This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for PF-04634817 Renal Impairment Study (NCT01791855), a non-randomized phase 1 study. The primary outcome is Area Under the Curve From Time Zero to 48 Hours[AUC (0 - 48)].
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01791855 |
| Phase | Phase 1 |
| Condition | Renal Insufficiency |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 32 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Pfizer |
| Results posted | Yes |
2. Clinical Question
Population
Participants with normal renal function and mild, moderate, or severe renal impairment. The registry lists renal insufficiency as the condition and gives an enrollment of 32. The pharmacokinetic analysis population is defined in the record as participants randomized and treated who had at least 1 of the PK parameters of primary interest. Because allocation is listed as non-randomized, the record's use of “randomized” in that definition is unexplained.
Intervention
A single dose of PF-04634817 was administered in this open-label study. Pharmacokinetics, safety, and toleration were to be assessed. The registry lists PF-04634817 as the intervention in each renal-function category; it does not give dose amounts in the record.
Comparator
The categories of renal function provide the groups for describing pharmacokinetics. The normal-renal-function group can be considered a reference category for descriptive comparisons, but this is not a randomized treatment-control comparison. The record explicitly identifies the allocation as non-randomized, so differences between categories should not be interpreted as though participants had been randomly assigned to renal-function status.
Primary question
How does renal impairment relate to plasma exposure to PF-04634817, measured by area under the concentration-time curve from time zero to 48 hours? The study's stated rationale is that the drug's clearance mechanism may mean exposure is increased in people with renal impairment. The registry record does not report the endpoint estimates or the results of comparisons between renal-function categories, so it does not establish the direction or size of any observed difference.
3. Trial Design
This is a Phase 1, single-dose, open-label study of PF-04634817 in participants classified by renal function. The registry lists a parallel model and non-randomized allocation, with no masking. The named categories are normal renal function, mild renal impairment, moderate renal impairment, and severe renal impairment. The study is therefore organized to assess pharmacokinetic patterns across renal-function categories, not to compare randomized treatment assignments.
The registry records an enrollment of 32 and lists the study as completed. The recorded start date is 2013-05-10, and the primary completion date is 2013-09-03. These dates and the completion status describe the record, but do not convey the primary endpoint findings. The brief summary says pharmacokinetics, safety, and toleration would be assessed. The stated rationale is that the drug's clearance mechanism may lead to increased exposure in subjects with renal impairment.
The primary outcome is AUC from time zero to 48 hours, reported as a geometric mean with geometric coefficient of variation. The record specifies blood-sampling times from pre-dose through 312 hours post dose, while the primary AUC measure covers the interval ending at 48 hours. Listed secondary outcomes concern unchanged drug excreted in urine over 48 hours, the percentage of the dose excreted unchanged over that period, and renal clearance over a 48-hour interval.
Group sizes in the safety record are 8 for normal renal function, 8 for mild impairment, 8 for moderate impairment, and 7 for severe impairment. These are safety denominators and should not automatically be assumed to be the analysis denominators for each pharmacokinetic measure. The record does not explain the difference between the enrollment figure and the listed safety denominators, or give outcome-specific analysis denominators. The PK population definition uses wording about randomized and treated participants even though allocation is listed as non-randomized; the record does not clarify that wording.
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
| Stage | Normal Renal Function | Mild Renal Impairment | Moderate Renal Impairment | Severe Renal Impairment |
|---|---|---|---|---|
| STARTED | 8 | 9 | 8 | 7 |
| Treated | 8 | 8 | 8 | 7 |
| COMPLETED | 8 | 8 | 8 | 6 |
| NOT COMPLETED | 0 | 1 | 0 | 1 |
Reasons for not completing this period:
| Reason | Normal Renal Function | Mild Renal Impairment | Moderate Renal Impairment | Severe Renal Impairment |
|---|---|---|---|---|
| Adverse Event | 0 | 0 | 0 | 1 |
| Randomized, not treated | 0 | 1 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: The pharmacokinetics (PK) parameter analysis population was defined as all participants randomized and treated who had at least 1 of the PK parameters of primary interest.
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
Population: Baseline analysis included the participants who received at least one dose of study treatment.
| Characteristic | Unit | Normal Renal Function | Mild Renal Impairment | Moderate Renal Impairment | Severe Renal Impairment | Total |
|---|---|---|---|---|---|---|
| Participants analysed | 8 | 8 | 8 | 7 | 31 | |
| Age, Continuous | Years | 60.0 (SD 5.2) | 66.5 (SD 3.9) | 61.9 (SD 3.2) | 59.0 (SD 12.0) | 61.9 (SD 7.5) |
| Sex: Female, Male: Female | Participants | 3 | 4 | 2 | 3 | 12 |
| Sex: Female, Male: Male | Participants | 5 | 4 | 6 | 4 | 19 |
6. Primary Endpoint
The registry lists the primary outcome as Area Under the Curve From Time Zero to 48 Hours[AUC (0 - 48)], measured over Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 16, 24, 32, 40, 48, 56, 64, 72, 84, 96, 108, 120, 132, 144, 156, 216, 312 hours post dose.
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | Geometric Coefficient of Variation |
| Unit | Nanogram*hour/milliliter (ng*h/mL) |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is area under the plasma concentration-time curve from time zero to 48 hours, written as AUC (0 - 48), in nanogram*hour/milliliter (ng*h/mL). It represents the accumulated plasma concentration of PF-04634817 over the stated period after dosing. An area measure captures exposure across the interval rather than describing concentration at just one sampling time. This makes it relevant to the study's question about whether renal function is associated with drug exposure.
The registry specifies a geometric mean as the summary parameter and a geometric coefficient of variation as the dispersion measure. A geometric mean is a summary suited to positive measurements that may be distributed asymmetrically; it describes a typical level on a multiplicative scale. The geometric coefficient of variation describes relative spread on that scale. These summaries do not, by themselves, show the size or uncertainty of a difference between renal-function categories. For that, the record would need to report comparison estimates and their uncertainty.
The endpoint description defines AUC (0 - 48) as the area under the plasma concentration versus time curve from pre-dose to 48 hours. Although the sampling schedule extends beyond that interval, the primary outcome concerns only the specified 48-hour window. The registry record does not report the geometric means, dispersion values, group contrasts, or confidence intervals for this endpoint. Thus, its definition and intended role are clear, while the observed primary endpoint results are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a pharmacokinetic question: whether exposure to PF-04634817 differs across categories of renal function. Its primary measure, AUC (0 - 48), is designed to summarize plasma exposure over the first 48 hours after dosing. However, the record does not include the observed AUC values, group-specific estimates, comparisons, confidence intervals, or p-values. The magnitude, direction, and precision of any difference therefore cannot be assessed from the registry results.
The design is non-randomized and open-label. Renal-function category is not a randomized intervention, so any observed between-category difference would be an association in this study rather than a randomized causal effect of renal impairment. The categories can support a descriptive comparison of pharmacokinetic summaries, but other differences among participants could also contribute to contrasts. The registry does not report adjustment methods or other information that would establish how such factors were handled.
The planned endpoint is a geometric mean, with geometric coefficient of variation describing dispersion. Those summaries can describe the distribution of exposure within each category, but a reader would also need a reported contrast and uncertainty interval to judge how precisely categories differ. The record does not provide those results. It also lists 0 analyses, so the posted registry record does not give inferential analysis results that could be used to evaluate the primary question.
The listed safety counts are descriptive. No serious adverse events are listed for the normal, mild, or moderate renal-function groups. In the severe renal impairment group, 1 participant is listed as having a serious adverse event, and 3 are listed as having other adverse events. Those figures do not establish whether events were caused by PF-04634817, nor do they provide a basis for comparing risk reliably across categories. The death fields are null, which means a death count is not reported in those fields; it should not be read as a reported zero.
Overall, the registry record establishes the study's purpose, design, endpoint definition, and some safety counts, but not the main pharmacokinetic findings. It cannot support a conclusion about whether exposure increased, decreased, or remained similar across renal-function categories. Nor does the lack of reported endpoint results imply that the groups had the same exposure. The interpretation is limited by missing outcome estimates and the non-randomized design, rather than by a demonstrated absence of a difference.
9. Statistical Methods Explained
What does the primary measure represent?
AUC (0 - 48) is the area under the plasma concentration-time curve from time zero to 48 hours. In general, an area-under-the-curve measure combines information across multiple concentration measurements, so it reflects exposure over an interval rather than a single observed concentration. The registry gives the unit as nanogram*hour/milliliter (ng*h/mL) and describes the window as pre-dose to 48 hours. The sampling schedule also lists later times through 312 hours post dose, but those later samples do not extend the stated primary AUC interval.
The intended comparison is across renal-function categories. In general, a comparison of exposure summaries can help describe whether measured pharmacokinetics vary with renal function. The registry does not report the group estimates or their contrasts, so no conclusion about the observed relationship can be drawn from the endpoint definition alone.
Why use a geometric mean?
The primary parameter is the geometric mean. In general, pharmacokinetic measurements are positive and can have a right-skewed distribution, where a few relatively high values stretch the upper tail. A geometric mean summarizes positive values on a multiplicative scale and is often useful for such measurements. It should not be interpreted as the arithmetic average. The record also specifies a geometric coefficient of variation, which describes relative variability rather than variability in the original units.
Neither a geometric mean nor a geometric coefficient of variation is a comparison test. They summarize the data, but do not alone indicate how uncertain a difference between categories is. A confidence interval, in general, represents a range of values compatible with the data and analysis assumptions; its width conveys precision. No confidence intervals for the primary endpoint are reported in the registry record. There is consequently no reported precision measure for a contrast between renal-function categories.
How should the group structure be understood?
The study is listed as parallel and non-randomized, with no masking. The categories are normal renal function, mild renal impairment, moderate renal impairment, and severe renal impairment. Because participants were not randomized to renal-function category, this is not a randomized comparison of assigned treatments. A descriptive difference between categories could reflect renal function, but the design alone cannot rule out other systematic differences among participants. The registry does not report a statistical adjustment strategy.
The record defines the pharmacokinetic analysis population as all participants randomized and treated who had at least 1 of the PK parameters of primary interest. That wording is difficult to reconcile with the non-randomized allocation listed for the study, and the registry does not explain it. The record also does not give the analysis denominator for AUC (0 - 48) by category, so the safety group denominators should not be treated as confirmed pharmacokinetic denominators.
What can be inferred from the safety summaries?
Safety event counts describe how many participants in each listed group were recorded with serious or other adverse events. In general, such counts are descriptive and do not establish that the study drug caused an event. They also do not, by themselves, provide a precise estimate of event risk, especially when group counts are limited. A causal safety claim would require more than the presence or absence of a recorded event. The registry provides no analysis of comparative safety or attribution in the record.
The serious event fields list 0 affected participants in the normal, mild, and moderate groups, and 1 in the severe group. The other adverse-event fields list 0 affected participants in the first three groups and 3 in the severe group. The death entries are null, not reported numerical values. The listed top serious term is Pyrexia at 14.3%; the record does not establish from that listing alone whether the event was attributed to study drug or which group it occurred in.
What analysis information is absent?
The registry lists 11 outcome measures and 0 analyses. This is not a report of 0 effects; it means the record does not contain analysis entries from which endpoint estimates or statistical tests can be read. The statistical analysis plan, model details, covariate choices, confidence interval methods, and handling of any protocol deviations are not reported in the registry record. Interim analyses are not reported in the registry record either.
The record includes a description of planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. It describes the effect to detect as a stated fraction of the observed effect. Those are planning assumptions, not evidence about the trial's observed power, and no planning result values are reported in the record. Since the observed primary effect itself is not reported, the registry information does not support reproducing or interpreting such an illustration.
In general, statistical conclusions depend on both the numerical results and the analysis procedures. A well-defined endpoint does not substitute for estimates, uncertainty intervals, or a clearly described comparison method. For this study, the endpoint and summary types are specified, but the inferential results needed to quantify the relationship between renal function and exposure are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 11 outcome measures, including the primary AUC (0 - 48) endpoint and secondary measures of unchanged drug excreted in urine over 48 hours, the percentage of the dose excreted unchanged over 48 hours, and renal clearance over a 48-hour interval. When a study examines multiple endpoints or comparisons, general statistical practice considers whether the chance of false-positive findings across analyses needs to be controlled. The registry record does not report a multiplicity adjustment, a hierarchy of testing, or a statistical plan specifying which comparisons would be confirmatory.
The record lists 0 analyses. It therefore does not provide outcome estimates, hypothesis tests, or confidence intervals with which to evaluate the primary or secondary outcomes. No interim analyses are reported in the registry record. The absence of analyses in the registry should not be mistaken for evidence of no difference or no effect; it indicates that the record does not present those results.
The pharmacokinetic analysis population is described as participants randomized and treated who had at least 1 of the PK parameters of primary interest. The study allocation is listed as non-randomized, and the record does not explain the discrepancy in wording. It also does not report endpoint-specific analysis denominators or how missing concentration measurements, incomplete profiles, or missing outcome values were handled. No missing-data imputation or sensitivity analysis is reported in the registry record.
These omissions matter because the interpretation of an estimate depends on who contributed data and how incomplete observations were handled. With no reported estimates, analysis populations, missing-data procedures, or multiplicity approach, readers cannot determine the extent to which the planned endpoint analyses were carried out as intended or how uncertainty and multiple comparisons were addressed.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Normal Renal Function | 0 | 8 | 0.0% |
| Mild Renal Impairment | 0 | 8 | 0.0% |
| Moderate Renal Impairment | 0 | 8 | 0.0% |
| Severe Renal Impairment | 1 | 7 | 14.3% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Normal Renal Function | 0 of 8 |
| Mild Renal Impairment | 0 of 8 |
| Moderate Renal Impairment | 0 of 8 |
| Severe Renal Impairment | 3 of 7 |
Most frequent serious adverse event terms
| Event term | Organ system | Normal Renal Function | Mild Renal Impairment | Moderate Renal Impairment | Severe Renal Impairment |
|---|---|---|---|---|---|
| Pyrexia | General disorders | 0 of 8 | 0 of 8 | 0 of 8 | 1 of 7 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Normal Renal Function | Mild Renal Impairment | Moderate Renal Impairment | Severe Renal Impairment |
|---|---|---|---|---|---|
| Constipation | Gastrointestinal disorders | 0 of 8 | 0 of 8 | 0 of 8 | 2 of 7 |
| Tachycardia | Cardiac disorders | 0 of 8 | 0 of 8 | 0 of 8 | 1 of 7 |
| Abdominal pain | Gastrointestinal disorders | 0 of 8 | 0 of 8 | 0 of 8 | 1 of 7 |
| Diarrhoea | Gastrointestinal disorders | 0 of 8 | 0 of 8 | 0 of 8 | 1 of 7 |
| Nausea | Gastrointestinal disorders | 0 of 8 | 0 of 8 | 0 of 8 | 1 of 7 |
| Vomiting | Gastrointestinal disorders | 0 of 8 | 0 of 8 | 0 of 8 | 1 of 7 |
| Chills | General disorders | 0 of 8 | 0 of 8 | 0 of 8 | 1 of 7 |
| Back pain | Musculoskeletal and connective tissue disorders | 0 of 8 | 0 of 8 | 0 of 8 | 1 of 7 |
| Flank pain | Musculoskeletal and connective tissue disorders | 0 of 8 | 0 of 8 | 0 of 8 | 1 of 7 |
| Pulmonary mass | Respiratory, thoracic and mediastinal disorders | 0 of 8 | 0 of 8 | 0 of 8 | 1 of 7 |
Serious events with the highest arm-level rate: pyrexia (14.3%).
The safety record separates participants by renal-function category and reports serious adverse events, other adverse events, and deaths. For normal renal function, mild impairment, and moderate impairment, the listed serious-event counts are 0 affected participants, with 8 at risk in each group. The other-event counts are also 0, with 8 at risk in each of those groups. For severe renal impairment, 1 of 7 is listed as having a serious adverse event and 3 of 7 as having other adverse events.
These are observed counts, not proof that an event was caused by PF-04634817. The registry record does not report a causal attribution analysis or a comparative safety analysis. The top serious term is listed as Pyrexia at 14.3%; the record does not establish from that listing alone its group or relationship to the drug. The death entries are null. A null entry means a death count is not reported there, rather than documenting a count of 0.
Because the groups are non-randomized and the denominators are limited, raw counts should be read descriptively. They do not establish that the safety experience differs across categories, and a zero count in a group does not demonstrate that an event cannot occur. These safety denominators also should not be assumed to be the denominators used for pharmacokinetic analyses.
12. What the Result Does, and Does Not, Mean
The record shows that the study was designed to examine pharmacokinetics, safety, and toleration after a single dose of PF-04634817 across renal-function categories. It specifies AUC (0 - 48) as the primary measure of plasma exposure and identifies urinary excretion and renal clearance as secondary outcomes. It also records adverse-event counts for the listed categories.
What the registry record does not show is the primary endpoint result. There are no reported geometric mean AUC values, group contrasts, confidence intervals, or p-values in the record. Therefore it is not possible to say whether measured exposure was greater, lower, or similar in participants with renal impairment compared with those with normal renal function. The study rationale proposes that exposure may increase because of the drug's clearance mechanism; that rationale is not itself a finding.
The observed safety counts are not equivalent to a conclusion about the drug's safety. Event counts do not establish causation, and the record does not provide event attribution or comparative statistical analyses. Null death entries do not establish that there were no deaths. The registry also does not report how missing data were handled or provide analysis denominators for each pharmacokinetic endpoint.
The non-randomized design matters for interpretation. Renal-function categories are descriptive groups rather than randomly assigned conditions. If results were available, differences between categories would be associations that could be influenced by other differences among participants. The design cannot on its own isolate renal impairment as the cause of a difference.
In short, the record establishes the clinical pharmacology question and the planned measurement strategy, but the outcome estimates needed to answer the question are not reported in the registry record. Missing results should not be interpreted as evidence of no effect, and the study's rationale should not be treated as proof of increased exposure.
13. Why This Trial Matters Statistically
This study addresses a statistical question in clinical pharmacology: how measured drug exposure varies across categories of renal function. AUC (0 - 48) provides a defined exposure measure, and the geometric mean and geometric coefficient of variation are summaries commonly suited to positive, potentially asymmetric pharmacokinetic measurements. The design also includes urine excretion and renal clearance outcomes, which address related aspects of drug disposition.
Its design makes the distinction between description and causal comparison especially important. Participants are grouped by renal function, and allocation is listed as non-randomized. Statistical descriptions can characterize exposure within these categories, but differences cannot automatically be attributed to renal impairment alone. The record does not report an adjustment model or other method intended to address potential differences between groups.
The registry record also illustrates why endpoint definitions and results are separate kinds of information. The primary endpoint is clearly named, its unit and time window are specified, and a summary parameter is stated. Yet the actual estimates and their precision are not reported. Without those, readers cannot assess the size, direction, or uncertainty of the association that motivated the study.
Finally, the safety record requires careful interpretation. Group-specific event counts provide descriptive information, but do not establish drug causality or comparative risk. The study's purpose and measures are statistically informative as a design description; the posted record, however, does not contain the primary pharmacokinetic findings needed to resolve its central question.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The most direct limitation in the registry record is that it does not report the primary endpoint estimates or statistical comparisons. There are no group-specific AUC (0 - 48) values, contrasts, confidence intervals, or p-values available in the record. As a result, neither the direction nor the precision of any exposure difference can be evaluated.
Allocation is listed as non-randomized, and the study is open-label. The renal-function categories are not randomized treatment groups, so potential differences among participants may complicate interpretation of a between-category contrast. The registry does not report covariate adjustment, matching, or another strategy to address such differences. No statistical analysis plan is reported in the registry record.
The PK analysis population definition refers to participants randomized and treated, which does not align clearly with the non-randomized allocation designation. The record does not explain this wording or provide endpoint-specific analysis denominators. The safety denominators therefore cannot be assumed to describe who contributed to each pharmacokinetic endpoint. Missing-data handling, completeness of concentration profiles, and sensitivity analyses are not reported.
The registry gives a total enrollment of 32, while the listed safety denominators are 8 for normal renal function, 8 for mild impairment, 8 for moderate impairment, and 7 for severe impairment. The record does not explain the distinction between these figures. The safety counts are descriptive, with no reported event attribution or statistical comparison. Death fields are null rather than numerical values. Together, these limitations restrict interpretation to the study's stated design and the limited posted safety counts; they do not support a conclusion about the primary pharmacokinetic result.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: PF-04634817 Renal Impairment Study — NCT01791855.
- Registry record last updated 2024-03-01; status last verified 2023-08.
- Results first posted 2024-03-01.
- 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.
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18. Record Summary
NCT01791855, titled PF-04634817 Renal Impairment Study, is a completed Phase 1, single-dose, open-label, non-randomized parallel study sponsored by Pfizer. It examines pharmacokinetics, safety, and toleration across normal renal function and mild, moderate, and severe renal impairment. Enrollment is listed as 32; the recorded start date is 2013-05-10 and primary completion date is 2013-09-03.
The primary outcome is AUC (0 - 48), summarized as a geometric mean with geometric coefficient of variation. Listed secondary outcomes concern unchanged drug excreted in urine, the percentage of dose excreted unchanged, and renal clearance over 48 hours. The registry record does not report the primary endpoint results, statistical comparisons, missing-data procedures, or a multiplicity approach. Safety counts are descriptive; death entries are null rather than reported counts.