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 A Safety and Efficacy Study of Xyrem® in Subjects With Fibromyalgia (NCT00371137), a randomized phase 3 study. The primary outcome is Pain VAS (Visual Analog Scale) Response. Percentage of Subjects With a Greater Than or Equal to 30% Reduction in Pain VAS From Baseline (BOCF)..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00371137 |
| Phase | Phase 3 |
| Condition | Fibromyalgia |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 548 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Jazz Pharmaceuticals |
| Results posted | Yes |
2. Clinical Question
Population
People with fibromyalgia. The registry record describes the trial population as subjects with fibromyalgia, but does not report further eligibility details or a demographic profile in the record.
Intervention
Xyrem®. The safety results distinguish Xyrem 4.5g and Xyrem 6.0g groups. The registry record does not give further dosing or treatment-duration details in the record.
Comparator
Placebo. The trial is described as placebo-controlled. The safety results include a placebo group.
Primary question
What percentage of participants met the pain VAS response definition from baseline to Week 14, with response defined as at least a 30% reduction and missing observations handled using baseline observation carried forward? The registry record does not report a single efficacy comparison or the response percentages needed to answer that question numerically.
This is a question about the proportion of participants crossing a prespecified response threshold, rather than the average change in pain score. It asks whether participants achieved a reduction large enough to count as a response under the registry definition. It does not, by itself, describe the distribution of changes among all participants, the size of improvement for responders, or the experience of participants who did not meet the threshold.
The trial objective was to evaluate safety and efficacy of Xyrem® compared with placebo in fibromyalgia. The registry record identifies a randomized, double-blind, placebo-controlled, parallel-group design. Its primary endpoint specifies a baseline-to-Week 14 assessment. However, the posted record does not give a clear single contrast, arm-level responder percentages, an effect estimate, or uncertainty around an efficacy estimate. The clinical question can therefore be described, but its numerical answer is not reported in the registry record.
3. Trial Design
The registry identifies this as a Phase III, randomized, double-blind, placebo-controlled, parallel-group trial in people with fibromyalgia. Its stated objective was to evaluate the safety and efficacy of Xyrem® compared with placebo. The record lists 548 participants enrolled and gives the study status as completed. The study start is recorded as 2006-08, and primary completion as 2008-09.
The registry lists Xyrem® and placebo as interventions. The safety results distinguish three groups: placebo, Xyrem 4.5g, and Xyrem 6.0g. The record does not include arm descriptions that explain allocation, dose assignment, or how the groups relate to the trial's overall intervention description. The randomized allocation ratio is not reported in the registry record.
Masking is recorded as quadruple. This describes the registry's masking classification, but the record does not identify which roles were masked or provide operational details about how masking was maintained. General explanation: masking is intended to limit the influence of treatment knowledge on participant experience, study conduct, or outcome assessment. The degree to which it achieves that aim depends on implementation, which is not described in the registry record.
The primary outcome is a percentage of participants meeting a pain VAS response definition from baseline to Week 14. The record specifies that missing data were handled using baseline observation carried forward. It does not report a detailed statistical analysis plan, sample-size justification, allocation procedure, or analysis population. These omissions prevent a full reconstruction of the planned design and analysis from the registry entry alone.
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 | Placebo | Xyrem 4.5g | Xyrem 6.0g |
|---|---|---|---|
| STARTED | 183 | 182 | 183 |
| Treated | 183 | 182 | 182 |
| COMPLETED | 111 | 119 | 104 |
| NOT COMPLETED | 72 | 63 | 79 |
Reasons for not completing this period:
| Reason | Placebo | Xyrem 4.5g | Xyrem 6.0g |
|---|---|---|---|
| Adverse Event | 20 | 35 | 42 |
| Withdrawal by Subject | 11 | 10 | 15 |
| Lost to Follow-up | 6 | 3 | 5 |
| Lack of Efficacy | 30 | 12 | 13 |
| Sponsor Decision | 2 | 1 | 2 |
| Physician Decision | 1 | 1 | 1 |
| Protocol Violation | 2 | 1 | 1 |
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 | Placebo | Xyrem 4.5g | Xyrem 6.0g | Total |
|---|---|---|---|---|---|
| Participants analysed | 183 | 182 | 183 | 548 | |
| Age Continuous | years | 46.5 (SD 11.43) | 47.0 (SD 11.76) | 47.5 (SD 10.61) | 47.0 (SD 11.26) |
| Age, Customized: 18 - 39 years | participants | 40 | 57 | 40 | 137 |
| Age, Customized: 40 - 49 years | participants | 70 | 47 | 57 | 174 |
| Age, Customized: 50 - 64 years | participants | 64 | 69 | 78 | 211 |
| Age, Customized: >=65 years | participants | 9 | 9 | 8 | 26 |
| Sex: Female, Male: Female | Participants | 167 | 166 | 167 | 500 |
| Sex: Female, Male: Male | Participants | 16 | 16 | 16 | 48 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 2 | 2 | 2 | 6 |
| Race (NIH/OMB): Asian | Participants | 3 | 2 | 2 | 7 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 8 | 13 | 12 | 33 |
| Race (NIH/OMB): White | Participants | 167 | 164 | 167 | 498 |
| Race (NIH/OMB): More than one race | Participants | 3 | 0 | 0 | 3 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 1 | 0 | 1 |
| Region of Enrollment: United States | participants | 183 | 182 | 183 | 548 |
6. Primary Endpoint
The registry lists the primary outcome as Pain VAS (Visual Analog Scale) Response. Percentage of Subjects With a Greater Than or Equal to 30% Reduction in Pain VAS From Baseline (BOCF)., measured over Baseline to Week 14.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Percentage of Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the percentage of participants classified as pain VAS responders from baseline to Week 14. A participant counts as a responder when pain VAS has fallen by at least 30% from baseline to endpoint; all other participants count as non-responders. The pain VAS ranges from 0, meaning no pain, to 100, meaning worst imaginable pain. The measure was collected in the morning, afternoon, and evening.
Baseline is defined as the average value recorded during the week before the end-of-baseline visit. Endpoint is the average value recorded during the week before Week 14. Missing data were handled using baseline observation carried forward, abbreviated BOCF in the registry description. In general, this method uses a participant's baseline observation in place of a missing later observation.
A responder endpoint is used to express how many participants meet a defined threshold, rather than only reporting an average score change. It can be readily interpreted as a proportion meeting the trial's criterion, but it discards information about the amount of change within each category. Participants just short of the threshold and participants with little change are both classified as non-responders. Conversely, participants who cross the threshold are counted together despite potentially different changes.
The registry record does not report the arm-level responder percentages or a single treatment contrast. The endpoint definition is therefore available, but the numerical result and its precision are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record states the primary pain VAS response definition and assessment period, but it does not provide a single numerical comparison that can be interpreted as the primary efficacy result. It reports three analyses, while the endpoint information is described as having several categories or time points and not being reduced to one comparison. Arm-level responder percentages, an effect estimate, and a confidence interval are not reported in the registry record. As a result, the magnitude and precision of an efficacy contrast cannot be evaluated from the posted information.
This absence is important for interpreting a binary endpoint. A response percentage in each group would show how often participants met the threshold. A difference or ratio between groups could then quantify the contrast, and an interval estimate could show how uncertain that contrast is. None of those numerical efficacy results is reported in the registry record. The trial's stated objective and endpoint definition do not substitute for outcome estimates.
The endpoint defines response as a reduction of at least 30% on the pain VAS from baseline to Week 14. The registry describes BOCF for missing observations, but does not report the number of missing endpoint observations or how many participants were classified as responders under this rule. Without those details, the influence of missingness on the reported analysis cannot be assessed.
The safety information does contain group counts. Serious adverse events affected 1 of 183 participants in the placebo group, 0 of 182 in the Xyrem 4.5g group, and 2 of 182 in the Xyrem 6.0g group. Other adverse events affected 105 of 183, 149 of 182, and 145 of 182 participants, respectively. These are descriptive counts, not a complete assessment of comparative safety. The registry does not report deaths for these groups; a blank death value should not be read as confirmation that no deaths occurred.
Overall, the posted record allows a reader to identify the trial design, endpoint definition, and selected safety counts. It does not report enough efficacy statistics to determine the observed pain-response contrast or how precisely it was estimated. The numerical findings should therefore be interpreted only within the limits of what the registry record reports, without inferring efficacy from the trial objective or from the endpoint definition alone.
9. Statistical Methods Explained
General explanation: a binary endpoint assigns each participant to one of two categories, such as responder or non-responder. The primary endpoint in this trial is expressed as a percentage of participants who meet the responder definition. That percentage depends both on the threshold chosen and on how missing observations are classified. The registry defines response as at least a 30% reduction in pain VAS from baseline to Week 14.
What does the response threshold capture?
The endpoint converts a score measured on a scale into a yes-or-no outcome. This can make a result easier to describe as the fraction of participants reaching a stated target. It also loses detail: the binary classification does not preserve the exact size of each participant's change. Someone who narrowly misses the threshold is counted with someone whose score changes very little, while responders are grouped together regardless of how far they exceed the threshold.
The pain VAS ranges from 0, no pain, to 100, worst imaginable pain. The registry says it was collected morning, afternoon, and evening. It defines baseline as the average value recorded during the week before the end-of-baseline visit, and endpoint as the average value recorded during the week before Week 14. Averaging observations across these periods describes how the trial defined its assessment values; the registry does not provide the underlying individual observations or distributions.
How does BOCF affect classification?
BOCF means baseline observation carried forward. General explanation: when a later observation is missing, this approach substitutes the participant's baseline observation. If the carried-forward value is used as the endpoint, it represents no change from baseline under the stated comparison. Given the registry's rule that all participants who do not meet the response threshold are non-responders, a baseline value carried forward would not meet the reduction threshold. The registry record does not report how many observations were missing, why they were missing, or the number of participants whose classification was affected by this rule.
Missing-data methods require assumptions about what missing observations would have shown. BOCF is a specific imputation rule; it does not establish what the unobserved outcome actually was. General explanation: if missingness is related to participants' outcomes or experience, a simple carry-forward rule can give a different result from other reasonable approaches. Assessing that possibility usually requires information about missingness and sensitivity analyses. Such analyses are not reported in the registry record.
What does a treatment contrast normally add?
General explanation: a comparison of responder percentages can be expressed in different ways. A difference describes separation between the group percentages on the percentage-point scale; a ratio describes their relative relation. A confidence interval gives a range of values compatible with the data and analysis under its assumptions. It conveys uncertainty around an estimate, rather than the probability that a particular treatment effect is true. The registry record does not report a single primary contrast, its confidence interval, or the group percentages needed to examine such a contrast.
The record reports three analyses for the primary endpoint, but does not reduce the outcome information to one comparison. Their estimates, labels, and analysis details are not reported in the registry record. Without those details, it is not possible to identify which analysis should be treated as the principal efficacy estimate or to assess whether analyses differed in population, time point, or method.
What can safety counts establish?
General explanation: event counts and the number of participants at risk provide a descriptive account of how many participants experienced events in each group. They do not, by themselves, establish that a difference between groups is statistically distinguishable from chance or attributable to treatment. Interpretation also depends on event definitions, observation time, completeness of reporting, and the prespecified analysis. The registry provides counts for serious and other adverse events, but a full comparative safety analysis is not reported in the registry record.
The sample-size note describes planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is specified as a fraction of the observed effect. It explicitly distinguishes these illustrations from the trial's own design. Such planning calculations are not observed power, and they do not establish that the trial was designed around those assumptions. The registry's sample-size justification and its own design calculations are not reported in the registry record.
General explanation: when a study has limited information about its analysis plan, readers should distinguish the stated endpoint definition from the results and from assumptions used in later planning exercises. In this record, the endpoint definition is clear enough to explain the intended responder classification, but the numerical efficacy contrast, its uncertainty, and key analysis details are not reported. Statistical interpretation must remain correspondingly limited.
10. Multiplicity, Missing Data and Analysis Populations
The registry record reports three analyses for the primary endpoint, but the available outcome description is not reduced to one comparison. The analysis labels, estimates, and relationship among those analyses are not reported in the registry record. It is therefore not possible to determine which result was designated as primary, whether the analyses address different categories or time points, or how their results were intended to be interpreted together.
General explanation: multiplicity arises when more than one hypothesis, endpoint, time point, or analysis is considered. The more opportunities there are to identify a notable result, the more important it is to understand whether and how the analysis plan accounted for those opportunities. No multiplicity adjustment or other strategy is reported in the registry record. It would be inappropriate to assume that one was used or that it was unnecessary.
The endpoint description specifies BOCF for missing data. The number of missing observations, reasons for missingness, and number of participants affected are not reported in the registry record. The record also does not describe sensitivity analyses that might examine the effect of alternative assumptions about missing outcomes. BOCF is thus identifiable as the stated rule, but the robustness of the result to missing-data assumptions cannot be assessed.
The analysis population is not reported in the registry record. The record does not clarify whether the primary analysis included all randomized participants, only participants with an endpoint observation, or another defined group. It also does not report how withdrawals or protocol deviations were handled. These details matter because the participants included in an analysis can affect the estimate and the interpretation of a randomized comparison.
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 |
|---|---|---|---|
| Placebo | 1 | 183 | 0.5% |
| Xyrem 4.5g | 0 | 182 | 0.0% |
| Xyrem 6.0g | 2 | 182 | 1.1% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 2% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Placebo | 105 of 183 |
| Xyrem 4.5g | 149 of 182 |
| Xyrem 6.0g | 145 of 182 |
Most frequent serious adverse event terms
| Event term | Organ system | Placebo | Xyrem 4.5g | Xyrem 6.0g |
|---|---|---|---|---|
| Colitis | Gastrointestinal disorders | 1 of 183 | 0 of 182 | 0 of 182 |
| Sleep Paralysis | Nervous system disorders | 0 of 183 | 0 of 182 | 1 of 182 |
| Unresponsive to stimuli | Nervous system disorders | 0 of 183 | 0 of 182 | 1 of 182 |
| Large Intestine Perforation | Gastrointestinal disorders | 0 of 183 | 0 of 182 | 1 of 182 |
| Abscess Intestinal | Infections and infestations | 0 of 183 | 0 of 182 | 1 of 182 |
| Diverticulitis | Infections and infestations | 0 of 183 | 0 of 182 | 1 of 182 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Placebo | Xyrem 4.5g | Xyrem 6.0g |
|---|---|---|---|---|
| Headache | Nervous system disorders | 20 of 183 | 27 of 182 | 42 of 182 |
| Nausea | Gastrointestinal disorders | 10 of 183 | 26 of 182 | 39 of 182 |
| Dizziness | Nervous system disorders | 5 of 183 | 24 of 182 | 31 of 182 |
| Vomiting | Gastrointestinal disorders | 7 of 183 | 8 of 182 | 19 of 182 |
| Diarrhoea | Gastrointestinal disorders | 5 of 183 | 10 of 182 | 14 of 182 |
| Upper Respiratory Tract Infection | Infections and infestations | 10 of 183 | 7 of 182 | 8 of 182 |
| Anxiety | Psychiatric disorders | 2 of 183 | 12 of 182 | 10 of 182 |
| Nasopharyngitis | Infections and infestations | 7 of 183 | 8 of 182 | 8 of 182 |
| Sinusitis | Infections and infestations | 1 of 183 | 12 of 182 | 8 of 182 |
| Somnolence | Nervous system disorders | 9 of 183 | 4 of 182 | 8 of 182 |
Serious events with the highest arm-level rate: sleep paralysis (0.5%), unresponsive to stimuli (0.5%), large intestine perforation (0.5%), abscess intestinal (0.5%), diverticulitis (0.5%).
The registry reports serious adverse event counts and participant counts at risk for three groups. In placebo, 1 of 183 participants had a serious adverse event; in Xyrem 4.5g, 0 of 182 did; in Xyrem 6.0g, 2 of 182 did. The counts are small, so they should be read as descriptive observations rather than as a precise estimate of comparative risk. The registry does not provide a formal statistical comparison or uncertainty intervals for these counts.
Other adverse events affected 105 of 183 participants in placebo, 149 of 182 in Xyrem 4.5g, and 145 of 182 in Xyrem 6.0g. These counts refer to participants affected, not necessarily the total number of events; one participant may have experienced more than one event. The record does not give further details needed to assess event duration, severity distribution, or exposure-adjusted rates.
The registry lists Sleep Paralysis, Unresponsive to stimuli, Large Intestine Perforation, Abscess Intestinal, Diverticulitis, and Colitis among the serious-event terms, each reported as 0.5%. The group assignment for these terms is not reported in the registry record. Death values are not reported, which is different from a report of zero deaths.
12. What the Result Does, and Does Not, Mean
The record supports a limited description of the trial: it was a randomized, double-blind, placebo-controlled, parallel-group Phase III study in people with fibromyalgia, with a pain VAS responder endpoint assessed from baseline to Week 14. The response threshold and missing-data rule are stated. Selected safety counts are also available for placebo and two Xyrem dose groups.
Those details do not establish the size or direction of an efficacy contrast. The registry does not report a single arm-to-arm result for the primary endpoint, responder percentages, or an interval estimate. It is therefore not possible to judge from this record how much separation was observed, how precisely it was estimated, or whether the data were compatible with a range of materially different effects. No conclusion about efficacy should be drawn from the trial's objective or the endpoint definition alone.
General explanation: an endpoint definition tells readers what was measured and how participants were classified; it does not reveal the resulting values. Likewise, a trial design can describe how a comparison was intended to be conducted without showing its outcome. A confidence interval, when reported, would help describe precision, while an analysis plan would clarify which comparisons were prespecified. Those elements are not reported in the registry record for a single primary efficacy comparison.
The safety counts describe the number of affected participants in each group for the categories reported. They do not by themselves provide a comprehensive safety profile, establish causal attribution, or quantify uncertainty. The registry's missing death values should not be interpreted as evidence that no deaths occurred. A fuller interpretation would require additional reporting about the safety definitions, observation period, and analysis.
The appropriate reading is therefore descriptive and bounded: the endpoint and selected safety observations are identifiable, but the principal numerical efficacy finding and several analysis details are not reported in the registry record. The information does not support a broader claim about the treatment's effects or about the balance of benefits and risks.
13. Why This Trial Matters Statistically
This trial illustrates why a clearly named endpoint is not the same as a fully interpretable result. The registry defines a binary pain VAS response threshold, an assessment window, and a missing-data rule. Those details explain what a responder means in this study. Yet without arm-level responder percentages and a treatment contrast, readers cannot quantify the efficacy result or its uncertainty.
The design also highlights the importance of connecting intervention descriptions to outcome reporting. The trial objective describes comparison of Xyrem® and placebo, while the safety information distinguishes placebo, Xyrem 4.5g, and Xyrem 6.0g. The record does not explain the relationship between these descriptions through arm details. A reader can identify the reported groups, but cannot reconstruct the full assignment and analysis structure from the registry record alone.
Missing-data handling matters especially for a threshold-based endpoint. BOCF is specified, but the record does not report how many outcomes were missing or whether alternative assumptions were examined. General explanation: when an imputation rule can affect responder classification, reporting its use together with the amount of missing data and sensitivity analyses helps readers assess how dependent a result may be on that choice.
The entry also separates trial findings from planning illustrations. The sample-size note describes assumptions for illustrative calculations and states that they are not the trial's own design. Such illustrations can help frame planning questions, but they cannot replace a reported estimate, uncertainty interval, or documented sample-size justification. They should not be read as observed power.
Statistically, the record is a useful example of the difference between identifying a study question and assessing its answer. It supplies enough information to explain the endpoint and some safety counts, but not enough to evaluate the primary efficacy contrast, multiplicity handling, or analysis population. Careful interpretation makes those gaps visible without filling them with assumptions.
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 main limitation for interpreting efficacy is that the registry record does not report a single primary comparison. Although it records three analyses, the corresponding estimates and analysis details are not reported in the registry record. Responder percentages, an effect estimate, and its precision are therefore unavailable for interpretation.
The record does not explain the relationship between the overall intervention description and the three groups named in the safety information. Arm descriptions are empty, and the allocation ratio is not reported. The registry also does not describe the randomization procedure or which roles were masked under its quadruple-masking classification.
Important analysis details are not reported in the registry record: the analysis population, handling of withdrawals and protocol deviations, and any multiplicity strategy. The record gives BOCF as the missing-data method but does not report the extent or reasons for missing data or sensitivity analyses. This limits assessment of how the analysis choices might affect the responder result.
Safety reporting is also incomplete for a full comparison. The record gives participant counts for serious and other adverse events, but does not provide a formal comparative analysis, uncertainty intervals, or details such as exposure-adjusted rates. Death values are not reported. The listed serious-event terms are not assigned to groups in the information reported.
Finally, the sample-size justification and the trial's own statistical plan are not reported in the registry record. The planning note describes illustrative assumptions, not a reconstruction of the study's original design. These gaps mean the record can support a description of the study and selected observations, but not a complete evaluation of its efficacy analysis or statistical robustness.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Safety and Efficacy Study of Xyrem® in Subjects With Fibromyalgia — NCT00371137.
- Registry record last updated 2011-12-29; status last verified 2011-12.
- Results first posted 2011-11-30.
- 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
NCT00371137 is a completed Phase III randomized, double-blind, placebo-controlled, parallel-group trial of Xyrem® in people with fibromyalgia. The registry reports 548 participants enrolled, a start date of 2006-08, and primary completion in 2008-09.
The primary endpoint is the percentage of participants with at least a 30% reduction in pain VAS from baseline to Week 14, with missing observations handled using baseline observation carried forward. A single efficacy comparison and its numerical estimates are not reported in the registry record.
Safety information distinguishes placebo, Xyrem 4.5g, and Xyrem 6.0g groups. Serious adverse events affected 1 of 183, 0 of 182, and 2 of 182 participants, respectively; other adverse events affected 105 of 183, 149 of 182, and 145 of 182. Death values and several analysis details are not reported in the registry record.