A Safety and Efficacy Study of Relamorelin in Diabetic Gastroparesis 01: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Safety and Efficacy Study of Relamorelin in Diabetic Gastroparesis 01 (NCT03285308), a randomized phase 3 study. The primary outcome is Change From Baseline to Week 12 in the Weekly Diabetic Gastroparesis Symptom Severity Score (DGSSS).

2. Clinical Question

The study was designed to evaluate safety and efficacy in participants with diabetic gastroparesis. Participants recorded symptom severity daily in an electronic diary. The registry record lists nausea, abdominal pain, bloating and postprandial fullness responder outcomes among the secondary outcomes, alongside several safety outcomes. However, it does not report results for these secondary outcomes either. The clinical question can therefore be described from the registered design and endpoint definitions, but the posted record does not establish the observed symptom changes or how they compared between groups.

3. Trial Design

This was a Phase 3, randomized, double-blind, parallel-group, placebo-controlled study of relamorelin in people with diabetic gastroparesis. The official study title describes a 12-week treatment period. The registry lists enrollment of 336 participants and identifies Allergan as the sponsor. The study began on 2017-09-29, and its primary completion date is listed as 2020-07-08. Its status is terminated; the reason for termination is not reported in the registry record.

Both groups had a 2-week placebo run-in before treatment. Participants assigned to relamorelin received 10 μg by subcutaneous injection twice daily for up to 12 weeks. Participants assigned to placebo received placebo-matching injections on the same schedule for up to 12 weeks. The registered masking is double, although the registry record does not specify which roles were masked or describe the procedures used to maintain masking. Details of the randomization method and allocation concealment are not reported in the registry record.

The primary outcome was change from baseline to Week 12 in the weekly Diabetic Gastroparesis Symptom Severity Score. Baseline was defined using the average of the two weekly scores during the run-in period. The registry lists 12 outcome measures overall, including symptom responder outcomes and safety outcomes. The symptom outcomes concern nausea, abdominal pain, bloating and postprandial fullness during each of the last 6 weeks of treatment. Safety outcomes include treatment-emergent adverse events, potential clinically significant laboratory results, clinically meaningful vital-sign trends and clinically significant electrocardiogram results.

Although the study’s design and outcome definitions are recorded, the registry record does not report a primary outcome analysis. It also does not report a reason for termination, a statistical analysis plan, or a trial-specific sample-size justification.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Modified Intent-to-treat (mITT) Population included all randomized participants with ≥1 postbaseline assessment of DGSSD. Number analyzed is the number of participants with data available at the given time-point.

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: ITT Population included all randomized participants.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline to Week 12 in the Weekly Diabetic Gastroparesis Symptom Severity Score (DGSSS), measured over Baseline (Day-14 to Day-1) to Week 12.

The primary endpoint was change from baseline to Week 12 in the weekly Diabetic Gastroparesis Symptom Severity Score, a mean-based measure of symptom severity. Participants rated symptoms daily using the Diabetic Gastroparesis Symptom Severity Diary in an electronic diary. The score was derived from the weekly averages of four items: nausea, abdominal pain, postprandial fullness and bloating.

Each symptom used an 11-point ordinal scale from 0, meaning no discomfort, to 10, meaning the worst possible or most uncomfortable. The combined score ranged from 0, best, to 40, worst. Baseline was the average of the two weekly scores from the run-in period. A negative change from baseline indicates improvement in the score; it does not, by itself, describe the size or clinical importance of a change.

A combined symptom score can summarize several aspects of the condition in one outcome, while the listed symptom-specific responder outcomes address individual symptoms. The primary endpoint’s interpretation depends on the observed group values and their uncertainty, neither of which is reported in the registry record. The registry also does not report a threshold defining a clinically important change in this score. The endpoint definition alone therefore explains what was intended to be measured, but cannot show the treatment comparison.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a continuous score summarized as a mean. A mean describes the central value of a set of measurements, while the standard deviation describes the spread of individual measurements around that mean. These statistics answer different questions: a mean characterizes the group’s average score, and a standard deviation describes variability among participants. Neither statistic alone gives the uncertainty in a treatment comparison. The registry record identifies the endpoint as a mean with standard deviation, but does not report the primary outcome values or a comparative estimate.

What does change from baseline represent?

Change from baseline expresses each participant’s follow-up score relative to their baseline score. In this study, baseline was defined as the average of the two weekly Diabetic Gastroparesis Symptom Severity Scores during the run-in period. The endpoint compares that baseline with the Week 12 score. Because higher scores represent worse symptoms, a negative change indicates improvement in the score. A between-group comparison of mean changes would describe how the average changes differed between randomized groups, but that comparison is not reported in the registry record.

The score combines weekly averages for nausea, abdominal pain, postprandial fullness and bloating. Each diary item is ordinal: its response categories have an order from lower to higher reported severity. Adding weekly averages creates a summary score intended to represent the combined symptom burden. As a general statistical consideration, analyzing such a score as a continuous measure treats differences on the scale in a way that supports calculating means and standard deviations. The record describes that scoring approach, but does not report diagnostics or analyses assessing its assumptions.

Why does randomization matter?

As a general concept, random assignment aims to make comparison groups similar, on average, with respect to measured and unmeasured factors at the start of a study. This supports interpreting a between-group difference as a comparison of assigned treatments, subject to the conduct of the trial, missing data and the analysis. Here, the registry identifies the study as randomized, double-blind and parallel-group. The specific randomization procedure, allocation concealment details and statistical model are not reported in the registry record. Double-blinding can reduce some influences of treatment knowledge on reporting or assessment, but the record does not specify which participants or study personnel were masked.

What would uncertainty estimates tell a reader?

In general, a confidence interval expresses the range of estimates compatible with the observed data under the stated method and its assumptions. A narrow interval indicates greater precision than a wide interval, while the interval’s position helps show the direction and plausible size of an effect. A p-value, when reported, summarizes how compatible the data are with a specified null hypothesis under the analysis assumptions; it does not measure the probability that a treatment works. The registry record does not report a confidence interval, p-value or primary endpoint estimate, so the precision and statistical evidence for the primary comparison cannot be evaluated from this record.

Over-dispersion is a general concern when data vary more than an assumed statistical model allows. It can make standard errors too small if the model does not account for the extra variability, leading to overly precise inference. The primary outcome is described as a continuous mean score, and no model for repeated diary measurements or any over-dispersion assessment is reported in the registry record. It would therefore be inappropriate to attribute a particular model or adjustment to this trial.

How should the planning assumptions be understood?

In general, a sample-size calculation is a planning exercise that relates an intended effect size, variability, significance level, allocation and desired power to a target number of participants. The registry record describes a planning illustration based on a fraction of the observed effect, with a two-sided significance level of 0.05, equal allocation and a normal approximation. Such an illustration is not an observed power calculation and does not replace the trial’s own design justification. A trial-specific sample-size justification is not reported in the registry record, and no numerical planning results are available in the posted information.

For continuous outcomes, the planning illustration is expressed as participants per arm. In general, its value depends on the assumed effect and variability; using a smaller assumed effect usually requires more participants to detect it under otherwise comparable assumptions. These are planning principles, not a statement about the number needed for this study or the result it achieved. The record does not provide an analyzed primary endpoint result from which to judge the actual effect or its precision.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple outcome measures, including a primary symptom-severity endpoint, symptom-specific responder outcomes and safety outcomes. When several outcomes, symptoms or time points are examined, the chance of obtaining at least one apparently notable result can increase. As a general statistical principle, a prespecified multiplicity strategy can control the interpretation of multiple tests, for example by defining a primary comparison or adjusting inference across a set of comparisons. The statistical plan and any multiplicity adjustment are not reported in the registry record.

The primary outcome is defined at Week 12, while the listed nausea, abdominal pain, bloating and postprandial fullness responder outcomes concern each of the last 6 weeks of treatment. The registry’s skip note indicates that the primary outcome has several categories or time points and is not reduced to one comparison. No single primary comparison is reported in the posted analyses, and the record lists no analyses. The intended hierarchy among outcomes, how repeated time points were to be handled, and whether any outcome was designated for confirmatory inference are not reported in the registry record.

The primary population includes randomized participants with at least one postbaseline diary assessment. The record notes that the analyzed number depends on data available at a given time point, but does not state how missing diary data were handled, whether participants were excluded after randomization for other reasons, or how sensitivity analyses were planned. As a general matter, missing outcomes can affect both the estimate and its uncertainty, particularly if the probability of missingness is related to symptom severity or treatment assignment. No assumptions or methods for addressing missing data are reported in the registry record.

The distinction between the randomized population and the outcome population matters: the stated mITT definition requires at least one postbaseline assessment. The record does not report the number contributing data at Week 12, the extent or pattern of missingness, or the results of any analysis population sensitivity checks. These omissions limit assessment of both the robustness of a future estimate and the consistency of the analysis with the randomized design.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pneumonia (1.8%), diverticulitis (1.2%), urinary tract infection (1.2%), sepsis (1.2%), fall (1.2%).

The registry reports serious adverse events for 15 participants in the placebo group and 16 participants in the relamorelin 10 μg group. The number at risk is listed as 163 in each group. For other adverse events, it reports 9 participants in each group, again with 163 at risk in each group. The death count is 0 in both groups. These are counts of participants, not estimates of comparative effect, and the record does not report a formal statistical comparison of these figures.

The registry also lists serious adverse event terms and percentages: pneumonia, 1.8%; diverticulitis, 1.2%; urinary tract infection, 1.2%; sepsis, 1.2%; fall, 1.2%; and acute kidney injury, 1.2%. These listed terms should be read as event categories recorded in the registry, not as a complete description of every participant’s clinical course. The record does not explain the denominator or event-level counting details for each listed percentage.

As a general statistical point, counts alone do not describe timing, duration, recurrence, exposure or severity beyond the registry’s serious-event classification. Nor do they establish that any observed difference is caused by treatment. The adverse-event figures therefore describe what was recorded, while the comparative interpretation remains limited by the absence of a reported safety analysis and additional clinical context.

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

The registry record establishes that a randomized, double-blind, placebo-controlled Phase 3 study of relamorelin in diabetic gastroparesis was conducted and later marked terminated. It describes treatment schedules, the primary symptom score and several secondary and safety outcomes. It does not report the primary endpoint analysis, so there is no posted estimate of how the mean symptom score changed in either group or how the groups compared. No conclusion about the magnitude, direction or precision of the primary outcome contrast can be drawn from the recorded design alone.

The lack of a posted analysis is not the same as evidence that the treatment groups had identical outcomes, nor does it show that one group had better outcomes. It means the registry record does not contain the results needed to evaluate that comparison. The reason for termination is also not reported in the registry record, so the status cannot be used to infer the reason the trial stopped or what the investigators found.

The safety counts provide some descriptive information: the record lists serious adverse events, other adverse events and deaths by group. They do not substitute for a full safety assessment or a formal comparison. The listed serious adverse event terms and percentages add detail about reported categories, but do not provide a complete account of event context or causality.

In general, statistical evidence depends on both an estimate and its uncertainty, interpreted in light of the design, analysis and completeness of data. Those elements are not available for the primary endpoint in this registry record. The score’s definition explains what the study intended to measure, but the definition is not an outcome result. The registered study question is clear; the posted information is insufficient to answer it statistically.

13. Why This Trial Matters Statistically

This trial is statistically notable as a planned randomized, double-blind comparison using daily symptom reporting and a composite measure of diabetic gastroparesis symptom severity. The primary score combines four symptoms into one weekly measure, while the registry also identifies symptom-specific responder outcomes. This structure highlights a common design challenge: a study can define a central endpoint and also collect multiple related outcomes that may tell different parts of the clinical story. Interpreting such outcomes requires clarity about which comparisons are primary and how multiplicity is addressed.

The endpoint is based on participant-reported ordinal ratings summarized as weekly averages and then combined. As a general statistical issue, an aggregate score can be useful for summarizing several symptoms, but it may conceal differences among its component symptoms. The separate responder outcomes could address those components, but the registry record does not report their analyses or how the outcome family was to be interpreted.

The record also illustrates why trial registration and trial results are distinct sources of information. Registration documents the population, assigned interventions, outcome definitions and some design features. Here, the record does not include a primary outcome analysis, a statistical plan or the reason for termination. Consequently, the design can be described, but the treatment comparison cannot be evaluated from the posted results.

For biostatisticians and clinical researchers, the combination of a termination status and missing outcome analyses underscores the importance of transparent reporting of participant flow, analysis populations, missing-data handling, effect estimates and uncertainty. The available record is informative about what was intended to be studied and about selected safety counts, while leaving the main efficacy question unresolved in the registry.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The principal limitation for statistical interpretation is that the registry record does not report a primary endpoint result or a comparative analysis. Group means, standard deviations for the endpoint, the between-group estimate, confidence intervals and p-values are not reported in the registry record. Without these, neither the direction nor the precision of the primary comparison can be assessed.

The study is listed as terminated, but the reason for termination is not reported in the registry record. The record also does not report a statistical analysis plan, the sample-size justification, the randomization procedure, allocation concealment details, or which people were included in the double-blind masking. These omissions prevent assessment of several design and analysis decisions beyond the broad labels recorded for the trial.

The outcome population is defined as randomized participants with at least one postbaseline diary assessment. The number analyzed depends on data available at the time point, but Week 12 participant counts, missing-data patterns, exclusions and methods for handling missing outcomes are not reported in the registry record. This limits assessment of how closely the analyzed population represents the randomized groups and how missingness could affect an estimate.

The registry lists multiple symptom and safety outcomes, but the analysis hierarchy and multiplicity procedures are not reported. The safety figures are descriptive counts and selected serious-event terms; exposure details, event timing and a formal comparative safety analysis are not reported. The primary score’s definition is detailed, but no threshold for a clinically important score change is reported in the registry record. Together, these gaps mean the available record describes the intended study questions more completely than it reports answers to them.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Safety and Efficacy Study of Relamorelin in Diabetic Gastroparesis 01 — NCT03285308.
• Registry record last updated 2021-07-29; status last verified 2021-07.
• Results first posted 2021-07-29.
• 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

NCT03285308 is a Phase 3 randomized, double-blind, parallel-group, placebo-controlled study of relamorelin in participants with diabetic gastroparesis. The registry lists enrollment of 336 and identifies Allergan as the sponsor. Participants received relamorelin 10 μg or placebo by subcutaneous injection twice daily for up to 12 weeks after a 2-week placebo run-in. The study is listed as terminated; its reason for termination is not reported in the registry record.

The primary endpoint was change from baseline to Week 12 in the weekly Diabetic Gastroparesis Symptom Severity Score, derived from weekly averages of nausea, abdominal pain, postprandial fullness and bloating ratings. The registry record does not report a primary endpoint analysis. It lists safety counts by group, including serious adverse events, other adverse events and deaths, but no formal comparative safety analysis. Missing-data methods, a trial-specific sample-size justification, and the statistical analysis plan are not reported in the registry record.