A Dose Ranging Study Of PF-00868554 In Combination With PEGASYS And COPEGUS In Patients With Chronic Hepatitis C Genotype 1 Infection: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Dose Ranging Study Of PF-00868554 In Combination With PEGASYS And COPEGUS In Patients With Chronic Hepatitis C Genotype 1 Infection (NCT00720434), a randomized phase 2 study. The primary outcome is Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Week 4 - Full Analysis Set.

2. Clinical Question

3. Trial Design

This was a Phase 2, randomized, double-masked, parallel study. It enrolled 35 participants and is listed as completed. The registry record gives a start date of 2008-08 and a primary completion date of 2010-03. The study concerned chronic hepatitis C infection, with the title specifying genotype 1, and evaluated PF-00868554 alongside peginterferon alfa-2a and ribavirin.

Participants were assigned among four listed regimens: PF-00868554 200 mg BID, 300 mg BID, or 500 mg BID, each with peginterferon alfa-2a and ribavirin, or placebo with the same background therapies. Randomization means allocation was intended to be determined by chance rather than by clinical choice. Double masking indicates that the registry classified the study as masked at two levels; which specific people were masked is not reported in the registry record. A parallel design means the listed arms were concurrent groups, rather than a design in which each participant necessarily received every regimen.

The stated purpose was to further assess PF-00868554’s potency by evaluating its antiviral activity in combination with the then-described standard-of-care therapies. That purpose gives context for the Week 4 HCV RNA endpoint, but it does not substitute for arm-level outcome results. The registry record does not report the allocation ratio, the treatment duration, the detailed sequence of study procedures, or the planned statistical analysis. Nor does the enrollment count alone establish how many participants contributed to the primary endpoint in each arm.

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.

Double-Blind Period (Week 1-4)

Reasons for not completing this period:

Open-Label Period (Week 5-72)

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set (FAS) included all randomized participants who received at least 1 dose of study drug and had both baseline and at least 1 valid post-baseline endpoint measurements for HCV viral load. Here 'n' signifies participants evaluable for this measure at specified time points for each arm, respectively.

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 Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Week 4 - Full Analysis Set, measured over Baseline, Week 4.

The primary endpoint was the change from baseline in plasma HCV RNA at Week 4, expressed in log10 IU/mL. It was defined as a mean, with standard deviation as the measure of dispersion. Baseline was calculated as the average of the screening and Day 1 pre-dose measurements. HCV RNA was measured using the Roche COBAS Taqman assay, whose stated limit of detection was 25 IU/mL.

Viral RNA is a direct laboratory measure of the amount of virus detected in plasma. Expressing it on a log10 scale represents changes on a logarithmic rather than an ordinary additive scale; in general, this can make a wide range of concentrations easier to describe and compare. A change-from-baseline endpoint uses each participant’s starting measurement as the reference for describing the later measurement. Comparing arm-level changes can therefore address whether the measured viral-load trajectory differed across assigned regimens over the stated interval.

The record identifies the endpoint and its measurement details, but does not report the mean changes, standard deviations, participant counts contributing to each arm’s estimate, or between-arm comparisons. The endpoint definition alone does not establish the size or direction of any observed change.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the endpoint summarize?

The primary outcome is continuous: each evaluable participant contributes a measured change in HCV RNA, and the arm-level outcome is expressed as a mean. In general, a mean gives a compact description of the central value of a set of measurements. It is sensitive to all observed values, so unusually large or small changes can affect it. The standard deviation describes how spread out participant-level measurements are around the mean. It is not the same as a confidence interval: the standard deviation describes variation among outcomes, while a confidence interval describes uncertainty around an estimated quantity.

The registry record names the baseline and Week 4 time points and defines baseline as the average of screening and Day 1 pre-dose measurements. In general, using a change from baseline places the follow-up measurement in relation to a participant’s starting value. A group mean change then describes the average of those participant-level changes, if calculated that way; the exact analysis implementation is not reported in the registry record. The reported endpoint unit, log10 IU/mL, indicates that the viral RNA measurement is represented on a logarithmic scale.

Why use a logarithmic viral-load scale?

As a general statistical matter, concentrations can span a broad range, and logarithmic transformation can make multiplicative changes more manageable to analyze and communicate. Differences on a log scale represent changes in the transformed measure, not ordinary differences in the original concentration scale. The registry record specifies log10 IU/mL and the assay limit of detection of 25 IU/mL, but it does not describe how measurements below that limit, if any, were handled. No assumption about such values or their treatment in the analysis is warranted.

What does randomization contribute?

Random allocation is intended to reduce systematic differences between treatment groups at the point of assignment. In general, it supports comparisons based on assigned groups, but it does not guarantee that the groups will be identical, especially in a small study. The record states that 35 participants were enrolled, but does not report the allocation ratio or arm-specific numbers in the primary analysis. The statistical uncertainty of an arm comparison depends in part on the number of observations and their variability, neither of which can be assessed for the endpoint without its results.

How should uncertainty be assessed?

In general, an estimated difference between arms is more informative when accompanied by an uncertainty interval. The estimate describes the contrast in the observed data; the interval conveys the range of values that remain compatible with the data under the method’s assumptions. A p-value, when reported, addresses compatibility with a specified null model and is not a measure of effect size or clinical importance. The primary endpoint’s estimates, confidence intervals, and p-values are not reported in the registry record, so these aspects of the comparison cannot be evaluated.

Variation also matters. When outcomes vary considerably between participants, the mean may be estimated less precisely than when outcomes are more consistent, for a given sample size. The standard deviation is the specified dispersion measure, but its value is not reported. General concerns about skewness or unusual observations cannot be assessed without participant-level data or detailed summaries.

What do the analysis-population terms mean?

The stated Full Analysis Set includes randomized participants who received at least one dose and had both baseline and at least one valid post-baseline HCV viral-load measurement. This definition is narrower than simply counting everyone enrolled or randomized. It also does not, by itself, specify which Week 4 observations were included in a particular analysis or how missing values were handled. The record states that the value of n signifies participants evaluable for the measure at specified time points for each arm, but the arm-specific endpoint counts are not reported in the record details available.

In general, excluding participants without required measurements can affect how representative the analyzed group is of everyone randomized. The direction and size of any such effect cannot be inferred from the definition alone. The registry record does not report the number or reasons for missing measurements, an imputation method, or a sensitivity analysis.

What can planning calculations establish?

In general, a sample-size planning illustration asks how many observations might be needed under stated assumptions to detect a chosen effect with a chosen error rate and power. Such an illustration is not the study’s observed power, and it is not evidence that the original trial was designed using those assumptions. The registry record does not report a protocol sample-size justification or the trial’s own planned statistical analysis. It therefore cannot establish that the enrollment target was chosen to detect a particular effect. Any planning exercise based on an observed effect should be understood as a conditional illustration, not as a replacement for a prespecified design justification.

Finally, a dose-ranging design can make comparisons across several dose groups relevant, but interpreting a pattern requires the actual estimates and their uncertainty. Without the Week 4 results, there is no basis in the registry record for describing a dose trend, distinguishing dose groups, or judging the precision of a dose comparison.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists five outcome measures and 42 analyses. It does not explain how those analyses map to the outcome measures, which comparisons were primary or secondary, or whether a hierarchy of hypotheses was prespecified. Procedures for controlling multiplicity, such as adjusting interpretation for multiple comparisons, are not reported in the registry record. With several arms and outcomes, multiplicity can matter because examining more comparisons increases the chance of finding an apparently notable result by chance. The record does not provide enough detail to assess how that issue was addressed.

The primary endpoint population is defined as the Full Analysis Set: randomized participants who received at least one dose and had baseline and at least one valid post-baseline HCV viral-load measurement. The number meeting this definition for the Week 4 endpoint in each arm is not reported in the registry record. The outcome description also says that n represents participants evaluable at the specified time points for each arm.

The registry record does not report the amount or pattern of missing Week 4 data, reasons for missingness, or a method for handling missing measurements. It does not state whether missing values were imputed, whether participants with incomplete data were excluded from particular analyses, or whether sensitivity analyses were conducted. These omissions matter because analysis populations and missing-data methods can affect the estimates and the interpretation of uncertainty. The Full Analysis Set definition alone does not resolve those questions.

The record also does not report an intention-to-treat analysis definition, a per-protocol population, or how deviations from assigned treatment were addressed. No particular method should be assumed from the randomized design or the population label.

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: thyroiditis (12.5%), gait disturbance (12.5%), metastatic gastric cancer (12.5%), confusional state (12.5%), pulmonary embolism (12.5%).

The registry record lists serious adverse events by arm. The listed counts were 0 among 10 participants at risk in the PF-00868554 200 mg plus peginterferon alfa-2a/ribavirin group, 2 among 9 in the 300 mg group, 1 among 8 in the 500 mg group, and 2 among 8 in the placebo plus peginterferon alfa-2a/ribavirin group. These are descriptive counts; the record does not provide a statistical comparison of serious adverse events between arms.

The record also lists the following serious-event terms with their reported percentages: thyroiditis, 12.5%; gait disturbance, 12.5%; metastatic gastric cancer, 12.5%; confusional state, 12.5%; pulmonary embolism, 12.5%; and blood creatinine increased, 11.1%. The registry information available does not clarify the denominator or arm assignment for these listed percentages, so they should not be attributed to a particular regimen.

For the separate “other” adverse-event category, the record lists 10 affected among 10 at risk in the 200 mg group, 9 among 9 in the 300 mg group, 8 among 8 in the 500 mg group, and 8 among 8 in the placebo group. The record does not provide additional details about event severity or individual event patterns for this category. Deaths are not reported in the registry record. Small arm counts and missing detail limit how much can be inferred from these descriptive summaries.

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

The record documents a randomized, double-masked, parallel Phase 2 study comparing three PF-00868554 doses plus peginterferon alfa-2a and ribavirin with placebo plus those background therapies. It identifies a Week 4 change in plasma HCV RNA as the primary endpoint and describes how baseline and the Full Analysis Set were defined. These details establish the study question and the intended measurement framework.

They do not establish the primary outcome result. Arm-specific mean changes, standard deviations, participant counts for the endpoint, and comparative estimates are not reported in the registry record. Consequently, the posted information cannot show the size or direction of the Week 4 changes, whether the dose groups differed, or how precisely any difference was estimated. The study’s stated purpose is not itself evidence of an observed effect.

The record’s secondary outcome list and safety summaries provide additional descriptions of what was assessed and some reported adverse-event counts. They do not replace the missing primary efficacy results, and the safety counts are not comparative analyses. A count of events or affected participants, without uncertainty estimates and context about the event definitions and follow-up, does not establish a between-arm difference.

In general, statistical evidence needs to be read alongside the estimate, its uncertainty, the analysis population, and the methods used to address missing data and multiple comparisons. Several of those elements are not reported in the registry record. The total enrollment of 35 should not be mistaken for the number analyzed for every outcome, since the primary endpoint has additional evaluability criteria.

The available information therefore supports a careful description of design, endpoint, and recorded safety summaries, but not a conclusion about the magnitude, reliability, or clinical importance of an antiviral effect. It also does not establish the study’s sample-size justification or its prespecified inferential plan.

13. Why This Trial Matters Statistically

This trial is statistically notable as a dose-ranging comparison with three active-dose arms and a placebo arm under the same listed background therapies. That structure makes the central question broader than a single active-versus-placebo contrast: dose-specific estimates and their uncertainty would be needed to assess how outcomes varied across the assigned regimens. The design alone does not reveal whether a pattern was observed.

The primary endpoint is a continuous laboratory measure recorded as change from baseline on a log10 scale. This illustrates why endpoint definitions matter: the time point, baseline construction, assay, unit, and analysis population all shape what an estimate means. Here, baseline uses the average of screening and Day 1 pre-dose measurements, and the measure is specified as plasma HCV RNA at Week 4 using the Roche COBAS Taqman assay. The stated detection limit also provides measurement context, although handling of values below that limit is not reported in the registry record.

The analysis population is not simply all enrolled participants. The Full Analysis Set requires randomization, receipt of at least one dose, and qualifying baseline and post-baseline measurements. Knowing the number contributing to each arm’s endpoint estimate is important for interpreting precision, but those counts are not reported in the available record details. This distinction makes clear why enrollment and analysis denominators should not be treated as interchangeable.

The record also lists multiple outcomes and analyses, while leaving multiplicity procedures and detailed statistical methods unreported. That combination highlights a general reporting principle: readers need enough information to connect estimates to hypotheses and analysis populations. Without the primary outcome estimates and their uncertainty, the dose-ranging question cannot be answered quantitatively from the posted results, regardless of the design’s stated aim.

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 consequential limitation for statistical interpretation is that the registry record identifies the primary endpoint but does not report its results. There are no arm-specific mean changes, standard deviations, Week 4 participant counts, or comparative estimates in the information available. The effect and its precision therefore cannot be assessed.

The enrollment count is 35, but the primary endpoint’s Full Analysis Set has additional criteria. Arm-level counts for that endpoint are not reported, nor are the number of missing measurements and reasons for missingness. The record does not explain how missing data were handled or whether sensitivity analyses were conducted. It is therefore not possible to determine how much the analyzed population differed from everyone randomized.

The record lists five outcome measures and 42 analyses, but does not describe their relationship, specify the multiplicity strategy, or report the statistical model used for the primary outcome. It does not provide a protocol sample-size justification, details of any interim analyses, or a complete prespecified statistical plan. These items are not reported in the registry record and should not be inferred from the phase, enrollment, or study design.

The serious adverse-event information is descriptive and limited: arm-level counts are available, but the listed serious-event percentages are not linked to a specific arm in the information available. Deaths are not reported in the registry record. The registry’s “other” adverse-event counts do not provide the event-level detail needed to characterize types or patterns. These limitations call for restraint in drawing comparisons from the safety summaries.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Dose Ranging Study Of PF-00868554 In Combination With PEGASYS And COPEGUS In Patients With Chronic Hepatitis C Genotype 1 Infection — NCT00720434.
• Registry record last updated 2013-08-26; status last verified 2013-06.
• Results first posted 2013-08-26.
• 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

NCT00720434 is a completed Phase 2 randomized, double-masked, parallel study of PF-00868554 in participants with chronic hepatitis C genotype 1 infection. It enrolled 35 participants and compared PF-00868554 200 mg BID, 300 mg BID, or 500 mg BID, each with peginterferon alfa-2a and ribavirin, with placebo plus those background therapies. The record lists a start date of 2008-08 and primary completion date of 2010-03.

The primary endpoint was mean change in plasma HCV RNA from baseline to Week 4, measured in log10 IU/mL. The registry record describes the assay, baseline definition, and Full Analysis Set criteria, but does not report the primary outcome estimates or their uncertainty. It also lists secondary outcomes concerning undetectable HCV RNA, ALT levels, and population pharmacokinetics. Serious adverse-event counts are reported by arm; deaths are not reported in the registry record.