First in Human Study of RVP-001, a New Manganese Based MRI Contrast Agent: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for First in Human Study of RVP-001, a New Manganese Based MRI Contrast Agent (NCT05413668), a randomized phase 1 study. The primary outcome is Pharmacokinetic (PK) Parameter Cmax.

2. Clinical Question

The record describes a first-in-human study in healthy adults, with safety, tolerability, pharmacokinetics and elimination as its objectives. The primary posted outcome is Cmax, summarized separately for the RVP-001 dose groups. Its stated measurement schedule begins before dosing and continues through 120 hours after dosing, with multiple collection times in between. This allows concentration over time to be observed and the maximum measured plasma concentration to be identified.

The registry record describes four dose cohorts, with six subjects assigned to RVP-001 and two to placebo in each cohort. The primary outcome population is defined by receipt of at least one RVP-001 dose and sufficient data to calculate at least one pharmacokinetic parameter. The posted Cmax summaries report six participants for each of the four RVP-001 dose groups. The primary outcome does not provide an equivalent placebo concentration comparison: the outcome is explicitly the maximum observed concentration of RVP-001.

The clinical question is therefore principally descriptive and pharmacokinetic: what concentrations were observed after the studied doses, and how variable were those summaries? Safety counts offer additional descriptive information. Neither the primary outcome nor the posted record supplies a treatment-effect estimate for a patient-centered clinical outcome.

3. Trial Design

NCT05413668 is listed as a randomized, quadruple-masked, parallel-group phase 1 study conducted at a single center. It enrolled 32 participants with the condition recorded as healthy. The trial status is completed. The registry dates the start to 2022-05-18 and primary completion to 2022-07-22.

The intervention groups were RVP-001 and placebo. The arm descriptions specify four cohorts, each with six subjects receiving RVP-001 and two receiving saline placebo. The RVP-001 doses were 2, 4, 7 and 12 mg Mn/kg. This is an ascending-dose arrangement, with pharmacokinetic and safety observations reported by dose rather than as one pooled treatment group. The posted primary outcome summaries include six subjects in each RVP-001 dose group.

Randomization and masking describe features of the planned design; they do not by themselves establish how allocation was generated, concealed or maintained in practice. Details of those procedures are not reported in the registry record. The record also does not report the sequence in which cohorts proceeded, rules for dose escalation, or decisions governing whether an additional cohort could be opened. Those operational details should not be inferred from the arm descriptions alone.

The trial's stated objectives were to evaluate safety and tolerability of single ascending doses in healthy adult volunteers and to determine pharmacokinetics and elimination. The primary endpoint was Cmax, with the measurement timeframe running from pre-dose through 120 hours post-dose. The secondary outcome listed is the percentage of the RVP-001 dose excreted. Six outcome measures are recorded, but a detailed analysis is not posted for all of them. There are no posted analyses counted in the registry record. The specific statistical plan, including any planned hypothesis tests and model specifications, is not reported in the registry record.

The design is suited to describing early exposure and safety observations across dose cohorts. It is not, from the information recorded, a confirmatory comparison of clinical outcomes. The placebo participants may provide context for safety observations, but the primary pharmacokinetic endpoint is defined around RVP-001 concentrations, and the record does not post a pooled active-versus-placebo estimate for Cmax.

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: All subjects who received at least one dose of RVP-001 and had sufficient data to calculate at least one PK parameter

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 Pharmacokinetic (PK) Parameter Cmax, measured over pre-dose, 2, 5, 10, 20, 30 min and 1, 2, 4, 8, 12, 24, 48, 72, 96, 120 hours post-dose.

The primary endpoint is pharmacokinetic parameter Cmax, measured in nmol/mL. Cmax is defined in the registry record as the maximum observed blood plasma concentration of RVP-001. Blood samples were scheduled pre-dose and at 2, 5, 10, 20 and 30 minutes, then at 1, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post-dose. The endpoint therefore represents the highest measured concentration among the scheduled observations, rather than a concentration at one fixed time.

Cmax is used in pharmacokinetic studies to characterize peak systemic exposure after administration. In general, describing the peak concentration can help characterize how exposure changes across dose levels and complements other pharmacokinetic measures, such as measures of total exposure or elimination. The record lists six outcome measures but does not provide all of their details in the posted results excerpt; the primary endpoint is specifically Cmax.

The endpoint is reported as a geometric mean with geometric coefficient of variation. A geometric mean is appropriate for summarizing measurements that are positive and may vary multiplicatively, while the geometric coefficient of variation describes relative spread on a multiplicative scale. These are descriptive summaries; they are not, by themselves, a test of whether dose groups differ. No confidence intervals for the Cmax summaries are reported in the registry record. The registry record also does not post a direct statistical contrast between RVP-001 and placebo for this endpoint.

The measurement schedule and endpoint definition matter when interpreting the reported maximum. Cmax is the highest concentration captured at scheduled sampling times, so it is tied to the observation schedule and the adequacy of the available samples. The specified primary population also requires enough data to calculate at least one pharmacokinetic parameter, which means the outcome is not necessarily defined for every enrolled participant.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical quantities reported for the primary endpoint are geometric means and geometric coefficients of variation. The registry record identifies the endpoint as Cmax in nmol/mL and defines Cmax as the maximum observed blood plasma concentration. The summaries are reported separately by RVP-001 dose, rather than as a single pooled estimate. No inferential analysis is posted for these data.

What does a geometric mean summarize?

General statistical explanation: an arithmetic mean summarizes values on an additive scale, while a geometric mean summarizes positive values on a multiplicative scale. It is commonly used when measurements are right-skewed or when proportional changes are more meaningful than equal absolute changes. The geometric mean can be understood as averaging on a logarithmic scale and then returning to the original scale. It describes a typical level under that multiplicative framing; it does not indicate the range of individual observations.

In this trial, the geometric means are 264.0, 685.0, 992.0 and 1960.0 nmol/mL across the 2, 4, 7 and 12 mg Mn/kg groups, respectively. Those values are the posted summaries and should be interpreted in the context of six participants reported per group. They do not reveal the individual concentrations or the uncertainty around the group estimates. Confidence intervals are not reported in the registry record.

What does the geometric coefficient of variation describe?

General statistical explanation: a coefficient of variation expresses variability relative to a measure of central tendency. Its geometric form is used with multiplicative or log-scale data and communicates relative spread rather than spread in the original measurement units. It is useful when the scale of the outcome changes across groups, but it is not an interval estimate and is not a hypothesis test. It cannot by itself establish that two group summaries differ.

The reported geometric coefficients of variation are 21.6, 31.1, 20.2 and 20.3 for the dose groups in ascending order. The registry record does not provide a confidence interval or other uncertainty measure for these variability estimates. Because the groups are small, the figures are descriptive of the observed data and should not be treated as precise population parameters.

Why does the sampling schedule matter?

Cmax is the highest concentration observed among the scheduled samples. The schedule includes pre-dose collection, several early post-dose times measured in minutes, and later samples extending through 120 hours. This schedule is part of the endpoint's meaning: a maximum based on observed samples may differ from the unknown continuous-time peak if the true peak falls between sampling times. General statistical explanation: more frequent sampling around the expected peak can better characterize its timing and magnitude, but the registry record does not state an expected peak time or explain how the schedule was selected.

The primary population required receipt of at least one dose and sufficient data to calculate at least one pharmacokinetic parameter. This eligibility definition is relevant because available sampling determines whether Cmax can be calculated. How partial profiles, missing samples or unusable measurements were handled is not reported in the registry record.

What can a group comparison establish?

General statistical explanation: an inferential comparison combines an estimated difference with its uncertainty, often through a confidence interval or hypothesis test. A confidence interval describes a range of values compatible with the data under the method's assumptions; it is not a guarantee that the true value lies in that range. A test result alone also does not convey the magnitude or precision of an effect. For this endpoint, the registry record does not report confidence intervals, p-values, or a specified comparison among doses. The observed ordering of the means is therefore descriptive, not proof of a dose-response relationship.

The trial is randomized and parallel-group according to the record, but those design labels do not substitute for an analysis plan. The statistical model, transformation details, handling of repeated concentration measurements, and any adjustment for covariates are not reported in the registry record. Nor is a formal contrast between RVP-001 and placebo posted for Cmax. A reader should not infer such analyses from the fact that placebo was included in the trial.

How should planning illustrations be read?

General statistical explanation: sample-size planning uses assumptions about an effect, variability, significance level and allocation to estimate the number of participants needed for a target probability of detecting that effect under a specified model. The planning assumptions recorded for the illustrations use a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation and an effect defined as a stated fraction of the observed effect. The illustrations are computed from the observed effect and are not the trial's original design calculation. They are planning illustrations, not observed power, and do not establish what power this trial actually had.

The record describes multiple dose groups and placebo cohorts, whereas the planning assumptions refer to equal allocation between two arms. The illustrations therefore address hypothetical two-arm planning scenarios and should not be mistaken for a retrospective analysis of the full multi-cohort design. The trial's own sample-size justification is not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists six outcome measures and identifies one secondary outcome by name: percentage of RVP-001 dose excreted. It does not provide a complete listing of the outcome definitions in the information summarized for this analysis. The number of posted analyses is recorded as zero. No inferential results for multiple endpoints or multiple dose comparisons are posted.

Multiplicity arises when several outcomes, time points or group contrasts are examined. General statistical explanation: conducting many tests can increase the chance of at least one apparently notable result, so a prespecified analysis plan may define a primary comparison or adjust how results are interpreted. Whether multiplicity adjustments were planned or used is not reported in the registry record. The primary endpoint and its collection schedule are stated, but the record does not describe a testing hierarchy or any correction for multiple dose comparisons.

The primary outcome population consists of participants who received at least one dose of RVP-001 and had sufficient data to calculate at least one pharmacokinetic parameter. This is a stated population definition, but the registry record does not report participant flow into each analysis population or explain how missing concentration samples were handled. It also does not state whether the analysis included every participant meeting that definition for each parameter, or how any protocol deviations or unusable measurements were treated.

Missing data can matter for pharmacokinetic summaries because incomplete sampling may affect whether a maximum can be identified. General statistical explanation: methods for incomplete data depend on why observations are missing and on the endpoint; excluding incomplete profiles, imputing measurements or using a model can lead to different interpretations. The registry record does not specify which approach, if any, was used. It does not report a missing-data sensitivity analysis.

The study objectives include safety, tolerability, pharmacokinetics and elimination, but a full statistical analysis plan, analysis populations beyond the stated primary population, and procedures for multiplicity are not reported in the registry record. Conclusions should therefore stay close to the descriptive results actually posted.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The posted serious adverse event counts are zero in each RVP-001 dose group and zero in the placebo group. Deaths are also recorded as zero in every group. The numbers at risk for serious adverse events are six in each RVP-001 dose group and eight in the placebo group. These are counts within the recorded groups, not estimates of the probability of a future event.

General statistical explanation: observing no serious adverse events in a small group does not demonstrate that the underlying risk is zero. A count of zero describes what was recorded during the trial; it does not rule out events that are uncommon or that could occur in a larger or different population. The registry record does not provide confidence intervals for these safety counts or a formal comparison between groups.

Other adverse events affecting participants are recorded for the RVP-001 dose groups as 1, 2, 2 and 0, and for the placebo group as 1. The at-risk counts are six in each RVP-001 group and eight for placebo. These are descriptive participant counts. They do not indicate severity, relatedness, duration or whether an individual experienced more than one event; such details are not reported in the record. Serious adverse events and other adverse events are distinct categories, so the other-event counts should not be conflated with the serious-event counts.

These findings should be read as safety observations from a small, early-phase study in healthy adults. The record gives counts, but does not provide enough detail to determine attribution or compare risks statistically.

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

The Cmax summaries describe the maximum observed plasma concentration of RVP-001 for participants in each dose group. The geometric means increase across the listed dose groups, from 264.0 nmol/mL at 2 mg Mn/kg to 1960.0 nmol/mL at 12 mg Mn/kg. The reported summaries also include geometric coefficients of variation, which describe relative variability. These results provide a descriptive account of exposure in the participants contributing to the pharmacokinetic analyses.

They do not establish that increasing dose caused a particular change in Cmax. The registry record does not report a formal dose-response model, uncertainty intervals for the group means, or statistical tests comparing the dose groups. The pattern is compatible with increasing observed peak concentrations across the groups, but the precision and reproducibility of that pattern cannot be determined from the posted summaries alone.

The endpoint is pharmacokinetic, not a clinical outcome. It measures drug concentration rather than a health benefit or patient experience. The primary endpoint also does not compare RVP-001 with placebo. Placebo was part of the design, but a placebo comparison for Cmax is not reported in the registry record. The record therefore cannot support an estimate of an active-versus-placebo effect for this primary endpoint.

The safety summaries report no serious adverse events or deaths in the listed groups. Other adverse events were recorded in some groups. These counts are limited observations from the trial and are not proof that serious events cannot occur or that the groups have equivalent safety. The registry record does not provide detailed event descriptions, attribution, or inferential comparisons.

The trial's population is healthy adults, and the study is identified as phase 1. Its results should be understood within that early research context. They do not establish effects in people with a medical condition, nor do they answer questions about clinical benefit. The record also does not report a complete analysis plan or all details needed to evaluate missing observations and uncertainty. The appropriate reading is therefore narrow: the posted data describe dose-specific pharmacokinetic summaries and recorded safety counts, with important limits on comparative and broader interpretation.

13. Why This Trial Matters Statistically

Early-phase trials often collect detailed pharmacokinetic observations before questions about clinical outcomes can be addressed. In this study, Cmax is defined from scheduled blood plasma measurements and reported separately across ascending RVP-001 dose groups. This provides a concrete example of how a primary endpoint can describe exposure rather than clinical benefit, and why endpoint definition is essential to interpretation.

The summaries also illustrate the distinction between a central estimate and its variability. The geometric means describe typical concentration on a multiplicative scale, while the geometric coefficients of variation provide relative-spread information. Neither quantity is a substitute for an uncertainty interval or a comparison test. Keeping these statistical roles distinct helps prevent descriptive summaries from being read as conclusive evidence about dose effects.

The record's design includes randomization, masking, multiple dose cohorts and placebo recipients, but the primary pharmacokinetic outcome is reported for active dose groups. That structure highlights an important analysis issue: a randomized design does not guarantee that every endpoint has a direct randomized contrast. Readers need to check what was measured, for whom, and which comparisons were actually reported.

The safety data provide another useful statistical lesson. Zero serious adverse events in the recorded groups is informative as a count of observed events, but it does not show that the risk is zero. Small group sizes limit what such counts can say about uncommon harms. The record offers a basis for describing observations, not for drawing broad safety conclusions.

Finally, the record demonstrates why missing analysis details matter. The specific statistical plan, missing-data procedures and sample-size justification are not reported. Without them, readers can interpret the descriptive results but cannot reconstruct all analytic decisions or judge the intended inferential framework. Transparent reporting of populations, uncertainty and analysis methods is central to sound interpretation.

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 posted Cmax summaries are based on six participants in each RVP-001 dose group. The record does not report confidence intervals for the geometric means or coefficients of variation, nor individual-level concentration data. This limits evaluation of precision, distributional shape and the influence of unusual observations.

The primary endpoint is explicitly about RVP-001 concentration. Although placebo is included in the study design, the registry record does not report a placebo Cmax summary or a direct placebo comparison for this endpoint. The available results therefore do not quantify an active-versus-placebo contrast.

The record states that the primary pharmacokinetic population required at least one dose and sufficient data to calculate at least one parameter. It does not report how many participants were excluded from any particular endpoint calculation, how incomplete sampling was handled, or whether all available measurements were used. Missing-data handling and sensitivity analyses are not reported in the registry record.

Although the record identifies the study as randomized, quadruple-masked and parallel-group, details of sequence generation, allocation concealment, masking procedures and cohort progression are not reported. A statistical analysis plan, the model used for any formal analyses, covariate adjustments, hypothesis-testing procedures and multiplicity handling are also not reported.

The registry lists six outcome measures but provides limited detail about the posted analyses; no analyses are counted in the record. The sample-size justification for the trial is not reported. The trial is identified as phase 1 and enrolled healthy adults, so the reported findings have limited scope beyond the studied participants and design. These limitations do not negate the descriptive observations, but they constrain claims about precision, comparative effects, safety and generalizability.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: First in Human Study of RVP-001, a New Manganese Based MRI Contrast Agent — NCT05413668.
• Registry record last updated 2025-04-22; status last verified 2025-04.
• Results first posted 2023-10-23.
• 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

NCT05413668 is a completed, randomized, quadruple-masked, parallel-group phase 1 study at a single center, with 32 healthy adult participants recorded. The trial's objectives were to evaluate safety and tolerability of single ascending RVP-001 doses and determine pharmacokinetics and elimination. Four cohorts were described, with RVP-001 doses of 2, 4, 7 and 12 mg Mn/kg and saline placebo recipients.

The primary endpoint was Cmax, the maximum observed blood plasma concentration of RVP-001, reported as a geometric mean with geometric coefficient of variation. The posted dose-specific summaries show geometric means of 264.0, 685.0, 992.0 and 1960.0 nmol/mL, with six participants in each group. No confidence intervals or formal dose comparisons are reported in the registry record.

Serious adverse events and deaths are recorded as zero in each group. Other adverse events affecting participants are also listed by group. The record does not report the full statistical plan, missing-data procedures, multiplicity handling or trial sample-size justification. The results are descriptive and should be interpreted within the early-phase study population and the analyses actually posted.