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 First-in-Human Trial of Single Ascending Dose, Multiple Ascending Dose and Malaria Challenge Model in Healthy Participants (NCT03261401), a randomized phase 1 study. The primary outcome is Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation of Study Treatment.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03261401 |
| Phase | Phase 1 |
| Condition | Healthy |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 88 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Merck KGaA, Darmstadt, Germany |
| Results posted | Yes |
2. Clinical Question
Population
Healthy adult male and female participants, as described in the official title. The registry identifies the condition as healthy. The overall enrollment was 88, across the study's parts and dose cohorts; the cohort-specific safety counts show that group sizes varied.
Intervention
Oral M5717 at ascending single doses in Part A and at 150 mg, 400 mg or 800 mg in Part C, the malaria challenge component. Part A also included pooled placebo. The registry title refers to single and multiple ascending doses, but specific multiple-dose schedules are not reported in the registry record.
Comparator
Part A included pooled placebo matched to M5717. The listed Part C cohorts received M5717 after malaria inoculation; a Part C placebo arm is not described in the registry record. The design is identified as randomized, double-blind and parallel, but cohort-level allocation details are not reported in the registry record.
Primary question
How many participants experienced treatment-emergent adverse events, serious treatment-emergent adverse events, or treatment-emergent adverse events leading to study-treatment discontinuation during baseline up to Day 55? The study also aimed to characterize M5717 pharmacokinetics and the relationship between drug exposure and parasite clearance after Plasmodium falciparum infection.
This is principally an early-phase safety and characterization question, not a definitive comparison of clinical benefit. The primary outcome is a count of participants with event categories, rather than a continuous measure or time-to-event endpoint. Its stated population for Part A is the Safety Analysis Set: participants who received investigational medicinal product, either M5717 or placebo. Safety counts are reported separately across dose cohorts, with the placebo group pooled. The registry does not provide a single adjusted comparison between M5717 and placebo, and the posted counts do not establish whether an event was caused by treatment. The malaria challenge component addresses antimalarial activity in a controlled infection model, but parasite-clearance estimates are not reported in the registry record. Thus the question has two distinct parts: the tolerability of exposure in healthy participants and the relationship between M5717 exposure and parasite clearance in the challenge setting. The available event counts speak only to the safety part; they do not answer the pharmacokinetic or parasite-clearance questions.
3. Trial Design
The registry identifies this study as Phase I, randomized, double-blind and parallel, with overall enrollment of 88. Its official title describes a first-in-human investigation of single and multiple ascending doses of oral M5717, together with a malaria challenge model. The study status is completed. The reported start date is 2017-09-15 and the primary completion date is 2019-06-14.
Part A comprises single ascending dose cohorts and a pooled placebo group. The listed M5717 dose cohorts were 50 mg, 100 mg, 200 mg, 400 mg, 600 mg, 1000 mg, 1250 mg, 1800 mg and 2100 mg. The descriptions state that dosing was oral, after an 8-hour fasting period, with a 4-hour post-dose fast. The placebo description also specifies a 50 milligram (mg) matched capsule. The title refers to multiple ascending doses, but specific multiple-dose arms, schedules and results are not reported in the registry record.
Part C involved healthy participants given a single oral M5717 dose after intravenous malaria inoculation. The listed doses were 150 mg, 400 mg and 800 mg, administered eight days after the inoculum; the descriptions also specify fasting around dosing. The registry's intervention list includes M5717 and placebo, but the listed challenge cohorts do not describe a placebo group.
The reported primary safety timeframe was baseline up to Day 55. Part A's safety population included participants who received M5717 or placebo. Cohort-specific allocation methods, the number assigned to each arm before treatment, masking procedures in practice, and the protocol's sample-size justification are not reported in the registry record. The total enrollment does not establish the number analyzed in every outcome or cohort. The design and small, unequal group sizes make the event counts useful as descriptive early-phase observations, while limiting the precision and scope of comparisons.
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: The study was planned to be conducted in 3 parts: Part A, B and C. Part B of the study was optional and sponsor decided not to perform part B of the study. In each cohort of Part A, participants were randomized in a 6:2 ratio to receive M5717 or matching placebo.
Only the first 6 of 13 groups are shown.
Overall Study
| Stage | Part A: Placebo (Pooled) | Part A: Cohort 1 SAD: M5717 50 mg | Part A: Cohort 2 SAD: M5717 100 mg | Part A: Cohort 3 SAD: M5717 200 mg | Part A: Cohort 4 SAD: M5717 400 mg | Part A: Cohort 5 SAD: M5717 600 mg |
|---|---|---|---|---|---|---|
| STARTED | 17 | 6 | 6 | 6 | 6 | 6 |
| COMPLETED | 17 | 6 | 6 | 6 | 6 | 5 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 1 |
Reasons for not completing this period:
| Reason | Part A: Placebo (Pooled) | Part A: Cohort 1 SAD: M5717 50 mg | Part A: Cohort 2 SAD: M5717 100 mg | Part A: Cohort 3 SAD: M5717 200 mg | Part A: Cohort 4 SAD: M5717 400 mg | Part A: Cohort 5 SAD: M5717 600 mg |
|---|---|---|---|---|---|---|
| Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 1 |
| Participant Unable To Attend Final Visit | 0 | 0 | 0 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Safety Analysis Set included all participants who received investigational medicinal product (M5717 or placebo for Part A).
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: Safety Analysis Set included all participants who received investigational medicinal product (M5717 or placebo for Part A; M5717 for Part C).
Only the first 6 of 14 groups are shown.
| Characteristic | Unit | Part A: Placebo (Pooled) | Part A: Cohort 1 SAD: M5717 50 mg | Part A: Cohort 2 SAD: M5717 100 mg | Part A: Cohort 3 SAD: M5717 200 mg | Part A: Cohort 4 SAD: M5717 400 mg | Part A: Cohort 5 SAD: M5717 600 mg |
|---|---|---|---|---|---|---|---|
| Participants analysed | 17 | 6 | 6 | 6 | 6 | 6 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 | 0 | 0 | 2 |
| Age, Categorical: Between 18 and 65 years | Participants | 17 | 6 | 6 | 6 | 6 | 4 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Sex: Female, Male: Female | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Sex: Female, Male: Male | Participants | 17 | 6 | 6 | 6 | 6 | 6 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 1 | 1 | 1 | 0 | 1 | 1 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 16 | 5 | 5 | 6 | 5 | 5 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 1 | 1 | 0 | 1 | 0 |
| Race (NIH/OMB): Asian | Participants | 2 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 1 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 1 | 0 | 1 | 0 | 0 | 0 |
| Race (NIH/OMB): White | Participants | 13 | 4 | 4 | 6 | 5 | 6 |
| Race (NIH/OMB): More than one race | Participants | 1 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation of Study Treatment, measured over Baseline up to Day 55.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint counts participants with treatment-emergent adverse events (TEAEs), serious TEAEs, and TEAEs that led to discontinuation of study treatment. The registry defines an adverse event as an untoward medical occurrence after study drug administration, whether or not it is considered related to the medicinal product. A TEAE is an event that starts or worsens after the first intake of study drug. Serious events are defined by outcomes such as death, a life-threatening event, persistent or significant disability or incapacity, initial or prolonged inpatient hospitalization, congenital anomaly or birth defect, or another medically important event.
This endpoint is used in an early-phase study to describe tolerability and identify clinically important safety events during exposure and follow-up. Counting participants, rather than all event episodes, answers how many people had at least one event in a category. A participant may have more than one event, but the participant count does not reveal how many total episodes occurred, their duration, severity apart from seriousness, timing, or cause. The primary outcome title includes treatment discontinuations, but separate discontinuation counts are not reported in the registry record.
For Part A, the specified population is the Safety Analysis Set, consisting of participants who received investigational medicinal product. The timeframe is baseline up to Day 55. These definitions clarify the endpoint's scope, but the posted group counts do not provide event narratives or a causal assessment. Accordingly, they describe reported safety observations and do not by themselves demonstrate that M5717 caused or did not cause an event.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted safety counts are descriptive and vary across the dose cohorts. In Part A, the pooled placebo group had 17 participants at risk for serious events and 17 at risk for other events. No serious events were reported; 13 participants had other reported events. Among the M5717 single-dose cohorts, the 50 mg group had 6 participants at risk for other events and 6 affected; the 100 mg group had 6 at risk and 5 affected; the 200 mg group had 6 at risk and 3 affected; the 400 mg group had 6 at risk and 4 affected; the 600 mg group had 6 at risk and 3 affected; the 1000 mg group had 6 at risk and 4 affected; the 1250 mg group had 6 at risk and 5 affected; the 1800 mg group had 6 at risk and 6 affected; and the 2100 mg group had 1 at risk and 1 affected. No serious events were reported in these listed Part A groups.
In Part C, the 150 mg cohort had 6 participants at risk for other events and 6 affected; the 400 mg cohort had 8 at risk and 8 affected; and the 800 mg cohort had 8 at risk and 7 affected. No serious events were reported in the listed Part C groups. Deaths were reported as zero in every listed group. These are counts of participants with events, not counts of event episodes. The registry does not provide a corresponding treatment-discontinuation breakdown or more detailed event descriptions in the posted results.
The counts do not form a direct dose-response pattern that can be interpreted reliably from these data alone. Cohorts are small, some sizes differ, and the placebo group is pooled while M5717 is listed by dose. The challenge cohorts also differ in context from the Part A dose-escalation cohorts. The registry record does not report confidence intervals, hypothesis tests, adjusted comparisons, or a formal dose-trend analysis for these safety counts. Therefore, the counts should not be read as precise estimates of event rates or as evidence of a between-group effect.
Zero reported serious events and deaths are observations in the listed groups, not proof that such outcomes are impossible or that risk is absent. With limited group sizes, uncommon events could remain unobserved. Conversely, the frequency of other reported events does not establish that study drug caused them: the registry definition explicitly includes events regardless of whether they are considered related. Pharmacokinetic measures, parasite clearance results, and the statistical analysis of those outcomes are not reported in the registry record, so the posted safety counts cannot answer those efficacy-related or exposure-response questions.
9. Statistical Methods Explained
Statistical interpretation depends first on what is counted and who is included. The primary endpoint is a count of participants with event categories, not a comparison of event episodes. The registry defines TEAEs by their timing in relation to the first study-drug intake: an event must start or worsen after that point. The safety population for Part A includes participants who received M5717 or placebo. This approach describes events among exposed participants; it does not include people who were randomized but never received study product, if any. Whether there were such participants, and how they were handled in other analyses, is not reported in the registry record.
What participant counts can and cannot say
For each group, the number at risk provides the denominator for the reported count of participants affected. A participant is counted as affected if they experienced at least one event in the relevant category. These counts do not indicate the total number of event episodes, and they do not show whether one participant had repeated events. Nor do they convey event duration, severity apart from the serious-event classification, clinical details, or relatedness to M5717. The registry record does not give a separate count for TEAEs leading to treatment discontinuation.
A comparison of raw counts between groups requires care because group sizes vary. Counts from groups of different sizes are not directly comparable as measures of frequency. Even when denominators are similar, small cohorts provide limited information about the range of plausible event frequencies. General statistical principle: estimates based on few participants are usually less precise than estimates based on many participants, and absence of observed events does not establish absence of risk. No confidence intervals or formal comparisons for these safety counts are reported in the registry record.
Randomization, masking and dose cohorts
Randomization and double blinding can reduce certain sources of bias in a trial, as a general methodological principle. However, the registry's broad design labels do not specify the allocation sequence, concealment procedures, masking implementation, or cohort-level allocation. Part A includes pooled placebo and multiple separate M5717 dose groups; Part C is a challenge setting with three listed M5717 dose groups. This means the safety counts should be read in their cohort and study-part context rather than treated as one simple comparison. The description does not establish that Part C had a placebo group.
Ascending-dose studies commonly explore tolerability over increasing exposure, but the specific escalation rules and dose-selection rationale are not reported in the registry record. The listed Part A doses alone do not establish that each cohort was enrolled sequentially under a particular decision rule. The title refers to multiple ascending doses, while the listed arms chiefly describe single ascending doses and challenge doses; the multiple-dose schedules are not reported in the registry record. No conclusion about unlisted dose periods or their results can be drawn from the listed safety groups.
Uncertainty, testing and multiplicity
General statistical principle: a confidence interval expresses the range of values compatible with the data under a specified method and assumptions. It helps distinguish a point estimate from its uncertainty. Without intervals or another uncertainty measure, the event counts give no direct quantitative indication of precision. The registry lists zero analyses for the reported outcomes, and no inferential analysis of the primary safety outcome is reported. It is therefore not possible to assess a prespecified testing procedure, adjustment for multiple comparisons, or a statistical model from the registry record.
Multiplicity arises when many outcomes, doses, time points or comparisons are assessed; repeated testing can increase the chance of a nominally notable result arising by chance. This trial lists a primary safety outcome and multiple pharmacokinetic secondary outcomes, and describes more than one study part. Whether a formal multiplicity strategy was specified or used is not reported in the registry record. General explanation of over-dispersion is not pertinent to the posted primary data: the outcome is a participant count with group denominators, not a reported count model with a variance assumption. No model-based estimates are reported for these event counts.
Planning calculations are not trial results
General statistical principle: sample-size planning asks how many participants might be needed under stated assumptions to detect a specified effect with a chosen error rate. A planning illustration is not an observed treatment effect, does not show the probability that the completed trial detected an effect, and cannot substitute for outcome estimates or uncertainty intervals. The stated planning assumptions use a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect expressed as a fraction of an observed effect. The registry does not report the trial's own sample-size justification. In particular, no planning illustration changes the interpretation of the observed safety counts or supplies missing analyses.
10. Multiplicity, Missing Data and Analysis Populations
The registry record does not report a multiplicity-control plan, a hierarchy of hypothesis tests, or a confirmatory testing strategy. It lists a primary safety outcome and multiple secondary pharmacokinetic outcomes, with several dose cohorts and study parts. General statistical principle: when many outcomes, doses or comparisons are examined, the chance of at least one apparently unusual finding can rise if each is tested independently. Whether that concern was addressed in the protocol or analysis is not reported in the registry record. No analysis results are listed for the outcomes, so there are no reported p-values or inferential comparisons to interpret for multiplicity.
Missing-data methods are also not reported in the registry record. The posted safety counts identify participants at risk in each listed group, but do not explain whether any participants had incomplete follow-up, whether event status was unavailable for any period, or how missing observations were handled. The total enrollment of 88 does not determine the analyzed denominator for every outcome. Missing-data assumptions, imputation methods, and sensitivity analyses are not reported in the registry record.
The Part A Safety Analysis Set is defined as participants who received investigational medicinal product, M5717 or placebo. Analysis populations for Part C, the pharmacokinetic outcomes, parasite clearance, or any other endpoint are not reported in the registry record. The registry also does not describe whether there were separate per-protocol or intention-to-treat analyses. Because the population definition and missing-data handling affect what the counts represent, the reported safety counts should be interpreted within the stated Part A population and not generalized to an unreported analysis set.
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 |
|---|---|---|---|
| Part A: Placebo (Pooled) | 0 | 17 | 0.0% |
| Part A: Cohort 1 SAD: M5717 50 mg | 0 | 6 | 0.0% |
| Part A: Cohort 2 SAD: M5717 100 mg | 0 | 6 | 0.0% |
| Part A: Cohort 3 SAD: M5717 200 mg | 0 | 6 | 0.0% |
| Part A: Cohort 4 SAD: M5717 400 mg | 0 | 6 | 0.0% |
| Part A: Cohort 5 SAD: M5717 600 mg | 0 | 6 | 0.0% |
| Part A: Cohort 6 SAD: M5717 1000 mg | 0 | 6 | 0.0% |
| Part A: Cohort 7 SAD: M5717 1250 mg | 0 | 6 | 0.0% |
| Part A: Cohort 8 SAD: M5717 1800 mg | 0 | 6 | 0.0% |
| Part A: Cohort 9 SAD: M5717 2100 mg | 0 | 1 | 0.0% |
| Part C: M5717 150 mg | 0 | 6 | 0.0% |
| Part C: M5717 400 mg | 0 | 8 | 0.0% |
| Part C: M5717 800 mg | 0 | 8 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Part A: Placebo (Pooled) | 0 of 17 |
| Part A: Cohort 1 SAD: M5717 50 mg | 0 of 6 |
| Part A: Cohort 2 SAD: M5717 100 mg | 0 of 6 |
| Part A: Cohort 3 SAD: M5717 200 mg | 0 of 6 |
| Part A: Cohort 4 SAD: M5717 400 mg | 0 of 6 |
| Part A: Cohort 5 SAD: M5717 600 mg | 0 of 6 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Part A: Placebo (Pooled) | 13 of 17 |
| Part A: Cohort 1 SAD: M5717 50 mg | 6 of 6 |
| Part A: Cohort 2 SAD: M5717 100 mg | 5 of 6 |
| Part A: Cohort 3 SAD: M5717 200 mg | 3 of 6 |
| Part A: Cohort 4 SAD: M5717 400 mg | 4 of 6 |
| Part A: Cohort 5 SAD: M5717 600 mg | 3 of 6 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Part A: Placebo (Pooled) | Part A: Cohort 1 SAD: M5717 50 mg | Part A: Cohort 2 SAD: M5717 100 mg | Part A: Cohort 3 SAD: M5717 200 mg | Part A: Cohort 4 SAD: M5717 400 mg | Part A: Cohort 5 SAD: M5717 600 mg |
|---|---|---|---|---|---|---|---|
| Headache | Nervous system disorders | 3 of 17 | 0 of 6 | 2 of 6 | 1 of 6 | 3 of 6 | 2 of 6 |
| Upper respiratory tract infection | Infections and infestations | 2 of 17 | 2 of 6 | 2 of 6 | 0 of 6 | 1 of 6 | 1 of 6 |
| Sunburn | Injury, poisoning and procedural complications | 3 of 17 | 0 of 6 | 1 of 6 | 1 of 6 | 0 of 6 | 0 of 6 |
| Contusion | Injury, poisoning and procedural complications | 1 of 17 | 1 of 6 | 0 of 6 | 1 of 6 | 1 of 6 | 0 of 6 |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | 0 of 17 | 3 of 6 | 0 of 6 | 0 of 6 | 0 of 6 | 0 of 6 |
| Neck pain | Musculoskeletal and connective tissue disorders | 1 of 17 | 1 of 6 | 0 of 6 | 0 of 6 | 0 of 6 | 0 of 6 |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | 1 of 17 | 1 of 6 | 0 of 6 | 0 of 6 | 0 of 6 | 0 of 6 |
| Tachycardia | Cardiac disorders | 0 of 17 | 1 of 6 | 0 of 6 | 0 of 6 | 0 of 6 | 0 of 6 |
| Abdominal pain | Gastrointestinal disorders | 1 of 17 | 0 of 6 | 0 of 6 | 0 of 6 | 0 of 6 | 0 of 6 |
| Diarrhoea | Gastrointestinal disorders | 1 of 17 | 0 of 6 | 0 of 6 | 0 of 6 | 0 of 6 | 0 of 6 |
The serious-event figures are participant counts within each listed group. In Part A, the pooled placebo group had 0 serious events among 17 participants at risk. Each listed M5717 single-dose cohort also had 0 serious events: the groups at 50 mg, 100 mg, 200 mg, 400 mg, 600 mg, 1000 mg, 1250 mg and 1800 mg each had 6 participants at risk, while the 2100 mg group had 1 participant at risk. In Part C, the 150 mg group had 0 serious events among 6 participants at risk, and the 400 mg and 800 mg groups each had 0 among 8 participants at risk. Deaths were reported as 0 in every listed group.
These zero counts mean no serious event or death was recorded in the listed groups during the reported safety observation, not that the risk is known to be zero. Small cohorts provide limited information about uncommon outcomes, and no confidence intervals are reported in the registry record. The endpoint definition also includes medically important events and several specified serious outcomes. A zero count does not reveal whether other non-serious events occurred; those are reported separately, and affected participants were present in every listed group. The counts alone do not establish whether any event was caused by M5717. Event narratives, relatedness assessments, and separate discontinuation counts are not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The results establish what was reported for the listed safety groups: no serious TEAEs or deaths were recorded, while other TEAEs affected participants in the placebo, M5717 single-dose and challenge cohorts. The observations are relevant to describing early exposure in healthy participants. They are not, by themselves, a causal comparison between M5717 and placebo, because raw counts do not adjust for differences among cohorts or establish event relatedness. The registry's AE definition explicitly allows events that are not considered related to the medicinal product.
The counts do not show that M5717 is safe in every setting or that serious events cannot occur. The groups are small, and zero observed serious events cannot rule out events that were not observed in this sample. Nor do the counts establish a dose-response relationship. The data list different dose cohorts, but the record does not provide a formal dose-trend analysis, uncertainty intervals or adjusted comparisons.
The stated study purpose also included pharmacokinetics and the relationship between M5717 exposure and parasite clearance after Plasmodium falciparum infection. The registry lists pharmacokinetic outcomes such as maximum observed plasma concentration, time to maximum concentration, terminal elimination measures and area-under-the-curve measures. Their results, as well as parasite-clearance results, are not reported in the registry record. The available safety counts therefore cannot establish antimalarial activity, exposure-response, or clinical benefit.
Overall, these data are best understood as descriptive observations from a completed Phase I study, rather than as a definitive test of treatment effects. The record does not report the detailed statistical analyses, missing-data methods, or sample-size justification needed to assess inferential claims beyond the observed participant counts.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of the distinction between early-phase description and confirmatory comparison. Its central posted result is a set of participant counts across small dose cohorts, including a pooled placebo group in Part A and separate M5717 cohorts in Part C. Those counts can document what was observed in each group, but they are not equivalent to a precise estimate of the difference between treatment groups. The variation in cohort sizes, including the 2100 mg Part A group with 1 participant at risk, makes context especially important.
The design also spans different questions. Part A examines ascending single doses and includes placebo, while Part C uses a controlled malaria challenge context and lists M5717 dose groups. Combining the parts into one overall safety conclusion would obscure their different settings and group structures. The study title additionally refers to multiple ascending doses, but specific schedules and outcomes for that component are not reported in the registry record. That gap illustrates why a registry summary should be read as an account of what is documented, not as a substitute for full protocol or analysis reporting.
Another statistical lesson is that a count of participants with at least one event is different from a count of event episodes and from an estimate of causal risk. The absence of serious events in these cohorts is an observed finding, but the small denominators limit the precision with which uncommon outcomes can be assessed. No inferential analyses or confidence intervals for the safety counts are listed. This constrains the strength of any comparison that can be made from the posted figures.
Finally, the trial planned to address pharmacokinetics and parasite clearance as well as safety. Those domains require outcome results and analysis details beyond adverse-event counts. Their absence from the registry record means that statistical conclusions should remain confined to the posted safety observations. The record demonstrates why endpoint definitions, analysis populations, denominators and uncertainty are essential for interpreting early clinical data.
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 principal limitation is the scale and structure of the reported safety groups. Several Part A M5717 cohorts had 6 participants at risk, the 2100 mg cohort had 1, and the Part C cohorts had 6 or 8. Such counts offer limited precision, particularly for serious or uncommon events. The registry record reports no confidence intervals or inferential comparisons for the safety outcome.
The posted result categories are incomplete for a detailed safety assessment. Although the primary endpoint includes TEAEs leading to treatment discontinuation, separate discontinuation counts are not reported in the registry record. Event narratives, specific non-serious event terms, severity grades, timing, duration and treatment-relatedness assessments are also not reported in the registry record. The event counts therefore cannot distinguish among different clinical patterns or establish causality.
Interpretation is further limited by the study's multiple parts and cohorts. Part A includes pooled placebo and dose-specific M5717 groups, while the listed Part C challenge cohorts describe M5717 doses without a listed placebo cohort. The registry does not report cohort-level randomization details or an analysis that accounts for the different settings. Specific multiple-dose schedules are not reported in the registry record despite the title's reference to multiple ascending doses.
The registry does not report the trial's sample-size justification, statistical analysis plan, missing-data handling, multiplicity approach, or outcome-specific analysis populations beyond the Part A Safety Analysis Set definition. Results for the listed pharmacokinetic outcomes and the parasite-clearance objective are not reported in the registry record. These omissions prevent assessment of the trial's precision for its broader objectives and limit the conclusions to the posted safety counts.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: First-in-Human Trial of Single Ascending Dose, Multiple Ascending Dose and Malaria Challenge Model in Healthy Participants — NCT03261401.
- Registry record last updated 2023-10-16; status last verified 2022-12.
- Results first posted 2023-10-16.
- 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
NCT03261401 is a completed Phase I randomized, double-blind, parallel study with overall enrollment of 88. It examined oral M5717 in healthy adult participants through Part A single ascending dose cohorts and Part C malaria challenge cohorts. Part A included pooled placebo and M5717 doses from 50 mg through 2100 mg; Part C listed M5717 doses of 150 mg, 400 mg and 800 mg after intravenous malaria inoculation.
The primary outcome counted participants with TEAEs, serious TEAEs and TEAEs leading to discontinuation from baseline up to Day 55. The listed groups reported zero serious events and zero deaths; other TEAEs were reported in both placebo and M5717 groups. Part A's safety population included participants who received M5717 or placebo. No inferential analyses are listed for the outcomes. Pharmacokinetic results, parasite-clearance results, separate discontinuation counts, and details of multiplicity and missing-data methods are not reported in the registry record.