Phase 1b/2a Study to Evaluate Safety and Efficacy of Setmelanotide in Obese Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase 1b/2a Study to Evaluate Safety and Efficacy of Setmelanotide in Obese Patients (NCT02041195), a randomized phase 1, phase 2 study. The primary outcome is Body Weight - Stage A.

2. Clinical Question

These elements describe the trial’s intended comparison and the outcome data that are actually posted. The brief summary states that mean percent body weight loss and other weight-loss parameters were among the study aims, but the primary result available in the registry is a baseline measurement. The distinction matters: baseline means describe the groups before treatment assessment, whereas an estimate of treatment effect requires a post-dose result or a comparison of change over time.

3. Trial Design

This was a Phase 1b/Phase 2a study with randomized allocation, double masking, and a parallel-group model. The registry lists an enrollment of 99 and describes the study as completed. The study started in 2014-01, with primary completion in 2014-08. Rhythm Pharmaceuticals, Inc. is listed as the sponsor.

The study was staged. In Stage A, the listed regimens were setmelanotide 0.75 mg twice daily, setmelanotide 1.5 mg once daily, and placebo. The arm descriptions specify morning and evening administration: the once-daily setmelanotide regimen used an equivalent placebo in the evening, while the twice-daily regimen split the dose between morning and evening. The placebo regimen used placebo at both times. Stage B lists setmelanotide 1.5 mg once daily and placebo 1.5 mg once daily. Stage C lists setmelanotide 2 mg once daily and placebo 2 mg once daily.

The primary outcome named in the record is limited to Stage A. The baseline analysis lists 10 participants for the 0.75 mg twice-daily group, 9 for the 1.5 mg once-daily group, and 6 for placebo. The record says data from two placebo groups were combined for the efficacy analysis. The enrollment figure is the study-wide total, not the count in each Stage A group.

Randomization and masking describe how treatment allocation and knowledge of allocation were handled in the design, but details such as the randomization procedure and how masking was maintained are not reported in the registry record. The protocol’s sample-size justification, planned interim analyses, and detailed statistical analysis plan are also not reported. The staged structure and listed regimens describe the design, but the posted baseline outcome alone does not establish how treatment groups compared after dosing.

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.

Only the first 6 of 8 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set (FAS) included all participants with a baseline and at least one post-dose efficacy observation. Data from 2 placebo groups were combined for the efficacy analysis.

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 Population included all participants who received at least 1 dose of study drug and had a post-baseline observation.

Only the first 6 of 9 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Body Weight - Stage A, measured over Baseline.

The primary outcome is titled Body Weight - Stage A, with kilograms as the unit, a mean as the summary measure, and standard error as the reported measure of uncertainty. Its timeframe is Baseline. The registry defines the Full Analysis Set as participants with a baseline and at least one post-dose efficacy observation.

Body weight is a continuous measurement, so a group mean gives a concise description of the group’s average measured weight. The standard error describes uncertainty around an estimated mean; it is not a description of how widely individual participants’ weights vary. General statistical interpretation: a post-dose mean or a change-from-baseline measure can help describe how an outcome evolves during a trial, while a comparison between randomized groups can help quantify a treatment contrast. A baseline value instead characterizes the groups before the outcome is assessed after dosing.

The registry reports baseline means of 101.7 kg for setmelanotide 0.75 mg twice daily, 101.7 kg for setmelanotide 1.5 mg once daily, and 94.5 kg for placebo. The corresponding standard errors are 5.09, 4.24, and 3.85. These values do not provide a post-dose change or a treatment-effect estimate. The reason for recording baseline body weight is clear as a starting description, but the posted primary outcome does not by itself show what happened to body weight during treatment.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods help distinguish a descriptive summary from an estimate of a treatment effect. In this record, the primary result is a mean body weight at baseline, with a standard error. That combination describes the average measured weight in each listed group and the uncertainty associated with estimating that average. It is not a change score, a comparison between groups, or a measure of variation among individual participants.

What does the mean describe?

For a continuous outcome such as body weight, a mean summarizes the measurements in a group. The registry reports means in kilograms for the Stage A setmelanotide and placebo groups. These values can be read as group-level baseline descriptions for the participants included in the relevant analysis. A group mean does not reveal the full distribution of individual measurements, and it does not indicate how many participants had values near or far from the mean.

General statistical explanation: the standard error reflects uncertainty in an estimated mean and is often used when constructing an interval estimate or conducting an inferential test. It should not be mistaken for the standard deviation, which describes variation among individual observations. The registry identifies the dispersion measure as standard error, but does not post confidence intervals for the means in the available primary result. No additional interval should be inferred from the standard errors alone.

Why does the timeframe matter?

The listed timeframe is Baseline. A baseline measurement is taken as a starting description, not as evidence of what occurred after treatment. To estimate change, an analysis would need post-dose measurements or a reported change-from-baseline outcome. To compare treatment strategies, an analysis would need a contrast between groups, with an estimate of uncertainty. The registry record does not report those elements for the primary outcome. General statistical explanation: randomized groups are compared using post-treatment outcomes, changes, or a model that accounts for baseline and follow-up measurements, depending on the prespecified analysis. The actual method intended for this trial is not reported in the registry record.

What does the analysis population mean?

The Full Analysis Set is defined in the record as all participants with a baseline and at least one post-dose efficacy observation. This definition indicates that inclusion depended on both a baseline measure and at least one post-dose efficacy observation. It does not, on its own, explain how missing observations were handled, whether any participants were excluded from a particular analysis, or how the analysis population relates to the randomized population in every stage. Those details are not reported in the registry record.

The record also states that data from two placebo groups were combined for the efficacy analysis. This describes the handling of placebo data for that analysis, but the registry entries do not specify the complete rationale or statistical procedure used to combine the groups. The baseline result lists a placebo count of 6. The separate safety listing includes two Stage A placebo groups with 3 participants each at risk. Those safety counts should not be substituted for the baseline efficacy count.

Why is a treatment contrast necessary?

A treatment-effect estimate is a comparison between groups, rather than a description of one group in isolation. It generally includes an estimated contrast and a measure of uncertainty, such as a confidence interval. A confidence interval gives a range of values compatible with the data and the method used, under its assumptions; it is not a guarantee that the true effect lies in that range. General statistical explanation: the interval’s width communicates precision, while its position communicates the range of estimated effects. Neither an interval nor a test result for the primary treatment contrast is reported in the registry record.

The posted results therefore support descriptive statements about baseline means and standard errors, but not an inferential statement about post-dose body weight. The record’s indication that a continuous-endpoint comparison is missing or not estimable reinforces this limit. No treatment contrast should be reconstructed from the baseline means alone.

What can sample-size planning tell a reader?

The sample-size assumptions describe a planning illustration based on the observed effect, not the trial’s own design. The illustration uses 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. These assumptions describe how a planning exercise would be framed; they do not establish the trial’s sample-size justification or the method used to plan enrollment. That justification is not reported in the registry record. The illustration is not observed power and should not be interpreted as a result of the trial.

General statistical explanation: sample-size planning estimates how much information a future study might need under specified assumptions. The result depends on the target effect, outcome variability, allocation, and statistical procedure. If the estimated effect used as the planning basis is not available as a treatment contrast, the illustration cannot be interpreted as a clinical finding. The record does not report a primary treatment-effect estimate from which to assess such an effect in this case.

How should multiple outcomes be considered?

The registry lists 15 outcome measures, including 6 secondary outcomes, and reports 4 analyses. Multiple outcomes can create a multiplicity issue because testing many hypotheses can increase the chance of at least one apparently notable result under a general statistical framework. The detailed analysis plan, which would say whether and how multiplicity was addressed, is not reported in the registry record. It is therefore not possible to say whether the listed outcomes were subject to a formal testing hierarchy or adjustment. No p-values for the primary treatment comparison are reported in the available primary result.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Stage A: Setmelanotide 0.75 mg BID", "Stage A: Setmelanotide 1.5 mg QD", "Stage A: Placebo")
n   <- c(10, 9, 6)
m   <- c(101.7, 101.7, 94.5)
sp  <- c(5.09, 4.24, 3.85)
sd  <- sp * sqrt(n)      # standard errors converted to SDs
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Stage A: Setmelanotide 0.75 mg BID  10  101.700  16.096  90.186  113.214
CARM  Stage A: Setmelanotide 1.5 mg QD  9  101.700  12.720  91.923  111.477
CARM  Stage A: Placebo  6  94.500  9.431  84.603  104.397

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 15 outcome measures, including 6 secondary outcomes, and reports 4 analyses. The secondary outcomes include setmelanotide concentrations during a 24-hour steady-state interval on Day 8 in Stages A and C, changes in ambulatory blood pressure monitoring parameters between Days 8 and 15 in Stages A and C, and changes in heart rate using ambulatory monitoring in those stages. The detailed statistical plan for these outcomes is not reported in the registry record.

When a study assesses multiple outcomes or makes multiple comparisons, multiplicity can affect how results should be interpreted. General statistical explanation: repeated testing can raise the chance of finding at least one result that appears statistically notable when no underlying effect exists. Whether that concern was addressed through a prespecified hierarchy, adjustment, or another strategy is not reported. The available record does not support a claim that multiplicity was or was not controlled.

The Full Analysis Set includes participants with baseline and at least one post-dose efficacy observation. This is the reported population definition, but missing-data procedures beyond that definition are not reported. The registry does not specify how participants without post-dose measurements were handled, whether imputation was used, or what sensitivity analyses were planned. These details should not be inferred from the population definition alone.

The primary outcome result is a baseline mean rather than a post-dose comparison. A treatment-effect estimate and its uncertainty are not reported in the registry record. The record also does not report the trial’s sample-size justification, interim-analysis plan, or complete statistical analysis plan. These omissions limit assessment of the intended inferential framework and the handling of missing data and multiple outcomes.

12. 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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: muscle strain (3.6%), chest pain (3.4%).

The safety listing reports serious adverse events and other adverse events separately by stage and group. In Stage A, no serious adverse events are listed among 10 participants receiving setmelanotide 0.75 mg twice daily, 9 receiving setmelanotide 1.5 mg once daily, or either placebo group of 3 participants. Other adverse events are listed for 10, 8, 2, and 3 participants in those groups, respectively. No deaths are listed in any group.

In Stage B, no serious adverse events are listed among 11 participants receiving setmelanotide 1.5 mg once daily or 6 receiving placebo; other adverse events are listed for 9 and 3 participants, respectively. In Stage C, 1 serious adverse event is listed among 29 participants receiving setmelanotide 2 mg once daily, and 1 among 28 receiving placebo. Other adverse events are listed for 29 and 21 participants, respectively. No deaths are listed in either Stage C group.

The registry lists Muscle strain at 3.6% and Chest pain at 3.4% among the top serious adverse event terms. The available record does not associate these terms with a specific group in the information, so they should not be assigned to one. These counts describe events recorded in the trial; they do not establish that an event was caused by treatment. The record does not provide a basis for drawing broader safety conclusions.

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

The posted result is a baseline description of body weight in Stage A. It gives group means and standard errors for the listed setmelanotide and placebo arms. The primary outcome timeframe is Baseline, and the available result does not include a post-dose value, change from baseline, or between-group treatment-effect estimate.

That distinction sets the limit on what can be concluded statistically. Baseline summaries can describe the starting measurements of the analysis groups. They cannot establish whether participants’ weight changed during the study or whether any change differed between randomized groups. The stated study aim included mean percent body weight loss and other weight-loss parameters, but those treatment-effect results are not reported in the registry record.

The record also describes a Full Analysis Set and says that two placebo groups were combined for the efficacy analysis. These details clarify aspects of the analysis population and placebo handling, but they do not replace an outcome comparison. The baseline means and standard errors do not provide a confidence interval or p-value for a treatment contrast. No such inferential result is reported for the primary outcome.

The safety counts are separate descriptive information. They show how many participants in each listed group had serious or other adverse events, and no deaths are listed. They should be read as recorded counts rather than as evidence that an event was or was not caused by a study drug. The registry record also lists serious adverse event terms, but the available information does not assign those terms to specific groups.

In short, the posted statistics characterize baseline weight and record adverse-event counts. They do not determine efficacy, establish a treatment difference, or support a conclusion about the precision of a treatment effect. Those conclusions would require results and analyses that are not reported in the registry record.

14. Why This Trial Matters Statistically

This study illustrates why the label and timing of an outcome are central to statistical interpretation. Body weight is a continuous measure, and the registry reports Stage A means with standard errors. But the recorded timeframe is Baseline. A precise description of starting values is not the same as an estimate of change during treatment, and neither is automatically a comparison of treatment effects.

The record also makes the analysis population explicit: participants needed a baseline and at least one post-dose efficacy observation to be included in the Full Analysis Set. It states that two placebo groups were combined for efficacy analysis. Such details matter because they define which observations contribute to a result and how comparator data are handled. At the same time, these definitions do not reveal how missing observations were addressed or what inferential method was planned.

The study’s staged structure and multiple listed outcomes make it especially important to distinguish trial design information from posted results. The record identifies 15 outcome measures, 6 secondary outcomes, and 4 analyses, but the detailed statistical plan and multiplicity strategy are not reported. Without those details and without a post-dose primary comparison, readers cannot determine how the planned outcomes were prioritized or how uncertainty in the treatment effect was evaluated.

The statistical lesson is not that baseline data are uninformative. They provide a description of the groups at the stated timeframe. The lesson is that a result must be interpreted according to the outcome, population, and analysis actually reported. Here, those data describe baseline body weight; they do not answer the study’s intended treatment-effect question.

15. 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 primary outcome result is confined to Stage A baseline body weight. The registry does not report a post-dose primary weight result, a change-from-baseline estimate, or a treatment contrast. As a result, the principal efficacy question cannot be assessed from the posted primary figures.

The record defines the Full Analysis Set as participants with a baseline and at least one post-dose efficacy observation, but further missing-data methods are not reported. The relationship between the study-wide enrollment of 99 and the participants included in each stage or analysis is not fully described by the available primary result. The Stage A baseline counts are 10, 9, and 6; they should not be treated as the study-wide enrollment.

The record states that two placebo groups were combined for efficacy analysis, while the safety listing presents those placebo groups separately. The details of the efficacy combination and its rationale are not reported. The detailed statistical plan, sample-size justification, interim analyses, multiplicity approach, and sensitivity analyses are also not reported in the registry record.

The safety information is presented as group-level counts and selected serious adverse event terms. The available information does not establish causality or provide further context for the terms’ group assignments. The findings therefore remain descriptive, and broader conclusions about treatment effects or safety cannot be drawn from these posted figures alone.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Phase 1b/2a Study to Evaluate Safety and Efficacy of Setmelanotide in Obese Patients — NCT02041195.
• Registry record last updated 2023-08-07; status last verified 2023-07.
• Results first posted 2023-08-07.
• 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.

19. Record Summary

The registry record describes a completed Phase 1b/Phase 2a randomized, double-blind, parallel-group study of setmelanotide and placebo in participants with obesity. Enrollment is listed as 99. The study started in 2014-01 and reached primary completion in 2014-08. The sponsor is Rhythm Pharmaceuticals, Inc.

The Stage A primary outcome is baseline body weight in kilograms, summarized as a mean with standard error. The record defines the Full Analysis Set as participants with baseline and at least one post-dose efficacy observation and says two placebo groups were combined for efficacy analysis. The posted primary values are baseline summaries, not a post-dose treatment comparison.

The record lists 15 outcome measures, 6 secondary outcomes, and 4 analyses. It also reports adverse-event counts by group. Further statistical-plan details, including sample-size justification, missing-data procedures, and multiplicity handling, are not reported in the registry record.