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 Dose-Escalation Safety and Pharmacokinetic Study of K305 (NCT01304316), a na phase 2 study. The primary outcome is Cmax of Oxymetazoline.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01304316 |
| Phase | Phase 2 |
| Condition | Anesthesia |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 12 |
| Arms in the primary outcome | n/a |
| Lead sponsor | St. Renatus, LLC |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned healthy volunteers, as stated in its official title. The registry record lists enrollment of 12 participants. It does not report further participant characteristics or eligibility details in the information available for this trial.
Intervention
Participants received intranasal tetracaine hydrochloride with oxymetazoline hydrochloride, identified as Kovacaine Nasal Spray. The listed standard dose was 6 sprays of 0.1 mL, for totals of 18 mg tetracaine HCl and 0.3 mg oxymetazoline HCl. This was followed by 12 sprays of 0.1 mL, for totals of 36 mg tetracaine HCl and 0.6 mg oxymetazoline HCl.
Comparator
The registry describes a single-group study with allocation listed as not applicable and no masking. It does not describe a randomized control group or a like-for-like comparison. The standard-dose and high-dose labels should therefore be read in the context of the listed dose escalation, not as evidence of independently assigned comparison groups.
Primary question
The primary outcome was the maximum plasma concentration, or Cmax, of oxymetazoline, measured in ng/mL. The study description focused on pharmacokinetics and pharmacodynamics, safety, and cardiovascular changes after intranasal administration. Numerical Cmax results are not reported in the registry record, so the recorded information does not establish the size or precision of the observed concentration response.
3. Trial Design
This completed Phase 2 study was titled as a dose-escalation safety and pharmacokinetic study of K305. The official title identifies healthy volunteers and describes cardiovascular changes and tetracaine pharmacokinetics after standard and high doses of Kovacaine Mist, a combination of tetracaine hydrochloride and oxymetazoline hydrochloride. The brief description says the purpose was to assess pharmacokinetics, pharmacodynamics and safety of the nasal spray.
The registry lists enrollment of 12, a single-group model, allocation as not applicable, and no masking. It does not describe a randomized comparison. The dose description lists 6 sprays of 0.1 mL, totaling 18 mg tetracaine HCl and 0.3 mg oxymetazoline HCl, followed by 12 sprays of 0.1 mL, totaling 36 mg tetracaine HCl and 0.6 mg oxymetazoline HCl. This sequence is consistent with the dose-escalation framing, but details about the protocol and how participants proceeded through the dose levels are not reported in the registry record.
The study start is listed as 2010-09, primary completion as 2010-11, and status as completed. The primary outcome was Cmax of oxymetazoline. Secondary outcomes included maximum changes from baseline in pulse oximetry, diastolic blood pressure, systolic blood pressure and pulse rate. The registry lists 10 outcome measures, but it does not report numerical results for the primary endpoint in the available record. It also lists no analyses. Allocation, masking, the detailed visit schedule and the full analysis plan 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 | Kovacaine Nasal Spray |
|---|---|
| STARTED | 12 |
| COMPLETED | 12 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: Only 11 subjects in the 0.3 mg dose group had sufficient concentration levels to calculate Cmax.
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 | Kovacaine Nasal Spray |
|---|---|---|
| Participants analysed | 12 | |
| Age, Continuous | years | 30.2 (SD 7.45) |
| Sex: Female, Male: Female | Participants | 6 |
| Sex: Female, Male: Male | Participants | 6 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 1 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 11 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 1 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 1 |
| Race (NIH/OMB): White | Participants | 10 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Cmax of Oxymetazoline, measured over Baseline, 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120 minutes.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | ng/mL |
| Endpoint classification | Continuous Endpoint |
The primary endpoint was Cmax of oxymetazoline, expressed in ng/mL. Cmax is the highest observed concentration of a substance in plasma over the relevant sampling period. It is used in pharmacokinetic research to describe the peak systemic concentration after administration. The value alone does not describe the full concentration-time profile, total exposure, or clinical consequences.
The registry describes an extra-vascular, non-compartmental approach to deriving pharmacokinetic parameters. It says estimates use observed plasma concentrations, the administered dose, area-under-the-curve values and the terminal elimination-phase rate constant for each dose group. The listed sampling time points extend from baseline through 120 minutes. Such concentration data can help characterize how a drug is absorbed and present in plasma over time after administration; the registry does not provide enough numerical results to describe the resulting profile.
The primary outcome is reported as a mean with standard deviation. The record says only 11 subjects in the 0.3 mg dose group had sufficient concentration levels to calculate Cmax. This indicates that the endpoint could not be calculated for every participant in that dose group, but the reasons and handling of unavailable measurements are not reported in the registry record. Numerical means, standard deviations, confidence intervals and statistical comparisons for Cmax are also not reported in the registry record. Consequently, the endpoint definition can be described, but its observed magnitude and precision cannot be assessed from the recorded information.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies Cmax of oxymetazoline as the primary outcome, but it does not report a numerical Cmax estimate or its standard deviation. It also lists zero analyses. Therefore, the registry record does not establish the measured peak concentration, the variability among participants, or a statistical estimate of the difference between dose levels. It would be inappropriate to infer these findings from the study title, dose descriptions or stated purpose.
The record notes that only 11 subjects in the 0.3 mg dose group had enough concentration data to calculate Cmax. This is important when considering how much evidence the primary endpoint could represent: at least one subject in that group did not contribute a calculable Cmax. The reason for the insufficient concentration data and the method for handling that unavailable endpoint are not reported in the registry record. The information also does not say whether all enrolled participants contributed to every secondary outcome.
The study is described as single-group, with allocation listed as not applicable and masking as none. The registry specifically flags that the arms are not a like-for-like control comparison. In this setting, the standard-dose and high-dose labels do not support treating the groups as randomized, independent arms. The intervention description lists a standard dose followed by a high dose, but further details about sequence, timing and analysis are not reported in the registry record. Differences between dose-labelled groups, if reported elsewhere, would need interpretation in light of the study design rather than as an unbiased randomized treatment contrast.
The safety record lists no serious adverse events among the 12 participants at risk in either the standard-dose or high-dose category. It lists other adverse events among 8 of 12 at risk in the standard-dose category and 12 of 12 in the high-dose category. These counts describe the registry’s categories; they do not establish a causal dose effect. The record does not explain whether participants in the two categories are distinct or represent exposure during sequential dose escalation. Death counts are not reported in the registry record.
Overall, the registry documents the study’s purpose, design labels, dose descriptions, outcome definitions and selected safety counts, but not numerical primary-endpoint findings or inferential analyses. The evidence that can be interpreted from this record is therefore limited to those design and safety descriptions. It cannot establish a precise pharmacokinetic estimate, a comparative effect, or a clinical conclusion.
9. Statistical Methods Explained
The registry describes the primary endpoint as a continuous measure: Cmax of oxymetazoline in ng/mL, summarized as a mean and standard deviation. A mean describes the average observed value in the analyzed participants. A standard deviation describes how dispersed individual values are around that average. These are different summaries: the mean concerns the group’s central value, while the standard deviation concerns participant-to-participant variability. The registry does not report either numerical summary for Cmax.
What does Cmax represent?
Cmax is the maximum plasma concentration observed over the sampling period. It is one pharmacokinetic summary, not a complete description of drug exposure. It does not, by itself, indicate how long concentrations remain elevated or the total concentration over time. The record lists a series of time points from baseline through 120 minutes. A concentration-time profile can show how concentrations change across those observations, while Cmax reduces that profile to its maximum value.
The endpoint description says pharmacokinetic parameters were derived using an extra-vascular, non-compartmental analysis. In general, non-compartmental methods summarize observed concentration data without requiring the data to be represented by a specified compartment model. The record says the derivation used observed plasma concentrations, administered dose, area-under-the-curve values and the terminal elimination-phase rate constant for each dose group. The actual calculations, concentration values and resulting estimates are not reported in the registry record.
How should a mean and standard deviation be read?
In general, a mean is most informative when read alongside the number of participants contributing data and a measure of uncertainty. A standard deviation characterizes spread among observations, but it is not itself a confidence interval for the mean. A confidence interval, when reported, gives a range of values compatible with the data and the analysis assumptions, and communicates uncertainty about an estimated parameter. No confidence interval for the primary endpoint is reported in the registry record.
The registry states that only 11 subjects in the 0.3 mg dose group had sufficient concentration levels to calculate Cmax. That statement identifies a limitation in the available endpoint data for that group. It does not explain why a value was unavailable or how the analysis dealt with it. Without the numerical estimates and further details, neither the observed spread nor the precision of the mean can be evaluated.
What does the design imply for comparisons?
The study is recorded as single-group, with allocation not applicable and no masking. The registry also notes that it is not a randomized comparison and that the arms are not a like-for-like control comparison. General statistical interpretation of a dose-escalation study differs from interpretation of a randomized parallel-group trial: observed differences associated with dose categories can reflect the dose sequence, time, or other factors, as well as dose itself. The registry does not report enough design detail to determine how such factors were addressed. It does not report a comparative estimate or an inferential test.
For general context, a statistical test evaluates how compatible observed data are with a specified null hypothesis under the test’s assumptions. A p-value is not a measure of effect size or clinical importance. A confidence interval helps communicate precision, but neither a p-value nor interval can be interpreted for the primary endpoint because numerical analyses are not reported in the registry record. The record lists zero analyses.
How do the planning illustrations differ from trial findings?
Planning illustrations based on an observed effect are not observed trial outcomes and are not observed power. In general, such illustrations estimate the participants per arm that might be required under stated assumptions, including significance level, allocation, an approximation method and a chosen fraction of an observed effect. The stated assumptions for the illustrations are a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect defined as a fraction of the observed effect. These are planning assumptions, not evidence that the study used that design or that it had a particular probability of detecting an effect.
The trial itself is recorded as single-group, not a randomized equal-allocation comparison. The registry does not report the trial’s own sample-size justification or its statistical plan. Thus, planning illustrations should not be read as a reconstruction of the study design. Nor can they compensate for the missing endpoint estimates or establish that the study was adequately powered.
Why can over-dispersion matter?
In general, over-dispersion occurs when observed variability is greater than a statistical model assumes. It can make standard errors and uncertainty estimates too small if the model does not accommodate the extra variability. This concept is relevant when interpreting models for count or event outcomes, but the registry record does not report a model for the listed safety outcomes. The primary outcome is described as a continuous measure, and no fitted model or variance adjustment is reported. Over-dispersion should not be presumed to have been assessed in this trial.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 10 outcome measures, including Cmax of oxymetazoline as the primary outcome and secondary measures of maximum change from baseline in pulse oximetry, diastolic blood pressure, systolic blood pressure and pulse rate. When multiple outcomes or analyses are examined, general statistical practice considers whether the chance of a false-positive finding is increased and whether any adjustment or hierarchy was specified. The registry record does not report a multiplicity strategy, a hierarchy beyond identifying the primary outcome, or numerical analyses for these outcomes.
The registry lists zero analyses. It therefore does not provide tests, confidence intervals, model specifications or adjustment details for the primary or secondary outcomes. Whether any interim analyses were planned or conducted is not reported in the registry record. The statistical analysis plan is not reported in the registry record.
For the primary endpoint, the record says only 11 subjects in the 0.3 mg dose group had sufficient concentration levels to calculate Cmax. The reason for the unavailable value and the approach to missing concentration measurements are not reported in the registry record. The record does not specify an analysis population, such as whether all enrolled participants or only participants with evaluable measurements were included in each analysis. It also does not describe how missing data for cardiovascular outcomes were handled.
These omissions limit assessment of selection and analysis choices. Without a prespecified analysis plan and numerical results, readers cannot determine whether outcomes were analyzed as intended, whether all available participants contributed, or whether multiplicity or missingness affected uncertainty. Those details should not be inferred from the endpoint labels or study purpose.
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 |
|---|---|---|---|
| Standard K305 Dose | 0 | 12 | 0.0% |
| High K305 Dose | 0 | 12 | 0.0% |
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 |
|---|---|
| Standard K305 Dose | 8 of 12 |
| High K305 Dose | 12 of 12 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Standard K305 Dose | High K305 Dose |
|---|---|---|---|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | 6 of 12 | 9 of 12 |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | 5 of 12 | 9 of 12 |
| Headache | Nervous system disorders | 3 of 12 | 3 of 12 |
| Nasal discomfort | Respiratory, thoracic and mediastinal disorders | 0 of 12 | 4 of 12 |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | 2 of 12 | 1 of 12 |
| Throat irritation | Respiratory, thoracic and mediastinal disorders | 0 of 12 | 2 of 12 |
| Upper-airway cough syndrome | Respiratory, thoracic and mediastinal disorders | 0 of 12 | 2 of 12 |
| Tinnitus | Ear and labyrinth disorders | 0 of 12 | 1 of 12 |
| Nausea | Gastrointestinal disorders | 0 of 12 | 1 of 12 |
| Vomiting | Gastrointestinal disorders | 0 of 12 | 1 of 12 |
The registry lists serious adverse events for two dose categories. For the standard K305 dose, 12 participants were at risk and 0 were recorded as affected by a serious adverse event. For the high K305 dose, 12 were at risk and 0 were recorded as affected. These are counts within the registry’s categories; they do not show that the categories are independent groups or that the study had a randomized comparison.
For other adverse events, the registry lists 8 affected participants among 12 at risk in the standard-dose category and 12 among 12 at risk in the high-dose category. These figures describe participants with events, not the total number of event episodes or their severity. The registry does not provide the event terms or further detail for these other events in the information recorded. No serious adverse-event terms are listed.
The study is described as a single-group dose-escalation study. The record does not explain whether the same participants contributed to both dose categories or how exposure sequence was handled in these safety summaries. The counts therefore should not be interpreted as a controlled comparison or as evidence that dose caused a difference. Death counts are not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The record identifies a small Phase 2 dose-escalation study in healthy volunteers, with a primary pharmacokinetic endpoint and cardiovascular and safety outcomes. It documents the two dose descriptions and selected adverse-event counts. Those details clarify what the trial set out to examine and how the intervention was described.
However, the registry record does not report numerical results for Cmax of oxymetazoline, despite identifying it as the primary endpoint. It does not provide its mean, standard deviation, confidence interval or a statistical comparison. It also lists no analyses. The record therefore cannot show the measured peak concentration or how precisely it was estimated. The note that 11 subjects in the 0.3 mg dose group had sufficient levels to calculate Cmax further indicates that not every subject in that group contributed a calculable endpoint, while the reason and handling are not documented.
The safety counts show no recorded serious adverse events among the participants at risk in either dose category. Other adverse events were recorded in the counts listed for each category. Without event descriptions and clarification of participant overlap and dose sequence, those numbers do not establish a causal relationship or support a valid comparative conclusion. The registry’s own note that this was not a randomized comparison is especially important.
These findings do not establish whether the product is effective or ineffective, nor do they establish clinical benefit or harm. The study description and safety counts should not be treated as a substitute for endpoint estimates, uncertainty intervals or a complete analysis. The evidence in the registry record supports a description of the research question, design labels and reported counts, but not a definitive estimate of pharmacokinetic response or a treatment comparison.
13. Why This Trial Matters Statistically
This trial is statistically informative in part because its design labels shape what can be inferred. It is recorded as a single-group study with no masking and allocation listed as not applicable. The dose description presents a standard dose followed by a high dose, and the registry warns that the arms are not a like-for-like control comparison. That context matters: dose-labelled categories should not automatically be treated as randomized parallel groups.
The primary endpoint also illustrates the distinction between defining a measure and reporting evidence about it. Cmax is clearly named, its unit is given, and the registry describes the non-compartmental derivation. Yet the numerical endpoint results and analyses are absent. A well-defined outcome alone does not provide an estimate, uncertainty, or basis for comparing dose levels.
The note that only 11 subjects in the 0.3 mg dose group had sufficient concentration data to calculate Cmax draws attention to endpoint availability. Knowing how many participants contribute to an analysis is essential for understanding its scope and precision. The record does not explain why the endpoint was unavailable for the remaining subject or how missing measurements were handled.
Finally, the adverse-event counts demonstrate why safety summaries need design context and event detail. Counts can describe what was recorded, but they do not by themselves establish causation or comparison. Together, the trial’s single-group structure, limited enrollment, unavailable endpoint result and absent analysis details make careful separation of recorded details from unsupported inference especially important.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The registry record contains limited results for evaluating the primary objective. It identifies Cmax of oxymetazoline as the primary outcome and describes its units and derivation, but does not report numerical endpoint values, measures of uncertainty or inferential analyses. It lists zero analyses. Consequently, the magnitude and precision of the primary pharmacokinetic result cannot be assessed.
The record lists enrollment of 12 and says only 11 subjects in the 0.3 mg dose group had sufficient concentration levels to calculate Cmax. It does not explain why data were insufficient for the other subject or how unavailable values were handled. Details about participant characteristics, eligibility, withdrawals and analysis populations are not reported in the registry record.
The study is identified as single-group, with allocation not applicable and no masking. The dose sequence is described, but further protocol details, including how participants proceeded through dose escalation and the timing of measurements relative to administration, are not reported in the registry record. The registry itself cautions that the dose categories are not a like-for-like control comparison, limiting causal interpretation of differences between them.
The safety information lists serious and other adverse-event counts but does not provide the terms for other events or explain possible overlap between dose categories. Death counts are not reported in the registry record. The statistical analysis plan, multiplicity approach, missing-data methods, sample-size justification and any interim analyses are also not reported in the registry record. These gaps limit assessment of both the completeness and the inferential strength of the recorded findings.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Dose-Escalation Safety and Pharmacokinetic Study of K305 — NCT01304316.
- Registry record last updated 2017-08-31; status last verified 2017-07.
- Results first posted 2017-08-31.
- 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
NCT01304316 is a completed Phase 2 study titled as a dose-escalation safety and pharmacokinetic study of K305. It enrolled 12 participants and is described as a single-group study with allocation not applicable and no masking. The official title identifies healthy volunteers and intranasal Kovacaine Mist, containing tetracaine hydrochloride and oxymetazoline hydrochloride.
The dose description lists 6 sprays of 0.1 mL, totaling 18 mg tetracaine HCl and 0.3 mg oxymetazoline HCl, followed by 12 sprays of 0.1 mL, totaling 36 mg tetracaine HCl and 0.6 mg oxymetazoline HCl. Cmax of oxymetazoline was the primary outcome. The registry says 11 subjects in the 0.3 mg dose group had sufficient concentration levels to calculate it, but numerical results and analyses are not reported in the registry record.
The safety categories list no serious adverse events among 12 participants at risk in either category. Other adverse events were recorded among 8 of 12 at risk in the standard-dose category and 12 of 12 in the high-dose category. The registry warns that this is not a randomized, like-for-like comparison.