Telbivudine in Adults Previously Treated in Idenix-Sponsored Telbivudine Studies: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Telbivudine in Adults Previously Treated in Idenix-Sponsored Telbivudine Studies (NCT00142298), a na phase 3 study. The primary outcome is Percentage of Participants Who Maintained Therapeutic Response [Group A: Feeder Studies 2401/2402/010].

2. Clinical Question

This question concerns maintenance of a combined response definition during longer-term telbivudine treatment in people already treated with telbivudine in feeder studies. It is not a question about starting treatment in an untreated population, nor does the single-group design estimate a contrast against an untreated or alternative-treatment group. The primary outcome title specifies Group A participants from feeder studies 2401, 2402, and 010. The registry separately describes efficacy assessment for HBeAg-positive and HBeAg-negative participants, and defines the primary analysis population as per protocol. The number eligible for the response analysis was intended to be represented by the relevant subgroup denominator, but the subgroup counts and response values are not reported in the registry record. Secondary aims include longitudinal assessment of longer-term antiviral and clinical efficacy, durability of HBeAg responses, and virologic breakthrough with characterization of associated mutations. Those aims provide context for the extended-term follow-up, but numerical findings for them are not reported in the registry record.

3. Trial Design

This was a phase 3, open-label, single-group trial of telbivudine in adults with chronic hepatitis B who had previously completed an Idenix-sponsored telbivudine study. The registry lists enrollment as 1869 and the status as completed. Novartis Pharmaceuticals is listed as the sponsor. The study started in 2005-03, and primary completion is recorded as 2009-11.

Participants received telbivudine 600 mg p.o. daily for 104 weeks. Masking was none, and allocation is listed as not applicable. The design therefore describes an extended treatment cohort rather than a randomized, blinded comparison of telbivudine with a concurrent control. The feeder studies are relevant to participants’ prior treatment history and to the named efficacy population; they should not be mistaken for concurrent control groups in this trial.

The primary endpoint is a percentage of participants maintaining therapeutic response at 52 weeks and 104 weeks. The registry defines the per-protocol population for this analysis and specifies separate assessment for HBeAg-positive and HBeAg-negative subpopulations, according to status at feeder baseline. The registry lists 11 outcome measures, while the number of posted analysis entries is 0. The record does not provide a detailed statistical analysis plan, a sample-size justification, or information about interim analyses; those details are not reported in the registry record.

The study’s secondary aims concern longer-term antiviral and clinical efficacy, durability of HBeAg responses, and the frequency and characterization of virologic breakthrough. They describe intended areas of assessment, not results. As no concurrent comparator was assigned, estimates from this design can describe outcomes in the enrolled study population, but cannot by themselves separate treatment effects from other explanations for change over time.

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.

Only the first 6 of 10 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Per protocol (PP) population. The PP analysis was done on separately for the HBeAg-positive and HBeAg-negative subpopulation (status at feeder baseline). n = the number of HBeAg-positive/HBeAg-negative patients who were eligible for maintained therapeutic response.

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.

Only the first 6 of 11 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants Who Maintained Therapeutic Response [Group A: Feeder Studies 2401/2402/010], measured over 52 weeks, 104 weeks.

The primary endpoint is the percentage of eligible Group A participants from feeder studies 2401, 2402, and 010 who maintained a therapeutic response. Assessment was specified at 52 weeks and 104 weeks. A response required HBV DNA below 5 log10 copies/mL together with either HBeAg loss or ALT normalization. HBeAg loss means loss of detectable serum HBeAg among participants who were HBeAg-positive at feeder baseline. ALT normalization means ALT within normal limits for participants whose ALT was elevated above 1.0 × ULN at feeder baseline or feeder screening.

This definition combines a virologic criterion with one of two additional markers: a serologic response for eligible HBeAg-positive participants or a biochemical response for participants meeting the ALT eligibility description. As a general statistical point, a composite definition can represent more than one aspect of a clinical response in a single endpoint, but its meaning depends on every component and on the population eligible for each component. The registry specifies separate efficacy assessment by HBeAg status, which matters because the HBeAg-loss component applies to participants who were positive at feeder baseline.

The registry lists the endpoint as a number and gives a 95% confidence interval as its dispersion measure. The actual percentages, denominators, and confidence limits are not reported in the registry record. The registry does not state why this endpoint was selected beyond defining it as the primary outcome.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary participant-level classification: a participant either meets the maintained-response definition at an assessment time or does not. For such an outcome, a percentage describes the share of eligible participants classified as responders. The denominator matters as much as the percentage, especially when eligibility differs between HBeAg-positive and HBeAg-negative subgroups. The registry defines the analysis population as per protocol and says efficacy data were assessed separately by HBeAg status at feeder baseline. The actual subgroup denominators and response counts are not reported in the registry record.

What does the confidence interval convey?

The endpoint’s stated dispersion measure is a 95% confidence interval. In general, a confidence interval gives a range of values compatible with the data under a particular statistical method, and it expresses uncertainty around an estimate. A narrower interval indicates greater precision under that method; a wider interval indicates less precision. The registry does not report the interval limits or state which calculation method was used. It is therefore not possible to assess the observed precision, or to evaluate whether the method accounts for the subgroup structure and any missing endpoint observations.

How should the per-protocol population be understood?

The registry says the per-protocol analysis was conducted in the per-protocol population, separately for HBeAg-positive and HBeAg-negative participants. It describes the endpoint denominator as the number of participants eligible for maintained therapeutic response. A per-protocol analysis generally focuses on participants meeting specified study criteria, rather than necessarily including everyone enrolled; the particular eligibility and exclusion rules beyond the endpoint description are not reported in the registry record. Therefore, overall enrollment of 1869 should not be treated as the endpoint denominator. The record does not give the number of participants in each analysis group, the number excluded from the per-protocol population, or the reasons for exclusion.

What can a single-group design estimate?

In general, a single-group study can describe the observed outcome in the participants followed under its treatment regimen. It does not provide a concurrent randomized comparison that would estimate how outcomes differed under another assigned treatment. This is important for interpretation: a percentage meeting the response definition is descriptive of the analyzed cohort, not a randomized estimate of a treatment effect. The trial was open label and masking was none, according to the registry. The effect, if any, of open-label assessment on outcome measurement is not quantified in the record.

What do the planning assumptions mean?

The sample-size planning assumptions describe an illustration based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The planning effect is described as a stated fraction of the observed effect. These assumptions do not describe this trial’s single-group design, and they do not establish that the trial enrolled a particular number to achieve a specified power. Such planning figures are illustrations, not observed power. The numerical planning estimates and the fractions used are not reported in the registry record. A trial-specific sample-size justification is also not reported in the registry record.

What remains unknown about the statistical analysis?

The registry identifies the primary endpoint, its time points, and the use of 95% confidence intervals, but does not report the calculation method, a full prespecified statistical plan, adjustment for covariates, or rules for repeated measurements. It also does not report interim analyses. The registry lists 11 outcome measures and no analysis entries. That absence means the record does not provide posted analysis details; it should not be read as evidence that no analyses were conducted outside the registry. The record does not state whether estimates were adjusted for multiplicity or how multiplicity across time points, subgroups, and outcomes was addressed.

For binary outcomes, general statistical considerations include the number eligible, the number meeting the definition, and the way uncertainty is calculated. If observations are clustered or otherwise dependent, standard methods that assume independent observations may not represent uncertainty well; the registry does not describe such a structure or any adjustment for it. Over-dispersion is a general concern when observed variability exceeds what a chosen model assumes, but the registry does not identify a model for the endpoint or report an assessment of over-dispersion. No specific modeling conclusion can therefore be drawn.

The endpoint has multiple components and is assessed at two specified times. General interpretation should keep the compound definition, eligibility criteria, time point, denominator, and uncertainty together. Without numerical results and the detailed analysis plan, the registry record supports description of the intended statistical summary, not reconstruction or independent verification of the analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry describes a primary endpoint at 52 weeks and 104 weeks, separate efficacy assessment for HBeAg-positive and HBeAg-negative participants, and 11 outcome measures overall. It does not report whether statistical testing was planned for the primary endpoint, whether comparisons across time points or subgroups were adjusted for multiplicity, or how secondary outcomes were incorporated into an overall testing strategy. Multiplicity handling is not reported in the registry record. The record also does not describe interim analyses or stopping rules.

The primary analysis is described as per protocol, with the eligible response denominator considered separately by HBeAg status. The record does not provide an intention-to-treat analysis, a comparison between analysis populations, or participant counts by subgroup. The specific criteria for inclusion in the per-protocol population, beyond the stated endpoint eligibility, are not reported in the registry record.

Missing-data procedures are not described. In particular, the record does not state how unavailable HBV DNA, HBeAg, or ALT measurements were handled, whether participants with missing follow-up were counted as nonresponders, or whether any imputation or sensitivity analysis was used. These decisions can affect both the endpoint estimate and its uncertainty, so the reported analysis population and missing-data approach would be needed for a fuller assessment.

The registry lists 11 outcome measures and no analysis entries. That means analysis details are not posted in the registry record; it does not establish that no analyses were undertaken. The record does not report a prespecified statistical analysis plan, sample-size justification, or multiplicity procedure. These omissions limit assessment of how the reported endpoint, if available elsewhere, relates to all planned outcomes and analyses.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hepatic neoplasm malignant (30.8%), lower limb fracture (7.7%), proteinuria (7.7%), myocardial infarction (4.3%), abdominal pain (4.3%).

The registry’s serious-adverse-event listing presents feeder-study or pooled categories, with counts at risk and counts affected. For Group A LdT Pool 2302/015, 45 participants are listed as affected among 655 at risk; the corresponding LAM Pool 2302/015 category lists 21 affected among 626 at risk. Other categories include Group A Feeder Study 010, Feeder 2401, and Feeder 2402, as well as Group B and Group C categories. Their denominators differ, and the categories reflect different feeder-study groupings. They should not be treated as randomized arms or compared as if they were like-for-like populations.

The listing also reports other adverse events, but these figures do not replace the serious-event counts and should be interpreted as a separate listing. The record names hepatic neoplasm malignant at 30.8% among the listed serious-event terms, followed by lower limb fracture and proteinuria at 7.7% each, and myocardial infarction, abdominal pain, and oesophageal haemorrhage at 4.3% each. The denominator and calculation basis for these term percentages are not specified in the information reported. Death counts are not reported in the registry record.

These listings are descriptive. They do not by themselves establish that telbivudine caused an event or support a comparative safety conclusion.

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

The registry record gives a defined primary outcome for longer-term telbivudine follow-up among adults who had previously completed an Idenix-sponsored telbivudine study. It specifies treatment as 600 mg p.o. daily for 104 weeks and describes a response measured at 52 weeks and 104 weeks. The definition links HBV DNA below 5 log10 copies/mL with either HBeAg loss or ALT normalization, using eligibility criteria tied to feeder baseline or screening measurements.

However, the primary endpoint percentages, eligible participant counts, and confidence limits are not reported in the registry record. The registry therefore does not provide the numerical efficacy information needed to describe how many eligible participants met the definition or how precisely an estimate was measured. Overall enrollment of 1869 does not resolve this, because it is not the stated endpoint denominator.

Even with numerical outcome values, this single-group, open-label design would describe outcomes in the enrolled cohort rather than establish a randomized comparison with another treatment or with no treatment. Participants entered after prior telbivudine studies, so findings would pertain to that previously treated population and study context. The separate HBeAg-status analyses and the endpoint’s alternative response components also matter when interpreting any overall percentage.

The safety listings provide counts in several feeder-study and pooled categories, but their differing denominators do not create a controlled comparison. The serious-event term percentages are listed without a stated calculation basis in the record. Neither the efficacy description nor the safety listings, as reported, establish causal treatment effects. They describe the intended outcome framework and the posted adverse-event categories, while leaving important numerical and analytic details unavailable.

13. Why This Trial Matters Statistically

This trial is statistically notable for the distinction between an extended-term cohort and a conventional randomized comparison. The registry identifies a single-group, open-label study of adults already treated with telbivudine in feeder studies. That design can frame questions about whether a defined response is maintained over time in this selected population, but it does not supply a concurrent control for attributing changes to treatment.

The endpoint also illustrates why a percentage needs its denominator and definition. Eligibility for maintained response depended on feeder-baseline HBeAg status and ALT history, and the registry specifies separate efficacy assessment by HBeAg status. The response itself required a virologic threshold together with either HBeAg loss or ALT normalization. Without subgroup counts, response counts, and confidence limits, the endpoint cannot be quantitatively evaluated from the registry record.

The listed safety categories similarly demonstrate why group labels and denominators matter. Feeder-study and pooled categories are not equivalent to randomized arms, and the record does not provide a common comparison that supports causal contrasts. Its 11 outcome measures, with no posted analysis entries, also underscore the difference between listing intended outcomes and reporting an analysis plan or estimates.

For biostatisticians and clinical researchers, the entry highlights the importance of transparent reporting of analysis populations, missing-data procedures, endpoint denominators, uncertainty methods, and multiplicity handling. Those details are not reported in the registry record. The study’s design and outcome definitions can be described, but the available record does not support a numerical assessment of primary efficacy or an inferential treatment comparison.

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.

Several limitations follow directly from the registry description. The study is single group, open label, and has no concurrent comparator. It therefore cannot provide a randomized estimate of a treatment contrast. Its participants had previously completed Idenix-sponsored telbivudine studies, limiting the population described to people with that treatment history rather than a general chronic hepatitis B population.

The primary outcome is restricted to Group A feeder studies 2401, 2402, and 010, and the analysis is per protocol with separate HBeAg-positive and HBeAg-negative subpopulations. The record does not report the numbers eligible in these groups, the number meeting the endpoint, or the numerical estimates and 95% confidence intervals. The total enrollment of 1869 should not be substituted for these missing analysis denominators.

The response definition relies on several measurements and eligibility criteria, but the record does not specify how missing measurements were handled, how participants lost to follow-up were treated, or what sensitivity analyses were performed. It also does not give detailed per-protocol criteria. The methods used to calculate confidence intervals and any adjustments across outcomes, subgroups, or assessment times are not reported in the registry record.

Safety categories draw on different feeder-study or pooled groups, with differing numbers at risk. Their structure does not permit a like-for-like comparison. The basis for the listed serious-event term percentages, and death counts, are not reported in the registry record. Together, these gaps constrain both quantitative interpretation and assessment of the analysis process.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Telbivudine in Adults Previously Treated in Idenix-Sponsored Telbivudine Studies — NCT00142298.
• Registry record last updated 2020-08-21; status last verified 2020-08.
• Results first posted 2011-07-25.
• 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

NCT00142298 is a completed phase 3, open-label, single-group study sponsored by Novartis Pharmaceuticals. It enrolled 1869 adults with chronic hepatitis B who had previously completed an Idenix-sponsored telbivudine study. Participants received telbivudine 600 mg p.o. daily for 104 weeks.

The primary endpoint was the percentage of eligible Group A participants from feeder studies 2401, 2402, and 010 maintaining therapeutic response at 52 weeks and 104 weeks. Response required HBV DNA below 5 log10 copies/mL and either HBeAg loss or ALT normalization. The analysis population was per protocol, with separate assessment by HBeAg status at feeder baseline.

Numerical primary endpoint results, subgroup denominators, confidence limits, detailed statistical methods, missing-data procedures, and multiplicity handling are not reported in the registry record. Safety listings include feeder-study and pooled categories that are descriptive rather than randomized comparisons.