A Single-Dose Crossover Study of MK0893 in Patients With Type 2 Diabetes (0893-019 AM4)(COMPLETED): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Single-Dose Crossover Study of MK0893 in Patients With Type 2 Diabetes (0893-019 AM4)(COMPLETED) (NCT00902161), a randomized phase 1 study. The primary outcome is Recovery Time (Rt[65] From Insulin-induced Hypoglycemia.

2. Clinical Question

3. Trial Design

This was a Phase 1, randomized, double-blind, placebo-controlled, single-dose crossover study of MK0893 coadministered with propranolol in participants with type 2 diabetes. The registry lists enrollment of 22 and study status as completed. The study began in 2009-05, with primary completion in 2009-10.

In a crossover study, participants receive more than one treatment condition in sequence, so the comparison can use observations from the same participant under different conditions. The registry describes two sequences: propranolol plus placebo followed by propranolol plus MK0893, and propranolol plus MK0893 followed by propranolol plus placebo. The arm descriptions state that participants received propranolol for 7 weeks before the first single-dose period, and that a 3-week washout followed Period 1 while propranolol continued. The detailed descriptions are truncated in the registry record, so further sequence and period details are not reported in the registry record.

The masked, randomized design was intended to compare the two single-dose conditions while limiting the influence of treatment assignment on participants and study personnel. The placebo condition provided a comparator while propranolol continued. The primary outcome was recovery time after insulin-induced hypoglycemia, measured during a hypoglycemic clamp. The registry also lists secondary outcomes concerning MK0893 plasma concentrations and adverse events.

The primary outcome analysis included data for 21 participants in the MK0893 plus propranolol condition and 17 in the placebo plus propranolol condition. These condition-specific available-data counts are not identical. The record does not state why data were unavailable or whether the primary analysis used a particular named analysis population. The planned sample-size justification, randomization procedure details, and specific masking procedures are not reported in the registry record.

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.

Pre-study Washout/Propanolol Run-in

Period 1

Post-clamp Washout

Period 2

Analysis population for the primary outcome, as defined in the registry: 21 participants who received MK0893 + Propanolol while on study had data available, and 17 participants who received Placebo + Propanolol while on study had data available

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.

6. Primary Endpoint

The registry lists the primary outcome as Recovery Time (Rt[65] From Insulin-induced Hypoglycemia, measured over From the time of hypoglycemic clamp (t=0 minutes) through 270 minutes.

The primary endpoint was recovery time, in minutes, from insulin-induced hypoglycemia to a blood glucose level of 65 mg/dL. The endpoint definition begins with a controlled low glucose target of 50 mg/dL and measures the time required to reach 65 mg/dL. It is therefore a time-based measure of recovery under the study’s clamp procedure, rather than a measure of longer-term glucose control.

The registry describes a hypoglycemic clamp on the morning of Day 1 or Day 22. Insulin infusion was increased to achieve a blood glucose concentration of 50 mg/dL (2.8 mmol/L), within approximately 30-90 minutes. After a 30-minute clamp interval, insulin and glucose infusions were stopped, and recovery time was followed for up to 270 minutes. The timeframe for the endpoint runs from the time of the hypoglycemic clamp, t=0 minutes, through 270 minutes.

This endpoint offers a standardized way to compare recovery under the two treatment conditions after a deliberately induced episode of hypoglycemia. A shorter or longer measured time describes the observed recovery interval in this experimental setting; it does not by itself characterize outcomes outside the clamp procedure. The registry does not report additional endpoint validation or explain how observations that did not reach the target within follow-up were handled.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: each measured value is a recovery time expressed in minutes. The registry reports least-squares means and a least-squares mean treatment difference. A least-squares mean is a model-based estimate of a group mean. It may differ from a simple arithmetic average because it is derived from the fitted analysis model rather than by adding observed times and dividing by a count.

The reported analysis used a linear mixed effect model. In general, mixed effect models are useful when data have a grouped or repeated structure. In crossover studies, repeated measurements from one participant are typically related: characteristics shared by that participant can make their measurements more alike than measurements from different participants. A mixed model can represent such dependence while estimating the treatment contrast. The general purpose of accounting for this structure is to avoid treating related measurements as if they were independent.

The registry record does not report the fitted model’s detailed specification. In particular, the fixed and random effects, covariance structure, adjustment variables, treatment of period or sequence, and handling of incomplete participant records are not reported in the registry record. It is therefore not possible to assess those choices from the posted description or to reproduce the model-based estimate from the reported group summaries alone.

What does the confidence interval express?

The registry gives a 95% confidence interval from 15 to 49 minutes for the treatment difference. In general, a confidence interval conveys the precision of an estimate under the assumptions of its statistical method. Its endpoints represent values compatible with the data and model at the stated confidence level. The interval does not mean that a participant’s recovery time has a 95% chance of falling within those limits, and it is not a prediction interval for individual outcomes.

The interval is informative alongside the estimated difference of 32 minutes. It shows that the reported estimate is not presented as an exact value; there is uncertainty around it. Interpreting the interval still depends on the appropriateness of the model and the quality and completeness of the underlying data. Those considerations matter especially when the registry does not give reasons for missing primary outcome data or a full account of the model specification.

How should the p-value be read?

The reported p-value is 0.005. In general, a p-value describes how unusual the observed result, or a more extreme result, would be under a specified null model. It is not the probability that the null model is true, and it does not state the probability that the result will recur. It also does not measure the practical importance of the estimated difference. The estimate and confidence interval provide information about magnitude and precision; the p-value addresses compatibility with the null model under the stated analysis.

The registry does not report whether the primary comparison was adjusted for testing multiple outcomes or analyses. Without that information, the p-value should be understood as reported for the stated model, rather than assumed to incorporate any multiplicity adjustment.

What does a crossover design change?

In a crossover design, participants receive the conditions in sequence, rather than being assigned to only one condition throughout the study. This allows within-participant comparisons, which can reduce the influence of stable differences between participants when the analysis appropriately accounts for repeated measurements. The design also makes sequence, period, and carryover considerations relevant. The record describes randomization, double masking, and a washout, but the detailed model terms and any evaluation of carryover are not reported in the registry record.

The washout was described as 3 weeks, with propranolol continued. A washout is generally intended to separate treatment periods, but the registry record does not report the rationale for its duration or any assessment of whether carryover occurred. No conclusion about those design features can be inferred from the treatment contrast alone.

What can be learned from the reported group summaries?

The arm-level least-squares means and their intervals describe estimated recovery times within each treatment condition. The treatment-difference estimate directly addresses the comparison and is reported from the linear mixed effect model. The individual arm intervals should not be subtracted to create a separate treatment interval: in a crossover analysis, the uncertainty of the contrast depends on the relationship between measurements within participants, as well as on the model. The registry does not provide the paired covariance information needed to reconstruct that uncertainty from the arm summaries.

Planning illustrations, when used, are distinct from observed trial results. Sample-size calculations are prospective illustrations based on chosen assumptions and an effect to detect; they are not evidence that a study had a particular probability of detecting its result. The registry’s sample-size assumption description refers to a two-sided significance level of 0.05, equal allocation, a normal approximation, and effects expressed as fractions of the observed effect. The trial’s own sample-size justification is not reported in the registry record. No planning count should be interpreted as observed enrollment or as observed power.

10. Analyses Reported by the Sponsor

The registry’s reported treatment comparison is the linear mixed effect model estimate: a least-squares mean treatment difference of 32 minutes, with a 95% confidence interval from 15 to 49 minutes and p = 0.005. This is the inferential contrast posted for the primary outcome. The registry also reports the condition-specific least-squares means and confidence intervals.

A separate unadjusted re-calculation of the crossover treatment contrast is not available from the posted summary statistics. In general, the uncertainty of a within-participant contrast depends on how each participant’s measurements under the two conditions are related. The registry does not report participant-level paired data or the relevant covariance information. The arm-level estimates alone therefore do not provide the information needed to independently reconstruct the treatment-difference interval or test.

No discrepancy between a recalculation and the registry analysis is indicated in the posted record. Since the reported mixed-model comparison is the available analysis and a separate contrast cannot be reconstructed from the posted summaries, it should be read as the registry’s own model-based result, not as an independently replicated calculation. The full model details are not reported in the registry record.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 5 outcome measures, including the primary recovery-time endpoint and secondary outcomes. The secondary outcomes concern maximum plasma concentration and concentration average over 8-12 hours after a single MK0893 dose, plasma concentration at 32 hours, the number of participants with an adverse event, and the number who discontinued study treatment due to adverse events. The record lists 4 secondary outcomes, but the posted primary result does not describe how the family of outcomes was handled statistically.

Whether the primary p-value or secondary analyses were adjusted for multiple testing is not reported in the registry record. The number and timing of any interim analyses are also not reported in the registry record. Without a stated strategy, the primary p-value should not be assumed to account for all outcomes or analyses that may have been considered.

The primary outcome data counts were 21 in the MK0893 plus propranolol condition and 17 in the placebo plus propranolol condition, while total enrollment was 22. The record does not explain why these counts differ, identify the participants without available outcome data, or state how missing measurements were treated in the model. The planned analysis population and whether the primary analysis included all randomized participants are not reported in the registry record.

The crossover structure adds an important missing-data consideration: an incomplete record may lack one condition, one period, or other observations, but the registry does not describe which pattern occurred. The record also does not report a sensitivity analysis for missing outcomes or assumptions about why data were unavailable. These unknowns limit assessment of how robust the model-based estimate is to incomplete observations.

The registry provides a description of the primary analysis method, but not a complete statistical analysis plan. Specific covariates, period and sequence terms, model diagnostics, missing-data procedures, and multiplicity procedures are not reported in the registry record. The absence of those details does not establish that an analysis was or was not performed; it means the posted account does not permit that assessment.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The adverse-event record lists 22 participants at risk in each of three conditions: MK0893 plus propranolol, placebo plus propranolol, and propranolol alone. It records 0 serious adverse events in each condition. These are condition-specific registry counts, and the crossover design means the groups should not automatically be interpreted as separate sets of participants.

The record lists 10 participants with other adverse events in the MK0893 plus propranolol condition, 4 in the placebo plus propranolol condition, and 9 in the propranolol-alone condition. These counts are distinct from the serious adverse-event counts. The registry does not provide serious adverse-event terms, and the death counts are not reported in the registry record.

Zero recorded serious adverse events in these conditions means none were entered in the posted serious-event counts; it does not establish that serious events are impossible or that no safety concerns exist. The study enrolled 22 participants, and the registry record does not provide enough detail to characterize the likelihood of uncommon events or compare risks precisely. The other adverse-event counts should likewise be read as descriptive counts in this study, not as a complete account of event severity, timing, or causality. The registry lists an outcome for treatment discontinuations due to adverse events, but no result for that outcome is included in the posted information.

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

The reported result is a model-based comparison of recovery time after experimentally induced hypoglycemia in participants with type 2 diabetes. The estimated least-squares mean was 103 minutes with MK0893 plus propranolol and 71 minutes with placebo plus propranolol. The estimated treatment difference was 32 minutes, with a 95% confidence interval from 15 to 49 minutes and p = 0.005. In this study setting, the posted estimate is consistent with longer recovery time in the MK0893 condition than in the placebo condition.

The result does not establish what recovery would look like in circumstances outside the controlled clamp procedure. It does not address long-term glucose control, outcomes beyond the reported recovery measure, or other populations not described in the registry. The trial was a Phase 1 study with enrollment of 22, and the available primary outcome counts were 21 and 17 across the two conditions. The estimate should therefore be interpreted in the context of a small study and incomplete outcome counts, without assuming that the observed data represent all participants equally in both periods.

The confidence interval communicates uncertainty around the estimated difference under the reported model. It does not describe the distribution of individual response times, and it cannot resolve limitations arising from unreported model details or missing-data handling. The p-value likewise does not establish the probability that the finding is true or that it will recur in another study.

The adverse-event record lists no serious adverse events in the three treatment conditions, while recording other adverse events in each. Those descriptive counts do not prove safety or rule out uncommon events. The record does not include the full details needed to interpret event timing, severity, or attribution.

Overall, the posted results quantify a difference in a specific physiological recovery measure under a controlled experimental procedure. They do not, on their own, settle broader questions about benefits, harms, or the applicability of the result beyond this study.

14. Why This Trial Matters Statistically

This trial illustrates how a crossover design can frame a clinical comparison. Rather than comparing only separate groups assigned to one condition each, a crossover study observes treatment conditions in sequence. When analyzed appropriately, this structure can use within-participant information and account for stable participant characteristics. It also makes repeated-measure dependence, sequence, period, and washout considerations important to interpretation.

The primary result demonstrates why it is useful to distinguish group summaries from the treatment contrast. The registry reports least-squares mean recovery times for each condition and a model-based difference with its confidence interval and p-value. The difference is the direct estimate for the comparison. The separate condition intervals do not contain all the information needed to recreate the uncertainty of a crossover contrast.

The study also highlights the importance of transparent reporting. The registry identifies a linear mixed effect model and reports the primary estimate, but does not state the detailed model specification, reasons for unavailable outcome data, missing-data procedures, or multiplicity approach. These details matter because they affect how readers assess assumptions and robustness, especially when outcome counts differ by condition.

Finally, a controlled hypoglycemic clamp produces a narrowly defined endpoint: time to recover from a target glucose level to a stated threshold. That can support a focused comparison within the study procedure, while remaining distinct from broader clinical outcomes. Keeping the endpoint, design, analysis, and limits in view helps readers interpret statistical evidence without extending it beyond what the registry reports.

15. Limitations

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

The primary outcome counts differ between treatment conditions: 21 participants had data available for MK0893 plus propranolol and 17 for placebo plus propranolol, although enrollment was 22. The registry does not explain the difference or describe the pattern of incomplete data. Because the study was a crossover, the missingness pattern could affect the within-participant comparison, but the posted record does not provide enough information to evaluate that issue.

The registry names a linear mixed effect model but does not report its detailed specification. Terms for treatment period or sequence, covariance assumptions, adjustment variables, model diagnostics, and handling of incomplete records are not reported in the registry record. The observed contrast therefore cannot be independently reproduced from the available arm summaries.

The record describes a 3-week washout while propranolol continued, but does not report the rationale for the washout duration or any assessment of carryover. The sequence descriptions are truncated, and further protocol details are not reported in the registry record. Randomization and double masking are stated, but the procedures used to implement them are not reported.

The study enrolled 22 participants and was classified as Phase 1. The sample-size justification and the trial’s intended precision or power are not reported in the registry record. No interim analysis information or multiplicity strategy is reported. The registry lists secondary pharmacokinetic and adverse-event outcomes, but the results for those outcomes are not included in the posted information.

The primary endpoint reflects a controlled clamp procedure and follow-up through 270 minutes. The registry does not describe how measurements that did not reach the target during follow-up were handled, or provide evidence about the endpoint’s relation to outcomes outside the procedure. These limitations constrain both reproducibility and the scope of conclusions that can be drawn from the reported estimate.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Single-Dose Crossover Study of MK0893 in Patients With Type 2 Diabetes (0893-019 AM4)(COMPLETED) — NCT00902161.
• Registry record last updated 2015-07-03; status last verified 2015-06.
• Results first posted 2012-05-08.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

NCT00902161 was a completed, randomized, double-blind, placebo-controlled, single-dose crossover Phase 1 study of MK0893 with propranolol in participants with type 2 diabetes. Enrollment was 22. The study began in 2009-05 and reached primary completion in 2009-10.

The primary endpoint was recovery time from insulin-induced hypoglycemia to a blood glucose level of 65 mg/dL. The registry reports least-squares mean recovery times of 103 minutes for MK0893 plus propranolol and 71 minutes for placebo plus propranolol. The reported treatment difference was 32 minutes, with a 95% confidence interval from 15 to 49 minutes and p = 0.005, using a linear mixed effect model.

The primary outcome data were available for 21 participants in the MK0893 condition and 17 in the placebo condition. The registry also lists plasma concentration and adverse-event outcomes. It records 0 serious adverse events in each of the three listed conditions; other adverse-event counts were 10, 4, and 9. Further details on the analysis specification, missing data, and secondary results are not reported in the registry record.