Efficacy, Tolerability, PK of OZ439 in Adults With Acute, Uncomplicated P.Falciparum or Vivax Malaria Mono-infection: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy, Tolerability, PK of OZ439 in Adults With Acute, Uncomplicated P.Falciparum or Vivax Malaria Mono-infection (NCT01213966), a non-randomized phase 2 study. The primary outcome is Derived Parasite Reduction Rate at 24 Hours (PPR24).

2. Clinical Question

The study's stated aims also included preliminary assessment of tolerability and pharmacokinetics. These aims describe what the study set out to assess; they do not establish what the results showed. Although the registry records 82 enrolled participants and four dose cohorts, it does not report infection-type breakdowns, cohort assignment details, or a control condition for interpreting changes in parasite counts.

3. Trial Design

This was a Phase IIa exploratory, open-label study of OZ439 in adults with acute, uncomplicated falciparum or vivax malaria mono-infection. The registry classifies allocation as non-randomized, masking as none, and the model as single group. These design features mean that the listed dose cohorts were not allocated through a randomized comparison, and treatment was not masked.

The registry lists four cohorts: OZ439 200 mg, 400 mg, 800 mg, and 1200 mg, each described as a single oral dose. The adverse-event record gives cohort sizes at risk of 20, 20, 20, and 21, respectively. The overall recorded enrollment is 82. The registry does not explain how participants were assigned to cohorts or whether cohort entry was sequential.

The study description refers to single-dose and multiple-dose testing, while the arm descriptions in the record identify single-dose cohorts. The detailed regimen beyond those arm descriptions is not reported in the registry record. The primary endpoint was the derived parasite reduction rate at 24 hours after study drug administration. The registry gives it as a median, with full range as the dispersion measure.

There is no randomized comparator arm, and the registry explicitly flags the arms as not being a like-for-like control comparison. Differences across dose cohorts could reflect factors besides dose, but the registry record does not provide information that would allow those factors to be assessed. The record is marked completed, and enrollment was 82. Further details on recruitment, follow-up, protocol deviations, and the analysis population 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.

Before assignment: There was no washout, run-in or transition following enrolment but prior to group assignment.

Overall Study

Reasons for not completing this period:

5. Baseline Characteristics

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

6. Primary Endpoint

The registry lists the primary outcome as Derived Parasite Reduction Rate at 24 Hours (PPR24), measured over 24 hours after study drug administration.

The primary endpoint is the derived parasite reduction rate at 24 hours, abbreviated PPR24, with units of log10 parasites per 24 hours. It is intended to characterize the change in parasite count over the period after study drug administration. Parasite counts were measured at multiple time points, and a regression model was fitted separately for each patient.

According to the registry description, the model allowed for a variable lag phase followed by a linear decline in the relationship between time and the natural logarithm of parasite count. The slope of that log-linear relationship was designated the primary endpoint. The endpoint description calls the measure a log10 change in parasitemia over 24 hours; the registry does not report the actual cohort medians or full ranges.

Using repeated measurements in a patient-level model is a way to describe the pattern of parasite counts over time rather than relying only on a single pair of measurements. A lag phase allows the fitted pattern to include an interval before the modeled decline. These are general features of the stated approach, not evidence that a particular decline occurred in this study.

The registry says the selected regression time points were those yielding the highest significance when assessing the regression, when the number of time points was at least 3. It also says that no extrapolation was performed. The endpoint's result, its uncertainty, and the analysis population used to derive it are not reported in the registry record. Without those results, the size and precision of the observed parasite reduction cannot be characterized.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

How is PPR24 constructed?

The registry describes a patient-level regression of parasite counts over time. The model first allows a variable lag phase and then fits a linear decline to the relationship between time and the natural logarithm of parasite count. The slope of that log-linear relationship is designated the primary endpoint. The endpoint is expressed as a log10 change in parasitemia over 24 hours.

In general, regression estimates a trend by relating observed values to a predictor, in this case time. Modeling each patient separately means that the endpoint is derived from that patient's measurements rather than from a single pooled regression across all participants. The registry does not provide the individual measurements, fitted slopes, or the transformation details needed to reproduce the reported endpoint.

What does the lag phase allow?

As a general modeling concept, a lag phase allows the fitted pattern to include an initial interval that does not follow the later linear trend. This can be useful when the time course is not well represented by one straight line from the start. The record says that a variable lag phase was fitted but does not report the estimated lag periods or describe how they varied across participants.

The registry also states that when there were at least 3 time points, the chosen time points were those yielding the highest degree of significance when assessing the regression. Selecting time points based on the strength of a fitted relationship can affect how the resulting slope should be interpreted. The record does not give further detail about the selection procedure, its prespecification, or any adjustment for that selection.

Why does the record say no extrapolation was performed?

In general, extrapolation means extending a fitted trend beyond the range of observed data. The registry states that no extrapolation was performed. This indicates that the endpoint was not described as relying on a projected trend outside the observations used for fitting. The record does not give the measurement schedule or the observed time range, so the extent of the data supporting each fitted slope cannot be assessed.

What does median with full range convey?

The registry specifies the median as the summary measure and the full range as the dispersion measure. In general, the median describes the middle of an ordered set of values, while the full range identifies its endpoints. The full range gives information about spread but can be strongly influenced by extreme values; it is not a confidence interval and does not directly express uncertainty about the median. Neither the median nor the range is numerically reported for PPR24 in the registry record.

A confidence interval, as a general statistical concept, describes a range of values compatible with an estimate under a specified procedure and assumptions. No confidence interval for PPR24 is reported. Without an estimate and an uncertainty measure, the precision of the primary endpoint cannot be evaluated.

How should the dose cohorts be compared?

The registry classifies allocation as non-randomized and the model as single group. Randomization is a general method for making treatment groups comparable, on average, with respect to measured and unmeasured characteristics. Because this study is not described as randomized and has no listed control group, the dose cohorts should not be treated as randomized, like-for-like comparisons. The record does not report how participants entered each cohort or whether cohort characteristics differed.

The dose descriptions identify single oral doses of 200 mg, 400 mg, 800 mg, and 1200 mg. They do not establish that dose was the only difference between cohorts. If outcome values differ across cohorts, the record alone cannot separate a dose-related pattern from other possible differences in participants, timing, or study conduct.

What can the safety counts establish?

The registry lists the number at risk and the number affected by serious and other adverse events for each cohort. These are descriptive counts. In general, counts can show how many participants in a recorded group had an event, but interpretation also depends on event definitions, follow-up, exposure, and how events were collected. Details on these matters are not reported in the registry record.

For other adverse events, the record lists 4 affected in the 800 mg cohort, 6 in the 400 mg cohort, 10 in the 200 mg cohort, and 8 in the 1200 mg cohort. For serious adverse events, it lists 0 affected in the 800 mg and 400 mg cohorts, and 1 affected in the 200 mg and 1200 mg cohorts. The record does not give event-level timing or causal attribution. These counts should not be interpreted as evidence of a comparative effect between doses.

What statistical planning information is missing?

The registry record does not report the statistical analysis plan, any sample-size justification, interim analyses, or a planned multiplicity procedure. It also does not report confidence intervals, p-values, or the primary endpoint values. General explanations of these methods cannot fill those gaps: without the registered analysis details and the endpoint results, it is not possible to determine how the primary analysis was conducted beyond the endpoint description or how its precision was assessed.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 1 outcome measure and 1 analysis, and identifies PPR24 as the primary endpoint. It does not report a statistical plan explaining whether additional analyses or comparisons were planned, or how multiplicity was handled. Multiplicity refers, in general, to the issue that conducting several statistical tests can increase the chance of obtaining an apparently notable result by chance. Whether that issue arose in this study cannot be determined from the registry record.

The record does not report interim analyses, prespecified dose comparisons, or adjustments for selecting regression time points. It says that, when at least 3 time points were available, the time points yielding the highest degree of significance in assessing the regression were selected. Further information about whether this procedure was prespecified or how its statistical implications were considered is not reported in the registry record.

Enrollment was 82, but the number included in the primary endpoint analysis is not reported. The registry does not describe missing parasite measurements, exclusions, withdrawals, or how incomplete data were handled. It also does not identify an analysis population, such as all enrolled participants or participants meeting a stated analysis definition. These details matter because the analyzed participants and their available measurements determine which observations contribute to the result.

The record gives a median and full range as the intended endpoint summary but does not provide those values, a confidence interval, or a p-value. The statistical plan and missing-data procedures are not reported in the registry record. As a result, the endpoint's numerical estimate, its precision, and the sensitivity of the result to missing data cannot be assessed.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: malaria relapse (5.0%), pyelonephritis (4.8%).

The registry lists serious adverse events for each OZ439 cohort. In the 800 mg cohort, 0 of 20 participants at risk were listed as affected; in the 400 mg cohort, 0 of 20; in the 200 mg cohort, 1 of 20; and in the 1200 mg cohort, 1 of 21. The record separately lists other adverse events: 4 of 20, 6 of 20, 10 of 20, and 8 of 21 participants affected in those cohorts, respectively.

These are cohort-level counts, not randomized comparisons. The record does not report event timing, duration, severity grading beyond the serious-event category, causal attribution, or whether participants could contribute more than one event. The registry also lists Malaria relapse at 5.0% and Pyelonephritis at 4.8% among the top serious-event terms, without linking those terms to specific cohorts in the record.

Deaths are not reported in the registry record. The counts describe events recorded during the study; without further details they cannot establish that OZ439 caused an event or that one dose had a different safety profile from another. They also do not provide a comparison with untreated participants or another treatment.

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

This registry record documents an exploratory Phase IIa study of OZ439 in adults with acute, uncomplicated falciparum or vivax malaria mono-infection. It identifies a model-derived parasite reduction rate at 24 hours as the primary endpoint and describes the regression approach used to derive it. It also records four single-dose cohorts and adverse-event counts.

The record does not report the numerical PPR24 result. Without the median and full range, there is no basis in this record for describing the observed endpoint value or its variability. The record also does not report a confidence interval or other uncertainty measure, so the precision of the endpoint cannot be characterized.

The design was open label, non-randomized, and classified as single group. The cohorts were not randomized control groups, and the registry explicitly cautions that the arms are not a like-for-like control comparison. Therefore, the design does not support treating differences among cohorts as randomized evidence of a dose effect. No conclusion about comparative efficacy or safety follows from the cohort labels alone.

The study description states that preliminary efficacy, tolerability, and pharmacokinetics were assessed. Those objectives are not results. The registry record does not report pharmacokinetic findings or a numerical efficacy result, and it does not provide enough detail to determine how missing measurements or the analysis population were handled.

The adverse-event counts indicate how many participants in each cohort were recorded as affected, but do not establish causation or comparative risk. Event attribution, timing, and other interpretive details are not reported. The record is therefore useful for understanding the study's basic design and endpoint method, while leaving the primary outcome's magnitude and precision unresolved.

13. Why This Trial Matters Statistically

This study is statistically notable for defining a patient-level, time-course endpoint rather than relying only on a single parasite-count measurement. The endpoint description specifies a variable lag phase followed by a linear decline in log parasite count, with the fitted slope serving as the primary measure. This makes the modeling choices, measurement schedule, and data available for each patient important to interpretation.

The registry also illustrates why a detailed endpoint method is not a substitute for a reported result. Although the method and summary form are described, the median PPR24 and full range are not reported. Without the estimate and its uncertainty, readers cannot assess the magnitude or precision of the primary outcome from this record.

Its design is equally important to statistical interpretation. The study was non-randomized and single group, with dose cohorts rather than a randomized control arm. That structure can support descriptive reporting of outcomes within cohorts, but it limits the extent to which differences among cohorts can be interpreted as effects caused by dose. The record itself cautions that the arms are not like-for-like control comparisons.

Finally, the record makes visible distinctions between study aims, endpoint construction, and results. It identifies preliminary efficacy, tolerability, and pharmacokinetics as objectives, but does not report the primary endpoint value or pharmacokinetic findings. For clinical researchers, this is a reminder that registry descriptions can establish what was intended and how an endpoint was defined while still leaving key result and analysis details unreported.

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 most important limitation for interpreting the primary endpoint is that its numerical result is not reported in the registry record. The median PPR24, full range, and any confidence interval are absent. The record describes how the endpoint was modeled but does not provide the measurements, fitted slopes, or sufficient detail to reproduce the calculation.

The time-point selection rule also deserves attention. The record states that when the number of time points was at least 3, the points yielding the highest degree of significance when assessing the regression were chosen. It does not state whether this selection rule was prespecified or how its impact on inference was addressed. The measurement schedule and the number of observations available for each patient are not reported.

Because the study was open label and non-randomized, with no listed control arm, comparisons across the dose cohorts are not randomized comparisons. The record does not explain how participants were assigned to cohorts, nor does it give cohort characteristics that could help assess whether groups were comparable. The single-group classification and absence of a like-for-like control constrain causal interpretation.

The registry records 82 enrolled participants but does not report the primary analysis population, the number with usable endpoint data, or how missing observations and withdrawals were handled. The statistical analysis plan, sample-size justification, interim analyses, and multiplicity approach are also not reported in the registry record.

For safety, the record gives affected counts and selected serious-event terms but lacks details on event timing, attribution, and ascertainment. Deaths are not reported in the registry record. These gaps limit interpretation of both the primary endpoint and the adverse-event summaries.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Efficacy, Tolerability, PK of OZ439 in Adults With Acute, Uncomplicated P.Falciparum or Vivax Malaria Mono-infection — NCT01213966.
• Registry record last updated 2014-12-03; status last verified 2014-11.
• Results first posted 2014-11-18.
• 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.

18. Record Summary

The registry record describes NCT01213966, a completed, open-label Phase IIa exploratory study of OZ439 in adults with acute, uncomplicated falciparum or vivax malaria mono-infection. It records 82 enrolled participants and a non-randomized, single-group design. Listed cohorts received single oral doses of 200 mg, 400 mg, 800 mg, or 1200 mg OZ439.

The primary endpoint was derived parasite reduction rate at 24 hours, reported by design as a median with full range. It was estimated using a regression fitted separately for each patient, with a variable lag phase followed by a linear decline in log parasite count. The endpoint result is not reported in the registry record.

The registry includes cohort-level serious and other adverse-event counts, but does not report detailed event attribution or timing. The analysis population, missing-data handling, confidence intervals, statistical plan, and sample-size justification are not reported in the registry record.