This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Efficacy and Safety of Lanreotide Autogel® 60, 90 or 120 mg With Lanreotide 40 mg Prolonged Release (PR) in Acromegaly (NCT02493517), a randomized phase 3 study. The primary outcome is Standardised Mean Change From Baseline in Age-adjusted IGF-1 Levels at the EOST/EW Visit.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02493517 |
| Phase | Phase 3 |
| Condition | Acromegaly |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 128 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Ipsen |
| Results posted | Yes |
2. Clinical Question
Population
Subjects with active acromegaly were eligible for the trial. The primary efficacy analysis used a Per Protocol population: randomized and treated subjects with at least one baseline and one postbaseline assessment of the primary efficacy parameter, and no major protocol deviations affecting efficacy assessment.
Intervention
Lanreotide Autogel began at 90 mg, with injections every 4 weeks from day 1 through week 13. At week 17, subjects were titrated to 60 mg, 90 mg or 120 mg, then received injections every 4 weeks through week 29.
Comparator
The comparison group received lanreotide 40 mg prolonged release. Injections were given every 10 days from day 1 through week 15. At week 16, the injection frequency could remain every 10 days, change to every 14 days or change to every 7 days through week 30 or 31.
Primary question
The trial assessed the standardized mean change from baseline in age-adjusted IGF-1 levels at the end-of-study or early-withdrawal visit. The registry record describes this outcome for both treatment groups but does not report the numerical efficacy estimates or a single between-group result.
3. Trial Design
This was a phase III, prospective, randomized, open-label, parallel-group study in subjects with active acromegaly. The registry record lists 128 enrolled participants and a completed trial. The study began in 2014-10, with primary completion in 2016-11. Ipsen is listed as the sponsor.
The treatment strategies differed in both dose and injection schedule. The lanreotide Autogel group started at 90 mg, with injections every 4 weeks through week 13. At week 17, the dose was titrated to 60 mg, 90 mg or 120 mg, followed by injections every 4 weeks through week 29. The comparator group received lanreotide 40 mg prolonged release every 10 days from day 1 through week 15. At week 16, injection frequency could remain every 10 days, change to every 14 days or change to every 7 days, through week 30 or 31.
Because the study was open label, masking was not used. The registry record does not report further details about how randomization was generated or concealed, whether the titration decisions followed additional rules, or how treatment adherence was assessed. Those details should not be inferred from the stated schedules.
The primary outcome timeframe extended from baseline to the end-of-study or early-withdrawal visit, up to week 33 for lanreotide Autogel and up to week 32 for lanreotide prolonged release. These different maximum follow-up times are part of the stated endpoint definition. The record does not report the number of participants who completed follow-up in each group or the reasons for withdrawal.
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: 170 subjects were screened and 128 eligible subjects were stratified according to surgical history (previous pituitary surgery or no previous pituitary surgery) and randomised in a 1:1 ratio to receive lanreotide Autogel or lanreotide prolonged release (PR). All randomised subjects were treated.
Overall Study
| Stage | Lanreotide Autogel | Lanreotide PR |
|---|---|---|
| STARTED | 64 | 64 |
| COMPLETED | 62 | 57 |
| NOT COMPLETED | 2 | 7 |
Reasons for not completing this period:
| Reason | Lanreotide Autogel | Lanreotide PR |
|---|---|---|
| Protocol Violation | 1 | 2 |
| Withdrawal by Subject | 1 | 2 |
| Adverse Event | 0 | 2 |
| Missed study visit | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: The Per Protocol population consisted of all subjects who were randomised and treated with at least one baseline and at least one postbaseline assessment of the primary efficacy parameter and for whom no major protocol deviations occurred with impact on efficacy assessment.
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: Baseline characteristics are presented for the Safety population which consisted of all randomised subjects who received at least one dose of study treatment. The Safety population was analysed using subjects as treated.
| Characteristic | Unit | Lanreotide Autogel | Lanreotide PR | Total Title |
|---|---|---|---|---|
| Participants analysed | 64 | 64 | 128 | |
| Age, Continuous | years | 37.9 (SD 11.2) | 40.8 (SD 12.6) | 39.4 (SD 11.9) |
| Sex: Female, Male: Female | Participants | 38 | 40 | 78 |
| Sex: Female, Male: Male | Participants | 26 | 24 | 50 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 64 | 64 | 128 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): White | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Standardised Mean Change From Baseline in Age-adjusted IGF-1 Levels at the EOST/EW Visit, measured over Baseline to EOST/EW Visit (up to Week 33 for the lanreotide Autogel group and up to Week 32 for the lanreotide PR group)..
| Element | Registry entry |
|---|---|
| Result type | Least Squares Mean |
| Measure of spread | Standard Error |
| Unit | SDS |
| Endpoint classification | Continuous Endpoint |
The primary endpoint was the standardized mean change from baseline in age-adjusted, log-transformed IGF-1 standard deviation score (SDS) at the end-of-study or early-withdrawal visit. IGF-1 is an outcome measure in the trial’s assessment of acromegaly, and the registry defines the SDS as a standardized value relative to age-category reference limits.
For each subject, the SDS was derived from IGF-1 and the age-specific mean and standard deviation. The registry gives the relation between those reference limits and the mean: the upper limit of normal is the mean plus 2 standard deviations, and the lower limit of normal is the mean minus 2 standard deviations. An SDS of 0 corresponds to the mean; negative values are below the mean, and positive values are above it. A negative change indicates a decrease in mean age-adjusted IGF-1 values.
Standardization places a measurement on a scale expressed in standard deviations from a reference mean. This can make changes interpretable relative to age-specific reference values rather than only in the original measurement scale. The registry states that results were to be presented both without back-transformation and after back-transformation. The numerical endpoint estimates and their uncertainty are not reported in the registry record, so the magnitude and precision of change cannot be described.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies the primary outcome and its analysis population, but it does not report the primary efficacy estimates. In particular, it does not provide the mean change for either treatment group, the between-group estimate, a confidence interval, a standard error value, or a p-value. Consequently, the direction and size of the observed difference between treatment strategies cannot be characterized from the registry record.
The named outcome is a least-squares mean, with standard error listed as the measure of dispersion. A least-squares mean is generally an estimate from a statistical model, rather than necessarily the simple arithmetic mean of the observations. However, the model specification, any covariates, and the exact contrast used for a between-group comparison are not reported in the registry record. It would therefore be inappropriate to infer how the estimate was adjusted or to reconstruct a treatment effect.
The endpoint is a change in age-adjusted IGF-1 SDS, and its sign has a stated interpretation: a negative change represents a decrease in mean age-adjusted IGF-1 values. That definition does not by itself establish which group had a larger change, whether a between-group difference was statistically distinguishable from zero, or how clinically important any difference might be. None of those conclusions can be drawn without the numerical results and the analysis details.
The primary outcome timeframe ends at the end-of-study or early-withdrawal visit, with different maximum weeks specified for the two treatment groups. The record does not give group-specific follow-up distributions or explain how outcomes at different visit times were handled in the analysis. The reported endpoint is therefore defined, but the timing and completeness of observed assessments cannot be evaluated from the available record.
The record also lists secondary outcomes involving age-adjusted IGF-1, GH, tumour volume and symptoms. Their definitions indicate that the trial considered several dimensions of disease-related outcomes, but numerical results for these outcomes are not reported in the registry record. The existence of multiple outcomes does not establish that any particular one favored either treatment strategy. Overall, the registry describes what was intended to be measured, not a sufficiently detailed numerical efficacy result for judging the comparative estimate or its precision.
9. Statistical Methods Explained
The registry labels the primary endpoint as a least-squares mean and identifies the standard error as its dispersion measure. These labels describe the form of the reported estimate and one way to express its sampling uncertainty, but they do not identify the complete statistical model. Details such as model terms, assumptions, handling of repeated observations and the exact between-group contrast are not reported in the registry record.
What does a least-squares mean represent?
In general, a least-squares mean is a model-based mean estimate. It can differ from a raw arithmetic average when the analysis adjusts for other variables or accounts for the structure of the data. The registry does not state which adjustments, if any, were made for this endpoint. Thus, the label alone does not support describing the estimate as adjusted for a particular baseline characteristic or as arising from a particular model.
The endpoint is a change from baseline in age-adjusted, log-transformed IGF-1 SDS. A change score compares a follow-up measure with the baseline measure for the same subject, while standardization expresses the measure relative to a reference distribution. The registry explains that the SDS represents the number of standard deviations from the age-category mean, and that negative change indicates a decrease in mean age-adjusted IGF-1. It also states that back-transformed results were presented in addition to results without back-transformation. The specific transformation procedure and the numerical estimates on either scale are not reported in the registry record.
How should a standard error be read?
In general, a standard error describes the estimated sampling variability of an estimate. It is not the spread of individual participant measurements. A smaller standard error indicates a more precisely estimated mean under the analysis assumptions, while a larger standard error indicates greater uncertainty. A confidence interval is another way to express uncertainty around an estimate, but the confidence level and interval for the primary outcome are not reported in the registry record. No standard error value is reported either, so precision cannot be evaluated numerically.
For a comparison between groups, inference depends on the estimated contrast and its uncertainty, not just on each group’s separate mean. A valid interpretation would need the contrast definition and an appropriate uncertainty measure. The registry record does not give a primary between-group contrast, confidence interval or p-value. A comparison of group estimates cannot be reconstructed from the endpoint description alone.
Why does the analysis population matter?
The primary endpoint population is defined as Per Protocol. It includes randomized and treated subjects with at least one baseline and one postbaseline assessment of the primary efficacy parameter and no major protocol deviations affecting efficacy assessment. This is a selected analysis population defined by treatment and assessment availability as well as protocol adherence. The record does not report how many participants met that definition in each group. It also does not report an intention-to-treat result or a comparison across alternative analysis populations.
In general, analysis-population choices affect which participants contribute to an estimate and can affect how well a comparison preserves the balance created by randomization. A Per Protocol analysis may answer a different question from an analysis that includes all randomized participants. The registry does not give enough detail to assess the potential impact of exclusions or deviations in this study.
What do the planning assumptions mean?
The registry’s sample-size assumptions describe a planning illustration, not the trial’s own design justification. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. For non-time-to-event outcomes, the planning quantity is participants per arm. Such calculations illustrate sample sizes under specified assumptions; they are not observed power and do not show that the trial was designed around a documented target effect. The registry does not report its own sample-size justification or the numerical planning outputs.
In general, sample-size planning depends on assumptions about the effect to detect, variability, significance level, allocation and analysis. If those assumptions differ from the eventual data or analysis, the resulting planning illustration may not describe the precision achieved in the trial. Since the registry record does not report the primary estimates or their standard errors, the precision of the observed treatment comparison cannot be assessed from the planning assumptions.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 9 outcome measures and 8 analyses. The secondary outcomes cover normal age-adjusted IGF-1 levels, GH thresholds, combinations of IGF-1 and GH criteria, change in GH, tumour-volume changes and acromegaly symptoms. This range of outcomes means that interpretation would need to distinguish the prespecified primary question from additional outcome questions. The registry record does not report a multiplicity adjustment or explain how statistical interpretation across the outcomes was controlled.
The registry metadata notes that the primary outcome has several categories or time points and is not reduced to one comparison. It does not provide the underlying set of numerical comparisons or identify a single primary contrast. Accordingly, the primary endpoint description should not be treated as if it represents one fully specified, reported treatment-effect estimate.
Missing-data methods are not reported in the registry record. It does not state how missing baseline or follow-up assessments were handled, whether any imputation was used, or whether sensitivity analyses assessed alternative assumptions about missing outcomes. The numbers of withdrawals, their reasons and the completeness of endpoint measurements by group are also not reported.
The primary efficacy population is Per Protocol, with inclusion requiring treatment, baseline and postbaseline assessments, and no major protocol deviations affecting efficacy assessment. The record does not report the size of that population or provide results for another analysis population. These omissions limit assessment of how exclusions, missing observations and protocol deviations might have affected the comparative estimate. No conclusion about robustness across analysis choices can be made from the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Lanreotide Autogel | 1 | 64 | 1.6% |
| Lanreotide PR | 2 | 64 | 3.1% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Lanreotide Autogel | 0 of 64 |
| Lanreotide PR | 0 of 64 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Lanreotide Autogel | 59 of 64 |
| Lanreotide PR | 62 of 64 |
Most frequent serious adverse event terms
| Event term | Organ system | Lanreotide Autogel | Lanreotide PR |
|---|---|---|---|
| Pituitary tumour | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 64 | 0 of 64 |
| Gastritis | Gastrointestinal disorders | 0 of 64 | 1 of 64 |
| Cerebral infarction | Nervous system disorders | 0 of 64 | 1 of 64 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Lanreotide Autogel | Lanreotide PR |
|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | 51 of 64 | 46 of 64 |
| Abdominal distension | Gastrointestinal disorders | 22 of 64 | 27 of 64 |
| Cholelithiasis | Hepatobiliary disorders | 23 of 64 | 18 of 64 |
| Upper respiratory tract infection | Infections and infestations | 21 of 64 | 18 of 64 |
| Abdominal pain | Gastrointestinal disorders | 18 of 64 | 20 of 64 |
| Abdominal pain upper | Gastrointestinal disorders | 13 of 64 | 16 of 64 |
| Headache | Nervous system disorders | 10 of 64 | 17 of 64 |
| Hyperglycaemia | Metabolism and nutrition disorders | 12 of 64 | 12 of 64 |
| Nausea | Gastrointestinal disorders | 7 of 64 | 16 of 64 |
| Sinus bradycardia | Cardiac disorders | 9 of 64 | 12 of 64 |
Serious events with the highest arm-level rate: pituitary tumour (1.6%), gastritis (1.6%), cerebral infarction (1.6%).
The registry reports 64 participants at risk in each group for serious adverse events and for other adverse events. In the lanreotide Autogel group, 1 participant was affected by a serious adverse event and 59 by other adverse events. In the lanreotide PR group, 2 participants were affected by a serious adverse event and 62 by other adverse events. No deaths were reported in either group.
These counts describe affected participants in the registry’s safety record; they do not give the timing, duration, severity distribution or clinical course of the events. The registry lists Pituitary tumour, Gastritis and Cerebral infarction among the top serious terms, each at 1.6%. It does not specify in this listing how those terms are distributed by treatment group or whether any participant had more than one listed event.
Serious adverse events and other adverse events are separate categories in the record and should not be conflated. The counts alone do not establish comparative safety, particularly without event definitions, exposure duration, event-level detail and a statistical comparison. The figures are descriptive and should be interpreted within those limits.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a randomized, open-label phase III study compared lanreotide Autogel, titrated to 60 mg, 90 mg or 120 mg, with lanreotide 40 mg prolonged release in subjects with active acromegaly. It defines a primary outcome based on change in age-adjusted IGF-1 SDS and lists secondary outcomes involving IGF-1, GH, tumour volume and symptoms. It also reports descriptive adverse-event counts.
However, the record does not report numerical primary efficacy results. It provides no treatment-group estimates, between-group difference, uncertainty interval or p-value for the primary endpoint. Therefore, the magnitude, direction and precision of the comparative efficacy result cannot be stated. The secondary outcome definitions likewise do not establish comparative findings, because their numerical results are not reported in the registry record.
The safety counts show the number of participants recorded as affected by serious and other adverse events, as well as the absence of reported deaths. They do not establish that one treatment strategy was safer than the other. Event details, exposure-adjusted rates and a formal comparison are not reported in the registry record.
More generally, a trial’s design and endpoint definitions explain what investigators intended to compare, while its estimates and uncertainty describe what the observed data support. Here, the design and outcome framework are available, but the essential comparative efficacy estimates are not. The registry record therefore cannot support a conclusion about whether either treatment strategy produced a larger primary endpoint change or how reliably any apparent difference was estimated.
13. Why This Trial Matters Statistically
This trial is statistically notable for comparing treatment strategies that differ in both dose and dosing frequency. Lanreotide Autogel was given every 4 weeks after an initial schedule and titration, while lanreotide prolonged release was given on a schedule that could change after titration. The comparison is therefore between the study’s treatment strategies as described, rather than a simple contrast of two fixed doses administered at identical intervals.
The primary outcome uses an age-adjusted standardized measure and specifies a Per Protocol analysis population. These choices matter because they define both the scale of the endpoint and which participants contribute to the efficacy estimate. The registry also states that results were presented with and without back-transformation, making the scale of any reported estimate relevant to interpretation.
The study’s open-label design and multiple listed outcomes are important context for evaluating results, but the registry record does not report the model specification, multiplicity approach or missing-data methods. Nor does it report numerical efficacy estimates. As a result, the record allows readers to identify the intended comparison and endpoint, but not to judge the treatment contrast, its precision or the consistency of findings across outcomes.
The safety record offers descriptive counts for serious and other adverse events, but does not provide the detail needed to interpret event patterns or compare risks formally. Overall, the statistical value of the record lies in its description of the randomized design, outcome definitions and analysis population; the absence of numerical efficacy findings limits what can be concluded about the comparative results.
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 most consequential limitation for interpreting this trial record is that numerical primary efficacy results are not reported. The registry identifies the endpoint and analysis population but gives no treatment-group estimates, between-group contrast, standard error, confidence interval or p-value. Consequently, the observed comparative effect and its precision cannot be assessed.
The statistical model is not described beyond the least-squares mean label and standard error measure. Covariates, model assumptions, handling of repeated or incomplete observations and the exact contrast are not reported in the registry record. The record also does not report a multiplicity strategy, despite listing multiple secondary outcomes and noting that the primary outcome has several categories or time points.
Participant disposition is not described in sufficient detail for evaluating attrition. The record gives overall enrollment and defines the Per Protocol population, but does not report the number included in that analysis, completion by group, reasons for withdrawal or missing-data methods. It also does not provide a comparison from another analysis population.
The study was open label, and the registry does not give additional information about randomization procedures or allocation concealment. Treatment schedules included titration and different injection frequencies; further operational details about dose selection and adherence are not reported. The safety listing is likewise limited: it reports affected-participant counts and selected serious-event terms, but not event-level details, exposure duration or a formal safety comparison. These gaps restrict interpretation to the stated design and descriptive information in the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Efficacy and Safety of Lanreotide Autogel® 60, 90 or 120 mg With Lanreotide 40 mg Prolonged Release (PR) in Acromegaly — NCT02493517.
- Registry record last updated 2019-01-29; status last verified 2019-01.
- Results first posted 2018-12-14.
- 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.
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18. Record Summary
NCT02493517 is a completed phase III, prospective, randomized, open-label, parallel-group study sponsored by Ipsen. It enrolled 128 subjects with active acromegaly and compared lanreotide Autogel titrated to 60 mg, 90 mg or 120 mg with lanreotide 40 mg prolonged release. The trial began in 2014-10, with primary completion in 2016-11.
The primary endpoint was standardized mean change from baseline in age-adjusted, log-transformed IGF-1 SDS at the end-of-study or early-withdrawal visit. The primary efficacy population was Per Protocol. The registry record does not report the numerical primary efficacy estimates, a between-group result or the associated uncertainty.
Safety counts list 1 serious adverse event-affected participant in the lanreotide Autogel group and 2 in the lanreotide PR group, with no deaths reported in either group. Other adverse events affected 59 and 62 participants, respectively. These are descriptive counts and do not establish a comparative safety conclusion.