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 Clinical Trial of Efficacy and Safety of Subetta in the Combined Treatment of Patients With Type II Diabetes Mellitus (NCT01868646), a randomized phase 4 study. The primary outcome is Changes in the Mean Value of HbA1c.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01868646 |
| Phase | Phase 4 |
| Condition | Type II Diabetes Mellitus |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 190 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Materia Medica Holding |
| Results posted | Yes |
2. Clinical Question
Population
Patients with type II diabetes mellitus. The primary endpoint specifies an Intention-to-Treat set; further eligibility details are not reported in the registry record.
Intervention
Subetta as part of combined treatment. The specific background treatments, dosing, and duration details beyond the primary endpoint time points are not reported in the registry record.
Comparator
Placebo in a randomized, placebo-controlled trial. The registry does not report detailed arm descriptions or the allocation ratio.
Primary question
How did the mean HbA1c value change from baseline at 12, 24, and 36 weeks of treatment in the Subetta and placebo groups?
The trial’s stated purpose was to assess the clinical efficacy and safety of Subetta in combined treatment of type II diabetes mellitus. The primary outcome was change in the mean value of HbA1c. The registry names the measurement unit as percentage of HbA1c and specifies comparison with baseline at 12, 24, and 36 weeks. It also identifies the Intention-to-Treat set as the primary outcome population.
This question is about an average change over time and a comparison between randomized groups. It is not a question about whether every participant’s HbA1c changed in the same way. The registry record does not report a single numerical comparison for the primary endpoint, nor does it give the group-level values, an estimated difference, or uncertainty around that estimate. It therefore does not support a conclusion about the direction or size of the primary outcome contrast.
The record also lists secondary outcomes covering fasting and self-monitored blood glucose, C-peptide, lipids, insulin dosage, use of oral blood-sugar-lowering drugs, and body weight. Their presence describes the scope of the registered assessment, but does not establish what the results were. Numerical findings for these outcomes are not reported in the registry record.
3. Trial Design
The registry describes a randomized, multicentre, double-blind, placebo-controlled, parallel-group clinical trial. Its official title also describes quadruple masking. It is registered as Phase 4 and has a completed status. The sponsor is Materia Medica Holding.
The registry lists 190 participants as the enrollment. The trial start date is 2013-05-07, and the primary completion date is 2016-06-15. The record identifies two interventions, Subetta and placebo. The brief study description places both in the setting of combined treatment for type II diabetes mellitus. Detailed descriptions of the treatment arms are not reported in the registry record, so the background therapies, specific dosing, and treatment procedures cannot be characterized from these details.
Randomization means that treatment assignment is determined by a chance-based process rather than being selected solely by participants or investigators. In general, random assignment can help make groups comparable at the start of a trial, although it does not guarantee that they will be identical. A parallel-group design assigns participants to a group and follows those groups over the study rather than having each participant receive both interventions in sequence. The registry does not report the allocation ratio or further details of the randomization procedure.
Masking is intended to limit the influence of knowledge about assigned treatment on trial conduct or assessment. The record labels the study double-blind and quadruple-masked, but does not specify which roles were masked or describe how masking was maintained. The detailed protocol, eligibility criteria, site locations, and treatment schedule are not reported in the registry record. The enrollment figure alone does not indicate how many participants completed follow-up or contributed data at each assessment.
The primary outcome is change in mean HbA1c at 12, 24, and 36 weeks compared with baseline. The registry also lists secondary measures, including blood glucose, C-peptide, lipid concentrations, insulin dosage, oral medication dose changes, and body weight. These registered measures indicate a broad assessment plan; they do not substitute for numerical results or clarify the statistical methods used for each measure.
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: Selection procedures were carried out after participant enrollment to determine whether the patient could participate in the study in accordance with the inclusion/exclusion criteria. Of the 190 patients enrolled, 42 did not meet inclusion criteria after screening procedures, they were not randomized
Overall Study
| Stage | Subetta | Placebo |
|---|---|---|
| STARTED | 76 | 72 |
| COMPLETED | 73 | 67 |
| NOT COMPLETED | 3 | 5 |
Reasons for not completing this period:
| Reason | Subetta | Placebo |
|---|---|---|
| Do not meet inclusion criteria | 3 | 5 |
Analysis population for the primary outcome, as defined in the registry: Intention-to-Treat set
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: Intention-to-Treat set
| Characteristic | Unit | Subetta | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 73 | 67 | 140 | |
| Age, Continuous | years | 57.9 (SD 7.1) | 57.3 (SD 6.2) | 57.6 (SD 6.7) |
| Sex: Female, Male: Female | Participants | 59 | 54 | 113 |
| Sex: Female, Male: Male | Participants | 14 | 13 | 27 |
| Weight | kilogram | 85.7 (SD 13.0) | 89.0 (SD 11.7) | 87.1 (SD 12.5) |
| Height | centimeter | 164.1 (SD 7.7) | 165.3 (SD 7.3) | 164.7 (SD 7.5) |
| BMI | kilogram/m^2 | 31.7 (SD 4.0) | 32.5 (SD 3.6) | 32.1 (SD 3.8) |
6. Primary Endpoint
The registry lists the primary outcome as Changes in the Mean Value of HbA1c, measured over In 12, 24 and 36 weeks of the treatment as compared to the baseline.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | percentage of HbA1c |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is change in the mean value of HbA1c, measured as percentage of HbA1c, from baseline at 12, 24, and 36 weeks of treatment. HbA1c is a measure used to assess longer-term blood glucose exposure, rather than a single glucose reading. As a general clinical concept, this makes it useful for evaluating glycemic status over time in people with diabetes.
The registry states that the HbA1c test used a method certified by the National Glycohemoglobin Standardization Program and standardized or traceable to the Diabetes Control and Complications Trial reference assay. Standardization is important because it helps make measurements more comparable across laboratories and settings. It does not, by itself, establish that the observed difference between randomized groups is precise or meaningful.
The endpoint is defined as a mean, with standard deviation as the listed measure of dispersion, and the primary population is the Intention-to-Treat set. A mean describes the group’s average; a standard deviation describes how spread out individual measurements are around that average. The endpoint description names several follow-up times, but the registry record does not report a single numerical result or a specific group contrast. The primary endpoint results are therefore not reported in the registry record in a form that permits an estimate of the treatment difference or its uncertainty.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies a clinically relevant primary measure and specifies when it was assessed: mean HbA1c change from baseline at 12, 24, and 36 weeks. It also identifies the Intention-to-Treat set for this endpoint. However, the numerical primary outcome results are not reported in the registry record as a single comparison. There are no group means, change estimates, between-group contrast, confidence interval, or p-value in the registry record for this analysis. Consequently, the direction, magnitude, and precision of the primary outcome effect cannot be described.
The record notes 11 outcome measures and 16 analyses. Those counts alone do not reveal which analyses correspond to which outcomes, how repeated time points were handled, or which comparison was designated as the principal statistical test. The registry record does not report the statistical model, contrast specification, confidence level, or approach to multiplicity. Without those details and the numerical results, it is not possible to assess whether the posted analysis aligns with a prespecified plan or how much uncertainty surrounds any outcome estimate.
The safety counts are reported separately for the two groups. For Subetta, 1 serious adverse event is listed among 76 participants at risk; for placebo, 1 is listed among 72 at risk. Other adverse events are listed for 22 of 76 participants in the Subetta group and 24 of 72 in the placebo group. These are event counts and at-risk group sizes, not a full account of event type, timing, severity, or duration. The registry record does not report deaths in the available safety details. That absence should not be interpreted as confirmation that no deaths occurred.
The registry lists Brain tumor NOS at 1.4% and Brain stem stroke at 1.3% among the top serious terms. The information does not link these terms to a treatment group or supply their full context, such as the number of events or the denominator used for each percentage. They should not be read as comparative risk estimates between Subetta and placebo.
The sample-size assumptions describe a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. Such an illustration is not observed power and does not replace the trial’s actual estimates or uncertainty. The trial’s own design justification and numerical sample-size planning results are not reported in the registry record. Overall, the available details support description of the design and reported safety counts, but not an efficacy conclusion or a precise estimate of the primary treatment contrast.
9. Statistical Methods Explained
The registry defines the primary outcome as a continuous measure: change in mean HbA1c from baseline at 12, 24, and 36 weeks. The general statistical ideas below explain how such an endpoint is often analyzed. They do not establish which methods were used in this trial; the specific analysis plan is not reported in the registry record.
What does a mean change represent?
For each participant, a change score is formed by comparing a follow-up measurement with the baseline measurement. A group mean change then describes the average change among the participants contributing data to that group and time point. In a randomized comparison, the central treatment contrast is often the difference between the groups’ mean changes, or an adjusted contrast that estimates the same question while accounting for specified factors.
These approaches are not interchangeable in every circumstance. For example, an analysis might compare change scores directly or model follow-up values while accounting for baseline values. The chosen model can affect the estimate and its uncertainty. The registry record specifies the outcome, time points, summary measure, and primary population, but the statistical model and exact contrast are not reported. No method should be attributed to this trial without that information.
What does standard deviation tell the reader?
The registry lists standard deviation as the dispersion measure for the mean endpoint. In general, a standard deviation describes variability among individual measurements around the group mean. It is not the same as the standard error, which describes uncertainty in an estimated mean, and it is not a confidence interval for the difference between treatment groups. A mean and standard deviation can describe the distribution of observed measurements, but do not alone provide the precision of a treatment contrast.
A confidence interval, in general, gives a range of values compatible with the data and the assumptions of the analysis at a stated confidence level. Its width reflects precision: a narrower interval indicates greater precision than a wider interval, under the same framework. The registry record does not report a confidence interval for the primary comparison, so the precision of that effect cannot be assessed from the endpoint definition.
Why do repeated time points matter?
The primary outcome is assessed at multiple follow-up times. Measurements from the same participant are generally correlated: a participant’s values over time are not independent observations. A statistical method that accounts for this structure can avoid treating repeated measurements as if they came from unrelated people. An analysis might estimate a separate treatment contrast at each time or model the time course jointly; the registry record does not report which strategy was used.
Multiple time points also create multiple opportunities to test a treatment contrast. If each is evaluated separately without accounting for multiplicity, the chance of at least one false-positive finding across a family of tests can rise. General approaches include prespecifying a primary time point, adjusting for multiple comparisons, or using a model with a planned overall test. The registry lists 12, 24, and 36 weeks for the primary endpoint but does not report a multiplicity procedure or clarify whether one time point had priority.
What does Intention-to-Treat mean?
As a general principle, an Intention-to-Treat analysis seeks to retain participants in the groups to which they were randomized, regardless of treatment adherence or changes after assignment. This preserves the randomized comparison when it is implemented appropriately. The registry identifies the Intention-to-Treat set as the primary population, but does not report how that set was operationalized, how many participants contributed data at each time point, or how missing values were handled.
Missing outcome data can affect an estimate if the participants with unavailable measurements differ from those with observed measurements. General methods for addressing missingness include analyses based on observed data under stated assumptions, imputation, or sensitivity analyses that assess how results change under alternative assumptions. The appropriate approach depends on why measurements are missing and on the analysis plan. The registry record does not report the amount or pattern of missing primary outcome data, the method used to address it, or sensitivity analyses.
How should safety counts be interpreted statistically?
The registry reports serious and other adverse-event counts with numbers at risk for each group. Counts describe how many participants were recorded with an event, while the number at risk supplies the group size associated with those counts. A complete safety interpretation would also consider how events were defined and collected, whether participants could have more than one event, and the duration of observation. Those details are not reported in the registry record. The listed counts should not be treated as adjusted comparisons or as evidence about causation.
The planning assumptions specify a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. They describe sample-size planning illustrations based on fractions of the observed effect. In general, a sample-size calculation estimates how many participants would be needed under stated assumptions to have a chosen probability of detecting an effect of a specified size. That probability is a planning quantity, not the trial’s observed power. The numerical planning illustrations and the trial’s own sample-size justification are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The primary HbA1c outcome has multiple follow-up times: 12, 24, and 36 weeks. The registry record does not report whether one time point was designated as the principal comparison, whether a joint repeated-measures test was used, or whether any adjustment was made for testing more than one time point. The record lists 11 outcome measures and 16 analyses, but does not map the analyses to specific outcomes or state how multiplicity was addressed. This makes it difficult to determine how to interpret any isolated statistically significant result, even if numerical results were available.
As a general statistical issue, testing several outcomes or time points can increase the chance of a false-positive result if each test is treated as an independent opportunity for significance. Prespecified priorities or an appropriate adjustment can help control that risk. Whether either approach was used in this trial is not reported in the registry record.
The primary outcome population is identified as the Intention-to-Treat set. The record does not report participant counts contributing to the primary endpoint at each follow-up, the amount or pattern of missing HbA1c data, or the method used to handle missing values. It also does not report whether sensitivity analyses were conducted. These details matter because complete-case and imputation approaches rely on assumptions about missingness and can yield different estimates.
The analysis model, covariate adjustments, handling of protocol deviations, and analysis populations for secondary outcomes are not reported in the registry record. The stated primary population therefore clarifies one part of the analysis definition, but does not resolve the remaining questions about missing data or multiplicity.
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 |
|---|---|---|---|
| Subetta | 1 | 76 | 1.3% |
| Placebo | 1 | 72 | 1.4% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Subetta | 22 of 76 |
| Placebo | 24 of 72 |
Most frequent serious adverse event terms
| Event term | Organ system | Subetta | Placebo |
|---|---|---|---|
| Brain stem stroke | Nervous system disorders | 1 of 76 | 0 of 72 |
| Brain tumor NOS | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 0 of 76 | 1 of 72 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Subetta | Placebo |
|---|---|---|---|
| acute respiratory infection | Infections and infestations | 4 of 76 | 10 of 72 |
| Increased blood pressure | Investigations | 4 of 76 | 2 of 72 |
| upper respiratory infection | Infections and infestations | 1 of 76 | 4 of 72 |
| Periodic pain in the left hypochondrium | Gastrointestinal disorders | 3 of 76 | 0 of 72 |
| upper respiratory tract infection | Infections and infestations | 3 of 76 | 0 of 72 |
| Chronic parenchymal pancreatitis | Gastrointestinal disorders | 1 of 76 | 1 of 72 |
| Fatty liver hepatosis | Hepatobiliary disorders | 1 of 76 | 1 of 72 |
| Pain in the lumbar spine | Musculoskeletal and connective tissue disorders | 1 of 76 | 1 of 72 |
| hypochromic anaemia | Blood and lymphatic system disorders | 0 of 76 | 1 of 72 |
| retinal angiopathy | Eye disorders | 1 of 76 | 0 of 72 |
Serious events with the highest arm-level rate: brain tumor nos (1.4%), brain stem stroke (1.3%).
The registry reports 1 serious adverse event among 76 participants at risk in the Subetta group and 1 among 72 at risk in the placebo group. It also lists other adverse events for 22 of 76 participants in the Subetta group and 24 of 72 in the placebo group. These counts should be read as recorded participant-level figures with their listed group sizes, not as a complete account of all safety experience.
The registry record does not provide the event definitions, collection procedures, observation time, severity details, or a description of how recurrent events were counted. The available information does not establish whether an individual could contribute to more than one event category. It also does not report deaths in the available safety details; that missing information should not be read as confirmation that no deaths occurred.
Brain tumor NOS at 1.4% and Brain stem stroke at 1.3% are listed as top serious terms. The registry information does not identify the treatment group for these terms or provide the denominator and event context needed to interpret them as group-specific risks. They should not be treated as a comparison of serious-event rates between groups. The counts are descriptive and do not, on their own, establish whether an event was caused by treatment.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a randomized, placebo-controlled Phase 4 study of Subetta in combined treatment for type II diabetes mellitus was completed, with 190 participants listed as enrolled. It defines a primary HbA1c outcome and identifies three assessment times relative to baseline. It also gives selected safety counts. These details describe the study’s question and some of its recorded results, but they do not provide the numerical primary comparison.
Without the group-specific HbA1c results, an estimated treatment contrast, and a measure of uncertainty, the size and precision of any difference cannot be assessed. The endpoint definition does not indicate whether average HbA1c moved up or down, whether the groups differed, or whether any observed contrast was compatible with a range of plausible effects. For that reason, the registry information does not establish a conclusion about the primary efficacy outcome.
The safety counts describe reported adverse events among the listed numbers at risk. They are not enough to establish a causal relationship between treatment and an event, and they do not supply a full comparison of safety over time. The listed serious-event terms are not assigned to a treatment group in the available information. Missing death details are not evidence that no deaths occurred.
More generally, a trial design can strengthen a comparison, but design labels are not a substitute for results. Randomization and masking are features intended to reduce certain biases; they do not answer whether the groups’ outcomes differed or how precisely any difference was estimated. Interpretation would require the outcome estimates, uncertainty intervals, analysis details, participant follow-up, and an account of missing data. Those details are not reported in the registry record used for this analysis.
13. Why This Trial Matters Statistically
This trial is statistically notable for its combination of a randomized, parallel-group comparison and a continuous primary endpoint assessed at multiple follow-up times. That structure raises familiar questions about how to define the treatment contrast, account for repeated measurements, and interpret results across time points. The registry identifies the outcome and its time points, but does not report the model or multiplicity strategy.
The record also distinguishes the primary population from the broader range of registered assessments. The primary HbA1c endpoint is specified for the Intention-to-Treat set, while the secondary outcomes include blood glucose measures, C-peptide, lipids, insulin dosage, changes in oral medication dose, and body weight. This breadth makes clear why it is important to know which analyses were prespecified as primary and how multiple comparisons were handled. The record lists 11 outcome measures and 16 analyses but does not detail their relationship.
Safety figures add another statistical dimension: a reader needs the counts, denominators, event definitions, and observation context to understand what the reported numbers mean. The listed serious and other adverse-event counts are useful descriptive information, but do not supply those additional details or a causal comparison.
Finally, the example illustrates the difference between a registered design and a fully interpretable result. A named endpoint and a randomized design define a question; estimates and uncertainty are needed to assess what the observed data say about that question. When those estimates and analysis details are not reported in the registry record, statistical interpretation must remain limited to the design and the descriptive information that is available.
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 primary limitation is that numerical HbA1c results are not reported in the registry record in a form that supports a treatment comparison. Group means, mean changes, between-group estimates, confidence intervals, and p-values are not available in the registry record for this analysis. The outcome is listed at 12, 24, and 36 weeks, but the record does not clarify how these time points were combined or prioritized.
Further analytical details are also not reported: the statistical model, covariate adjustments, multiplicity procedure, missing-data approach, and sensitivity analyses. The primary population is named as the Intention-to-Treat set, but participant counts at each follow-up and the implementation of that population are not described. These omissions limit assessment of the precision and robustness of any treatment estimate.
The detailed arm descriptions are not reported in the registry record. The exact treatment procedures, background therapies, doses, eligibility criteria, allocation ratio, and masking roles are not specified in the information available. This limits the ability to characterize the intervention contrast or assess how the trial was conducted.
The safety information is also incomplete for interpretation. Serious and other event counts are listed, but the definitions, timing, observation duration, event-level details, and death data are not reported. The top serious-event terms are not linked to a treatment group in the available details. The reported enrollment does not tell how many participants completed follow-up or contributed to each outcome analysis.
Finally, the trial’s own sample-size justification is not reported in the registry record. Planning assumptions based on an observed effect do not resolve that limitation and are not observed power. Together, these gaps constrain conclusions to the registered design and the selected descriptive counts.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Clinical Trial of Efficacy and Safety of Subetta in the Combined Treatment of Patients With Type II Diabetes Mellitus — NCT01868646.
- Registry record last updated 2019-05-31; status last verified 2019-05.
- Results first posted 2019-03-04.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
The registry identifies NCT01868646 as a completed Phase 4 randomized, multicentre, double-blind, placebo-controlled, parallel-group trial of Subetta in combined treatment for type II diabetes mellitus. The sponsor is Materia Medica Holding. Enrollment is listed as 190; the start date is 2013-05-07, and the primary completion date is 2016-06-15.
The primary outcome is mean HbA1c change from baseline at 12, 24, and 36 weeks, in the Intention-to-Treat set. Numerical primary outcome comparisons and detailed statistical methods are not reported in the registry record. The record lists 11 outcome measures and 16 analyses, along with secondary measures covering glucose, C-peptide, lipids, insulin dosage, oral medication dose changes, and body weight.
Safety details list 1 serious adverse event in each group and other adverse events for 22 participants in the Subetta group and 24 in the placebo group. Further event context and death information are not reported in the registry record.