Evaluation of Safety and Efficacy of RZL-012 in Subjects Seeking Fat Reduction in the Flanks: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluation of Safety and Efficacy of RZL-012 in Subjects Seeking Fat Reduction in the Flanks (NCT05445557), a randomized phase 2 study. The primary outcome is Number of Participants With Treatment-related Adverse Events [AEs].

2. Clinical Question

The design places both treatment conditions within each participant: each subject’s flanks were randomized separately, with one flank assigned to RZL-012 and the other to placebo in the double-blind phase. This is different from a conventional parallel-group trial in which each participant receives only one assigned treatment. It means that participants may contribute experience under both treatment conditions, and the two sets of observations are not necessarily independent.

The clinical question therefore has two related parts. The primary safety question concerns treatment-related adverse events across the stated phases. The registry also lists secondary efficacy outcomes concerning physician assessment, satisfaction, measured fat volume, reviewer identification, and blood drug concentration. The record does not report numerical results for those outcomes, nor does it specify a single efficacy result that can be interpreted as the main comparison.

3. Trial Design

This was a Phase 2 randomized trial with a parallel model and triple masking, according to the registry. Its official title describes a double-blind phase followed by an open-label phase. The sponsor was Raziel Therapeutics Ltd. The registry lists the study as completed, with 12 participants enrolled. The recorded start date is 2022-03-10, and the primary completion date is 2022-10-20.

During the double-blind phase, each participant’s flanks were randomized to treatment. One flank received RZL-012 and the other placebo, for a total of 24 randomized flanks. The RZL-012 and placebo sessions each involved 50-55 injections. The registry gives the per-injection dose and maximum dose for RZL-012, and the per-injection volume and maximum volume for placebo. These details describe the treatment sessions; they do not establish that every participant received the maximum number of injections or maximum dose.

Participants were monitored for safety and efficacy for 12 weeks in the double-blind phase. After codes were opened, a second treatment cycle was planned for the previously untreated contralateral flank. Monitoring continued for an additional 12 weeks in the open-label phase. The registry states that 9 subjects continued to that phase. It does not give participant flow details explaining why the other subjects did not continue, or clarify all analysis populations for the two phases.

The record lists 6 outcome measures and 0 analyses. It identifies a primary safety endpoint and lists secondary outcomes, but it does not report a complete statistical analysis plan, the allocation sequence method, or details of how the flank-level randomization was handled in analysis. These items are not reported in the registry record. The within-participant design is important when interpreting any comparison: observations from flanks belonging to the same person may be related, and repeated phases may involve different treatment exposure and masking conditions.

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.

Double Blind Part

Reasons for not completing this period:

Open Label - Active Only

Analysis population for the primary outcome, as defined in the registry: The data for double blind and open label phase are presented. A total of 9 subjects continued to open label phase.

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 Number of Participants With Treatment-related Adverse Events [AEs], measured over 12 weeks for the Double-Blind Phase and 12 weeks for the Open-Label Phase.

The primary endpoint is the number of participants with treatment-related adverse events. It is a safety measure: it counts participants who experienced an adverse event judged to be related to treatment, rather than measuring the amount of fat reduction. The registry gives the endpoint timeframe as 12 weeks for the Double-Blind Phase and 12 weeks for the Open-Label Phase and states that data for both phases are presented.

A participant count can communicate how many people experienced an event, but by itself it does not describe event severity, duration, recurrence, or the number of separate events. The registry separately reports serious adverse-event counts and other adverse-event counts, but does not provide the primary endpoint’s numerical results or define the relationship between those categories and the treatment-related endpoint in the available record. The primary results are not reported in the registry record.

Counting participants rather than individual events can be useful for a safety summary because it focuses on how many people were affected. However, interpretation depends on the event definition, attribution process, observation period, and analysis population. Those details are not reported in the registry record. The fact that both phases are included also matters: the open-label phase followed code opening and a second treatment cycle, so its observations do not have the same blinded comparison structure as the initial phase.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The trial is listed as randomized, triple-masked, and parallel, while its summary describes randomization of each participant’s flanks. These labels describe different aspects of design. Randomization assigns treatment according to a chance-based process; masking limits knowledge of assigned treatment; and the model label describes the registry’s classification. Here, the flank-level assignment means that one person can contribute observations associated with both treatments. The record does not provide enough detail to establish exactly how the parallel label was applied to the analysis.

What does a randomized within-person comparison mean?

In general, randomization is intended to reduce systematic differences in treatment assignment. In a within-person design, each participant contributes experience under both conditions, which can reduce the influence of characteristics that remain stable within a person. It also creates a statistical dependence: two flanks from the same participant may have more in common than flanks from different participants. An analysis that treats every flank as wholly independent can understate uncertainty if that dependence is not accounted for. The registry record does not report the method used to account for within-participant dependence.

The design also includes an open-label phase after codes were opened. General statistical interpretation distinguishes that phase from a blinded comparison, because treatment knowledge and treatment sequence can affect assessment or reporting. Here, the previously untreated contralateral flank received a second treatment cycle, and 9 subjects continued. The record does not report how open-label observations were combined with double-blind observations for each outcome or whether phase-specific analyses were conducted.

How should a count endpoint be understood?

In general, a binary participant-level outcome records whether each person did or did not experience the defined event during a specified period. A count of participants with an event is a summary of those individual outcomes. Interpretation needs a clear event definition and a clear denominator. It also needs to distinguish participants from flanks and from individual adverse-event episodes. The primary endpoint is described as the number of participants with treatment-related adverse events, but its result is not reported in the registry record. The adverse-event summaries give participant counts at risk and affected, but do not supply the full endpoint definition or phase-specific breakdown.

For binary outcomes, a comparison may be expressed as a difference in event proportions or another measure of relative or absolute association. No such treatment-effect estimate is reported for the primary endpoint. No calculation should be inferred from the adverse-event summary alone: the design has paired flank assignments, and the record does not state whether the posted group counts use participants, flanks, or a phase-specific analysis in a way that would support a particular contrast.

What do uncertainty measures contribute?

In general, a confidence interval shows the range of effect values reasonably compatible with the observed data under a statistical model. It is useful because it communicates precision and includes more information than a significance test alone. A broad interval can be consistent with a range of effects, while a narrow interval reflects greater precision. The registry record does not report a confidence interval for the primary endpoint or the listed secondary outcomes.

In general, a significance test evaluates data relative to a stated null hypothesis and analysis assumptions. A p-value is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. No primary endpoint test result or p-value is reported in the registry record. The record also does not state which statistical model or test was prespecified for the participant-level safety outcome.

What is over-dispersion, and why might it matter?

General explanation: over-dispersion occurs when observed variability in count data is greater than a statistical model expects. It can arise when observations are clustered, when participants differ substantially, or when events occur more variably than the model allows. Accounting for over-dispersion can prevent uncertainty from being understated. The primary endpoint is a participant count, not a reported event-rate model, and the registry record does not report a model or an over-dispersion assessment. The concept is relevant generally to count analyses, but it cannot be used to infer the method applied in this trial.

How should the planning illustrations be read?

The registry’s planning assumptions describe an illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. In general, such an illustration estimates the participants per arm needed to detect a specified fraction of an effect under stated assumptions. It is not a report of the enrolled trial’s power, and it does not show what power was achieved. The registry record does not report the trial’s original sample-size justification. The illustrations also cannot replace an observed effect estimate or its uncertainty, neither of which is reported for the primary endpoint.

For time-to-event planning, the registry’s general note says the illustration uses the total number of events; other planning illustrations are expressed as participants per arm. This distinction concerns how a planning quantity is presented, not an observed result. No time-to-event primary endpoint is listed in the available trial details. Overall, the record describes several design features, but its statistical analysis methods, handling of within-person observations, and numerical endpoint results are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 6 outcome measures: the primary safety endpoint and secondary measures concerning physician assessment, satisfaction, measured fat volume, reviewer identification, and blood drug concentration. Examining several outcomes can create a multiplicity issue: when many statistical tests are performed, the chance of at least one apparently notable finding can increase. In general, a statistical plan may address this through a prespecified hierarchy, adjustment, or another strategy. The registry record does not report a multiplicity strategy, so it is not possible to determine whether any adjustment was planned or used.

The record does not report numerical results for the primary endpoint or the secondary outcomes, and it lists 0 analyses. It therefore does not provide estimates, uncertainty intervals, or test results for judging the outcomes. The registry also does not report how missing observations were handled, whether participants were analyzed according to initial assignment, or how the analysis populations were defined. Those are important details because the open-label phase included 9 continuing subjects, while the enrolled group contained 12.

In general, missing-data methods depend on why measurements are absent and on the outcome and analysis design. Excluding people with missing data can alter the population represented by a result, while assumptions used to account for missing values can affect estimates and uncertainty. The reason that some participants did not continue to the open-label phase is not reported in the registry record. No imputation method, sensitivity analysis, or detailed participant flow is reported either.

The registry’s sample-size assumptions are planning illustrations rather than the original design justification or observed power. They do not resolve the absence of an analysis plan, endpoint results, multiplicity handling, or missing-data information.

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 adverse-event summary reports no serious adverse events among 12 participants at risk in the RZL-012 group and none among 12 at risk in the placebo group. It also reports no deaths in either group. For other adverse events, 12 participants are listed as affected among 12 at risk in each group. These are the counts recorded; the registry record does not include event descriptions or additional detail about severity, timing, duration, or recurrence.

Zero serious events in these summaries means that no serious events are recorded for the listed groups. It does not establish that serious events could not occur, nor does it answer whether treatment-related adverse events occurred. The primary endpoint specifically concerns treatment-related adverse events, while the adverse-event summary distinguishes serious events from other events. The record does not provide enough information to equate “other” events with treatment-related events.

The counts also require care because participants’ flanks were randomized to different treatments. The same participant may contribute to both treatment-group summaries; the groups should not automatically be interpreted as separate, independent participant samples. The registry says data for both phases are presented for the primary endpoint, but does not clarify the phase composition of these adverse-event counts. The primary endpoint’s numerical results are not reported in the registry record.

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

The posted registry entries establish that this was a completed randomized Phase 2 trial of RZL-012 and placebo in 12 subjects seeking flank fat reduction. They describe a double-blind phase in which each participant’s flanks were randomized, followed by an open-label phase for subjects who continued. The record also provides treatment-session details and selected adverse-event counts.

Those details do not establish the size or precision of a treatment effect. The primary endpoint is the number of participants with treatment-related adverse events, but its numerical results are not reported in the registry record. The adverse-event summary reports zero serious events and zero deaths in both listed groups, while it reports other adverse events in 12 participants at risk in each group. That summary does not specify whether those other events were treatment-related and does not replace the primary endpoint result.

The registry lists secondary efficacy and pharmacokinetic outcomes, but does not report their numerical findings. As a result, the record does not support conclusions about changes in fat volume, satisfaction, physician assessment, reviewer identification, or blood drug concentration. It also does not provide estimates or confidence intervals that would show how precisely any effects were measured.

In general, a study result should be interpreted in light of its design, analysis population, endpoint definition, and uncertainty. Here, the paired flank assignments mean that observations may be related within participants, and the open-label phase differs from the blinded phase. The registry does not report the analysis methods needed to assess how these features were handled. The enrollment of 12 participants and continuation of 9 subjects are descriptive design details; they do not alone establish the reliability or clinical importance of a result.

The planning illustrations are not observed power and are not evidence of an effect. They are based on an observed effect under stated assumptions, whereas a primary endpoint comparison is not reported. The record therefore supports a careful account of design and safety counts, but not a quantitative conclusion about efficacy or the overall treatment-related safety endpoint.

13. Why This Trial Matters Statistically

This trial is statistically notable for assigning treatment by flank within each participant. That structure can make comparisons informative by pairing treatment experiences within a person, but it also requires analysis that recognizes the paired observations. The unit of randomization and the unit used for outcome reporting are important: the trial randomized 24 flanks among 12 subjects, while the primary endpoint is expressed as a number of participants. The registry record does not report how those levels were reconciled in analysis.

The sequence of a double-blind phase followed by an open-label phase creates a second interpretive challenge. The first phase offers a masked comparison between RZL-012 and placebo flanks. After codes were opened, the previously untreated contralateral flank received a second treatment cycle, and 9 subjects continued. Results from these phases would need clear definitions and phase-specific interpretation, but the registry does not report how the data were analyzed or combined.

Safety counts are especially easy to misread if group labels are treated as separate participant populations. In this design, participants may have received both conditions on different flanks. The reported 12 at risk in each group therefore do not, by themselves, establish that the groups contain different people. Likewise, the report of other adverse events among all participants at risk does not identify treatment attribution or establish an effect without an appropriate comparison and analysis.

Finally, the registry lists several outcomes but provides no numerical results for the primary endpoint or the listed secondary measures. This leaves major statistical questions unresolved, including effect size, precision, analysis population, missing-data handling, and multiplicity. The design makes those details consequential: without them, the trial record is best read as a description of the study and selected event counts rather than as a complete statistical account of its findings.

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 registry record does not report the primary endpoint’s numerical results, an effect estimate, a confidence interval, or a statistical test. It therefore does not allow quantitative assessment of the treatment-related adverse-event endpoint. Although the adverse-event summary gives serious and other event counts, it does not provide event terms, timing, severity details, or treatment attribution for other events.

The unit structure is also a limitation for interpretation. Treatment was randomized by flank, whereas the primary endpoint is expressed as a participant count. A participant could contribute a flank to each treatment condition. The record does not report whether the analysis accounted for the relationship between flanks within a participant or how participant-level events were assigned to treatment groups.

The study included a double-blind phase and a later open-label phase, with 9 subjects continuing to the latter. Phase-specific primary endpoint counts and the reasons some subjects did not continue are not reported in the registry record. Nor are the analysis populations, missing-data methods, or details of how results from the two phases were combined.

The registry lists secondary outcomes but does not report their numerical results or the statistical methods used to analyze them. A multiplicity strategy, original sample-size justification, and detailed analysis plan are not reported in the registry record. The planning assumptions are illustrations rather than a record of the original design or observed power. Together, these omissions limit the ability to assess efficacy, precision, and the robustness of safety comparisons from the registry record alone.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Evaluation of Safety and Efficacy of RZL-012 in Subjects Seeking Fat Reduction in the Flanks — NCT05445557.
• Registry record last updated 2023-11-18; status last verified 2022-02.
• Results first posted 2023-11-18.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

The registry describes a completed randomized Phase 2 study sponsored by Raziel Therapeutics Ltd., with 12 participants enrolled. Participants’ flanks were randomized to RZL-012 or placebo during a double-blind phase, followed by an open-label phase in which the previously untreated contralateral flank received a second treatment cycle. The registry reports that 9 subjects continued to the open-label phase.

The primary endpoint is the number of participants with treatment-related adverse events over the stated 12-week periods for each phase. Its numerical results are not reported in the registry record. The adverse-event summary records 0 serious events and 0 deaths in each listed group, and other adverse events among 12 participants at risk in each group. The record does not provide a primary endpoint comparison, numerical secondary outcome results, or the statistical methods needed to interpret treatment effects and uncertainty.