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 Long Term Safety of Teriflunomide When Added to Interferon-Beta or Glatiramer Acetate in Patients With Multiple Sclerosis (NCT00811395), a randomized phase 2 study. The primary outcome is Overview of Adverse Events [AE].
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00811395 |
| Phase | Phase 2 |
| Condition | Multiple Sclerosis |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 182 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Sanofi |
| Results posted | Yes |
2. Clinical Question
Population
People with multiple sclerosis with relapses who successfully completed the initial PDY6045 or PDY6046 study and entered its extension. The primary outcome population is described as all randomized and treated participants, with participants classified according to the drug actually received. The registry record does not report further eligibility details for the extension population.
Intervention
Teriflunomide, at 7 mg or 14 mg once daily, added to ongoing interferon-β or glatiramer acetate for 24 additional weeks. The record describes continuation of the same compound and dose from the initial study for participants who completed it successfully.
Comparator
Placebo for teriflunomide, taken once daily with interferon-β or glatiramer acetate. Thus, the listed groups distinguish both the background treatment and whether teriflunomide or its placebo was taken alongside it.
Primary question
What adverse events were observed during the specified observation period among participants receiving teriflunomide or placebo with interferon-β or glatiramer acetate? The primary objective was long-term safety and tolerability. The registry record gives counts of participants with serious and other adverse events by group, but does not report a single inferential comparison or an estimate of a treatment effect.
3. Trial Design
This was a phase 2, randomized, triple-masked, parallel-group extension study with 182 participants enrolled. The registry lists multiple sclerosis as the condition and Sanofi as the sponsor. The recorded study start is 2007-10, primary completion is 2010-04, and status is completed.
The study extended the PDY6045 and PDY6046 studies. Participants who successfully completed an initial study were offered the opportunity to continue treatment for 24 additional weeks, using the same compound and dose. The six listed groups combined placebo or teriflunomide at 7 mg or 14 mg with either interferon-β or glatiramer acetate. The descriptions specify once-daily study medication alongside the background treatment.
Although the registry labels allocation as randomized and masking as triple, it does not report the randomization procedure, the identities of the masked parties, or how the extension offer and group assignment were implemented. The primary outcome population is described as all randomized and treated participants, classified according to the drug actually received. The record does not provide additional detail about how this population relates to the enrollment count.
The primary objective was to evaluate long-term safety and tolerability. Secondary objectives concerned relapse rate, disability progression, and MRI parameters. The primary adverse-event observation period began with first study-drug intake in the initial study and continued until 112 days after the last intake in the initial or extension study, whichever occurred last, with a maximum of 64 weeks.
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.
Before assignment: An Interactive Voice Response System was used to allocate kits containing the same treatment as in the initial study. Analysis included all participants randomized in the initial studies and all data collected from randomization according to intent-to-treat principal.
Initial Treatment (PDY6045 or PDY6046)
| Stage | Placebo + IFN-β | Teriflunomide 7 mg + IFN-β | Teriflunomide 14 mg + IFN-β | Placebo + GA | Teriflunomide 7 mg + GA | Teriflunomide 14 mg + GA |
|---|---|---|---|---|---|---|
| STARTED | 41 | 37 | 38 | 40 | 42 | 41 |
| COMPLETED | 38 | 33 | 36 | 38 | 37 | 35 |
| NOT COMPLETED | 3 | 4 | 2 | 2 | 5 | 6 |
Extension Treatment
| Stage | Placebo + IFN-β | Teriflunomide 7 mg + IFN-β | Teriflunomide 14 mg + IFN-β | Placebo + GA | Teriflunomide 7 mg + GA | Teriflunomide 14 mg + GA |
|---|---|---|---|---|---|---|
| STARTED | 31 | 28 | 27 | 37 | 30 | 29 |
| COMPLETED | 29 | 22 | 24 | 34 | 30 | 27 |
| NOT COMPLETED | 2 | 6 | 3 | 3 | 0 | 2 |
Reasons for not completing this period:
| Reason | Placebo + IFN-β | Teriflunomide 7 mg + IFN-β | Teriflunomide 14 mg + IFN-β | Placebo + GA | Teriflunomide 7 mg + GA | Teriflunomide 14 mg + GA |
|---|---|---|---|---|---|---|
| Adverse Event | 1 | 2 | 2 | 2 | 0 | 1 |
| Progressive disease | 1 | 1 | 0 | 0 | 0 | 0 |
| Participant did not wish to continue | 0 | 3 | 0 | 1 | 0 | 1 |
| Other than above | 0 | 0 | 1 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: All randomized and treated participants; Participants were included in the treatment group according to the drug actually received.
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 7 groups are shown.
| Characteristic | Unit | Placebo + IFN-β | Teriflunomide 7 mg + IFN-β | Teriflunomide 14 mg + IFN-β | Placebo + GA | Teriflunomide 7 mg + GA | Teriflunomide 14 mg + GA |
|---|---|---|---|---|---|---|---|
| Participants analysed | 41 | 37 | 38 | 40 | 42 | 41 | |
| Age, Customized: <38 years | participants | 17 | 9 | 15 | 11 | 12 | 13 |
| Age, Customized: >=38 years | participants | 24 | 28 | 23 | 29 | 30 | 28 |
| Sex: Female, Male: Female | Participants | 31 | 25 | 25 | 31 | 33 | 33 |
| Sex: Female, Male: Male | Participants | 10 | 12 | 13 | 9 | 9 | 8 |
| Region of Enrollment: Europe | participants | 28 | 25 | 24 | 22 | 22 | 22 |
| Region of Enrollment: North America | participants | 13 | 12 | 14 | 18 | 20 | 19 |
6. Primary Endpoint
The registry lists the primary outcome as Overview of Adverse Events [AE], measured over from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured last (64 weeks max).
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is an overview of adverse events among participants. An adverse event is defined in the registry as an unfavorable and unintended sign, symptom, syndrome, or illness observed by the investigator or reported by the participant during the study. The record reports participants with serious adverse events and participants with other adverse events by treatment group.
Safety endpoints are used to describe unwanted events observed during treatment and follow-up. Counts give a direct account of how many participants in each listed group had an event of the specified category. They do not, by themselves, establish that study treatment caused an event or that groups differ beyond what could arise from chance. The registry record does not provide a single combined endpoint value or a formal statistical comparison for this outcome.
The observation window is important to interpretation: events could be counted from first study-drug intake in PDY6045 or PDY6046 through the specified post-treatment period, subject to the 64-week maximum. It therefore encompasses time in the initial study as well as the extension, rather than only the additional 24 weeks. The record does not report event-specific timing or duration.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary safety results are counts of participants with serious and other adverse events across six combinations of teriflunomide or placebo and background therapy. For the interferon-β groups, serious events were reported for 2 of 41 participants with placebo, 4 of 37 with teriflunomide 7 mg, and 1 of 38 with teriflunomide 14 mg. Other adverse events were reported for 28 of 41, 33 of 37, and 32 of 38 participants, respectively.
For the glatiramer acetate groups, serious events were reported for 6 of 40 participants with placebo, 5 of 42 with teriflunomide 7 mg, and 2 of 41 with teriflunomide 14 mg. Other adverse events were reported for 34 of 40, 30 of 42, and 34 of 41 participants, respectively. These are descriptive counts, not estimates from a reported adjusted comparison.
The serious-event counts vary across the six groups, as do the counts for other adverse events. The record does not report confidence intervals, hypothesis tests, or a statistical model for comparing these primary safety counts. It is therefore not possible to use the posted primary results to judge the precision of differences between groups or whether an observed numerical contrast is compatible with chance variation. The counts should be read in the context of each group’s at-risk population and the specified observation period.
The registry also lists secondary outcomes for annualized relapse rate, sustained disability progression, and MRI measures. It names Poisson regression estimates for relapse rate and for the number of gadolinium-enhancing T1 lesions per scan, and Kaplan-Meier estimates for disability progression at timepoints. However, numerical results for those outcomes are not reported in the registry record. Their listing indicates what the study intended to assess, not what the results were.
The primary objective was safety and tolerability, and the available adverse-event counts address that descriptive objective. They do not, on their own, establish a causal effect of teriflunomide, quantify comparative risk with precision, or resolve how results differ between background therapies. The record does not report the statistical analysis needed to make those inferences.
9. Statistical Methods Explained
The record describes a randomized, triple-masked, parallel-group study. These labels characterize the design, but the registry record does not report the randomization procedure or identify which parties were masked. The six listed treatment combinations make clear that comparisons could involve both teriflunomide dose and background treatment. The record does not specify a single planned contrast among these possibilities.
What do the adverse-event counts represent?
The primary outcome is binary at the participant level: whether a participant had an event in a given category during the observation period. Counts are reported separately for serious and other adverse events, alongside the number of participants at risk in each group. A participant count is not the same as an event count: a person may have more than one event, but the primary results describe participants with events. The registry record does not report how recurrent events or participants with events in multiple categories were handled.
General statistical explanation: a binary outcome can be summarized as the number of participants with an event and the number assessed. A comparison may then use a difference or ratio between groups, often with a confidence interval to describe uncertainty. A confidence interval expresses the range of effect values compatible with the data under the assumptions of the analysis. No such comparative estimates or intervals are reported for the primary outcome in this record.
Why does the observation window matter?
The endpoint covers the period from first study-drug intake in PDY6045 or PDY6046 until 112 days after the last intake in the initial or extension study, whichever occurred last, with a maximum of 64 weeks. This is broader than the 24 additional weeks described for the extension itself. A participant’s opportunity to have an event depends on the time covered by observation. The record does not give group-specific follow-up durations or report an analysis accounting for differences in time at risk.
What methods are named for secondary outcomes?
The registry lists Poisson regression estimates for annualized relapse rate and for the number of gadolinium-enhancing T1 lesions per scan. General explanation: Poisson regression is commonly used for counts, often with an adjustment for differing observation time when the outcome is a rate. Count data can be more variable than a simple Poisson model assumes; this is called over-dispersion. If over-dispersion is present and not addressed, uncertainty estimates from a basic Poisson model may be too narrow. The registry record does not describe model covariates, time adjustments, checks for over-dispersion, or alternative models.
For time to 12-week sustained disability progression, the registry names Kaplan-Meier estimates of progression rates at timepoints. General explanation: a Kaplan-Meier method estimates the probability of remaining free of an event over time while allowing participants to have different observed follow-up, including follow-up that ends before an event is recorded. The registry record does not report the timepoints’ estimates, the number at risk over time, censoring rules, or a formal comparison between groups.
Other listed MRI outcomes are change from baseline in total lesion volume and total volume of gadolinium-enhancing T1 lesions per scan. The record does not state the specific analysis methods for these outcomes. It also does not provide the baseline values or numerical secondary outcome results.
What can be inferred from the posted analysis information?
The record lists nine outcome measures and no analyses. This means that the registry record does not supply analysis-level results for those listed measures. The adverse-event counts are available as descriptive results, but a detailed statistical plan, model specifications, adjustment strategy, and inferential results are not reported in the registry record. General statistical explanation: without the analysis details and uncertainty estimates, descriptive group counts should not be treated as evidence of a statistically established difference.
10. Multiplicity, Missing Data and Analysis Populations
The study lists several secondary outcomes covering relapse rate, sustained disability progression, and MRI parameters, alongside the primary adverse-event endpoint. When many outcomes or comparisons are examined, the chance of at least one apparently unusual result can increase. General statistical explanation: multiplicity procedures can address this issue by controlling the overall error rate or by setting a hierarchy for testing. The registry record does not report whether multiplicity was addressed, whether outcomes were ordered in a testing hierarchy, or which comparisons were prespecified.
Missing-data methods are not reported in the registry record. The record does not describe how missing endpoint information, incomplete follow-up, or discontinuation was handled, and it does not report imputation or sensitivity analyses. For outcomes measured over time, such as time to disability progression, details about censoring and loss to follow-up are also not reported.
The primary outcome population is described as all randomized and treated participants, with classification according to the drug actually received. This description does not establish whether an intention-to-treat analysis was used or how participants who did not complete the extension were included. The registry record does not report additional analysis-population definitions for the secondary outcomes.
These omissions limit assessment of how robust the results are to incomplete observations and how the study handled the several listed outcomes. They do not establish that a particular method was or was not used; those details are simply not reported in the registry record.
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 + IFN-β | 2 | 41 | 4.9% |
| Teriflunomide 7 mg + IFN-β | 4 | 37 | 10.8% |
| Teriflunomide 14 mg + IFN-β | 1 | 38 | 2.6% |
| Placebo + GA | 6 | 40 | 15.0% |
| Teriflunomide 7 mg + GA | 5 | 42 | 11.9% |
| Teriflunomide 14 mg + GA | 2 | 41 | 4.9% |
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 |
|---|---|
| Placebo + IFN-β | 28 of 41 |
| Teriflunomide 7 mg + IFN-β | 33 of 37 |
| Teriflunomide 14 mg + IFN-β | 32 of 38 |
| Placebo + GA | 34 of 40 |
| Teriflunomide 7 mg + GA | 30 of 42 |
| Teriflunomide 14 mg + GA | 34 of 41 |
Most frequent serious adverse event terms
| Event term | Organ system | Placebo + IFN-β | Teriflunomide 7 mg + IFN-β | Teriflunomide 14 mg + IFN-β | Placebo + GA | Teriflunomide 7 mg + GA | Teriflunomide 14 mg + GA |
|---|---|---|---|---|---|---|---|
| Alanine aminotransferase increased | Investigations | 1 of 41 | 1 of 37 | 0 of 38 | 0 of 40 | 2 of 42 | 0 of 41 |
| Suicidal ideation | Psychiatric disorders | 0 of 41 | 0 of 37 | 0 of 38 | 0 of 40 | 1 of 42 | 1 of 41 |
| Abscess | Infections and infestations | 0 of 41 | 0 of 37 | 0 of 38 | 1 of 40 | 0 of 42 | 0 of 41 |
| Cystitis | Infections and infestations | 0 of 41 | 0 of 37 | 1 of 38 | 0 of 40 | 0 of 42 | 0 of 41 |
| Herpes zoster | Infections and infestations | 0 of 41 | 0 of 37 | 0 of 38 | 1 of 40 | 0 of 42 | 0 of 41 |
| Lobar pneumonia | Infections and infestations | 0 of 41 | 0 of 37 | 1 of 38 | 0 of 40 | 0 of 42 | 0 of 41 |
| Mastoiditis | Infections and infestations | 0 of 41 | 0 of 37 | 0 of 38 | 0 of 40 | 1 of 42 | 0 of 41 |
| Otitis media | Infections and infestations | 0 of 41 | 0 of 37 | 0 of 38 | 0 of 40 | 1 of 42 | 0 of 41 |
| Suicide attempt | Psychiatric disorders | 0 of 41 | 0 of 37 | 0 of 38 | 0 of 40 | 1 of 42 | 0 of 41 |
| Cerebral ischaemia | Nervous system disorders | 0 of 41 | 0 of 37 | 0 of 38 | 1 of 40 | 0 of 42 | 0 of 41 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Placebo + IFN-β | Teriflunomide 7 mg + IFN-β | Teriflunomide 14 mg + IFN-β | Placebo + GA | Teriflunomide 7 mg + GA | Teriflunomide 14 mg + GA |
|---|---|---|---|---|---|---|---|
| Alanine aminotransferase increased | Investigations | 6 of 41 | 7 of 37 | 12 of 38 | 2 of 40 | 3 of 42 | 2 of 41 |
| Headache | Nervous system disorders | 2 of 41 | 2 of 37 | 6 of 38 | 7 of 40 | 6 of 42 | 7 of 41 |
| Fatigue | General disorders | 4 of 41 | 2 of 37 | 5 of 38 | 7 of 40 | 4 of 42 | 7 of 41 |
| Nasopharyngitis | Infections and infestations | 3 of 41 | 3 of 37 | 5 of 38 | 6 of 40 | 7 of 42 | 4 of 41 |
| Urinary tract infection | Infections and infestations | 7 of 41 | 4 of 37 | 1 of 38 | 6 of 40 | 5 of 42 | 4 of 41 |
| Diarrhoea | Gastrointestinal disorders | 6 of 41 | 4 of 37 | 4 of 38 | 2 of 40 | 3 of 42 | 8 of 41 |
| Nausea | Gastrointestinal disorders | 3 of 41 | 0 of 37 | 5 of 38 | 3 of 40 | 5 of 42 | 5 of 41 |
| Upper respiratory tract infection | Infections and infestations | 4 of 41 | 2 of 37 | 2 of 38 | 6 of 40 | 2 of 42 | 4 of 41 |
| Alopecia | Skin and subcutaneous tissue disorders | 1 of 41 | 3 of 37 | 3 of 38 | 1 of 40 | 5 of 42 | 7 of 41 |
| Back pain | Musculoskeletal and connective tissue disorders | 1 of 41 | 2 of 37 | 4 of 38 | 2 of 40 | 3 of 42 | 1 of 41 |
Serious events with the highest arm-level rate: alanine aminotransferase increased (4.8%), deep vein thrombosis (2.7%), musculoskeletal stiffness (2.7%), pseudarthrosis (2.7%), fall (2.7%).
The serious adverse-event figures count participants with at least one serious event in each group during the specified observation period. In the placebo and interferon-β group the count was 2 of 41; with teriflunomide 7 mg and interferon-β it was 4 of 37; and with teriflunomide 14 mg and interferon-β it was 1 of 38. For placebo with glatiramer acetate, the count was 6 of 40; with teriflunomide 7 mg and glatiramer acetate it was 5 of 42; and with teriflunomide 14 mg and glatiramer acetate it was 2 of 41.
These are participant counts, not counts of every serious event. The registry record does not report deaths. It lists serious-event terms with percentages, including Alanine aminotransferase increased at 4.8%, Deep vein thrombosis at 2.7%, Musculoskeletal stiffness at 2.7%, Pseudarthrosis at 2.7%, Fall at 2.7%, and Cystitis at 2.6%. The registry record does not clarify the denominator or group assignment for these term-specific percentages.
The counts are descriptive. Without comparative estimates and uncertainty intervals, they do not quantify how precisely group differences are estimated.
12. What the Result Does, and Does Not, Mean
The results give a descriptive account of participants with serious and other adverse events across the six listed treatment combinations. They also identify several serious-event terms with reported percentages. Together, these figures describe events recorded during the defined observation window, which began in the initial studies and could extend into the extension period.
The figures do not establish that a particular treatment caused an event. They also do not establish that groups are equivalent or that any numerical difference is statistically meaningful. The registry record does not report confidence intervals or formal comparative analyses for the primary safety outcome, so the precision of group contrasts cannot be assessed from these results alone.
The extension involved participants who successfully completed an initial study and were offered continuation for 24 additional weeks. The record therefore describes an extension population rather than supplying details about every participant who may have entered the initial studies. The registry record does not report the number who accepted the offer, group-specific follow-up time, or missing-data handling. These gaps matter when interpreting how representative the observed safety counts are and how much opportunity participants had to experience events.
Relapse rate, disability progression, and MRI outcomes appear as secondary objectives or measures, but their numerical results are not reported in the registry record. The named methods for some outcomes do not substitute for outcome estimates. In particular, the record does not support conclusions about comparative relapse, disability, or MRI results.
In short, the posted results support reading the adverse-event counts as a descriptive safety account for the recorded groups and observation period. They do not provide a complete inferential assessment of safety or results for the listed secondary outcomes.
13. Why This Trial Matters Statistically
This study illustrates a common statistical challenge in extension trials: the study question concerns longer-term safety, while the observed population consists of participants who successfully completed an initial study and continued treatment. That design can extend the observation of events, but its results describe the participants who entered the extension and the specified period of follow-up. The registry record does not report details that would allow a fuller assessment of selection into the extension.
The six treatment combinations also make clear why safety results need careful framing. Teriflunomide dose and background treatment vary across groups, so a count in one group cannot be interpreted as a simple comparison with every other group. The registry record gives descriptive counts but does not identify a primary pairwise comparison or provide inferential estimates to distinguish treatment contrasts.
Finally, the record lists several clinically distinct secondary outcomes and names methods for some of them, yet numerical results are not reported. This distinction between an outcome being named and an outcome having interpretable results is important when reading clinical trial registries. A methods label such as Poisson regression or Kaplan-Meier does not reveal the estimated effect, its precision, or how the analysis was implemented. The trial record is therefore most informative about its design objectives and descriptive adverse-event results, while leaving important comparative and secondary-outcome questions unanswered.
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 registry record does not report a detailed statistical analysis plan, the randomization procedure, the masked parties, or the specific planned treatment contrasts. It also does not report confidence intervals, hypothesis tests, or model-based comparisons for the primary adverse-event endpoint. Consequently, the precision and inferential status of between-group differences cannot be evaluated from the posted primary results.
The study is an extension of PDY6045 and PDY6046, and continuation was offered to participants who successfully completed the initial study. The record does not provide the number who entered the extension by group, the number who declined or did not qualify, or a comparison of those who continued with those who did not. Group-specific follow-up duration and missing-data handling are also not reported.
The primary endpoint covers the initial and extension studies, rather than only the 24 additional weeks. The record does not report when individual events occurred, how recurrent events were handled, or the denominator for the percentages attached to serious-event terms. Deaths are not reported in the registry record.
Although secondary outcomes are listed and methods are named for some, numerical results and analysis details for those outcomes are not reported in the registry record. Multiplicity handling, model covariates, censoring details, and sensitivity analyses are also not reported. These limitations restrict interpretation of comparative safety and prevent conclusions about the listed secondary outcomes.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Long Term Safety of Teriflunomide When Added to Interferon-Beta or Glatiramer Acetate in Patients With Multiple Sclerosis — NCT00811395.
- Registry record last updated 2012-12-31; status last verified 2012-12.
- Results first posted 2012-12-31.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
This completed phase 2 study evaluated long-term safety and tolerability of teriflunomide added to interferon-β or glatiramer acetate in people with multiple sclerosis with relapses. It was recorded as randomized, triple-masked, and parallel-group, with 182 participants enrolled. Participants who successfully completed the initial studies were offered continuation of the same compound and dose for 24 additional weeks.
The primary outcome was an overview of adverse events. The registry reports participants with serious and other adverse events across six groups and lists serious-event terms with percentages. Secondary outcomes concerned relapse rate, disability progression, and MRI parameters, but their numerical results are not reported in the registry record. Detailed statistical methods, missing-data handling, multiplicity procedures, and inferential comparisons for the primary safety outcome are also not reported.