Safety Study of RMJH-111b to Treat Essential Hypertension: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety Study of RMJH-111b to Treat Essential Hypertension (NCT02822222), a randomized phase 1, phase 2 study. The primary outcome is Safety and Tolerability of RMJH-111b Compared to Placebo Based on Treatment Emergent Adverse Events (TEAEs).

2. Clinical Question

The study also set out to examine blood pressure and magnesium measurements. Listed secondary outcomes included changes in daytime, nighttime, and 24-hour systolic blood pressure, as well as daytime and nighttime diastolic blood pressure. Other outcomes concerned serum and urine magnesium after single and repeated administration. These stated aims do not by themselves establish what the study found for those measures. The posted registry results summarized in the record focus on adverse-event counts, and no analyses for the blood pressure or pharmacokinetic outcomes are reported in the registry record.

3. Trial Design

This was a Phase 1/2, randomized, triple-masked, parallel-group, placebo-controlled study of RMJH-111b in adult subjects with essential hypertension. The registry lists an enrollment of 22 and marks the study completed. The study began on 2016-06-10, with primary completion on 2016-07-07. The record names RMJ Holdings, LLC as sponsor.

Participants assigned to RMJH-111b received four magnesium citrate, tribasic anhydrous soft gelatin capsules orally twice daily for 7 days. Each capsule contained 110 mg elemental magnesium. The placebo group received four placebo soft gelatin capsules on the same twice-daily, 7-day schedule; the capsules contained 0 mg elemental magnesium. The parallel-group design means the record describes separate active-treatment and placebo groups rather than a crossover sequence.

Randomization and triple masking are features of the design, but the registry record does not explain the randomization procedure, allocation concealment, or which roles were masked. The precise schedule for visits and measurements beyond the stated outcome timeframes is not reported in the registry record. Nor is a detailed protocol narrative available in the listed details to explain how the Phase 1/2 study components were organized.

The primary outcome concerned safety and tolerability, assessed through TEAEs during a stated timeframe of 14 days +/- 3 days. The TEAE definition further specifies events starting or increasing in severity after the first randomized dose on Day 4 through the Final Study Visit, described as 8 +/-3 days after the last randomized dose. This is a short treatment course with event observation extending beyond dosing, as described by the registry. The record does not provide a study-specific explanation of why the treatment duration or follow-up schedule was selected.

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: Randomization to treatment took place on Day 4, following the 7-day washout period \& the 3-day run-in placebo period. Only subjects that continued to meet eligibility criteria following the Day 4 baseline procedures were randomized.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety population = all randomized subjects who received at least one dose of Study Drug (active or placebo).

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 Safety and Tolerability of RMJH-111b Compared to Placebo Based on Treatment Emergent Adverse Events (TEAEs), measured over 14 days +/- 3 days.

The primary endpoint concerns treatment-emergent adverse events, or TEAEs, as a measure of safety and tolerability. The registry describes incidence by system organ class and preferred term, and also by categories: any TEAE, severe TEAE, serious TEAE, drug-related TEAE, drug-related severe TEAE, drug-related serious TEAE, TEAE leading to discontinuation, and TEAE with an outcome of death. Drug-related events were defined as events assigned a study-drug relationship of adverse reaction or suspected adverse reaction.

For this endpoint, an event had to start or increase in severity after the first randomized dose on Day 4 and before the Final Study Visit. The registry gives the outcome timeframe as 14 days +/- 3 days and describes the Final Study Visit as 8 +/-3 days after the last randomized dose. The record states that TEAEs were coded using the Medical Dictionary for Regulatory Activities, version 19.0, and graded using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03.

Counting participants with events is useful for describing how many people in each treatment group experienced a safety event during the defined observation period. It is not, by itself, a complete characterization of event timing, duration, clinical seriousness, or uncertainty around a treatment-group contrast. The registry presents several categories, so the primary safety question cannot be reduced to one undifferentiated event count. A single composite summary may conceal differences among event types and severity categories.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The record describes a randomized, parallel-group comparison of RMJH-111b with placebo. Randomization is intended, in general, to reduce systematic differences between groups at assignment. Masking can reduce the influence of treatment knowledge on participant experience, care, and assessment. These are general methodological purposes; the registry does not report the exact randomization or masking procedures used in this trial.

What does a participant count represent?

The safety outcome uses participants with an event, rather than a measure such as the number of event episodes. A participant count indicates how many people in a group were recorded as having the event category. A person may potentially experience more than one event, but the participant-level count does not communicate the total number of episodes or their timing. The registry’s stated safety population includes randomized participants who received at least one dose of active study drug or placebo. The event figures therefore need to be read alongside the group-specific number at risk.

The record distinguishes serious adverse events from other adverse events. Seriousness is a regulatory classification and is not interchangeable with severity. The endpoint description also specifies severity grading and drug-relatedness categories, but the posted figures summarized in the record do not give results for every category. The absence of serious events in the reported counts should not be read as an absence of all adverse events: other-event counts are also reported.

Why are there no single comparative estimates?

The primary outcome includes multiple event categories, while the listed analyses count is 0. The record therefore does not supply a single treatment contrast, confidence interval, or significance test for the safety outcome. In general, a comparative estimate could quantify a difference between groups, and its confidence interval could indicate how imprecisely that difference is estimated. Those quantities cannot be inferred from the posted counts without selecting an analysis method and making additional assumptions. No recalculated estimates are reported for this outcome.

Counts alone also do not reveal how events were distributed by preferred term, severity, relatedness, or onset time. The registry describes coding and grading standards, but the listed safety results do not provide the event-level detail needed to examine those patterns. The record reports no top serious-event terms.

What do the planning assumptions mean?

The record describes a planning illustration based on an observed effect, using a two-sided significance level of 0.05, equal allocation between groups, and a normal approximation. Such an illustration is a hypothetical design calculation: it describes a planning scenario under stated assumptions, not the power actually achieved by the completed study. The stated effect to detect is expressed as a fraction of the observed effect. For non-time-to-event outcomes, the planning convention is participants per arm; time-to-event calculations use a total event count. The registry entries do not include specific planning results for this primary safety outcome, and no numerical planning size should be inferred from the assumptions alone.

In general, power is the probability that a specified analysis detects an effect of a particular size under its assumptions. It is not a retrospective measure of whether a result is true. A small study can have limited ability to distinguish a real difference from chance variation, while a nonsignificant result, if one were reported, would not demonstrate equivalence. No observed-power result is reported in the registry record.

What statistical details remain unspecified?

The registry entries do not state a statistical model for the primary outcome, a method for handling repeated or multiple event categories, a missing-data method, or a multiplicity adjustment. They also do not describe an interim analysis or a sample-size justification. These details matter because choices about outcome definitions, analysis populations, missing observations, and multiple comparisons can affect estimates and their interpretation. Their absence from the registry record means they cannot be evaluated from the posted information. General statistical principles can explain why these choices matter, but they cannot substitute for the study’s unreported analysis plan.

10. Multiplicity, Missing Data and Analysis Populations

Multiplicity is relevant because the registry lists a primary safety outcome with several event categories and 22 outcome measures overall. Considering multiple outcomes or categories can increase the chance of finding at least one apparently notable result by chance when many statistical tests are conducted. In general, a prespecified testing strategy or adjustment can address this issue, but the registry record does not report a multiplicity plan or adjustment. The listed number of analyses is 0, so the record does not provide a set of inferential tests to evaluate.

The primary safety population is defined as randomized participants who received at least one dose of study drug. The record does not state how many randomized participants, if any, were excluded from that population, or describe a separate intention-to-treat analysis. The reported group-specific at-risk counts are available, but the handling of participants with incomplete follow-up or missing event information is not reported in the registry record.

Missing-data methods can matter when outcomes are not observed for everyone or when follow-up differs between groups. General approaches may range from analyzing available observations to using explicit assumptions or statistical models. The appropriate approach depends on the missingness pattern and the outcome; the registry record does not describe such a method or provide enough detail to assess missingness. It also does not state whether any participants discontinued treatment or follow-up.

These omissions limit the ability to judge whether the posted counts represent complete ascertainment for the defined safety population, how multiple outcomes were prioritized, or how any missing information affected analysis. No particular method or reason for missing data should be assumed.

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 registry reports serious adverse-event counts of 0 among 16 at risk in the RMJH-111b group and 0 among 6 at risk in the placebo group. Death counts are also 0 in each group. For other adverse events, the record reports 5 affected participants among 16 at risk with RMJH-111b and 1 among 6 at risk with placebo. These are group-specific observed counts, not estimates of a population-wide risk.

Seriousness and severity are different concepts. The endpoint description says severity was graded using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03, while serious events were separately categorized. The registry’s general endpoint definition also includes drug-related events, events leading to discontinuation, and events by system organ class and preferred term; the summarized counts do not provide results for each of these categories.

Zero serious events in the observed groups does not establish that the risk is absent, nor does it establish that the groups have equivalent safety. The record does not report an uncertainty interval or a statistical comparison for these counts. It also gives no top serious-event terms. The figures should therefore be read as a limited descriptive account for the study’s stated safety population and observation timeframe, not as a complete safety profile.

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

The record describes a short randomized comparison of RMJH-111b and placebo in adults with essential hypertension. Its primary focus was safety and tolerability, assessed through TEAEs. The posted counts document other adverse events in both groups and no serious adverse events or deaths in either group during the reported observation period. Those are the direct descriptive findings available for the safety outcome.

They do not establish that RMJH-111b is safe or unsafe in general, or that it is better, worse, or equivalent to placebo. Group counts from a limited study do not establish the frequency of uncommon events or what might occur with longer exposure. The record does not report an inferential analysis, so the precision of any treatment-group difference cannot be judged using a confidence interval or significance test.

The stated secondary aims included daytime, nighttime, and 24-hour systolic blood pressure, daytime and nighttime diastolic blood pressure, and serum and urine magnesium outcomes. Results for these outcomes are not reported in the registry record. The safety findings therefore cannot answer whether blood pressure or magnesium measures changed, or whether any changes differed between groups.

More broadly, interpretation is bounded by the treatment schedule, the specified follow-up period, the reported safety population, and the categories for which results are available. The registry does not describe the detailed statistical analysis plan, multiplicity handling, or missing-data approach. Those gaps do not erase the observed counts, but they limit what can be concluded from them. The appropriate reading is descriptive and specific to the recorded study, not a basis for broader claims about efficacy, long-term outcomes, or comparative safety.

13. Why This Trial Matters Statistically

This trial illustrates a common statistical distinction: observed safety counts are not the same as an estimated comparative treatment effect. The registry gives the number of participants affected and the number at risk in each group, which makes the descriptive findings interpretable. But without a reported contrast and uncertainty interval, the evidence does not show how precisely any difference between groups has been estimated.

Zero serious events can be reassuring as a description of what was observed, but it cannot establish that the underlying risk is zero. In general, rare outcomes require substantial information to characterize reliably. A small study can identify events that occur during its observation period, yet provide limited information about uncommon events or longer-term risks. This is why event counts need to be interpreted alongside group size, follow-up, and uncertainty.

The record also makes multiplicity a relevant consideration. The primary safety outcome includes several categories, and the registry lists 22 outcome measures. Without a stated analysis strategy, readers cannot determine how results across those categories and outcomes were prioritized or whether any statistical adjustment was intended. The registry lists no analyses, so inferential findings are unavailable for assessment.

Finally, the study’s safety focus should be kept distinct from its secondary aims. Blood pressure and magnesium outcomes are listed, but their results are not reported in the registry record. Recognizing that boundary prevents safety counts from being mistaken for evidence about efficacy or pharmacokinetics. Statistically, the trial matters as an example of why a clear endpoint definition, transparent analysis plan, and reporting of estimates with uncertainty are needed to move from descriptive observations toward a well-supported comparative conclusion.

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 information leaves several trial-specific limitations. The study used a 7-day treatment course, and the adverse-event timeframe is described as 14 days +/- 3 days, with the TEAE definition extending through a Final Study Visit described as 8 +/-3 days after the last randomized dose. These periods provide limited information about events that could arise after the recorded follow-up. The registry does not describe longer-term observation.

The group-specific safety counts are small, and the serious-event and death counts are zero in both groups. Such counts provide limited resolution for assessing uncommon outcomes. The registry does not report confidence intervals or a formal comparison, so uncertainty around differences cannot be quantified from the record. The other adverse-event counts are not accompanied in the listed results by detailed preferred terms, severity grades, relatedness, or event timing.

The record identifies a safety population of randomized participants who received at least one dose, but does not state how missing event information was handled or provide details about incomplete follow-up. It does not describe the randomization method, masking procedures, allocation concealment, analysis model, or prespecified multiplicity approach. A sample-size justification and interim-analysis plan are not reported in the registry record.

Although several blood pressure and magnesium outcomes are listed, their results and analyses are not reported in the registry record. This prevents assessment of those stated secondary questions from the posted information. The record also does not offer a single comparative summary for the several primary safety categories. These are limits on what can be concluded from this registry account, not evidence that an unreported procedure or analysis was or was not performed.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety Study of RMJH-111b to Treat Essential Hypertension — NCT02822222.
• Registry record last updated 2020-09-23; status last verified 2020-09.
• Results first posted 2020-09-23.
• 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

NCT02822222 is a completed Phase 1/2 randomized, triple-masked, parallel-group, placebo-controlled study of RMJH-111b in adults with essential hypertension. The record lists enrollment of 22 and identifies RMJ Holdings, LLC as sponsor. RMJH-111b was given as four capsules orally twice daily for 7 days, with 110 mg elemental magnesium per capsule; placebo capsules contained 0 mg elemental magnesium.

The primary outcome assessed TEAEs across several categories. The registry reports zero serious adverse events and zero deaths in both groups. Other adverse events affected 5 participants among 16 at risk with RMJH-111b and 1 participant among 6 at risk with placebo. The record lists 22 outcome measures and 0 analyses. Results for the listed blood pressure and pharmacokinetic outcomes, along with inferential safety comparisons and details of missing-data handling, are not reported in the registry record.