Multiple Rising Oral Dose Study of PG 760564 Administered Twice Daily to Healthy Male/Female Volunteers for 14 Days: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Multiple Rising Oral Dose Study of PG 760564 Administered Twice Daily to Healthy Male/Female Volunteers for 14 Days (NCT00791388), a randomized phase 1 study. The primary outcome is AUCτ Over a Dosing Interval (τ = 12 Hours) on Day 14.

2. Clinical Question

The study title and summary describe an assessment of safety, tolerability, and pharmacokinetics. The primary outcome with posted numeric results is pharmacokinetic: a continuous measurement of plasma exposure. The registry reports a mean and standard deviation for each active dose group, while listing no placebo value for this outcome.

The central interpretive question is therefore descriptive: how did the reported mean exposure and its variability differ across the four active dose groups? The registry does not provide an inferential test or an adjusted comparison among those groups. It also does not report a clinical outcome that would establish whether a given exposure is beneficial or harmful. Results should be read as measurements from this early-phase study in healthy volunteers, not as an estimate of a clinical treatment effect in a patient population.

3. Trial Design

This was a phase 1, randomized, double-blind, parallel study sponsored by Procter and Gamble. The registry describes the study as a multiple ascending oral dose study of PG 760564 in healthy male and female volunteers. The recorded study start is 2005-08, the primary completion is 2006-01, and the status is completed.

Participants were assigned to placebo or an active dose group. The active doses listed are 50 mg, 100 mg, 200 mg, and 400 mg; the study summary describes administration twice daily for 14 days, or 27 doses. The parallel model means the listed groups are separate study arms rather than repeated periods in which each participant necessarily receives every dose. Details of the randomization procedure, allocation concealment, and how blinding was maintained are not reported in the registry record.

The registry reports enrollment of 45. That enrollment figure should not be treated as the denominator for every outcome. For the primary exposure measurement, the reported group sizes are 7 at 50 mg, 8 at 100 mg, 8 at 200 mg, and 4 at 400 mg. The placebo group has no endpoint sample size or value because plasma concentrations were not measured for that arm. Safety results use separate at-risk counts, so their denominators should be read independently from the pharmacokinetic results.

The design is suited to describing exposure and safety observations across ascending doses in healthy volunteers. The registry record does not report a sample-size justification, a planned statistical comparison, or an efficacy objective. It therefore does not establish that the study was designed to test a particular clinical benefit, nor does it explain how its enrollment was selected.

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: Each Subject enrolled in the study, participated in one period only (e.g., subjects did not start in the 50mg dose group, then proceed to subsequent groups)

Period 1 - 50 mg Dose Group

Reasons for not completing this period:

Period 2 - 100 mg Dose Group

Reasons for not completing this period:

Period 3 - 200 mg Dose Group

Period 4 - 400 mg Dose Group

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: PG 760564 blood plasma concentrations were not measured for the placebo arm

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 AUCτ Over a Dosing Interval (τ = 12 Hours) on Day 14, measured over 14 days.

The primary endpoint is the area under the plasma concentration-time curve over a dosing interval on Day 14. The interval, written as τ, is 12 hours, and the unit is ng*h/mL. In general, an area under a concentration-time curve combines concentration measurements across time to describe overall exposure during the chosen interval. It is commonly used in pharmacokinetic studies because it summarizes more than a single concentration reading.

Measuring the interval on Day 14 characterizes exposure after repeated administration, rather than exposure following only an initial dose. The registry describes PG 760564 as given every 12 hours and names the outcome as AUCτ over that same interval. The posted statistic is the group mean, with standard deviation as the measure of dispersion. The mean describes the average observed exposure in a dose group; the standard deviation describes how spread out individual measurements were around that group mean. It is not a confidence interval and does not directly describe uncertainty in the estimated mean.

The endpoint is a pharmacokinetic measure, not a patient-centered clinical outcome. It can characterize exposure at the tested doses, but by itself it does not establish clinical efficacy, tolerability, or a safe dose. The registry says plasma concentrations were not measured for placebo, so the endpoint does not support a placebo comparison. Details of sampling times, assay procedures, and any endpoint-specific handling of measurements are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous, and the registry reports a mean with a standard deviation for each active-dose group. In general, a mean is the arithmetic average of the measured values in a group. It gives a compact description of the group’s central level, but it can be influenced by unusually high or low observations. A standard deviation describes the spread of observations around the mean. It is not the standard error, a confidence interval, or a test of whether one group differs from another.

A confidence interval, in general, gives a range of values compatible with the data and a stated method under repeated use of that method. It helps communicate uncertainty in an estimate. No confidence intervals are reported for the primary endpoint in the registry record. A reader therefore cannot use the posted mean and standard deviation alone to recover the reported precision of each mean or a formal interval for a difference between dose groups. Reconstructing such quantities would require additional assumptions and would not replace an analysis reported by the study sponsor.

The registry’s active-dose group summaries are descriptive. A formal comparison could use a statistical model to estimate dose-group differences or the pattern of exposure across doses, with uncertainty intervals and a prespecified testing approach. The statistical model and planned primary analysis are not reported in the registry record. No p-value or adjusted comparison is posted. It would be inappropriate to infer statistical significance from the ordering of the means, or to treat overlap or non-overlap of standard deviations as a hypothesis test.

The arm sizes are not the same across the endpoint groups. In general, estimates based on smaller groups tend to be less precise, all else being equal, though the actual precision also depends on the data distribution and analysis. The registry reports 4 endpoint participants at 400 mg, compared with 7 at 50 mg and 8 at each of the 100 mg and 200 mg doses. These counts are endpoint denominators, not an explanation of why fewer participants contributed at the highest dose. Reasons for differences between enrollment and endpoint counts are not reported in the registry record.

Pharmacokinetic measurements can be skewed, and a mean may not fully describe a distribution with a long upper tail. In general, examining individual observations, graphical distributions, and model diagnostics can help assess this issue. Such individual-level data and diagnostic results are not reported in the registry record. No transformation, distributional assumption, or robust method is specified there. The posted mean and standard deviation should therefore be read as summaries, without assuming a particular data shape or analysis method.

The outcome is measured over a defined interval on Day 14. In general, interpreting an AUC estimate depends on how concentration samples were collected and how the curve was estimated between measurements. The registry record gives the endpoint description, unit, and timeframe, but sampling schedules, assay details, and calculation procedures are not reported in the registry record. It is not possible to assess those procedural details from the posted summary alone.

The record reports zero analyses for the posted results. It gives no inferential analysis for the continuous primary endpoint. The registry also does not report whether any interim analyses were planned or conducted, or whether any adjustment for multiple testing was planned. A lack of a posted analysis should not be recast as a finding of no difference; it means the record does not supply a statistical comparison to interpret.

Planning illustrations based on an observed effect are conceptually different from the trial’s original design rationale. In general, such illustrations ask how many participants per arm might be needed under stated assumptions to detect a chosen effect with a chosen power and significance level. They are not observed power, and they do not show that the study was originally planned around the observed results. The registry record does not report its own sample-size justification. No planning illustration should be interpreted as evidence that this trial had a particular probability of detecting an effect.

Randomization can help balance prognostic factors across groups in expectation, while blinding can reduce some forms of bias in treatment administration or assessment. Those are general design principles; the registry identifies the study as randomized and double-blind but does not describe the randomization sequence, concealment, or blinding procedures. The parallel design identifies separate treatment groups. The exact statistical methods used by the sponsor, including any adjustments or analysis population definitions, are not reported in the registry record.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("50 mg PG 760564", "100 mg PG 760564", "200 mg PG 760564", "400 mg PG 760564")
n   <- c(7, 8, 8, 4)
m   <- c(12090.998, 23472.1329, 30005.781, 50354.938)
sp  <- c(2926.95, 9858.248, 9955.931, 9781.333)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  50 mg PG 760564  7  12090.998  2926.950  9384.021  14797.975
CARM  100 mg PG 760564  8  23472.133  9858.248  15230.431  31713.834
CARM  200 mg PG 760564  8  30005.781  9955.931  21682.414  38329.148
CARM  400 mg PG 760564  4  50354.938  9781.333  34790.654  65919.222

11. Multiplicity, Missing Data and Analysis Populations

The registry reports no posted analyses for the primary endpoint and no posted secondary outcome results. It does not state how many hypotheses were planned for formal testing, whether multiple doses were to be compared with one another, or whether multiplicity adjustment was planned. In general, testing several hypotheses can increase the chance of obtaining at least one apparently unusual result by chance, so a prespecified strategy may be important. Without the study’s statistical plan, the intended approach cannot be determined. No inferential claims across dose groups should be attributed to a testing strategy that the registry does not describe.

The primary results are reported as group means and standard deviations, with endpoint counts that vary across active doses. The registry does not report why endpoint counts differ from the overall enrollment or whether any values were missing, excluded, or otherwise unavailable. It also does not report an imputation method, a sensitivity analysis, or a description of how missing endpoint measurements were handled. The placebo endpoint is explicitly unavailable because plasma concentrations were not measured in that arm; this is a design feature for the pharmacokinetic outcome, not evidence of missing placebo measurements.

Analysis populations are not defined in the registry record. It does not say whether the primary summary includes all randomized participants who received a dose, only participants with evaluable concentration data, or another population. These distinctions matter because the result depends on which participants are included and how incomplete measurements are treated. The posted group counts identify the participants represented in the endpoint summaries, but do not explain the selection process.

The number enrolled should not be substituted for endpoint denominators or safety denominators. The registry reports separate counts for the endpoint and adverse events. Without participant-level records, the reasons for those differences and the overlap among reporting groups are not reported in the registry record.

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 1% reporting threshold.

Most frequent non-serious adverse event terms

The safety results list serious adverse events and other adverse events separately by arm. For serious adverse events, the registry reports zero affected participants in the placebo group, with 13 at risk; zero at 50 mg, with 8 at risk; zero at 100 mg, with 8 at risk; zero at 200 mg, with 8 at risk; and zero at 400 mg, with 8 at risk. These are counts in the registry’s reporting categories, not evidence that no adverse events of any kind occurred.

For other adverse events, the reported affected counts are 7 among 13 at risk for placebo, 7 among 8 at risk for 50 mg, 7 among 8 at risk for 100 mg, 8 among 8 at risk for 200 mg, and 8 among 8 at risk for 400 mg. The registry does not provide event-level descriptions for these other events in the posted results, so the counts do not convey their type, severity, timing, duration, or relationship to treatment.

Deaths are not reported in the registry record. Zero serious adverse events in these groups should be interpreted within the study’s reported at-risk counts and duration; it does not establish that a dose has no serious risk. The registry’s adverse-event summary also does not allow a direct comparison of event rates adjusted for differences among groups.

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

The results establish that the registry contains Day 14 AUCτ summaries for four active dose groups, reported as means and standard deviations. The means increase across the listed dose groups, from 12090 ng*h/mL at 50 mg to 50350 ng*h/mL at 400 mg. The registry also reports within-group variability and the number of endpoint participants represented at each active dose. These data describe the observed exposure summaries in the study.

They do not establish a statistical difference between dose groups. The registry posts no inferential test, confidence interval, or model for the dose-exposure relationship. Without those analyses, the numeric ordering of group means should not be treated as proof of a dose-response relationship, nor should it be used to conclude that the groups are statistically distinguishable. No placebo exposure result is available for this endpoint, so an active-versus-placebo pharmacokinetic contrast is not reported.

The endpoint measures drug exposure over a 12-hour interval on Day 14. It does not measure symptom improvement, disease progression, or another clinical benefit. The study enrolled healthy volunteers, and the registry does not report a patient population. Therefore, the exposure summaries do not establish how PG 760564 would perform in people with a condition, and they cannot show that any dose is clinically effective.

The safety counts offer a limited account of reported adverse events. No serious adverse events are listed in the arms, while other adverse events are reported in each arm. Because event descriptions and deaths are not reported in the registry record, and because the study is limited in size and duration, the posted counts do not determine the full safety profile or rule out uncommon or later events.

More broadly, the registry record does not provide the analysis plan, endpoint-level missing-data handling, or details of the pharmacokinetic measurement procedures. Those omissions constrain assessment of precision, bias, and reproducibility. The posted results are best understood as early-phase descriptive evidence about exposure and reported events under the study conditions, not as a definitive comparison or a clinical recommendation.

14. Why This Trial Matters Statistically

This trial illustrates a common distinction in early-phase research: pharmacokinetic evidence describes what happens to drug exposure under specified dosing, whereas clinical outcome evidence addresses whether participants experience a health benefit or harm. The primary endpoint is AUCτ over a dosing interval on Day 14. It can characterize plasma exposure after repeated dosing, but it does not itself answer a patient-centered efficacy question.

The four active-dose means form an increasing descriptive sequence, yet interpretation depends on more than the sequence of values. Group sizes differ, the reported standard deviations indicate variability, and the registry does not include confidence intervals or a statistical model of dose and exposure. This is a useful reminder that descriptive patterns and inferential conclusions are not interchangeable. A plotted or tabulated pattern may be informative, but formal uncertainty remains important when comparing groups.

The absence of placebo pharmacokinetic measurements also shows why the comparator must be considered outcome by outcome. Placebo is present in the study and has safety results, but the registry explicitly says plasma concentrations were not measured for that arm. It would therefore be inaccurate to describe the primary exposure result as a placebo-controlled comparison.

The study’s healthy-volunteer population and phase 1 status place the results within an early development context. The record describes exposure and adverse-event counts but does not post a clinical efficacy analysis. Reading the evidence in that scope prevents a pharmacokinetic summary from being mistaken for proof of clinical benefit, and prevents zero reported serious events from being interpreted as a guarantee of safety.

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 registry’s primary endpoint summaries are descriptive and do not include confidence intervals, hypothesis tests, or a dose-response model. As a result, the precision of the means and the inferential uncertainty in comparisons across doses are not reported. The different endpoint group sizes, including 4 participants at 400 mg, further limit how much can be learned from group summaries alone.

The registry does not report individual concentration data, sampling schedules, assay methods, or the procedure used to estimate the area under the curve. Those details would help readers evaluate the measurement and the distribution of exposure. The registry also does not explain the difference between overall enrollment and the endpoint counts, or describe missing-data handling and analysis populations.

Placebo plasma concentrations were not measured, leaving no placebo result for the primary pharmacokinetic endpoint. The posted safety counts cannot serve as a substitute for a pharmacokinetic comparison. The adverse-event reporting also lacks event-level descriptions, and deaths are not reported in the registry record.

The study was conducted in healthy male and female volunteers and is described as phase 1. The registry does not post clinical efficacy outcomes or a patient population, so the exposure data cannot be generalized into a claim about clinical benefit. Its recorded dosing period is 14 days, and the safety figures do not establish risks outside the reported study context.

Finally, the registry does not report the statistical analysis plan, sample-size justification, interim analyses, or multiplicity strategy. These missing details prevent assessment of whether the posted summaries match a prespecified analysis or how the study intended to handle multiple comparisons. The limitations concern what can be concluded from the registry record; they do not establish that a particular analysis or procedure was or was not performed outside the record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Multiple Rising Oral Dose Study of PG 760564 Administered Twice Daily to Healthy Male/Female Volunteers for 14 Days — NCT00791388.
• Registry record last updated 2011-11-04; status last verified 2011-09.
• Results first posted 2011-11-04.
• 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.

19. Record Summary

The registry record describes a completed, randomized, double-blind, parallel phase 1 study sponsored by Procter and Gamble. It enrolled healthy male and female volunteers and evaluated oral PG 760564 administered twice daily for 14 days, described as 27 doses. The active dose groups were 50 mg, 100 mg, 200 mg, and 400 mg, alongside placebo.

The primary outcome was mean AUCτ over a 12-hour dosing interval on Day 14, reported in ng*h/mL with standard deviations. Active-dose means increased across the listed groups, but the registry provides no inferential comparisons, and placebo plasma concentrations were not measured. Safety results list zero serious adverse events in each arm and report other adverse events by arm. Deaths are not reported in the registry record.

The record does not report the statistical analysis plan, sample-size justification, missing-data methods, or analysis-population definitions. Its results are descriptive summaries of exposure and reported adverse events in the study population, rather than a clinical efficacy comparison.