Effectiveness of OZ439 Against Early Plasmodium Falciparum Blood Stage Infection in Healthy Volunteers: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effectiveness of OZ439 Against Early Plasmodium Falciparum Blood Stage Infection in Healthy Volunteers (NCT02453581), a non-randomized phase 1 study. The primary outcome is Individual Parasite Reduction Ratio (PRR).

2. Clinical Question

The endpoint addresses parasite-density change after treatment in a controlled infection model. It is not a direct comparison of clinical outcomes in patients with naturally acquired malaria. The registry describes the study as an assessment of three dose levels, but it does not report a randomized dose comparison or numerical PRR results. Consequently, the statistical question that can be described is the calculation of individual PRR estimates for the 500mg cohort, rather than a quantified contrast between doses.

3. Trial Design

This was a Phase 1 study of OZ439 against early Plasmodium falciparum blood-stage infection in healthy volunteers. The registry describes a single-centre, open, controlled study using a blood-stage challenge inoculum. Its design model is parallel, allocation is non-randomized, and masking is none. The study status is completed. The recorded start is 2012-09 and primary completion is 2013-03.

The intervention was OZ439, listed as a drug and administered in oral suspension at 100mg, 200mg, or 500mg. The registry lists a cohort for each dose. The outcome description specifies that PRR calculations were undertaken only for subjects receiving 500mg in Cohort 3. For the 100mg and 200mg cohorts, the registry states that the doses were inadequate to eliminate parasites and regrowth occurred. These are important features of the endpoint population; the record does not give the individual PRR calculations for those cohorts.

Although the study is described as controlled, its non-randomized allocation and lack of masking limit the interpretation of comparisons across dose groups. The groups are not randomized, like-for-like control comparisons, and the registry does not report an untreated control arm. A dose-group difference, if estimated, would not on its own isolate a causal effect of dose from other differences between groups or their study conduct.

The sponsor is Medicines for Malaria Venture. The registry lists OZ439 Cmax and OZ439 AUC(0-144) as secondary outcomes. It identifies four outcome measures and zero analyses. The record does not report further details about cohort assignment procedures, follow-up beyond the stated endpoint timeframe, or the statistical 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

Analysis population for the primary outcome, as defined in the registry: As the doses of 100 mg and 200 mg of OZ439 in Cohorts 1 and 2 were inadequate to eliminate the parasites and regrowth occurred, PRR calculations were only undertaken for subjects receiving 500mg of OZ439 in Cohort 3.

5. Baseline Characteristics

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

Population: All subjects enrolled in the study received a single dose of OZ439.

6. Primary Endpoint

The registry lists the primary outcome as Individual Parasite Reduction Ratio (PRR), measured over 48 hours.

The primary outcome is the individual parasite reduction ratio (PRR), a ratio with no physical unit. The registry defines PRR as an estimate of antimalarial treatment efficacy based on the ratio of parasite density between admission and 48 hours after treatment. It reports that each individual subject’s PRR and corresponding 95% confidence interval were calculated using the slope and corresponding standard error of the mean from an optimal regression model.

In general, a parasite-density reduction measure is used to describe how parasite burden changes over a specified interval after treatment. A ratio provides a scale for expressing the change, while an individual estimate preserves information about variation between subjects rather than reducing the data to one group-level value. The confidence interval conveys the statistical precision of an estimate under the model used; it does not guarantee that the model is correct or that the result applies beyond the studied population and setting.

The registry sets the timeframe at 48 hours and restricts the PRR calculations to subjects in the 500mg Cohort 3. It explains that the 100mg and 200mg doses were inadequate to eliminate parasites and regrowth occurred, so PRR calculations were not undertaken for those subjects. Numerical PRR estimates, confidence limits, and a group summary are not reported in the registry record. Thus the endpoint’s definition and calculation method are described, but the magnitude and precision of the measured PRR cannot be assessed from the reported results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry says that individual PRR estimates and corresponding 95% confidence intervals were calculated from the slope and corresponding standard error of the mean from an optimal regression model. It does not describe the model’s functional form, the observations included in the fit, the criteria used to select the optimal model, or diagnostic checks. Those details are not reported in the registry record, so the exact calculation cannot be independently reproduced from the description alone.

What does a regression slope contribute?

In general, regression describes how an outcome changes in relation to another variable or over a sequence of observations. A slope represents the estimated rate or direction of that change under the specified model. In this study, the registry says the slope was used to calculate PRR, with its standard error contributing to the uncertainty estimate. The record does not state the specific regression equation or how parasite density was transformed, if at all. Neither detail should be inferred from the endpoint label.

A standard error describes the estimated sampling variability of a statistic under the model. A confidence interval combines an estimate with an uncertainty measure to express a range of values compatible with the data and model at the stated confidence level. In general, narrower intervals indicate greater precision, while wider intervals indicate less precision. The registry specifies 95% confidence intervals but does not report their numerical limits. Their width, or the precision of individual PRR estimates, therefore cannot be judged.

Why does the analysis population matter?

The registry states that calculations were undertaken only for subjects receiving 500mg in Cohort 3. It says the 100mg and 200mg doses were inadequate to eliminate parasites and regrowth occurred, which is why those subjects were not included in PRR calculations. This restriction means the primary endpoint results, if reported, would describe the specified cohort rather than a pooled estimate across all three dose groups. The record does not provide further information about exclusions, missing measurements, or the number of subjects contributing to the regression calculations.

In general, an analysis population should be clearly defined because changing which participants or observations contribute can change the estimand and the interpretation of a result. Here, the population restriction is stated in the outcome description, but the record does not describe additional population rules. It is therefore not possible to determine from the registry record whether all eligible subjects in Cohort 3 contributed measurements at every relevant time point, or how incomplete observations were handled.

What can be inferred from the study design?

The study was open, with no masking, and non-randomized, despite being described as controlled. In general, random allocation helps make groups comparable on measured and unmeasured characteristics in expectation; non-random allocation does not provide that protection. Lack of masking can also affect behavior, assessment, or reporting, depending on the setting and outcome. These are general design considerations, not evidence that a particular bias occurred in this study. The record does not report a randomized control comparison, so the three dose cohorts should not be treated as interchangeable arms in a randomized trial.

The study’s blood-stage challenge model and healthy-volunteer population define the context for interpreting the endpoint. The primary measure is parasite density over the stated 48-hour timeframe, not a clinical endpoint in a patient population. Generalization beyond this controlled study setting requires evidence not contained in the registry record.

What is the role of the sample-size illustrations?

Any sample-size values associated with the study are planning illustrations based on an observed effect, not the trial’s original design or observed power. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. For time-to-event outcomes, the illustration convention is a total number of events; for other outcomes, it is participants per arm. These are general planning assumptions, not results from the trial. The registry record does not report an original sample-size justification, and the primary effect estimate needed to evaluate an effect-based planning illustration is not reported.

More generally, sample-size calculations describe the amount of information a future study might need under chosen assumptions. They do not establish that a completed study had a particular probability of detecting an effect, and they are not a measure of the strength or validity of its findings. Assumptions about effect size, variability, allocation, and analysis all matter. The record does not report an observed-power analysis or the trial’s own statistical plan.

The record contains no numerical primary endpoint estimate, confidence limits, or comparative analysis. Thus, the calculation method can be explained conceptually, but its numerical output and the adequacy of the model cannot be evaluated. Any further statistical detail—including model selection, handling of repeated measurements, multiplicity adjustments, or sensitivity analyses—is not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry identifies four outcome measures and zero analyses. It lists individual PRR as the primary outcome and OZ439 Cmax and OZ439 AUC(0-144) among the secondary outcomes. The information available does not specify how the four measures were defined in full, whether any additional outcomes were tested, or whether a hierarchy of hypotheses was prespecified. A multiplicity strategy is not reported in the registry record.

In general, multiplicity arises when several outcomes, comparisons, time points, or analyses are considered. If each is tested separately, the chance of at least one chance finding can increase. Statistical plans may address this through a prespecified hierarchy or an adjustment, but the appropriate approach depends on the study questions and design. No adjustment, testing hierarchy, or confirmatory analysis strategy is described, so none should be assumed.

Missing-data handling and analysis populations are also not reported in the registry record. The endpoint description says PRR calculations were limited to subjects receiving 500mg in Cohort 3, but does not explain whether all such subjects had complete measurements, how incomplete data were treated, or whether any subjects were excluded for other reasons. The registry does not describe an intention-to-treat, per-protocol, or other named analysis population. These omissions limit the ability to assess how the reported analysis would represent the enrolled cohort, even apart from the absence of numerical PRR results.

The record also does not report interim analyses, a data-monitoring procedure, or a detailed statistical analysis plan. Their presence or absence cannot be inferred beyond what is recorded. In general, prespecified methods help readers distinguish planned analyses from choices made after examining data; without documentation, that distinction cannot be evaluated. The zero analyses entry and missing numerical results mean that multiplicity, missingness, and analysis-population decisions cannot be assessed from the registry record.

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 non-serious adverse event terms

The registry reports serious adverse events by dose group. For OZ439 100mg, zero subjects were affected among 8 at risk; for OZ439 200mg, zero were affected among 8 at risk; and for OZ439 500mg, zero were affected among 8 at risk. These are the serious-event figures recorded for the listed groups. The registry lists no serious adverse-event terms.

The record separately reports other adverse events: 1 subject affected in the 100mg group, 3 in the 200mg group, and 1 in the 500mg group, with 8 at risk in each group. These counts should not be combined with the serious-event figures; the registry distinguishes the categories. The deaths field is null for each group, so deaths are not reported in the registry record.

In general, a count of zero recorded serious events does not establish that an intervention is free of risk. Safety counts are interpreted in light of the population, observation period, event definitions, and completeness of reporting. The registry information does not describe those details or provide a formal comparison between groups. The study’s non-randomized design also means the dose groups are not like-for-like control arms. These safety counts therefore describe what the registry recorded and do not establish comparative safety.

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

The study offers a defined experimental setting for observing early blood-stage Plasmodium falciparum infection in healthy volunteers after OZ439 treatment. Its primary endpoint is an individual parasite reduction ratio over 48 hours, calculated from a regression slope with a corresponding 95% confidence interval. The registry also reports that only the 500mg Cohort 3 subjects were included in PRR calculations, because the 100mg and 200mg doses were described as inadequate to eliminate parasites and regrowth occurred.

What the record does not provide is the numerical PRR result or its confidence interval. Without those values, it is not possible to assess the estimated magnitude, precision, or range of individual responses. Nor does the record report a quantitative comparison between dose groups. The non-randomized allocation and absence of masking matter when considering any comparison: the groups were not assigned as randomized, like-for-like arms, and the registry cautions against treating them as such.

The outcome is a parasite-density measure in a challenge study, not a direct measure of clinical benefit in people with naturally acquired malaria. In general, findings from a controlled infection model and healthy-volunteer population have a defined scope; applying them to a different population or clinical setting requires additional evidence. The registry record alone does not establish how the findings relate to outcomes outside the study setting.

The reported safety counts are also limited in scope. They indicate zero subjects affected by serious adverse events in each listed group and report other adverse events separately. They do not, by themselves, establish a comparative safety profile, particularly without details about observation and event ascertainment. Overall, the record supports a description of the endpoint, study design, and recorded adverse-event counts. It does not support a numerical conclusion about PRR, a randomized dose comparison, or a broad claim about treatment effects.

13. Why This Trial Matters Statistically

This trial is statistically notable for the way its primary measure is defined and restricted. The registry describes individual parasite reduction ratios rather than a single pooled outcome and specifies that each estimate is paired with a 95% confidence interval based on a regression slope and standard error. That approach makes both the estimated change and its uncertainty relevant to interpretation. However, the registry does not report the resulting estimates or intervals, so their statistical precision cannot be examined.

The record also makes the analysis population part of the scientific interpretation: PRR calculations were conducted only for subjects receiving 500mg in Cohort 3. The stated reason is that the 100mg and 200mg doses were inadequate to eliminate parasites and regrowth occurred. This distinction prevents the endpoint from being misread as a common measure reported across every dose cohort.

Design information is equally important. The study is described as controlled, but allocation was non-randomized and masking was absent. These features mean that dose groups should not be interpreted as randomized comparison arms. General statistical reasoning emphasizes that observed group differences in non-randomized designs can reflect factors other than the intervention contrast. The registry’s warning against a like-for-like comparison is therefore central to reading the study, not a minor technical qualification.

Finally, the record illustrates the difference between a defined statistical method and an interpretable numerical result. The endpoint, timeframe, and general calculation approach are recorded, yet the PRR estimates and confidence intervals are not. Without them, readers cannot evaluate effect magnitude or precision. The study remains informative about how the outcome was intended to be assessed, while the posted information leaves the primary numerical result unavailable.

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 direct limitation of the registry information is that it does not report numerical PRR estimates or their 95% confidence intervals. As a result, the primary outcome’s size and precision cannot be evaluated. The method is described in broad terms, but the model specification, model-selection criteria, and diagnostic checks are not reported in the registry record, preventing independent reproduction or assessment of the regression approach.

PRR calculations were limited to the 500mg Cohort 3 subjects. The registry states that the 100mg and 200mg doses were inadequate to eliminate parasites and regrowth occurred, but provides no corresponding PRR calculations for those groups. The record also does not report the number of subjects with complete endpoint data, the handling of missing measurements, or additional analysis-population rules.

The open, non-randomized design constrains dose-group interpretation. Although the study is described as controlled, the registry cautions that the arms are not a like-for-like control comparison. There is no basis in the record for treating comparisons across dose groups as randomized estimates of a causal dose effect. The healthy-volunteer blood-stage challenge setting also limits the scope of what the study directly describes; it is not a clinical-outcome study in a patient population as.

Further limitations include the absence of a detailed statistical analysis plan, a reported multiplicity strategy, and numerical results for the listed secondary outcomes. The registry identifies four outcome measures and zero analyses, but does not provide enough information to assess prespecification, interim analyses, or sensitivity analyses. Safety reporting gives event counts, but details of ascertainment and observation are not reported. These gaps limit statistical and clinical interpretation without changing the registry entries that are recorded.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Effectiveness of OZ439 Against Early Plasmodium Falciparum Blood Stage Infection in Healthy Volunteers — NCT02453581.
• Registry record last updated 2015-08-17; status last verified 2015-08.
• Results first posted 2015-07-13.
• 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 completed Phase 1 study evaluated OZ439 in healthy volunteers using a single-centre blood-stage Plasmodium falciparum challenge model. It was open, non-randomized, and parallel, and the registry describes it as controlled. The recorded study start is 2012-09, with primary completion in 2013-03.

The primary endpoint was individual PRR over 48 hours, calculated from a regression slope with a corresponding 95% confidence interval. Calculations were undertaken only for subjects receiving 500mg in Cohort 3; the registry states that the 100mg and 200mg doses were inadequate to eliminate parasites and regrowth occurred. Numerical PRR results are not reported in the registry record.

The record lists OZ439 Cmax and AUC(0-144) as secondary outcomes, four outcome measures, and zero analyses. Serious adverse events affected zero subjects in each dose group; other adverse events were reported separately. Because allocation was non-randomized, the dose groups are not like-for-like control arms. The record does not report the detailed statistical plan, missing-data methods, or numerical primary endpoint estimates.