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 Evaluate Safety and Efficacy of the Coadministration of Ibrexafungerp With Voriconazole in Patients With Invasive Pulmonary Aspergillosis (NCT03672292), a randomized phase 2 study. The primary outcome is Number of Participants With Treatment-emergent Adverse Events (TEAEs), Drug-related Adverse Events (AEs), Discontinuations Due to AEs and Deaths.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03672292 |
| Phase | Phase 2 |
| Condition | Invasive Pulmonary Aspergillosis |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 22 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Scynexis, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
Patients with invasive pulmonary aspergillosis. The primary outcome describes a safety population that includes any participant treated with at least one dose of voriconazole or SCY-078. The registry record reports enrollment of 22, but it does not report further eligibility details in the information summarized.
Intervention
SCY-078 coadministered with voriconazole. The registry describes oral SCY-078 tablets alongside either intravenous or oral voriconazole. The specific dosing descriptions in the arm records are incomplete, so the full regimen is not reported in the registry record.
Comparator
Voriconazole monotherapy, with oral placebo tablets matching SCY-078 tablets. The registry describes either intravenous or oral voriconazole for this arm as well.
Primary question
How many participants experienced treatment-emergent adverse events, drug-related adverse events, discontinuations due to adverse events, or death, with treatment observed up to a maximum of 19 weeks? The record also lists secondary outcomes involving response, death, galactomannan index, and drug concentrations, but it does not list analysis results for these outcomes.
In statistical terms, the study set out to describe safety during treatment and to evaluate the coadministration regimen against voriconazole alone. The primary outcome is a set of participant counts, not a single continuous measurement or a single efficacy contrast. Its separate event categories can convey different aspects of tolerability: an event occurring after treatment begins, an event judged drug-related, an event leading to discontinuation, and death. These categories should not be treated as interchangeable.
The registry labels the study randomized, double-blind in its official title, quadruple-masked in its design information, and parallel in model. These design terms describe how participants were assigned and how treatment knowledge was handled, but the registry record does not report the masking roles or further implementation details. The available figures therefore address a narrow question: what safety counts were recorded in the two treatment groups? They do not establish a treatment effect on response or other clinical outcomes.
3. Trial Design
This was a phase 2, randomized, parallel-group study of SCY-078 plus voriconazole compared with voriconazole monotherapy in patients with invasive pulmonary aspergillosis. The registry record reports enrollment of 22. It lists the study status as terminated, the start date as 2019-01-22, and primary completion as 2023-03-27. The reason for termination is not reported in the registry record.
The two arms shared voriconazole treatment, which could be given intravenously or orally according to the arm descriptions. The combination arm also received oral SCY-078 tablets; the comparator arm received oral placebo tablets matching SCY-078 tablets. The descriptions include loading and maintenance dosing, but the combination-arm description is cut off and does not provide the complete SCY-078 regimen. The full dosing information is therefore not reported in the registry record.
Random assignment can reduce systematic differences between groups at the point of assignment, on average, when implemented as intended. It does not guarantee that groups will have similar characteristics in a small study. The registry identifies the design as quadruple-masked, while the official title describes it as double-blind. Which people were masked, how masking was maintained, and whether masking was assessed are not reported in the registry record.
The primary outcome covers treatment-emergent adverse events, drug-related adverse events, discontinuations due to adverse events, and deaths, with follow-up up to a maximum of 19 weeks. The registry defines the safety population as any participant treated with at least one dose of voriconazole or SCY-078. It also lists nine outcome measures and names secondary outcomes related to response, mortality, galactomannan index, and plasma concentrations. The record lists no analysis results for those outcomes. The protocol, allocation ratio, detailed eligibility criteria, and planned statistical analysis 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
| Stage | SCY-078 Plus Voriconazole | Voriconazole Mono-therapy |
|---|---|---|
| STARTED | 10 | 12 |
| COMPLETED | 6 | 8 |
| NOT COMPLETED | 4 | 4 |
Reasons for not completing this period:
| Reason | SCY-078 Plus Voriconazole | Voriconazole Mono-therapy |
|---|---|---|
| Adverse Event | 3 | 1 |
| Physician Decision | 0 | 1 |
| Withdrawal by Subject | 1 | 2 |
Analysis population for the primary outcome, as defined in the registry: Safety population including any participant treated with at least one dose of Voriconazole or SCY-078
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
| Characteristic | Unit | SCY-078 Plus Voriconazole | Voriconazole Mono-therapy | Total |
|---|---|---|---|---|
| Participants analysed | 10 | 12 | 22 | |
| Age, Continuous | years | 61.7 (SD 10.57) | 62.7 (SD 14.08) | 62.2 (SD 12.33) |
| Sex: Female, Male: Female | Participants | 3 | 2 | 5 |
| Sex: Female, Male: Male | Participants | 7 | 10 | 17 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 9 | 10 | 19 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 1 | 2 | 3 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 1 | 0 | 1 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 1 | 1 | 2 |
| Race (NIH/OMB): White | Participants | 8 | 10 | 18 |
| Race (NIH/OMB): More than one race | Participants | 0 | 1 | 1 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Treatment-emergent Adverse Events (TEAEs), Drug-related Adverse Events (AEs), Discontinuations Due to AEs and Deaths, measured over Up to a maximum of 19 weeks.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is described as the number of participants with treatment-emergent adverse events, drug-related adverse events, discontinuations due to adverse events, and deaths. It is a safety endpoint reported in participant counts, with observation up to a maximum of 19 weeks. The stated population includes any participant treated with at least one dose of voriconazole or SCY-078.
These categories capture different safety information. A treatment-emergent event is an event recorded after treatment begins; that timing alone does not establish that treatment caused it. A drug-related event reflects an attribution of relationship to a drug. Discontinuation due to an adverse event records a treatment consequence, while death is a distinct outcome. Combining them into one count would obscure these differences, so each category needs to be interpreted on its own terms.
Safety endpoints are used to describe the kinds and frequency of events observed during exposure and follow-up. Counts can identify events that warrant attention, but they do not by themselves establish comparative risk or causality. Interpretation also depends on how events were defined, collected, attributed, and followed. Those detailed procedures are not reported in the registry record.
The registry presents group counts for serious events, other events, and deaths, but the posted information does not give a full separate result for every component named in the primary endpoint. In particular, the corresponding values for all treatment-emergent events, drug-related events, and discontinuations are not reported in the registry record. These available safety counts should therefore not be mistaken for a complete result set for every part of the primary endpoint.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record provides descriptive safety counts for the two treatment groups. For SCY-078 plus voriconazole, it reports 6 participants with a serious event among 10 at risk, 10 with other events among 10 at risk, and 3 deaths. For voriconazole monotherapy, it reports 5 participants with a serious event among 12 at risk, 11 with other events among 12 at risk, and 1 death. These are observed counts as recorded, not adjusted estimates or tests of a treatment difference.
The counts do not, on their own, show whether the groups differed because of treatment. The study is small, and sparse event counts can be highly influenced by the experience of individual participants. Randomization helps support a fair comparison in principle, but chance differences between groups may remain. The registry does not provide confidence intervals, p-values, adjusted estimates, or a specified statistical comparison for these safety summaries.
The labels also matter. “Serious” and “other” event counts are not interchangeable with the primary endpoint’s complete set of treatment-emergent and drug-related events, discontinuations, and deaths. The record does not provide enough detail to map every event category onto the primary endpoint or to know whether participants could appear in more than one category. A participant count is not an event count: one participant may have experienced more than one event, but that detail is not reported in the registry record.
The registry lists serious-event terms and percentages, including haemophagocytic lymphohistiocytosis at 20.0%, anemia at 10.0%, febrile neutropenia at 10.0%, thrombocytopenia at 10.0%, atrial fibrillation at 10.0%, and vomiting at 10.0%. The record does not specify the treatment group or denominator for each listed percentage in the information summarized. These percentages should not be assigned to a group or treated as comparative estimates.
There are no listed analysis results for the secondary outcomes, despite their inclusion in the registry. The record therefore does not support a statistical interpretation of response, galactomannan changes, or drug concentrations. Nor does it report a formal comparison of the safety counts. A lack of reported inferential analysis is not evidence that groups are equal; it means the registry record does not quantify uncertainty around a treatment contrast.
The study is marked terminated, but the reason is not reported in the registry record. Termination alone does not explain why the study ended or what conclusions should be drawn. The record supports a descriptive account of the posted safety figures and the design context, while leaving efficacy findings, uncertainty estimates, and the circumstances of termination unresolved.
9. Statistical Methods Explained
Because the primary outcome is expressed as participant counts, the basic descriptive unit is the number of people in each group who met a particular event definition. A count is easy to read, but it depends on the number of participants observed and the length and completeness of follow-up. The registry also gives the number at risk for the reported group summaries, which supplies context for those counts. The figures should still be read as descriptions of this study, not as a stable estimate of what would occur in other populations.
What does randomization contribute?
In general, randomization assigns participants to treatment groups using a chance-based process. Its purpose is to reduce systematic differences between groups, including differences that researchers may not have measured. It does not ensure that every characteristic is balanced, particularly in a small study. Randomization also does not prevent missing observations, deviations from assigned treatment, or differences in care after assignment. The registry record states that the study was randomized but does not report the sequence-generation method, allocation concealment, or allocation ratio.
What does masking mean?
In general, masking limits knowledge of assigned treatment for people involved in a study. It can reduce the opportunity for expectations to affect care, event reporting, or assessment. The official title describes this study as double-blind, while the design information says quadruple-masked. Those labels do not identify the specific roles masked, the method used to maintain masking, or whether masking remained intact. Such details are not reported in the registry record, so the labels should not be expanded into assumptions about exactly who knew what.
How should event counts be interpreted?
A count of participants with an event answers how many participants met a definition, not how many total episodes occurred. If a participant had repeated events, a participant-level count may still count that person once for the category. Whether the registry’s event summaries use that convention for each category is not described in the information summarized. Event definitions, severity grading, coding, attribution, and rules for counting multiple events are also not reported in the registry record.
In general, a confidence interval describes the range of values reasonably compatible with observed data under a statistical model. For an event count or a treatment contrast, an interval helps communicate uncertainty that a point estimate alone cannot show. The registry record lists no confidence intervals or other uncertainty estimates for these group summaries. Consequently, readers cannot use the posted counts to assess the precision of a comparative effect.
Why does the safety population matter?
The stated safety population includes any participant treated with at least one dose of voriconazole or SCY-078. This is an exposure-based definition: it focuses on participants who received study treatment rather than everyone who may have been randomized. In general, a safety population is useful for describing events among exposed participants. It may differ from an analysis population used to estimate an efficacy effect. The registry record does not report a separate intention-to-treat population, a per-protocol population, or detailed participant flow.
The record reports no analysis results and no inferential comparison for the listed outcomes. It also does not give a statistical analysis plan, methods for handling missing data, adjustments for baseline characteristics, or rules for censoring follow-up. These absences prevent reconstruction of a planned or adjusted analysis. Descriptive counts remain interpretable as posted, but their limitations should not be filled in with assumptions about methods that are not documented.
What is the role of a planning illustration?
In general, a sample-size calculation estimates how many participants may be needed to detect a specified effect under stated assumptions. It is a planning exercise, not an observed finding and not proof that a completed study had adequate power. The registry’s stated illustration assumptions use a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect defined as a stated fraction of the observed effect. For time-to-event settings, the described approach concerns total events; other settings use participants per arm. The primary outcome has several categories and is not reduced to a single comparison, so no sample-size illustration is available for one primary contrast. Any such planning values would also depend on assumptions that may not match the study’s actual design.
General statistical interpretation should distinguish descriptive evidence from comparative inference. Counts identify what the registry recorded in each group. A valid estimate of a treatment difference would require a defined contrast and a method for quantifying its uncertainty. Neither is listed for these safety counts. The posted data therefore support description, not a precise estimate of comparative effect.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists nine outcome measures, including the primary safety outcome and secondary measures of response, death, galactomannan index, and SCY-078 and voriconazole plasma concentrations. When a study evaluates multiple outcomes, time points, or comparisons, the chance of finding at least one apparently notable result can increase. In general, a prespecified statistical plan may address this through a hierarchy of outcomes or other multiplicity procedures. The statistical plan and any multiplicity adjustment are not reported in the registry record.
The record lists no analysis results. It therefore does not show which outcomes were analyzed, which time points were selected for reporting, or whether any outcome was omitted from analysis. The listed secondary outcomes should be read as registered measures, not as evidence that results were posted or that a particular analysis was conducted.
Missing-data handling is also not reported in the registry record. The safety population definition indicates treatment exposure, but does not state how participants with incomplete follow-up were handled, whether outcome data were missing, or whether any imputation method was used. The registry record also does not report participant flow by analysis population or reasons for missing observations.
For a reader, these gaps matter because outcome selection, multiplicity, and missingness can affect how results should be interpreted. Without a documented analysis plan and reported results, it is not possible to assess whether analyses followed prespecified methods or how incomplete data might influence estimates. No assumption about those procedures is warranted from the posted information.
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 |
|---|---|---|---|
| SCY-078 Plus Voriconazole | 6 | 10 | 60.0% |
| Voriconazole Mono-therapy | 5 | 12 | 41.7% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| SCY-078 Plus Voriconazole | 3 of 10 |
| Voriconazole Mono-therapy | 1 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 |
|---|---|
| SCY-078 Plus Voriconazole | 10 of 10 |
| Voriconazole Mono-therapy | 11 of 12 |
Most frequent serious adverse event terms
| Event term | Organ system | SCY-078 Plus Voriconazole | Voriconazole Mono-therapy |
|---|---|---|---|
| Haemophagocytic lymphohistiocytosis | Immune system disorders | 2 of 10 | 0 of 12 |
| Anemia | Blood and lymphatic system disorders | 1 of 10 | 0 of 12 |
| Febrile Neutropenia | Blood and lymphatic system disorders | 1 of 10 | 0 of 12 |
| Thrombocytopenia | Blood and lymphatic system disorders | 1 of 10 | 0 of 12 |
| Atrial fibrillation | Cardiac disorders | 1 of 10 | 0 of 12 |
| Colitis | Gastrointestinal disorders | 0 of 10 | 1 of 12 |
| Vomiting | Gastrointestinal disorders | 1 of 10 | 0 of 12 |
| Disease progression | General disorders | 1 of 10 | 0 of 12 |
| Multiple organ dysfunction syndrome | General disorders | 0 of 10 | 1 of 12 |
| Hypertransaminasaemia | Hepatobiliary disorders | 1 of 10 | 0 of 12 |
Most frequent non-serious adverse event terms
| Event term | Organ system | SCY-078 Plus Voriconazole | Voriconazole Mono-therapy |
|---|---|---|---|
| Nausea | Gastrointestinal disorders | 5 of 10 | 1 of 12 |
| Photopsia | Eye disorders | 2 of 10 | 2 of 12 |
| Atrial fibrillation | Cardiac disorders | 1 of 10 | 2 of 12 |
| Diarrhoea | Gastrointestinal disorders | 3 of 10 | 0 of 12 |
| Vomiting | General disorders | 3 of 10 | 0 of 12 |
| Hypertransaminasaemia | Hepatobiliary disorders | 2 of 10 | 1 of 12 |
| Oral herpes | Infections and infestations | 0 of 10 | 3 of 12 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 0 of 10 | 3 of 12 |
| Dizziness | Nervous system disorders | 2 of 10 | 1 of 12 |
| Acute kidney injury | Renal and urinary disorders | 1 of 10 | 2 of 12 |
Serious events with the highest arm-level rate: haemophagocytic lymphohistiocytosis (20.0%), anemia (10.0%), febrile neutropenia (10.0%), thrombocytopenia (10.0%), atrial fibrillation (10.0%).
The registry reports three kinds of group-level safety counts. In the SCY-078 plus voriconazole group, the serious-event summary is 6 affected among 10 at risk, the other-event summary is 10 among 10 at risk, and the death count is 3. In the voriconazole monotherapy group, the corresponding figures are 5 among 12 at risk, 11 among 12 at risk, and 1 death. These are counts, not adjusted comparisons.
The serious-event terms listed include haemophagocytic lymphohistiocytosis, anemia, febrile neutropenia, thrombocytopenia, atrial fibrillation, and vomiting, with percentages reported for each term. The registry record does not specify the group or denominator for those term-level percentages in the information summarized. They therefore cannot be used to compare treatment groups or to infer the number of affected participants in a particular arm.
Serious events, other events, and deaths represent different summaries. They should not be combined or substituted for the full primary endpoint categories. The registry does not report a statistical test, confidence interval, or adjusted estimate for these figures. In general, safety counts describe what was observed, while comparative conclusions require attention to follow-up, event definitions, uncertainty, and study context.
12. What the Result Does, and Does Not, Mean
The posted results offer a descriptive view of safety observations in a randomized phase 2 study of SCY-078 plus voriconazole versus voriconazole monotherapy. The registry reports group counts for serious events, other events, and deaths. It also identifies serious-event terms and percentages, although the group and denominator associated with those percentages are not stated in the information summarized.
These figures do not establish that the treatment groups had the same or different safety profiles. The record gives no uncertainty estimates or formal comparison for the counts, and the study enrollment was 22. A small study can produce imprecise estimates, particularly for uncommon events. The available information does not quantify that imprecision, so a precise difference or a claim of equivalence cannot be inferred.
The record also does not provide analysis results for the listed secondary outcomes, which include response, galactomannan changes, and drug concentrations. The safety data cannot answer whether the regimens differed on those outcomes. Nor do event counts by themselves determine whether an event was caused by a treatment; attribution requires clinical and methodological information not reported in the registry record.
The study’s terminated status is recorded, but the reason for termination is not reported. That status should not be treated as a result or explanation of the safety data. Overall, the record permits a limited description of the posted safety counts and design, but does not support a definitive comparative conclusion or an efficacy conclusion.
13. Why This Trial Matters Statistically
This study is statistically informative as an example of the distance between a registered clinical question and a fully interpretable comparative result. The trial was randomized and parallel, and it set out to compare coadministration of SCY-078 with voriconazole against voriconazole alone. Its primary endpoint covers several distinct safety categories rather than one simple measurement. That structure makes clear endpoint definitions and separate reporting important.
The record also illustrates why a count should not be mistaken for a treatment effect. Counts describe observed participants, while a comparative estimate needs an explicit contrast and a way to express uncertainty. Without those elements, differences between groups cannot be assessed as more than descriptive observations. This is especially relevant when a study has limited enrollment and some safety events are uncommon.
Registration lists secondary outcomes concerning clinical response, mortality, galactomannan, and drug concentrations. Yet the record contains no analysis results for those outcomes. The distinction between outcome registration and result reporting is central: naming a measure does not reveal its result, precision, or analysis method.
Finally, a terminated status does not explain a study’s course. In the absence of a reported reason, statistical interpretation should remain focused on what the registry actually records: a randomized design, a defined safety population, and selected safety counts. The case underscores the value of transparent reporting of analysis plans, participant flow, outcome definitions, missing-data handling, uncertainty estimates, and reasons for study completion or termination.
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.
Several trial-specific limits constrain interpretation. Enrollment was 22, and the registry reports no confidence intervals or inferential comparisons for the safety counts. Small studies can yield imprecise estimates, and sparse events make a group comparison especially sensitive to individual observations. The record does not quantify this uncertainty, so the counts should not be treated as precise estimates of comparative risk.
The primary endpoint includes multiple categories, but the posted group summaries do not provide a full breakdown for every component. The record does not report separate values for all treatment-emergent events, drug-related events, or discontinuations due to adverse events. It also does not state whether participants could be counted in multiple categories or provide detailed event definitions and adjudication procedures.
The serious-event term percentages lack a stated group and denominator in the information summarized. This limits their interpretation and prevents an arm-specific reading. The registry also does not report follow-up completeness, participant flow, missing-data methods, or whether the reported at-risk counts correspond to complete observation for the maximum 19-week timeframe.
The record lists no analysis results for secondary outcomes and no statistical analysis plan, multiplicity approach, or reason for termination. The treatment-arm descriptions are incomplete for SCY-078 dosing. Further details on eligibility, allocation procedures, masking roles, and analysis populations are not reported in the registry record. These gaps mean that the posted data support only a narrow descriptive account, not a comprehensive appraisal of comparative safety or efficacy.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Evaluate Safety and Efficacy of the Coadministration of Ibrexafungerp With Voriconazole in Patients With Invasive Pulmonary Aspergillosis — NCT03672292.
- Registry record last updated 2024-08-09; status last verified 2024-08.
- Results first posted 2024-08-09.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
NCT03672292 is a randomized, parallel-group phase 2 study in invasive pulmonary aspergillosis. It compared SCY-078 plus voriconazole with voriconazole monotherapy and used placebo tablets matching SCY-078 in the comparator arm. The registry reports enrollment of 22, a terminated status, a start date of 2019-01-22, and primary completion on 2023-03-27.
The primary outcome concerns counts of treatment-emergent adverse events, drug-related adverse events, discontinuations due to adverse events, and deaths, with follow-up up to a maximum of 19 weeks. The registry gives group summaries for serious events, other events, and deaths, but no inferential comparison or uncertainty estimates. No analysis results are listed for the secondary outcomes. The reason for termination, detailed analysis methods, missing-data handling, and fuller outcome results are not reported in the registry record.