Peripheral Pharmacodynamics of Phentermine-Topiramate in Obese Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Peripheral Pharmacodynamics of Phentermine-Topiramate in Obese Patients (NCT01834404), a randomized phase 4 study. The primary outcome is Gastric Emptying of Solids Half-Time (T 1/2).

2. Clinical Question

The study’s stated aim was to examine peripheral pharmacodynamic effects of phentermine and topiramate ER in obese participants. Its broader focus included gastric emptying, gastric accommodation, satiety, and satiation. The primary endpoint was a physiological measure of solid-food emptying, rather than a measure of weight change, symptoms, or long-term clinical outcomes.

The registry also lists secondary outcomes covering the proportion of a meal emptied or remaining at specified times, postprandial gastric volume, fasting ghrelin, and postprandial levels of CCK, GLP-1, and PYY. These measures address related aspects of gastrointestinal function and appetite signaling. The available record does not establish that each measure was intended to explain the primary result or to serve as a clinical outcome.

The clinical question is therefore narrow: whether the groups differed in gastric emptying under the study conditions and what the posted estimates can establish about that comparison. It does not, by itself, answer whether the regimen changes body weight, produces lasting effects, or has a particular benefit for an individual.

3. Trial Design

The registry identifies this as a Phase 4, randomized, triple-masked, parallel-group study sponsored by Mayo Clinic. Its status is completed. Enrollment is recorded as 24, and the primary completion date is 2014-03; the study start is 2013-04. The record lists obesity as the condition under study.

The intervention groups were phentermine-topiramate ER and placebo. The primary endpoint summaries include 12 participants in each group. The active regimen began with phentermine 3.75 mg and topiramate 23 mg on days 1-5, then increased to phentermine 7.5 mg and topiramate 46 mg on days 6-14. The placebo pills matched the study drug in appearance for the two dose levels. The arm descriptions state that qualifying participants were assigned to their group for a minimum of 5 days.

The endpoint was assessed on Day 15, approximately 2 hours after ingestion of a radiolabeled meal. The registry describes a gastric-emptying scintigraphy test using a meal of scrambled egg, toast, and milk. Images were taken at specific intervals after the meal as participants stood in front of a special camera. The registry record does not report additional details about allocation concealment, the people covered by masking, the sequence generation process, or adherence.

The record does not report the study’s original sample-size justification, protocol assumptions, or detailed statistical analysis plan. It also does not provide participant flow, baseline characteristics, or a description of the analysis population. Those omissions limit assessment of how the enrolled group was selected, how participants were handled after assignment, and which covariates were included in the sponsor’s adjusted analysis. The reported group summaries and results can be interpreted as posted, but they do not fill in those design details.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

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 Gastric Emptying of Solids Half-Time (T 1/2), measured over Day 15, approximately 2 hours after radiolabeled meal was ingested.

The primary endpoint, gastric emptying of solids half-time (T 1/2), measures the time in minutes for half of the ingested solid food to leave the stomach. A longer half-time corresponds to slower emptying as defined by this measure; a shorter half-time corresponds to faster emptying. This is a continuous physiological outcome, and the registry reports group means with standard errors.

The endpoint was assessed on Day 15, approximately 2 hours after a radiolabeled meal was ingested. The registry describes a scintigraphy procedure: participants ate scrambled egg with toast and a glass of milk, with a small amount of radioactive substance in the eggs and milk. A special camera then captured images at specified intervals. The measurements from this procedure are used to characterize the passage of solids from the stomach over time.

Gastric emptying is relevant to the study’s stated pharmacodynamic question because it directly measures one of the physiological processes the investigators intended to examine. A half-time condenses the imaging observations into an interpretable time measure. It does not capture every feature of gastric function, and the registry record does not report a threshold that would define a clinically meaningful difference.

This endpoint is not itself a measure of weight, satiety, or long-term health. Its value for interpreting the study is limited to the gastric-emptying measure under the reported test conditions. General statistical interpretation also depends on the estimate’s uncertainty, the analysis method, and whether the result is consistent with the sponsor’s own analysis.

7. Results Posted in the Registry

• Phentermine-Topiramate ER: mean 109.00 versus 88.00 on control; difference 21.00 (95% CI 1.60 to 40.40), standardized effect d = 0.87; z-test p = 0.034.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Solid Gastric Emptying: Proportion of Meal Emptied at 2 Hours

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • Phentermine-Topiramate ER: mean 0.56 versus 0.66 on control; difference -0.10 (95% CI -0.18 to -0.02), standardized effect d = -0.96; z-test p = 0.018.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Phentermine-Topiramate ER than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Solid Gastric Emptying: Proportion Remaining at 4 Hours

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • Phentermine-Topiramate ER: mean 0.09 versus 0.16 on control; difference -0.07 (95% CI -0.13 to -0.01), standardized effect d = -1.01; z-test p = 0.013.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Phentermine-Topiramate ER than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Change in Postprandial Gastric Volume

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • Phentermine-Topiramate ER: mean 453.00 versus 420.00 on control; difference 33.00 (95% CI -33.52 to 99.52), standardized effect d = 0.40; z-test p = 0.331.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Phentermine-Topiramate ER and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists secondary measures related to solid gastric emptying, postprandial gastric volume, and appetite-related hormones. The posted secondary summaries include three outcomes: the proportion of the meal emptied at 2 hours, the proportion remaining at 4 hours, and change in postprandial gastric volume. Other listed secondary outcome results are not reported in the registry record.

Across the posted summaries, the two gastric-emptying proportions are lower in the phentermine-topiramate ER group than in the placebo group, while the posted postprandial gastric-volume mean is higher in the active-treatment group. These measures describe different aspects of gastrointestinal function, and their directions should not be treated as interchangeable with the primary half-time measure. They provide related physiological context, not an independent confirmation of a clinical outcome.

The registry reports ANCOVA p-values for the posted secondary comparisons, while unadjusted recalculations are also available. The adjusted and unadjusted results should be distinguished in the same way as for the primary endpoint. The record does not report a multiplicity adjustment or a prespecified hierarchy that would establish how these secondary tests were to be interpreted together.

When many outcomes are tested, the chance of obtaining at least one apparently noteworthy result by chance can increase. This is why unadjusted secondary results generally carry less confirmatory weight than a prespecified primary outcome analyzed according to a stated plan. The registry record reports 13 outcome measures and 13 analyses overall, but it does not report how the investigators controlled the family of tests. The secondary outcomes can help describe the range of measured responses, while remaining exploratory in the absence of a reported multiplicity strategy.

The listed measures of fasting ghrelin and postprandial CCK, GLP-1, and PYY relate to appetite signaling. Their results are not reported in the registry record, so no direction or association with the primary endpoint can be established from the posted information. The overall secondary pattern should therefore be treated as partial physiological context rather than a complete account of all planned or recorded secondary findings.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Solid Gastric Emptying: Proportion of Meal Emptied at 2 Hours
• Solid Gastric Emptying: Proportion Remaining at 4 Hours
• Change in Postprandial Gastric Volume
• Fasting Ghrelin
• Peak Postprandial Level of Cholecystokinin (CCK)
• Peak Postprandial Level of Total Glucagon-Like Peptide-1 (GLP-1)
• Peak Postprandial Level of Total Peptide Tyrosine-Tyrosine (PYY)

9. Statistical Interpretation

10. Statistical Methods Explained

For a continuous outcome, a group mean describes the average measurement among the participants included in that group’s summary. The primary endpoint is reported as a mean in minutes, with a standard error. A mean is useful for comparing the central values of two groups, but it does not show the full distribution of individual observations. The registry record does not provide participant-level measurements or a distributional summary beyond the posted means and standard errors.

A standard error describes the estimated uncertainty of a sample mean. It is different from a standard deviation, which describes variability among individual observations. The primary summaries report a standard error of 7.0 minutes for each arm. This indicates the precision of each estimated mean under the assumptions behind the summary; it should not be interpreted as the spread of individual gastric emptying times.

The registry’s reported primary comparison used ANCOVA. In general, analysis of covariance compares groups while adjusting for specified covariates, potentially improving precision or accounting for baseline differences. The registry record reports the ANCOVA method and p = 0.057, but the covariates, model specification, adjusted estimate, and uncertainty interval are not reported in the registry record. As a result, the adjusted result cannot be fully assessed or reproduced from the record.

The recalculation is an unadjusted comparison based on the posted group means and standard errors. It estimates the difference between the phentermine-topiramate ER mean and the placebo mean. The reported estimate is 21.0 minutes. The calculation also gives a pooled standard deviation of 24.25 and a standardized effect estimate of 0.866. These are simple recalculations from the group summaries; they are not the sponsor’s adjusted analysis and should not be presented as if they were.

A pooled standard deviation is a combined estimate of within-group spread used in a standardized comparison. A standardized effect expresses the mean difference relative to that spread, making the scale-independent effect easier to compare conceptually across measures. It does not replace the original scale, and it does not convey whether a difference matters clinically. The registry’s primary endpoint is naturally interpretable in minutes, so the mean difference in minutes remains central to understanding the observed contrast.

The recalculated p-value is 0.034. In general, a p-value is calculated under a statistical model that assumes no group difference and quantifies how unusual data at least as incompatible with that assumption would be. Its interpretation depends on the analysis assumptions, including the way variability is estimated. The recalculated p-value does not account for ANCOVA covariates or the broader set of outcomes and analyses in the registry record.

The posted interval for the recalculated mean difference runs from 1.597 to 40.4 minutes. In general, an interval gives a range of values compatible with the data and the method used, rather than a guaranteed range for the true effect. The registry record does not specify the confidence level for this recalculated interval. It should therefore be discussed as the reported recalculated interval without attaching an unreported confidence percentage.

Why can an unadjusted calculation differ from ANCOVA?

The two analyses can differ because they are based on different statistical approaches. The unadjusted calculation compares the posted group summaries directly. ANCOVA can adjust for covariates, and adjustment may change the estimated comparison or its uncertainty. Since the covariates and full model are not reported in the registry record, it is not possible to determine which model features account for the difference between the reported p-values. The sponsor’s analysis remains the relevant result for the trial’s own adjusted inference.

What does over-dispersion mean in general?

Over-dispersion occurs when observed variability is greater than a model expects. It can make standard errors too small if the model does not account for the extra variability, leading to overly confident statistical conclusions. This is a general issue in statistical modeling, especially for outcomes whose variability is not well represented by a simple model. The primary outcome is continuous, and the registry record does not report an over-dispersion assessment or a model feature of that kind. It would not be appropriate to claim that over-dispersion occurred in this trial.

What can the sample-size illustrations establish?

Planning calculations use assumptions about the effect to detect, variability, significance level, allocation, and analysis method. The posted illustrations use the observed effect and stated planning assumptions, rather than the trial’s original design rationale. They show how a hypothetical future study’s required participants per arm would change under the stated effect fractions and power targets. They do not establish what the original investigators planned, and they cannot demonstrate that the completed study had adequate power.

Statistical significance and effect magnitude are separate ideas. A p-value summarizes evidence under a model, while the mean difference describes the estimate on the clinical measurement scale. The interval describes precision under its calculation method. Interpreting the primary result requires considering all of these quantities and respecting the distinction between the registry’s ANCOVA result and the unadjusted recalculation.

11. Confidence Intervals and Precision

The unadjusted recalculated mean difference for gastric emptying of solids half-time is 21.0 minutes, and its reported interval extends from 1.597 to 40.4 minutes. The interval’s lower and upper bounds are both above zero, but this interval belongs to the unadjusted calculation. It should not be attributed to the sponsor’s ANCOVA, for which an effect estimate and interval are not reported in the registry record.

In general, an interval estimate communicates both the estimated direction and the degree of precision under a particular method. A narrower interval indicates less uncertainty under that method, while a wider interval indicates more. An interval is not a guarantee that the true value lies inside its bounds. The confidence level for this recalculated interval is not reported in the registry record, so it is not appropriate to label it with a confidence percentage.

The standard errors for the primary group means are 7.0 minutes in each arm. These quantify uncertainty around the group means, not variation across individual participants. The primary summaries include 12 participants per arm, and the limited group size means estimates can be sensitive to the observations included. The posted summaries do not allow inspection of individual values, outliers, or the shape of the outcome distribution.

The p-value from the sponsor’s ANCOVA is 0.057, but the registry does not provide its adjusted estimate or interval. That missing information prevents a direct assessment of the precision of the sponsor’s estimated contrast. The unadjusted interval can describe the recalculation, but it cannot substitute for uncertainty information from the adjusted model. Both the estimate and its method matter when judging how precisely the study answers its primary question.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm for 80% power and participants per arm for 90% power. They are not total event counts. In general, power is the chance that a study using a specified design would detect an effect of the assumed size under the planning model, if that effect were present. The 80% and 90% columns therefore describe different planning targets: the 90% target is intended to provide a greater chance of detecting the assumed effect than the 80% target.

The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The calculations use the observed effect or a stated fraction of it as the effect to detect. The table’s rows for smaller fractions represent planning for smaller effects relative to the observed effect. Smaller effects are harder to detect, so they require more participants per arm under these assumptions.

These are planning illustrations computed from the observed effect, not the trial’s original design assumptions. The original sample-size justification and design assumptions are not reported in the registry record. The figures are hypothetical estimates for planning; they do not describe the number of participants actually analyzed in the trial.

These figures are not observed power. Observed power calculated after a study is complete largely restates the observed estimate and its uncertainty, so the planning values should instead be read as conditional illustrations: if the assumed effect and model conditions held, the listed group size would correspond to the stated power target. They do not show the probability that the trial’s conclusion is correct.

The planning display should be read in relation to the endpoint and the assumptions used, not as a verdict on the completed trial. Different variability, analysis choices, missing data, or a true effect smaller than the observed estimate could change the group size required for a future study. The record does not report whether the investigators used these calculations in designing the trial.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 21.000; pooled standard deviation σ = 24.249.
2. n = 2 × (1.96 + 0.842)² × 24.249² / 21.000² = 20.9, rounded up to 21 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 21                      # observed difference in means
sigma <- 24.2487113059643                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(1834404)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 21 (80% power), 29 (90% power)
 75% of observed effect: n per arm = 38 (80% power), 50 (90% power)
 50% of observed effect: n per arm = 84 (80% power), 113 (90% power)
power.t.test: 21.9 
Simulated power at n = 21 per arm: 0.783 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The sponsor’s own primary analysis is reported as ANCOVA with p = 0.057. That result takes precedence when describing the trial’s inferential analysis. The registry record does not report the ANCOVA estimate, confidence interval, covariates, or enough model detail to reproduce the analysis.

The recalculation from the posted group summaries gives an unadjusted mean difference of 21.0 minutes, an interval from 1.597 to 40.4, and p = 0.034. It uses the group means and standard errors without the adjustment represented by ANCOVA. The recalculated result is useful for describing the contrast visible in the posted summaries, but it is not a substitute for the sponsor’s analysis.

The difference between p-values does not, by itself, establish why the analyses differ. ANCOVA may account for covariates, but the registry does not identify them or explain their contribution. The estimates may also differ in precision because the methods use information differently. Without the adjusted estimate and model details, the size and direction of any adjustment cannot be assessed.

Accordingly, the sponsor’s reported analysis should anchor statements about the trial’s own statistical test. The unadjusted recalculation should be clearly identified as such and used to describe the group summaries, not to overrule the sponsor’s result. Neither p-value alone establishes clinical importance, and the adjusted result’s missing estimate limits interpretation of its magnitude.

15. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study evaluates multiple outcomes, comparisons, time points, or analyses. If each is tested separately without adjustment, the chance of at least one low p-value under a collection of null hypotheses can be greater than for a single test. A prespecified testing hierarchy or multiplicity adjustment can help define how results should be interpreted. The registry record does not report a multiplicity strategy, adjustment, or hierarchy for the primary and secondary analyses.

The record lists 13 outcome measures and 13 analyses. Seven secondary outcomes are listed, including measures of gastric emptying, postprandial gastric volume, and appetite-related hormones. Because the approach to multiple testing is not reported in the registry record, the secondary p-values should not be treated as if they were adjusted confirmatory tests. The primary endpoint remains the main stated outcome, but the available record does not establish the full inferential plan.

Missing-data handling is not reported in the registry record. The record does not describe whether all randomized participants contributed endpoint measurements, how unavailable measurements were treated, or whether any imputation or sensitivity analysis was used. The primary group summaries include 12 participants per arm, but these summaries alone do not establish the completeness of follow-up or the analysis population.

The analysis population is also not reported in the registry record. It is therefore unclear whether the analysis followed an intention-to-treat approach, included only participants who completed the intervention, or used another definition. Random assignment supports a fair comparison when analyzed appropriately, but the interpretation depends on how departures from assignment and missing outcomes are handled.

Details of the sponsor’s ANCOVA are limited to the method and p-value. Covariates, model specification, assumptions, and any diagnostic checks are not reported in the registry record. The protocol, original statistical analysis plan, and interim analyses are also not reported in the registry record. These absences do not prove that such procedures were not used; they mean that their use and implications cannot be assessed from the registry record.

16. 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.

The registry reports 0 serious adverse events among 12 participants at risk in the phentermine-topiramate ER group and 0 among 12 participants at risk in the placebo group. It also reports 0 other adverse events among 12 participants at risk in each group. These are the adverse-event figures posted for the study.

These figures describe reported events during the registry’s safety assessment; they do not establish that no adverse events of any kind occurred outside the categories or reporting captured in the record. The registry record does not provide serious adverse-event terms, and deaths are not reported in the registry record. Details such as event definitions, observation duration for safety, severity grading, and the method for attributing events are not reported in the registry record.

With no serious adverse events recorded in either group, the posted results do not permit a comparative estimate of serious-event risk. Absence of recorded events in this study does not establish absence of risk, particularly when the registry reports a limited number of participants per arm and short treatment exposure. These safety figures should be read as a description of what was posted, not as a general safety conclusion.

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

The posted primary summaries show a longer mean gastric emptying half-time in the phentermine-topiramate ER group than in the placebo group. The unadjusted recalculation estimates a mean difference of 21.0 minutes. The sponsor’s ANCOVA result is p = 0.057, and the registry does not report the adjusted estimate or its interval. These results describe the study’s measured endpoint and the analyses recorded for it; they do not establish a broader clinical effect.

The endpoint is a physiological measure collected under a specific meal and imaging procedure on Day 15. It does not directly measure weight change, satiety, day-to-day symptoms, or long-term health outcomes. The registry’s stated interests include gastric emptying, gastric accommodation, satiety, and satiation, but the primary half-time alone cannot answer all of those questions.

The study is a randomized comparison, but the record does not provide detailed information about the analysis population, missing data, covariates, or multiplicity handling. Those omissions constrain how confidently the posted p-values and group estimates can be interpreted. The unadjusted recalculation and the sponsor’s ANCOVA result are not identical analyses, and the sponsor’s own result takes precedence for the trial’s reported inference.

The record reports no serious or other adverse events in either group, but those figures do not prove that the regimen is free of risk. The study’s exposure and endpoint timing are short, and no longer-term outcomes are presented. The results should therefore be understood as a limited set of physiological and safety observations from this completed study, not as a basis for personal medical decisions or claims about treatment effectiveness.

In general, a study result is most informative when its estimated magnitude, precision, analysis plan, and clinical context are considered together. Here, the group summaries provide a measurable contrast, while the missing adjusted estimate and undisclosed analysis details limit the ability to resolve the inferential difference between the recalculation and the sponsor’s analysis.

18. Why This Trial Matters Statistically

This trial illustrates why statistical interpretation should distinguish the observed group summaries from the model-based result reported by the sponsor. The means and unadjusted recalculation make the direction and scale of the measured contrast explicit. The ANCOVA p-value is the sponsor’s own analysis and takes precedence for describing the study’s inferential result. Without the adjusted estimate and model details, those results cannot be reconciled fully.

It also demonstrates why an endpoint’s meaning matters. Gastric emptying half-time is a direct physiological measure, reported in minutes, and its definition gives the direction of the measurement a clear interpretation. Yet the measure is not equivalent to a patient-important outcome or a long-term effect. Statistical evidence for a difference in a physiological endpoint does not automatically establish clinical importance.

The registry reports 12 participants per arm for the primary summaries. With a limited group size, estimates may be imprecise and sensitive to the observations included. The recalculated interval spans a range of possible differences, and the sponsor’s adjusted interval is not reported. Reading a point estimate without its uncertainty would give an incomplete account.

Finally, the record lists multiple secondary measures and analyses, while its multiplicity strategy and missing-data approach are not reported. These features matter because isolated secondary findings can be difficult to interpret when many outcomes are examined. Together, the study provides a useful example of how design, endpoint choice, model specification, precision, and reporting completeness shape the strength of statistical conclusions.

19. 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 summaries are based on 12 participants per arm, and the registry reports enrollment of 24. The record does not provide participant-level data, baseline characteristics, participant flow, or an account of missing outcomes. Consequently, it is not possible to assess whether the analyzed groups were comparable on measured baseline features or whether all assigned participants contributed to the reported summaries.

The active regimen was administered over a short period, with the primary endpoint measured on Day 15. This limits what the results can say about longer exposure, persistence of any physiological change, or longer-term clinical outcomes. The endpoint is a laboratory-style gastric-emptying measure under a specified meal and scintigraphy procedure. The registry record does not report a threshold for clinical importance.

The sponsor’s primary analysis is reported as ANCOVA, but its adjusted estimate, interval, covariates, and model details are not reported in the registry record. The unadjusted recalculation therefore cannot be checked against the sponsor’s adjusted effect estimate. The record also does not report the original sample-size rationale, multiplicity plan, interim analyses, or missing-data approach.

The registry lists secondary outcomes beyond those with posted summaries. Results for the remaining listed measures are not reported in the registry record, so the full pattern of the planned physiological assessments cannot be evaluated. The absence of reported secondary results should not be mistaken for evidence that those measures had no effect.

Safety interpretation is similarly limited: the record reports no serious or other adverse events in either group, but does not report deaths, adverse-event terms, detailed safety definitions, or a broader account of event ascertainment. These limitations are specific to the reporting and scope of this trial and constrain generalization beyond its measured endpoint and short study conditions.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Peripheral Pharmacodynamics of Phentermine-Topiramate in Obese Patients — NCT01834404.
• Registry record last updated 2015-02-23; status last verified 2015-02.
• Results first posted 2015-02-23.
• 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.

23. Record Summary

The registry record describes a completed Phase 4 randomized, triple-masked, parallel-group study sponsored by Mayo Clinic, with enrollment of 24. It compared phentermine-topiramate ER with placebo in obese participants. The active regimen used phentermine 3.75 mg with topiramate 23 mg on days 1-5 and phentermine 7.5 mg with topiramate 46 mg on days 6-14.

The primary endpoint was gastric emptying of solids half-time, measured in minutes on Day 15. The group means were 109.0 minutes for phentermine-topiramate ER and 88.0 minutes for placebo. The registry reports an ANCOVA p-value of 0.057. An unadjusted recalculation gives a mean difference of 21.0 minutes, with an interval from 1.597 to 40.4 and p = 0.034; the sponsor’s own analysis takes precedence.

The record lists secondary physiological and appetite-related outcomes, but results for several listed measures are not reported in the registry record. It reports 0 serious and 0 other adverse events in each group. Details on the adjusted model, analysis population, missing data, multiplicity, and original sample-size rationale are not reported in the registry record.