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 Randomized Placebo Controlled Efficacy And Safety Study Investigating GW876008 In Patients With Irritable Bowel Syndrome (NCT00421707), a randomized phase 2 study. The primary outcome is Number of Participants With Average Adequate Relief Rate During the Last 4 Weeks of the Treatment Periods (Weeks 3-6. in Period 1, Weeks 12-15 in Period 2)..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00421707 |
| Phase | Phase 2 |
| Condition | Irritable Bowel Syndrome (IBS) |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | Double |
| Enrollment | 133 |
| Arms in the primary outcome | n/a |
| Lead sponsor | GlaxoSmithKline |
| Results posted | Yes |
2. Clinical Question
The study asked whether GW876008, compared with placebo, was associated with adequate relief of irritable bowel syndrome symptoms during treatment periods. The planned assessment focused on participants’ reports of relief during the final four weeks of each period. However, the registry states that the question needed to assess this outcome was not collected in the IVRS system; primary endpoint data were therefore not collected.
Population
People with irritable bowel syndrome. The registry describes an intent-to-treat population comprising participants who were randomized, received at least one dose of double-blind medication, and had at least one valid post-baseline efficacy assessment. Further eligibility details are not reported in the registry record.
Intervention
GW876008. The safety record identifies a GW876008 125 mg group. The registry’s brief description characterizes the study as investigating the drug’s efficacy and safety.
Comparator
Placebo. The study is described as placebo-controlled. A placebo washout category also appears in the safety record; the details of that period and its role in the treatment sequence are not reported in the registry record.
Primary question
How many participants had an average adequate-relief response during the final four weeks of the treatment periods? The planned windows were weeks 3-6 in period 1 and weeks 12-15 in period 2. The assessment question was not collected, so the registry record contains no observed primary endpoint result with which to answer this question.
3. Trial Design
This was a phase 2, randomized, double-blind, placebo-controlled crossover study in participants with irritable bowel syndrome. The record gives enrollment as 133 and lists GlaxoSmithKline as sponsor. The study is marked completed; the recorded start date is 2006-10-14 and the primary completion date is 2008-06-25.
In a crossover design, participants receive more than one treatment over successive periods. In general, this can allow comparisons that account for stable differences between participants, because each participant may contribute observations under different treatments. Interpretation also depends on treatment order, changes over time, and whether effects from an earlier period carry into a later period. The registry confirms the crossover model but does not report the treatment sequence, the method used to handle period or carryover effects, or the washout duration. A placebo washout category appears in the safety information, but that label alone does not establish the details of the protocol.
Double masking means the study was described as double-blind, but the registry record does not specify which people were masked or how masking was maintained. Randomization is reported, while the sequence-generation and allocation-concealment methods are not reported in the registry record. The intervention list names GW876008 and placebo; the safety record gives the GW876008 dose as 125 mg.
The primary endpoint was planned for the last four weeks of each treatment period. The primary timeframe is described as up to Day 105, with weeks 3-6 in period 1 and weeks 12-15 in period 2. The registry lists secondary outcomes concerning pain, bowel function, symptom scores, drug concentrations, somatization, anxiety, and depression. It does not provide a fuller account of visit procedures or the statistical model used for the crossover design.
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.
Period 1: Treatment Period 1
| Stage | Sequence A/X/B | Sequence B/X/A |
|---|---|---|
| STARTED | 67 | 65 |
| COMPLETED | 56 | 56 |
| NOT COMPLETED | 11 | 9 |
Reasons for not completing this period:
| Reason | Sequence A/X/B | Sequence B/X/A |
|---|---|---|
| Withdrawal by Subject | 1 | 5 |
| Adverse Event | 7 | 2 |
| Lost to Follow-up | 2 | 2 |
| Protocol Violation | 1 | 0 |
Period 2: Washout
| Stage | Sequence A/X/B | Sequence B/X/A |
|---|---|---|
| STARTED | 56 | 56 |
| COMPLETED | 55 | 52 |
| NOT COMPLETED | 1 | 4 |
Reasons for not completing this period:
| Reason | Sequence A/X/B | Sequence B/X/A |
|---|---|---|
| Adverse Event | 1 | 1 |
| Withdrawal by Subject | 0 | 1 |
| Lost to Follow-up | 0 | 1 |
| Other: Pregnancy | 0 | 1 |
Period 3:Treatment Period 2
| Stage | Sequence A/X/B | Sequence B/X/A |
|---|---|---|
| STARTED | 55 | 52 |
| COMPLETED | 53 | 49 |
| NOT COMPLETED | 2 | 3 |
Reasons for not completing this period:
| Reason | Sequence A/X/B | Sequence B/X/A |
|---|---|---|
| Withdrawal by Subject | 1 | 1 |
| Protocol Violation | 1 | 0 |
| Adverse Event | 0 | 2 |
Analysis population for the primary outcome, as defined in the registry: Intent to Treat population comprised of all participants who were randomized to treatment, who received at least one dose of double blind medication and for whom at least one valid post baseline efficacy assessment was available.
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.
| Characteristic | Unit | Sequence A/X/B | Sequence B/X/A | Total |
|---|---|---|---|---|
| Participants analysed | 67 | 65 | 132 | |
| Age, Continuous | Years | 44.1 (SD 11.74) | 43.0 (SD 11.43) | 43.5 (SD 11.56) |
| Sex: Female, Male: Female | Participants | 52 | 48 | 100 |
| Sex: Female, Male: Male | Participants | 15 | 17 | 32 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 3 | 6 | 9 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 6 | 7 | 13 |
| Race (NIH/OMB): White | Participants | 58 | 52 | 110 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Average Adequate Relief Rate During the Last 4 Weeks of the Treatment Periods (Weeks 3-6. in Period 1, Weeks 12-15 in Period 2)., measured over Up to Day 105 (weeks 3-6. in period 1, weeks 12-15 in period 2).
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The planned primary endpoint concerned the number of participants with an average adequate-relief rate during the last four weeks of the treatment periods. The registry specifies weeks 3-6 in period 1 and weeks 12-15 in period 2. The planned assessment asked participants whether, during the past seven days, they had experienced adequate relief of IBS pain or discomfort.
As a general measurement principle, asking participants directly about symptom relief can capture an aspect of illness that may not be represented fully by a clinical or laboratory measure. A repeated weekly question can also describe symptom experience over a treatment window rather than relying on a single moment. The registry does not report the precise rule for turning weekly answers into an “average adequate relief rate,” such as how many positive responses would qualify a participant for the endpoint. That operational detail should not be inferred from the endpoint title alone.
Most importantly, the registry says the question was not collected in the IVRS system because of an error. It explicitly states that data for this endpoint were not collected during the study. Thus, the endpoint explains what the investigators planned to assess, but it cannot provide an observed estimate of adequate relief or a treatment comparison in this record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central interpretive fact is that the planned primary endpoint has no collected data in the registry record. The record explains that the question intended to measure adequate relief of IBS pain or discomfort was omitted from the IVRS system in error. Consequently, there is no posted primary endpoint estimate, uncertainty interval, or treatment comparison to interpret. The planned outcome should not be mistaken for a result.
The registry lists 13 outcome measures and 0 analyses. It gives names of secondary outcomes, including pain and discomfort, pain severity, pain-free days, bowel function, an IBS composite symptom score, plasma concentrations, somatization, anxiety, and depression. However, outcome results for these measures are not reported in the registry record. Their presence as named measures does not establish that they were analyzed or that they favored either treatment.
Randomization and double masking describe design features intended to support a fair comparison and reduce some forms of bias. They do not replace outcome data. The crossover structure also means that a complete treatment comparison would need to account for the fact that treatment periods occur within participants. In general, period effects and possible carryover can matter in crossover analyses. The registry record does not report the model or other methods used to address these issues, and the missing primary outcome prevents assessment of the planned primary comparison regardless.
The safety record reports serious adverse events for the listed treatment categories, other adverse events, and deaths. These counts are descriptive entries, not estimates of efficacy. The categories include GW876008 125 mg, placebo, and placebo washout. Because the design is crossover, categories may correspond to exposure periods rather than separate, independent participant groups; the record does not establish that they represent unique people. The category counts should therefore not be added together to infer a total number of people or events across the study.
Any statement about whether GW876008 changed symptom relief, pain, bowel function, or another clinical outcome would go beyond the posted results. The registry supports a description of the planned study and its missing primary endpoint, but not a conclusion about the comparative efficacy of the treatments.
9. Statistical Methods Explained
The registry identifies the study as randomized, double-blind, and crossover, but it does not report a full statistical analysis plan. The explanations below describe general statistical concepts; they are not claims about methods used in this trial unless the registry explicitly says so.
What does randomization contribute?
In general, randomization assigns treatment according to a chance-based process. Its purpose is to reduce systematic differences between treatment groups at the point of assignment. It does not guarantee identical groups, and it cannot prevent problems that arise after assignment, such as missing outcomes or deviations from planned measurement. The registry reports randomization but does not describe how the sequence was generated, how assignments were concealed, or how any departures from assigned treatment were handled.
What does a crossover design change?
In general, a crossover study gives participants different treatments in successive periods. A comparison can then use observations from the same participant under different treatments, which may reduce the influence of stable differences between people. This design also creates questions about treatment order, changes over time, and carryover: an earlier treatment could affect measurements in a later period. Appropriate analysis usually needs to reflect the repeated, within-participant structure rather than treat every period as an unrelated observation. The registry record does not report the crossover analysis model, the treatment sequence, or the method for assessing or addressing period and carryover effects.
The safety record includes a placebo washout category. Washout periods are used in some crossover designs to allow effects from one period to diminish before another begins. That is a general purpose, not confirmation of the details of this study. The duration and procedures for any washout are not reported in the registry record.
Why does the missing primary outcome matter?
The primary outcome was intended to measure participants’ adequate relief of IBS pain or discomfort during specified treatment windows. The registry says the question was not collected in the IVRS system because of an error and that primary endpoint data were not collected. This is different from an endpoint that was collected but had some unanswered items. Without the planned responses, a treatment effect for this endpoint cannot be estimated from the registry record.
In general, an estimate describes the observed contrast between treatments, while a confidence interval describes the range of values compatible with the data and the statistical method used. Neither can be recovered when the underlying endpoint observations were not collected. The record does not report a primary endpoint estimate, confidence interval, or p-value.
What can be concluded from the listed outcomes?
The registry names secondary outcomes, but names alone are not results. It lists 13 outcome measures and 0 analyses. Results for the listed secondary measures are not reported in the registry record. It is therefore not possible to assess their estimated treatment differences, precision, or consistency with the intended primary question.
When a study evaluates multiple outcomes, the chance of at least one apparently unusual result can increase if each is tested separately without an appropriate plan. General approaches to multiplicity include prioritizing a primary outcome, adjusting significance thresholds, or interpreting secondary findings as exploratory. The registry record does not report whether any multiplicity procedure was planned or used. Since the primary outcome was not collected and no analyses are listed, no claim about multiplicity-adjusted evidence can be made.
How should planning calculations be read?
General sample-size illustrations describe how many participants might be needed under stated assumptions; they do not show the number of participants who actually had an outcome, and they are not observed power. The registry’s planning assumptions specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The stated effect to detect is a fraction of the observed effect. Such illustrations depend on their assumptions and should not be confused with the study’s original design justification. The original sample-size justification and statistical plan are not reported in the registry record.
In a crossover setting, planning for a comparison may also depend on within-participant variability and correlation between repeated measurements. These are general considerations; the relevant values and the method used for the trial’s original planning are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry identifies a primary outcome and lists secondary outcomes, but it does not report a multiplicity strategy. In general, testing multiple outcomes can increase the chance of finding an apparently notable result by chance if the analyses are treated as independent opportunities for confirmation. A prespecified hierarchy, adjustment procedure, or clear distinction between confirmatory and exploratory outcomes can help readers interpret such findings. Whether any of these approaches was planned or used is not reported in the registry record.
For the primary outcome, the issue is not merely incomplete responses: the registry states that the intended IVRS question was not collected because of an error and that data for this endpoint were not collected during the study. The primary endpoint therefore has no reported result in this record. Results for the named secondary outcomes are also not reported in the registry record. The registry lists 13 outcome measures and 0 analyses.
The stated intent-to-treat population comprises participants who were randomized, received at least one dose of double-blind medication, and had at least one valid post-baseline efficacy assessment. This definition is narrower than a population that includes every randomized participant regardless of post-baseline measurement. The record does not report how many participants met this definition or provide results by analysis population. It also does not report the handling of missing secondary outcome data, withdrawals, protocol deviations, or sensitivity analyses.
In general, missing-data methods rely on assumptions about why measurements are absent and how missingness relates to observed or unobserved outcomes. No such method or assumption is reported for this study. Because the primary question itself was not collected, statistical adjustment cannot supply the missing responses or establish the treatment contrast for that endpoint.
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 |
|---|---|---|---|
| GW876008 125 mg | 0 | 119 | 0.0% |
| Placebo | 1 | 120 | 0.8% |
| Placebo Washout | 0 | 112 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| GW876008 125 mg | 0 of 119 |
| Placebo | 0 of 120 |
| Placebo Washout | 0 of 112 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| GW876008 125 mg | 9 of 119 |
| Placebo | 5 of 120 |
| Placebo Washout | 2 of 112 |
Most frequent serious adverse event terms
| Event term | Organ system | GW876008 125 mg | Placebo | Placebo Washout |
|---|---|---|---|---|
| Chondrosarcoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 0 of 119 | 1 of 120 | 0 of 112 |
Most frequent non-serious adverse event terms
| Event term | Organ system | GW876008 125 mg | Placebo | Placebo Washout |
|---|---|---|---|---|
| Nasopharyngitis | Infections and infestations | 9 of 119 | 5 of 120 | 2 of 112 |
Serious events with the highest arm-level rate: chondrosarcoma (0.8%).
The registry lists serious adverse events, other adverse events, and deaths by safety category. For GW876008 125 mg, the serious adverse event count is 0, the other adverse event count is 9, and deaths are 0; the recorded at-risk count is 119. For placebo, the corresponding figures are 1, 5, and 0, with an at-risk count of 120. For placebo washout, they are 0, 2, and 0, with an at-risk count of 112.
These are descriptive counts within the listed categories. In a crossover study, a person can contribute exposure to more than one treatment period, so the categories should not automatically be read as independent groups of different people. The record does not specify whether the adverse-event counts represent participants, event episodes, or a particular event-coding convention beyond the labels shown. They should not be added across categories to infer a study-wide count of distinct participants.
The registry also lists Chondrosarcoma at 0.8% among the top serious terms. The record does not establish a causal relationship between that term and a treatment. The counts alone do not determine comparative risk, and the absence of a listed death in a category is not evidence that other safety outcomes were absent.
12. What the Result Does, and Does Not, Mean
This record establishes that a phase 2 randomized, double-blind, placebo-controlled crossover study of GW876008 in people with irritable bowel syndrome was completed. It identifies the intended primary question: whether participants reported adequate relief of IBS pain or discomfort during the final four weeks of each treatment period. It also documents that the question needed for this endpoint was not collected in the IVRS system because of an error.
What the record does not establish is whether GW876008 improved adequate relief relative to placebo. There are no collected primary endpoint data in the registry record, so there is no posted estimate or measure of precision for that comparison. The named secondary outcomes likewise have no results reported in the registry record. The study’s design features cannot substitute for those missing observations.
The safety entries provide counts for serious adverse events, other adverse events, and deaths across the listed categories. They are useful as a description of what the registry reports, but they do not by themselves establish whether one treatment has a different safety profile from another. The crossover structure, category definitions, and lack of reported statistical comparisons all matter when interpreting those counts.
In general, a completed trial can still have unanswered questions when a planned outcome was not collected or when results are not reported. The record does not provide a basis for deciding whether the uncollected endpoint would have agreed with, differed from, or added to the secondary outcomes. It also does not report a complete statistical plan, a rationale for the enrollment target, or analyses that could resolve those uncertainties.
The careful conclusion is limited: the registry documents the design, planned symptom-relief measure, its failure of collection, and descriptive safety counts. It does not provide the evidence needed to quantify the treatment effect on the primary endpoint or to draw a comparative efficacy conclusion.
13. Why This Trial Matters Statistically
This trial illustrates an important distinction between a planned outcome and an observed result. The primary endpoint was designed to capture participants’ reports of adequate relief, but the registry states that the question was not collected in the IVRS system. Without those responses, the primary treatment contrast cannot be estimated from the registry record. The endpoint’s clinical relevance does not compensate for the absence of its measurements.
The crossover design also makes the analysis structure consequential. In general, repeated treatment periods within the same participant can support efficient comparisons, but valid interpretation depends on accounting for within-person measurements, treatment sequence, time effects, and possible carryover. The registry identifies the design but does not report the corresponding analysis methods. That gap limits assessment of how a completed comparison would have been estimated, even if outcome data were available.
The record further shows why outcome labels should not be mistaken for evidence. It names measures spanning pain, bowel function, symptom burden, and psychological scales, but reports 0 analyses and no outcome results. A long list of planned measurements does not reveal which findings were observed, how precise they were, or whether they support the primary hypothesis.
Finally, the safety categories illustrate the need to interpret exposure-group counts carefully in a crossover study. They describe the registry’s entries but do not necessarily represent separate participant groups. Together, the missing primary outcome, absent secondary results, and limited reporting of analysis methods make this record more informative about study conduct and reporting limitations than about comparative treatment effects.
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 trial-specific limitation in the registry record is that the planned primary outcome was not collected. The registry attributes this to an error in the IVRS system and states that data for the endpoint were not collected during the study. This prevents an estimate of the primary treatment comparison, rather than merely making that estimate less precise.
The registry names 13 outcome measures but lists 0 analyses; results for the secondary outcomes are not reported in the registry record. Therefore, the record cannot show whether other symptom measures were available, how they were analyzed, or whether their findings were consistent with the planned primary question.
Important design and analysis details are also not reported in the registry record. These include the treatment sequence, washout duration, randomization and allocation procedures, the statistical model for the crossover structure, handling of period or carryover effects, missing-data methods, multiplicity procedures, and sensitivity analyses. The registry’s description of an intent-to-treat population gives eligibility conditions for that population but does not report how many participants met them or provide results for it.
The safety categories should be interpreted cautiously because the crossover structure may allow participants to appear in more than one exposure category. The registry does not explain whether the adverse-event entries count participants or event episodes, and the category totals should not be combined to infer unique participant counts. Finally, the original sample-size justification is not reported in the registry record. The stated planning assumptions do not establish what assumptions governed the trial’s original design.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Randomized Placebo Controlled Efficacy And Safety Study Investigating GW876008 In Patients With Irritable Bowel Syndrome — NCT00421707.
- Registry record last updated 2018-01-31; status last verified 2017-11.
- Results first posted 2017-12-26.
- 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.
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18. Record Summary
NCT00421707 is a completed phase 2 randomized, double-blind, placebo-controlled crossover study sponsored by GlaxoSmithKline. It enrolled 133 participants with irritable bowel syndrome. The recorded study start date is 2006-10-14, and the primary completion date is 2008-06-25.
The planned primary endpoint was the number of participants with an average adequate-relief rate during the last four weeks of the treatment periods. The registry states that the required IVRS question was not collected because of an error, so primary endpoint data were not collected. The registry lists 13 outcome measures and 0 analyses; results for secondary outcomes are not reported in the registry record.
Safety entries are reported for GW876008 125 mg, placebo, and placebo washout. They include serious adverse events, other adverse events, and deaths, but do not establish comparative treatment effects. The record does not report a full statistical analysis plan or the methods used to account for the crossover structure.