Scale, measured over 1.5 to 2 hours on a Single visit.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | score on a scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is dyspnea intensity “now,” measured with a numeric rating scale ranging from 0, meaning “no shortness of breath,” to 10, meaning “worst possible shortness of breath.” It is a continuous patient-reported measure: a participant selects a score representing the intensity of breathlessness at the time of assessment. The record describes mean differences between the first and second 6-minute walk tests and between the first and third tests. The timeframe is 1.5 to 2 hours on a single visit.
Assessing symptoms around a standardized activity can capture breathlessness associated with exertion, rather than relying only on a general description of symptoms outside a test. A numeric scale also makes it possible to summarize scores across participants and compare changes in average scores. These are general reasons for using a continuous symptom measure; the registry record does not explain why this particular scale or timing was selected.
The record states that the 6-minute walk tests followed American Thoracic Society guidelines. It lists the Dyspnea Borg Scale and walk distance at 6 minutes as secondary outcomes, which represent additional symptom and activity-related measures. However, it does not report endpoint values, mean differences, confidence intervals, or statistical tests for the primary measure. The registered outcome definition therefore describes what was to be assessed, not the magnitude or precision of any observed result.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a randomized comparison of FPNS and placebo and defines a primary symptom outcome around repeated 6-minute walk tests. It does not report the primary outcome results. In particular, it gives no group means, mean differences, confidence intervals, p-values, or analysis estimates for the comparisons between the first and later walk tests. Without those results, the direction and magnitude of the observed symptom changes, and the precision of any comparison, cannot be assessed from the registry record.
The distinction between a planned endpoint and a reported result is important. Naming a scale and defining a measurement schedule establishes what the study intended to measure. It does not show what participants scored, whether scores changed, or whether the groups differed. The registry also lists secondary outcomes, but their results are not reported in the registry record. No conclusion about the study’s efficacy findings can be drawn from outcome names alone.
The enrollment field reports 35 participants, while the adverse-event groups each list 12 participants at risk. These figures refer to different pieces of registry information and do not establish the number analyzed for the primary endpoint. The number contributing usable primary outcome data, the reasons for any unavailable measurements, and the analysis population are not reported in the registry record.
The record reports no analyses among its outcome analyses. This means the registry entry does not furnish the inferential statistics needed to judge uncertainty around the primary endpoint. A confidence interval would ordinarily help describe the range of effect estimates compatible with the data under the analysis assumptions. Here, no such interval is reported for the primary outcome. The endpoint description does specify 95% confidence intervals as the dispersion measure, but that specification is not itself an observed interval.
The posted safety counts describe participants affected by serious or other adverse events in the listed walk-test groups. They are safety information, not evidence about the primary symptom endpoint. They should be read in light of the small listed at-risk groups and the absence of detailed event descriptions in the record. They cannot fill the gap left by missing primary outcome estimates.
Overall, the registry record documents a study design and outcome definitions, but does not provide the primary or secondary outcome findings needed for a statistical interpretation of treatment differences. The absence of those results is a limitation of what can be concluded from this record, rather than evidence that a difference was or was not present.
9. Statistical Methods Explained
What kind of outcome is this? The primary measure is a continuous score on a numeric rating scale. For a continuous outcome, a common summary is the mean, which describes the average score in a group. The registry specifies a mean difference between walk-test measurements and a 95% confidence interval as the dispersion measure. Those specifications indicate the intended form of reporting; the actual means and intervals are not reported in the registry record.
In general, a confidence interval conveys uncertainty around an estimated quantity under the assumptions of the statistical method used. A narrower interval indicates greater precision than a wider interval, but an interval does not by itself show that an effect is important to participants. Interpretation also depends on the scale, the clinical context, and the analysis design. In this study, no primary endpoint interval is reported, so its precision cannot be evaluated from the registry entry.
What does randomization contribute? In general, random assignment is intended to make treatment groups comparable on average at the start of a trial, including with respect to characteristics that may affect the outcome. Randomization does not guarantee identical groups, especially in a small study. The registry identifies the allocation as randomized, but does not report how the random sequence was generated, how assignment was concealed, or whether any departures from the assigned groups occurred. Those procedural details therefore cannot be assessed.
What does double masking mean? In general, masking is intended to limit the influence of treatment knowledge on participant reports, study conduct, or outcome assessment. This may be relevant when an outcome is a subjective report of breathlessness. The registry lists the study as double-masked and describes a placebo spray, but it does not report who was masked, how masking was maintained, or whether masking was assessed. No further conclusion about those procedures is possible from the registry record.
How should repeated walk-test measurements be understood? The primary outcome description identifies comparisons between the first and second tests and between the first and third tests within a single visit. Repeated measurements can provide information about symptom scores at different points in a testing sequence. Statistical analysis must account for the relationship between repeated measurements from the same participant; those observations are generally not independent. The registry record does not report the model or calculation used to handle the repeated measurements, nor whether the main treatment comparison was based on changes, scores at particular tests, or another contrast.
Why might over-dispersion matter? As a general statistical concept, over-dispersion occurs when observed variability is greater than a statistical model assumes. If a model underestimates variability, its uncertainty estimates may be too small. The primary endpoint is described as a continuous mean, but the registry record does not report a fitted model, a variance estimate, or an assessment of model assumptions. There is therefore no basis to say whether over-dispersion was relevant or how it was handled in this study.
What is multiplicity? In general, multiplicity arises when several outcomes, time points, or comparisons are tested. The more inferences made, the greater the chance that at least one apparently notable result could occur by chance if no adjustment or other strategy is used. The registry lists comparisons involving the first-to-second and first-to-third walk tests, along with secondary outcomes. It does not report whether these comparisons were treated as co-primary, how they were prioritized, or whether any multiplicity adjustment was planned or performed.
What do the sample-size assumptions mean? General planning illustrations can show how many participants per arm would be needed under stated assumptions about significance level, allocation, and an effect to detect. They are not observed trial results and do not establish the trial’s actual design rationale. The record describes an illustrative calculation based on a fraction of an observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. It does not report the trial’s own sample-size justification. Such illustrations should not be described as observed power, and no resulting participant counts are stated in the registry information.
What can be inferred from the listed analyses? The registry lists no outcome analyses. As a result, it does not offer test statistics or model estimates with which to assess an observed group contrast. A study’s randomized design and defined endpoint do not substitute for the estimated effect and its uncertainty. Readers need those results, together with information on the analysis population and missing data, to evaluate the statistical findings.
10. Multiplicity, Missing Data and Analysis Populations
The registry record identifies two primary comparisons: the mean difference in dyspnea numeric rating scale between the first and second 6-minute walk tests, and between the first and third tests. It also lists the Dyspnea Borg Scale and walk distance at 6 minutes as secondary outcomes. When multiple outcomes or comparisons are examined, interpretation can depend on which were prespecified as primary, how they were prioritized, and whether an adjustment for multiple testing was used. Those details are not reported in the registry record.
The entry does not report a statistical analysis plan, an adjustment for multiplicity, or whether the primary comparisons were analyzed separately or jointly. It also does not report how missing endpoint measurements were handled, whether any imputation was used, or how many participants had usable data at each assessment. The amount and pattern of missing data are therefore unknown from this record.
The registry enrollment is 35, but enrollment alone does not identify the population included in each outcome analysis. The record does not report an intention-to-treat, per-protocol, or other analysis population for the primary outcome, nor does it give outcome-specific denominators. It is not reported in the registry record whether participants were analyzed according to randomized assignment or whether any exclusions occurred.
These omissions limit interpretation because missingness, analysis-population choices, and multiple comparisons can affect estimates and uncertainty. They do not establish that any particular approach was or was not used; the relevant information is 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 |
|---|---|---|---|
| Interventional (Fentanyl Pectin Nasal Spray) Second Walk Test | 0 | 12 | 0.0% |
| Control (Placebo), Second Walk Test | 0 | 12 | 0.0% |
| Interventional (Fentanyl Pectin Nasal Spray),Third Walk Test | 0 | 12 | 0.0% |
| Control (Placebo), Third Walk Test | 0 | 12 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Interventional (Fentanyl Pectin Nasal Spray) Second Walk Test | 0 of 12 |
| Control (Placebo), Second Walk Test | 0 of 12 |
| Interventional (Fentanyl Pectin Nasal Spray),Third Walk Test | 0 of 12 |
| Control (Placebo), Third Walk Test | 0 of 12 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Interventional (Fentanyl Pectin Nasal Spray) Second Walk Test | 2 of 12 |
| Control (Placebo), Second Walk Test | 2 of 12 |
| Interventional (Fentanyl Pectin Nasal Spray),Third Walk Test | 5 of 12 |
| Control (Placebo), Third Walk Test | 5 of 12 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Interventional (Fentanyl Pectin Nasal Spray) Second Walk Test | Control (Placebo), Second Walk Test | Interventional (Fentanyl Pectin Nasal Spray),Third Walk Test | Control (Placebo), Third Walk Test |
|---|---|---|---|---|---|
| Dizziness | Nervous system disorders | 2 of 12 | 2 of 12 | 5 of 12 | 1 of 12 |
| Drowsiness | Nervous system disorders | 1 of 12 | 2 of 12 | 1 of 12 | 5 of 12 |
| Nose Dryness | Respiratory, thoracic and mediastinal disorders | 0 of 12 | 2 of 12 | 0 of 12 | 2 of 12 |
| Nausea | Gastrointestinal disorders | 0 of 12 | 0 of 12 | 2 of 12 | 0 of 12 |
| Stuffy Nose | Respiratory, thoracic and mediastinal disorders | 0 of 12 | 2 of 12 | 0 of 12 | 0 of 12 |
| Cough | Respiratory, thoracic and mediastinal disorders | 1 of 12 | 0 of 12 | 0 of 12 | 1 of 12 |
| Sore throat | Respiratory, thoracic and mediastinal disorders | 0 of 12 | 1 of 12 | 0 of 12 | 0 of 12 |
The registry lists four safety groups: FPNS and placebo at the second walk test, and FPNS and placebo at the third walk test. Each group lists 12 participants at risk. In the second-test groups, 0 participants are listed as affected by serious adverse events and 2 by other adverse events in each arm. In the third-test groups, 0 are listed as affected by serious adverse events and 5 by other adverse events in each arm. Deaths are listed as 0 in all four groups.
These counts describe the registry’s safety entries for the specified groups and testing points. They are not results for the dyspnea numeric rating scale, and they do not establish a treatment effect on breathlessness. The record does not provide serious adverse event terms, details of the other adverse events, or additional context about how events were collected and classified. It also does not clarify whether the same individuals may appear in more than one walk-test group. Accordingly, counts across the second- and third-test groups should not be added or treated as distinct participants. The small listed at-risk groups and the limited event descriptions constrain what can be concluded from these safety figures.
12. What the Result Does, and Does Not, Mean
The study record establishes that investigators planned a randomized, double-masked comparison of fentanyl pectin nasal spray with placebo in a phase 2 study involving people with advanced cancers. It defines a symptom endpoint based on a dyspnea numeric rating scale around 6-minute walk tests, and it names additional symptom and walking-distance outcomes. These are relevant features of the research question and design, but they are not findings about the effect of the spray.
The primary outcome results are not reported in the registry record. There is no reported mean difference, confidence interval, or p-value for either stated comparison. Consequently, the registry entry cannot show the direction or size of any observed difference, how precisely it was estimated, or whether results were consistent across the two comparisons. The secondary outcome results are also not reported in the registry record.
Likewise, absence of a reported result is not evidence that there was no difference. It is also not evidence that there was a difference. A treatment conclusion would require outcome estimates and uncertainty, as well as sufficient information about the analysis population, missing measurements, and analysis methods. Those details are not available in the registry entry.
The safety counts provide a limited description of affected participants in the listed walk-test groups. They do not resolve the lack of efficacy results and should not be interpreted as an overall assessment of safety. The registry record does not include detailed event terms or enough information to understand whether participants appear in more than one group.
Thus, the record supports a description of the study’s planned comparison, measurement approach, enrollment, and selected safety counts. It does not support a conclusion about whether FPNS changed dyspnea scores relative to placebo, or about the clinical importance of any such change. That distinction is central: trial design describes how a question was investigated, while results are needed to answer it.
13. Why This Trial Matters Statistically
This trial is statistically notable as a study of a subjective symptom measured in the setting of a standardized activity. Dyspnea intensity was assessed with a numeric rating scale during a visit that included repeated 6-minute walk tests. Such a design raises important questions about how repeated measurements are compared, how changes are defined, and how uncertainty is estimated. The registry record identifies the comparisons of interest but does not report the analysis method or estimates.
The randomized, double-masked, parallel design is intended to support a comparison between FPNS and placebo while limiting some sources of bias. In general, however, design labels do not reveal how successfully procedures were implemented or whether the resulting groups and analyzed participants were comparable. Details of randomization, masking, and the analysis population are not reported in the registry record.
The study also illustrates why a clearly stated endpoint is not enough for statistical interpretation. The scale’s range and the timing of assessment are described, but no outcome values or confidence intervals are reported. Without an estimate and its precision, readers cannot evaluate the observed pattern or distinguish a potentially meaningful finding from substantial uncertainty.
Finally, the entry identifies more than one walk-test comparison and additional secondary outcomes, while not reporting a statistical plan or multiplicity approach. These details matter because choices about primary comparisons, repeated measurements, and missing data affect how results should be interpreted. The record’s limitations make it useful for understanding the research question and registered design, but insufficient for evaluating the study’s outcome findings.
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.
A major limitation for interpretation is that the registry record does not report the primary outcome results or statistical analyses. Although it describes the scale, the assessment period, and two comparisons between walk tests, it gives no outcome means, effect estimates, confidence intervals, or p-values. Secondary outcome results are not reported either. Statistical conclusions about symptom changes or differences between treatment groups therefore cannot be drawn from this record.
The registry reports enrollment of 35, while the safety entries list 12 participants at risk in each of four groups. It does not report the number included in the primary endpoint analysis or explain the relationship between enrollment and the safety denominators. Outcome-specific sample sizes, participant flow, withdrawals, and reasons for missing measurements are not reported in the registry record.
The arm descriptions are incomplete. The FPNS description states a dose equivalent to 15-25% of the morphine equivalent daily dose and gives timing in relation to later walk tests, but additional details are not available. The record also does not report the precise randomization, allocation-concealment, or masking procedures, or whether masking remained intact.
The statistical plan is not reported in the registry record. This includes the model for repeated measurements, the treatment contrast, covariate adjustment, handling of missing data, and any approach to multiplicity across the primary comparisons and secondary outcomes. The record does not give a trial-specific sample-size justification. These gaps limit assessment of bias, precision, and the robustness of any unreported findings.
Safety reporting is also limited to counts of affected participants in the listed groups. Event terms and details are not reported, and the entry does not clarify whether participants overlap across walk-test groups. The counts should therefore be interpreted narrowly rather than as a complete safety account.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Fentanyl Pectin Nasal Spray (FNPS) for Exercise-Induced Breakthrough Dyspnea — NCT01832402.
- Registry record last updated 2023-06-08; status last verified 2023-06.
- Results first posted 2020-09-04.
- 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.
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18. Record Summary
The registry record identifies NCT01832402 as a completed, randomized, double-masked, parallel phase 2 study sponsored by M.D. Anderson Cancer Center, with enrollment of 35. It compares fentanyl pectin nasal spray with placebo nasal spray in people with advanced cancers. The primary endpoint is dyspnea intensity on a numeric rating scale during a single visit involving 6-minute walk tests, with comparisons between the first and second tests and between the first and third tests.
The record lists the Dyspnea Borg Scale and walk distance at 6 minutes as secondary outcomes. It also reports safety counts for 12 participants at risk in each of four walk-test groups. Primary and secondary outcome results, statistical analyses, missing-data methods, and the analysis population are not reported in the registry record. The entry therefore describes the study question and design, but does not provide the estimates needed to assess outcome differences or their precision.