A Study To Investigate The Pharmacokinetics, Safety And Tolerability Of An Intravenous And Oral Form Of A Compound In Subjects With Varying Degrees Of Renal Impairment And Normal Renal Function: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study To Investigate The Pharmacokinetics, Safety And Tolerability Of An Intravenous And Oral Form Of A Compound In Subjects With Varying Degrees Of Renal Impairment And Normal Renal Function (NCT00759564), a non-randomized phase 1 study. The primary outcome is Maximum Observed Plasma Concentration (Cmax) of CP-70429 Following CP-70,429 Intravenous Dose.

2. Clinical Question

The study asked how renal function status relates to the pharmacokinetics, safety, and tolerability of CP-70,429 administered intravenously and PF-03709270 administered orally. PF-03709270 is described in the registry record as an oral prodrug that is rapidly hydrolyzed after absorption to yield active CP-70,429. The primary endpoint was the maximum observed plasma concentration of CP-70429 after an intravenous CP-70,429 dose.

The registry record identifies participants with normal renal function and with mild, moderate, or severe renal impairment. The intervention listing and adverse-event groups also identify intravenous and oral dosing, including different dose levels in some groups. The record describes a crossover design, but it does not report the order in which each participant received the treatments or the interval between treatment periods. The study was open-label and non-randomized, so it was not a randomized comparison of treatment groups.

The clinical question is pharmacokinetic rather than a comparison of clinical benefit. The endpoint concerns the concentration of active drug measured in plasma after dosing. Other registered outcomes include elimination half-life, clearance, apparent oral clearance, and the duration of plasma concentrations above specified thresholds. These measures can characterize drug exposure and disposition, but the registry record does not provide their numerical results.

The record reports that 29 participants were enrolled. It does not report the primary endpoint values by renal-function group, uncertainty intervals, or a statistical comparison between groups. Therefore, the study's stated question can be described, but the magnitude and precision of any observed differences cannot be assessed from the registry record.

3. Trial Design

The registry identifies this as a Phase 1, open-label, 2-way crossover study with non-randomized allocation. It was completed and enrolled 29 participants. The record lists a start date of 2008-11 and a primary completion date of 2010-03. Pneumonia is listed as the condition, while the stated study purpose concerns the effects of renal dysfunction on the pharmacokinetics, safety, and tolerability of the intravenous and oral forms of the compound.

A crossover study gives participants treatment in more than one period, so observations can be collected after different treatments within a participant. As a general statistical concept, within-participant comparisons can account for some stable differences between people. That benefit depends on the actual treatment sequence and on suitable handling of period effects and any residual effect from an earlier treatment. The treatment sequence, washout interval, and methods for assessing period or carryover effects are not reported in the registry record.

The record names an arm as intravenous CP-70,429 followed by crossover to PF-03709270. It also presents safety groups for intravenous CP-70,429 at 800 mg among participants with normal, mild, moderate, and severe renal impairment; intravenous CP-70,429 at 200 mg among participants with severe renal impairment; and oral PF-03709270 at 1000 mg among participants in each renal-function category. These listed groups describe the dosing represented in the safety record; the registry does not provide a full account of assignment or treatment sequence.

Because allocation was non-randomized, renal-function categories should not be interpreted as randomly assigned arms. Differences between categories could reflect differences other than renal function, and the record does not describe adjustment for such differences. There is no randomized control comparison to support a causal treatment contrast. The study is best read as a pharmacokinetic and safety investigation across renal-function categories, with the posted record insufficient to determine the strength or precision of its pharmacokinetic findings.

The registry lists 26 outcome measures and 18 analyses. It does not describe the full statistical plan, how the analyses correspond to particular outcomes, or how results were combined across treatment periods and renal-function categories. Those design details are important when interpreting a crossover pharmacokinetic study, but they 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.

Before assignment: Participants were planned to receive CP-70,429 800 milligram (mg) in all reporting groups. For severe renal impairment group, CP-70,429 dose was decreased from 800 mg to 200 mg as per protocol amendment. Only 1 participant received 800 mg dose and was excluded from all descriptive and statistical analyses as per change in planned analysis.

First Intervention Period (4 Days)

Washout Period (at Least 14 Days)

Reasons for not completing this period:

Second Intervention Period (4 Days)

Analysis population for the primary outcome, as defined in the registry: The pharmacokinetic (PK) parameter analysis population included all treated participants who had at least 1 of the PK parameters of interest in at least 1 treatment period.

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 Maximum Observed Plasma Concentration (Cmax) of CP-70429 Following CP-70,429 Intravenous Dose, measured over 0 (pre-dose), 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose (for all participants) and 48 hours post-dose (for participants with moderate and severe renal impairment).

The primary endpoint is the maximum observed plasma concentration, or Cmax, of CP-70429 after an intravenous CP-70,429 dose. Concentration was recorded in nanograms per milliliter (ng/mL). The scheduled observations included pre-dose and post-dose timepoints through 24 hours for all participants, with an additional 48-hour observation for participants with moderate and severe renal impairment. The registry describes the endpoint as a geometric mean with standard deviation as its dispersion measure.

As a general pharmacokinetic concept, Cmax captures the highest concentration observed among the scheduled measurements. It is used to describe peak systemic exposure after a dose. It is not the same as total exposure over time, which is commonly characterized by an area-under-the-curve measure, nor does it by itself describe how quickly concentrations decline. The registry lists half-life and clearance among secondary outcomes, which address different aspects of drug disposition.

A geometric mean summarizes positive measurements on a multiplicative scale. Standard deviation describes variation in the data under the reported summary approach; it is not a confidence interval and does not alone indicate the precision of a group estimate. The registry record does not report the Cmax values, the corresponding standard deviations, or confidence intervals. It therefore identifies what was measured and how it was summarized, but does not allow readers to assess the observed peak concentrations or their uncertainty.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods are useful only when they match the outcome, design, and question. The registry identifies a crossover study, non-randomized allocation, a geometric-mean primary endpoint, and standard deviation as the dispersion measure. It does not report the detailed statistical methods used to estimate or compare Cmax. The explanations below describe general statistical concepts, not methods confirmed to have been used in this study.

What does a crossover design contribute?

In general, a crossover design measures participants in more than one treatment period. Comparing a participant with that same participant can reduce the influence of stable characteristics that differ between people. But the interpretation depends on treatment sequence, period effects, and whether effects from an earlier period persist into a later one. A crossover analysis typically needs to account for the structure of repeated observations rather than treating every period as an independent participant. The registry record does not report the sequence, washout details, or the model used for the crossover data, so it is not possible to determine how these issues were addressed.

Here, the study is also non-randomized. In general, randomization helps balance measured and unmeasured characteristics between assigned groups on average. Without random allocation, renal-function groups may differ in other ways. A crossover structure does not by itself make comparisons between renal-function categories randomized, because renal-function status is not described as an assigned intervention. The registry does not report adjustment strategies or enough participant-level detail to assess potential confounding.

What does the geometric mean describe?

As a general concept, the geometric mean is appropriate for positive measurements that are often interpreted on a multiplicative scale. It can be useful for pharmacokinetic concentrations, which may be asymmetrically distributed. The geometric mean is not an arithmetic average, and its interpretation concerns a central value on that multiplicative scale. Standard deviation describes dispersion under the reported summary, but the registry does not say whether it was calculated on the original or transformed scale. That detail can affect interpretation.

A confidence interval would provide a range of values compatible with the data and the stated statistical procedure, reflecting uncertainty in an estimate. It is distinct from standard deviation, which describes spread among observations. No confidence interval for the primary endpoint is reported in the registry record. Without an estimate and a measure of uncertainty, the apparent size and precision of a difference cannot be evaluated.

Why do timepoints and endpoint definitions matter?

Cmax is the largest observed concentration among measurements taken at scheduled times. As a general matter, the measured maximum can depend on the timing and density of sampling: a peak between scheduled draws might not be directly observed. The registry lists pre-dose and post-dose sampling through 24 hours for all participants, and a 48-hour observation for participants with moderate and severe renal impairment. It does not report the individual concentration profiles or explain how missing samples were handled. The schedule alone cannot establish whether the observed maximum captured the true peak for every participant.

Other pharmacokinetic measures answer different questions. Half-life concerns the terminal decline in concentration; clearance describes removal from the body in relation to exposure; apparent oral clearance incorporates bioavailability in the reported parameter. Duration above a concentration threshold describes time spent over that threshold. These outcomes complement Cmax, but none can be inferred from Cmax alone. The registry lists these measures but does not report their numerical results.

How should safety counts be interpreted?

Adverse-event counts are descriptive observations. A count of affected participants is not a measure of causal risk unless the comparison, follow-up, and event attribution support that interpretation. In a crossover study, participants may contribute exposure to more than one treatment period, so the same person could potentially appear in more than one treatment-specific safety group. The record does not explain whether that occurred or how safety exposure was defined. The group counts therefore should not be added together to infer a number of unique participants.

As a general statistical concept, small groups yield limited precision for uncommon events. A zero count means no affected participants were recorded in that particular group in the posted data; it does not establish that the underlying event risk is zero. The registry record also does not provide confidence intervals for the adverse-event counts or a comparative safety analysis.

What does the sample-size illustration represent?

The record describes a planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation. It describes the target effect as a stated fraction of the observed effect. Such calculations are planning illustrations, not observed power and not evidence that the trial was designed around those assumptions. The registry does not report the trial's own sample-size justification, and it gives no calculated sample-size values in the record. The planning assumptions therefore cannot establish that the enrolled sample was adequate for a particular hypothesis or precision target.

More generally, power calculations depend on the outcome, variability, target effect, allocation, and analysis assumptions. If those assumptions differ from the data or the final analysis, planning values may not reflect actual precision. For this study, the absent primary endpoint estimates and uncertainty intervals prevent a direct assessment of how informative the observed pharmacokinetic data were.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 26 outcome measures and 18 analyses, including the primary Cmax measure and several secondary pharmacokinetic measures. When a study examines multiple outcomes, timepoints, groups, or contrasts, the chance of obtaining at least one apparently notable result can increase. As a general statistical approach, investigators may define a primary analysis in advance, adjust for multiple testing, or emphasize estimation and uncertainty rather than isolated significance tests. The registry record does not report whether multiplicity was controlled, which outcomes were included in any adjustment, or which contrasts were prespecified.

The primary endpoint is identified, but the statistical plan for its analysis is not reported in the registry record. There is no reported description of the model, covariates, treatment-period handling, subgroup comparisons, or decision criteria. It is therefore not possible to determine whether the analyses were confirmatory or exploratory from the listed endpoint titles alone.

The pharmacokinetic population is described as treated participants with at least one parameter of interest in at least one treatment period. The record does not state the number included in the primary Cmax analysis, whether every participant contributed to every treatment period, or how missing concentrations and incomplete profiles were handled. It also does not report reasons for missing data or any sensitivity analyses. Missing observations can affect estimates when their occurrence is related to participant characteristics or observed concentrations; this is a general concern, not a claim that a particular missing-data pattern occurred in this study.

Information about interim analyses is not reported in the registry record. The trial's own sample-size justification is also not reported. These omissions limit assessment of the intended analysis strategy, but they do not establish that particular methods were or were not used outside what the record states.

11. 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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: fall (25.0%), humerus fracture (25.0%).

The safety record gives counts by dose and renal-function group. For serious adverse events, zero affected participants are listed in the intravenous 800 mg groups with normal, mild, moderate, and severe renal impairment; in the oral 1000 mg groups with normal, mild, and moderate renal function; and in the oral 1000 mg severe renal group. One affected participant is listed for intravenous 200 mg among participants with severe renal impairment. The record does not provide a death count; deaths are not reported in the registry record.

Other adverse events are also reported as counts. The number of participants affected varies across groups, including groups with no affected participants. These are descriptive counts, not randomized comparisons. The study was non-randomized, and the groups differ in size and dose. The record does not report event timing, duration, relatedness to treatment, or whether individuals contributed to more than one treatment-specific group.

The serious adverse-event terms listed are Fall and Humerus fracture, each with 25.0%. The registry record does not explain the denominator used for these percentages or link each term to a particular dose or renal-function group. The percentages should therefore be read as reported labels, not as group-specific incidence estimates. A zero recorded count does not establish absence of risk, and the listed counts alone do not support a comparative safety conclusion.

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

The study addresses an important statistical problem in pharmacokinetics: whether drug concentration measures differ across participants with varying renal function after intravenous and oral dosing. Its registered primary endpoint, Cmax after intravenous CP-70,429, is a direct measure of peak observed plasma concentration. The accompanying outcomes cover other aspects of exposure and disposition. The study's crossover design offers the possibility of collecting measurements across treatment periods within participants, while its non-randomized allocation limits interpretation of differences between renal-function groups as causal contrasts.

The record does not include numerical results for the primary endpoint or the secondary pharmacokinetic outcomes. It therefore cannot establish the direction or magnitude of any relationship between renal function and drug concentration, nor the precision of such a relationship. The lack of reported estimates should not be interpreted as a finding of no difference. It also does not establish equivalence between groups.

The safety counts describe recorded affected participants within the listed dose and renal-function categories. They can identify what was entered into the registry, but without a randomized comparison, event-level detail, and clear denominators, they do not provide a robust estimate of comparative risk. The serious adverse-event percentages have no stated denominator in the record, further limiting their interpretation.

General statistical interpretation separates three questions: what was measured, what estimate was observed, and how uncertain that estimate is. The registry gives substantial information about the first question, including the endpoint definition, measurement schedule, and analysis-population description. It does not supply the numerical endpoint estimates needed for the second or uncertainty measures needed for the third. Readers should therefore treat the record as a description of the study design and registered outcomes, not as a complete account of the evidence about pharmacokinetic differences.

13. Why This Trial Matters Statistically

Pharmacokinetic studies often focus on estimation: how concentrations and drug disposition vary across relevant populations. A well-defined endpoint such as Cmax can make the target quantity clear, while additional measures such as half-life and clearance can help describe distinct parts of the concentration profile. This study's registered objectives and outcome list make those different measurement targets visible.

The statistical design also matters. Crossover studies can use within-participant data, which may help account for stable individual variation. But interpretation depends on treatment sequence, period effects, and appropriate analysis of repeated measurements. The registry identifies a crossover model but does not report enough detail to evaluate those aspects. Non-randomized allocation also means that differences between renal-function groups cannot automatically be attributed to renal function alone.

Equally important is the distinction between registering an endpoint and reporting its result. The record names the primary measure and the times at which samples were scheduled, but numerical Cmax results and uncertainty estimates are not reported. Without those, readers cannot assess the magnitude, variability, or precision of the primary finding. This is a statistical reporting limitation, regardless of whether the study collected the measurements.

The safety data illustrate another general issue: descriptive counts from small, unequal groups are not equivalent to a comparative safety analysis. Counts need clear denominators and context about exposure and repeated treatment periods. The record gives some group sizes and event counts, but does not describe participant overlap, event attribution, or the denominator for the serious-event terms. These limits affect how much can be inferred from the posted figures.

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 central limitation for interpreting the study's pharmacokinetic findings is that numerical primary endpoint results are not reported in the registry record. The record identifies the summary measure and sampling schedule, but gives no group-specific Cmax estimates, standard deviations, confidence intervals, or statistical comparisons. Secondary pharmacokinetic results are likewise not reported as numerical estimates.

The record describes the study as open-label, non-randomized, and crossover, but does not report the treatment sequence, washout details, period-specific results, or model used for repeated measurements. It also does not say how potential period or carryover effects were addressed. Because allocation was not randomized, comparisons across renal-function categories may be affected by group differences beyond renal status; adjustment methods are not reported.

The pharmacokinetic analysis population is described, but the number contributing to the primary endpoint and the handling of incomplete concentration profiles are not reported. Missing-data methods and sensitivity analyses are not reported in the registry record. The record also does not report the full statistical plan, multiplicity approach, interim analyses, or the trial's own sample-size justification.

Safety interpretation is limited by the descriptive presentation of counts, different group sizes and doses, and the absence of details on participant overlap across treatment periods. Death counts are not reported in the registry record. The denominator for the serious adverse-event term percentages is also not reported. These limitations preclude strong comparative conclusions from the posted safety figures.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study To Investigate The Pharmacokinetics, Safety And Tolerability Of An Intravenous And Oral Form Of A Compound In Subjects With Varying Degrees Of Renal Impairment And Normal Renal Function — NCT00759564.
• Registry record last updated 2016-03-11; status last verified 2016-02.
• Results first posted 2016-01-18.
• 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

This completed Phase 1 study enrolled 29 participants and investigated intravenous CP-70,429 and oral PF-03709270 in people with normal renal function or varying degrees of renal impairment. It was open-label, non-randomized, and described as a 2-way crossover study. The primary endpoint was the geometric mean maximum observed plasma concentration of CP-70429 after intravenous dosing, with standard deviation as the stated dispersion measure.

The registry lists 26 outcome measures and 18 analyses, as well as safety groups by dose and renal-function category. Numerical primary and secondary pharmacokinetic results are not reported in the registry record. The posted safety information is descriptive, and the record does not provide enough detail to treat the group counts as a randomized comparison or to establish comparative risks.