Study of Rivoglitazone in Type 2 Diabetes Mellitus: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Rivoglitazone in Type 2 Diabetes Mellitus (NCT00484198), a randomized phase 3 study. The primary outcome is Hemoglobin A1c at Baseline and Week 26 Endpoint With Last Observation Carried Forward (LOCF) Following Rivoglitazone or Pioglitazone Compared to Placebo as Monotherapy Treatment of Type 2 Diabetes Mellitus.

2. Clinical Question

The study was designed to examine efficacy and safety in adults with type 2 diabetes, according to its stated condition and treatment context. The registry record describes a placebo and active-comparator controlled study of rivoglitazone as monotherapy. Its primary outcome was HbA1c measured at baseline and the Week 26 endpoint. The record names the Full Analysis Set as the population for HbA1c assessment.

The record does not give the numerical HbA1c results or a single treatment contrast. It therefore does not establish from the posted results how the groups differed on the primary outcome, nor how precisely any such difference was estimated. Secondary outcomes included fasting plasma glucose, insulin resistance, total cholesterol, and total triglycerides, with baseline-to-endpoint measures described for several of these outcomes. Numerical results for those outcomes are not reported in the registry record either. The clinical question is identifiable from the design and outcome definitions, but its answer cannot be quantified from the registry results.

3. Trial Design

This was a Phase 3, randomized, double-blind, parallel-group study with placebo and active-comparator control. The registry lists an enrollment of 1912. It describes rivoglitazone as monotherapy and lists treatment groups for placebo, rivoglitazone 1.0 mg, rivoglitazone 1.5 mg, and pioglitazone 45 mg. The placebo arm description is blank in the arm descriptions, although placebo is named as an intervention and appears as a group in the safety record.

The study summary describes a 26-week double-blind treatment period. A participant's total participation was approximately 30 weeks, including a 2-week placebo run-in period and a 2-week post-treatment follow-up period. The primary outcome timeframe is baseline up to the Week 26 post-dose endpoint. HbA1c was assessed in the Full Analysis Set, and the endpoint description specifies last observation carried forward (LOCF).

The record identifies Daiichi Sankyo as sponsor and the study status as completed. Its start date is 2007-04-23 and its primary completion date is 2009-02-12. Although enrollment, allocation, masking, and treatment groups are described, the registry record does not report the allocation ratio, the method used to generate or conceal the randomization sequence, or details of how masking was maintained. It also does not report the number of participants assigned to each group for the primary outcome, group-specific treatment adherence, or participant flow through the study. Those omissions limit assessment of how the planned design was implemented and how many observations contributed to the endpoint estimates.

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: During the 2-week stabilization/washout, single-blind, placebo run-in period, participants were to discontinue any previous therapy with oral anti-hyperglycemic agents and were to self-administer single-blind, double-dummy, placebo medication consisting of over-encapsulated pioglitazone-matching placebo tablets and rivoglitazone-matching placebo tablets once daily.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Hemoglobin A1c (HbA1c) levels were assessed using the Full Analysis 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: Baseline characteristics were assessed using the All Randomized set.

6. Primary Endpoint

The registry lists the primary outcome as Hemoglobin A1c at Baseline and Week 26 Endpoint With Last Observation Carried Forward (LOCF) Following Rivoglitazone or Pioglitazone Compared to Placebo as Monotherapy Treatment of Type 2 Diabetes Mellitus, measured over Baseline up to week 26 post-dose.

The primary endpoint concerns HbA1c at baseline and the Week 26 endpoint, with LOCF used to carry forward the last available observation for participants without a Week 26 value. HbA1c is a continuous measure of the proportion of hemoglobin that has glucose attached to it. As a general clinical measurement concept, HbA1c reflects glucose exposure over time rather than a reading at a single moment, so it can be used to assess changes in glycemic control across a treatment period.

The registry describes the outcome as a mean, with standard deviation as the dispersion measure, and gives the unit as percentage of HbA1c. It states that HbA1c levels were assessed using the Full Analysis Set. The endpoint is framed around baseline and the Week 26 endpoint, but the registry record does not report group means, changes from baseline, a between-group contrast, or uncertainty estimates for the primary outcome. It therefore supports identifying what was intended to be measured, but not quantifying the treatment-group results.

LOCF is an imputation approach: when an endpoint observation is missing, an earlier recorded value is carried forward. As a general statistical matter, this substitutes an assumed value for an unobserved endpoint and can affect estimated group means and their uncertainty. The registry record does not report how many values were carried forward or provide a sensitivity analysis using another missing-data approach.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study used a randomized, double-blind, parallel-group design. In general, random allocation aims to make treatment groups comparable at the time of assignment, while blinding is intended to reduce the influence of treatment knowledge on care, measurement, and reporting. A parallel-group design means that participants are assigned to a treatment group and followed in that group rather than crossing between treatments. These design features support a between-group comparison, but they do not guarantee that groups remain balanced or that all biases are absent. The registry record does not describe the randomization method, allocation concealment, or practical masking procedures.

What does a mean and standard deviation describe?

The primary outcome is continuous and is summarized in the record as a mean with standard deviation. In general, the mean describes the central value in a group, while the standard deviation describes how dispersed individual observations are around that mean. The standard deviation is not the same as the uncertainty in the estimated mean, and neither measure by itself gives a treatment contrast. To evaluate efficacy, readers would generally need the relevant group estimates and a clearly defined comparison, with an uncertainty measure such as a confidence interval. Those primary-outcome results are not reported in the registry record.

What does an endpoint comparison require?

A baseline-to-endpoint analysis can be framed in different ways. It may compare endpoint values between groups, compare changes from baseline, or use a model that adjusts for baseline values. These approaches answer related but not identical statistical questions and can yield different estimates. The registry record identifies the measured time points and describes the primary outcome as HbA1c at baseline and Week 26 endpoint, but it does not report the statistical model or specify whether the primary comparison used endpoint values, changes, or baseline adjustment. The analysis method for the primary comparison is therefore not reported in the registry record.

How should LOCF be understood?

The primary outcome description specifies last observation carried forward. In general, this method replaces a missing endpoint measurement with a participant's most recent earlier observation. It creates a complete value for the analysis under an assumption that the earlier measurement is an acceptable stand-in for the missing endpoint. That assumption may not hold if the outcome changes after the last recorded measurement. LOCF can understate or overstate change depending on the timing and pattern of missingness and the course of the outcome. The registry record does not report the amount or pattern of missing HbA1c data, how many records were carried forward, or sensitivity analyses that test different assumptions.

Why do analysis populations matter?

An analysis population defines which participants contribute to an estimate. The record says that HbA1c was assessed using the Full Analysis Set, but it does not define the set's membership or report the number included in each treatment group. In general, an analysis that retains participants according to their randomized assignment can preserve the benefits of randomization, while exclusions after allocation can affect comparability. Without the population definition and participant flow, it is not possible to determine from the registry record exactly how the named set was constituted.

What can be inferred from the registry's analysis listing?

The record reports 23 outcome measures and 0 analyses. These are registry reporting features, not estimates of treatment effect. The primary outcome is flagged as having several categories or time points and not being reduced to one comparison. That means the record does not present a single numerical primary contrast that can be interpreted as an effect estimate. No primary-outcome p-value, confidence interval, or model specification is reported in the registry record.

When results include multiple outcomes, treatment groups, or time points, multiplicity is a general statistical concern: the more comparisons examined, the greater the chance of at least one apparently unusual finding under a null scenario. Methods such as a prespecified hierarchy or adjustment can address some multiplicity concerns, but the statistical plan and any multiplicity procedure are not reported in the registry record. It is therefore not possible to tell which comparisons were intended as confirmatory or whether any adjustment was used.

In general, over-dispersion matters when observed variability exceeds what a statistical model assumes. For continuous outcomes, the choice of model and its variance assumptions can affect standard errors and confidence intervals. The registry record provides no primary analysis model or diagnostic information, so there is no basis to assess those assumptions for this trial. The record's design and outcome definitions can explain what was intended to be measured; they cannot substitute for the missing analysis estimates and methods.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 23 outcome measures, including the primary HbA1c outcome and secondary outcomes involving fasting plasma glucose, insulin resistance, total cholesterol, and total triglycerides. The record does not report a statistical analysis plan, a hierarchy of outcomes, or a multiplicity adjustment. As a general statistical matter, examining multiple outcomes and time points can increase the chance of finding an apparently notable result by chance. Without the planned testing strategy and the results for each comparison, the strength of confirmatory claims cannot be evaluated.

The primary endpoint specifies LOCF. The registry record does not report the number or pattern of missing HbA1c measurements, the number of participants analyzed by group, or the sensitivity of results to alternative missing-data assumptions. LOCF carries forward an earlier measurement rather than modeling the unobserved endpoint. In general, if the outcome changes after the last observed measurement, the carried-forward value may not represent the endpoint that would have been observed.

The Full Analysis Set is named for HbA1c, but its inclusion rules and group-specific sizes are not reported in the registry record. Nor is the relationship between that set and the randomized participants described. These details matter because analysis-population exclusions and missing observations can affect the interpretation of randomized comparisons. The registry record also does not describe interim analyses, sample-size justification, or a prespecified statistical plan. These items are not reported in the registry record, so no assumptions about them can be made.

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 2% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: gastritis (0.7%), non-cardiac chest pain (0.7%), hand fracture (0.7%), hypoglycemia (0.7%), cardiac failure congestive (0.4%).

The registry reports serious adverse event counts and other adverse event counts by listed group, with the number at risk stated for each category. For placebo, 3 of 137 participants were affected by serious adverse events and 56 of 137 by other adverse events; deaths were 0. For rivoglitazone 1.0 mg, the corresponding counts were 10 of 269 and 131 of 269; deaths were 0. For rivoglitazone 1.5mg, they were 22 of 741 and 408 of 741; deaths were 0. For pioglitazone 45 mg, they were 28 of 739 and 374 of 739; deaths were 2.

The record also lists serious event terms with percentages: Gastritis, Non-cardiac chest pain, Hand fracture, and Hypoglycemia are each reported at 0.7%; Cardiac failure congestive and Umbilical hernia are each reported at 0.4%. These entries describe the registry's reported terms and percentages; the record does not give comparative estimates or uncertainty intervals for them.

Counts alone do not establish whether a treatment caused an event or whether groups differ reliably. Group sizes and observation time can affect counts, while chance variation also matters. The registry record does not report adjusted safety comparisons, event-specific denominators, or a detailed account of exposure duration by group. These figures should therefore be read as descriptive safety reporting, not as proof of a treatment effect.

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

The record establishes that a randomized, double-blind study was conducted to evaluate rivoglitazone as monotherapy in type 2 diabetes, with placebo and pioglitazone 45 mg comparators. It identifies rivoglitazone 1.0 mg and rivoglitazone 1.5 mg groups and a primary HbA1c outcome assessed from baseline to the Week 26 endpoint. These details define the intended clinical comparison and the measure used to represent glycemic control.

The record does not provide numerical results for the primary HbA1c comparison. It therefore does not show the size or direction of any difference, nor its precision. No conclusion about a difference, lack of difference, or equivalence between groups can be drawn from the absence of a reported estimate. A nonsignificant result, if one existed, would also not by itself establish equivalence; equivalence requires an appropriate design and prespecified margin, neither of which is reported in the registry record.

Likewise, the listed secondary outcomes identify measures that were planned or recorded, but their presence does not reveal the results. The registry does not report numerical comparisons for fasting plasma glucose, insulin resistance, cholesterol, or triglycerides. The safety counts describe participants affected in each listed group, but counts without comparative analyses do not establish causation or quantify the uncertainty around between-group differences.

As a general principle, clinical interpretation depends on the estimated effect, its precision, the analysis population, the handling of missing data, and the relevance of the outcome to the clinical question. For this record, the outcome definition and LOCF approach are stated, but the effect estimates and key analysis details are unavailable. The registry entry can support an account of the trial's structure and what it intended to assess; it cannot support a quantitative efficacy conclusion from the posted results.

13. Why This Trial Matters Statistically

This trial illustrates an important distinction between registering an outcome and reporting an analyzable result. The registry specifies HbA1c as the primary outcome, identifies a baseline-to-Week 26 timeframe, names the Full Analysis Set, and states that the mean and standard deviation were used to describe the measure. Those details make the intended measurement understandable. But without group estimates and a treatment contrast, the central statistical question remains unanswered in the registry record.

The design also provides a useful setting for thinking about comparisons across several treatment groups. Rivoglitazone was listed at two doses, alongside placebo and an active comparator. A reader would need to know which comparisons were primary, how baseline HbA1c was handled, and what uncertainty accompanied each estimate to interpret the evidence. Those analysis details and numerical results are not reported in the registry record. Their absence makes it especially important not to infer a rank ordering or a dose pattern from the list of treatment arms.

Missing-data choices are another statistical feature worth noticing. LOCF is explicitly named, so readers can recognize that missing endpoint values were handled by carrying forward earlier observations. Yet the record does not state how often this occurred or whether results were checked under different assumptions. Statistical interpretation depends not only on the method label but also on the extent and pattern of missingness and the assumptions behind the method.

Finally, the safety listing shows why descriptive counts and comparative inference should be kept separate. Counts provide a record of affected participants in each group, while comparative estimates would be needed to assess differences with uncertainty. The registry provides the former but not the latter. Together, these features make the record a useful example of how trial design information can be present while the statistical evidence needed to answer the main treatment question remains unavailable.

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 interpretation is that numerical efficacy results are not reported in the registry record. The primary outcome has several categories or time points and is not reduced to one comparison; no HbA1c group means, changes, contrasts, confidence intervals, or p-values are available. Secondary outcome definitions are listed, but their numerical results are also not reported. This prevents assessment of effect magnitude and precision.

Important analysis details are absent. The registry record does not report the primary statistical model, the allocation ratio, the randomization method, or the definition of the Full Analysis Set. Group-specific primary-outcome sample sizes and participant flow are also not reported. The record states that LOCF was used but does not quantify missing data or describe sensitivity analyses. These omissions limit assessment of whether the analysis matches the randomized design and how robust the estimates would be to missing-data assumptions.

The record does not report a statistical plan, multiplicity handling, interim analyses, or a sample-size justification. As a result, the intended hierarchy of comparisons and the basis for the study's planned enrollment cannot be assessed. It also does not provide detailed exposure duration, adjusted safety comparisons, or event-specific denominators for the serious event terms. The safety counts are therefore descriptive rather than comparative evidence. These limitations apply to the registry record; they do not establish that the underlying trial lacked analyses or procedures that were not reported there.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of Rivoglitazone in Type 2 Diabetes Mellitus — NCT00484198.
• Registry record last updated 2021-07-27; status last verified 2021-07.
• Results first posted 2021-07-27.
• 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

NCT00484198 is a completed Phase 3 randomized, double-blind, parallel-group study sponsored by Daiichi Sankyo. It enrolled 1912 participants and compared rivoglitazone 1.0 mg and rivoglitazone 1.5 mg with placebo and pioglitazone 45 mg as monotherapy for type 2 diabetes. The study summary describes a 26-week double-blind treatment period, with approximately 30 weeks of total participation including a 2-week placebo run-in and a 2-week post-treatment follow-up.

The primary outcome was HbA1c at baseline and the Week 26 endpoint, using LOCF, with assessment in the Full Analysis Set. The registry lists 23 outcome measures and 0 analyses; it does not report a single numerical primary comparison. Serious and other adverse event counts are listed by group, as are deaths, but comparative safety estimates are not reported in the registry record. The study start date was 2007-04-23 and the primary completion date was 2009-02-12.