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, Tolerability and Efficacy Study of AFQ056 in Adult Patients With Fragile X Syndrome (NCT01348087), a na phase 2 study. The primary outcome is Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01348087 |
| Phase | Phase 2 |
| Condition | Fragile X Syndrome |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 148 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Novartis Pharmaceuticals |
| Results posted | Yes |
2. Clinical Question
Population
Adults with Fragile X Syndrome who had participated in the CAFQ056A2212 study or the earlier proof-of-concept CAFQ056A2204 study were eligible for this long-term extension. The safety analysis included participants who received at least one dose of extension-study medication and had at least one safety assessment after their first dose.
Intervention
AFQ056 was given in an open-label treatment period. The planned titration began at 25 mg twice daily, with weekly steps to 50 mg, 75 mg and 100 mg twice daily. Dose increases or decreases were permitted to address tolerability issues.
Comparator
There was no concurrent control group. The registry describes a single-group study with no masking and no randomized allocation. The adverse-event categories reflect treatment periods and dose levels, not a randomized comparison between separate groups.
Primary question
The primary outcome was the incidence and severity of adverse events and serious adverse events during the extension study. The record also describes a period before the first extension dose for some participants. No efficacy data were presented because the study was terminated.
In practical terms, the registry record asks what adverse events were recorded while eligible adults entered and continued open-label AFQ056 treatment, including how reported events were distributed across dose periods. It does not set up a comparison that can establish whether AFQ056 caused an event or whether event rates differ from those under another treatment.
The record lists 148 participants as the study enrollment. The safety outcome uses a safety-set definition: participants had to receive at least one dose of study medication and have at least one safety assessment after that first extension-study dose. The adverse-event results give counts of participants with events and counts at risk for the reported periods. They do not provide an efficacy assessment. The registry record does not report further eligibility criteria or an explicit research hypothesis beyond the safety, tolerability and efficacy aims in the study description.
3. Trial Design
This was a phase 2, open-label, single-group study of AFQ056 in adult patients with Fragile X Syndrome. The registry lists Novartis Pharmaceuticals as the sponsor, enrollment of 148, a start date of 2011-08, primary completion in 2014-09 and a terminated status. A termination date and the reason for termination are not reported in the registry record.
The study was described as a long-term extension for eligible adults who had participated in CAFQ056A2212 or the earlier proof-of-concept study CAFQ056A2204. All patients initiated AFQ056 at a starting dose of 25 mg twice daily. The dose was titrated through 50 mg, 75 mg and 100 mg twice daily at weekly intervals. Dose adjustments in either direction were permitted to manage tolerability issues. The available arm description ends before all details are given, so further dosing rules are not reported in the registry record.
Open-label means that the treatment was not masked in the study record. Allocation is listed as not applicable, and the design is identified as single-group. Therefore, the dose-period entries should not be read as concurrent randomized treatment arms. The adverse-event description assigns events to the last AFQ056 dose taken on or before onset, while events continuing from the core study or beginning before the first extension dose are presented separately for a specified entry category.
The primary outcome concerned adverse events and serious adverse events, with a timeframe spanning the period before the first extension dose and the period from baseline at extension-treatment start to the end of trial. The registry record reports no efficacy data because the study was terminated. Details of the termination decision, the planned duration of individual treatment and the reasons participants may have stopped treatment are not reported in the registry record.
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: A total of 148 patients were enrolled and treated, including 1 patient who discontinued and was later re-enrolled under a new patient number. Category 1 patients received AFQ056 in the core study and enrolled in the extension within 7 days of completing the core study; Category 2 included all other patients enrolled into the extension study
Overall Study
| Stage | AFQ056 Total |
|---|---|
| STARTED | 148 |
| COMPLETED | 0 |
| NOT COMPLETED | 148 |
Reasons for not completing this period:
| Reason | AFQ056 Total |
|---|---|
| Unsatisfactory therapeutic effect | 35 |
| Administrative problems | 79 |
| protocol deviation | 1 |
| Lost to Follow-up | 1 |
| Subject withdrew consent | 7 |
| Adverse Event | 25 |
Analysis population for the primary outcome, as defined in the registry: The analysis was performed in the safety set (SS) population, defined as participants who received at least one dose of study medication and had at least one safety assessment occurring after first dose of extension study medication. Here, 'Number of Participants Analyzed' signifies those participants who were evaluable for this outcome measure
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 | AFQ056 |
|---|---|---|
| Participants analysed | 148 | |
| Age, Continuous | Years | 26.6 (SD 6.85) |
| Sex: Female, Male: Female | Participants | 10 |
| Sex: Female, Male: Male | Participants | 138 |
6. Primary Endpoint
The registry lists the primary outcome as Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)., measured over Prior to first dose in extension study, Baseline (start of study treatment in extension study) to End of trial.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint concerns the incidence and severity of adverse events (AEs) and serious adverse events (SAEs), reported as numbers of participants. It is a safety-focused endpoint: it describes how many participants were recorded as having events during the specified treatment periods. The registry record separates events occurring before the first extension dose from those occurring during open-label treatment and presents treatment-period events according to the last AFQ056 dose taken on or before event onset.
Safety endpoints are used in clinical studies to characterize unwanted medical events during treatment, including events classified as serious. General: counting participants with an event is a direct way to describe how widely an event was observed in the analyzed population. It does not by itself establish that treatment caused the event, and it does not convey the duration, recurrence or individual clinical course of each event.
The registry record does not describe the criteria used to classify an event as serious, provide graded severity categories, or report event-level details for all outcomes. Seriousness and severity are distinct concepts in safety reporting; the record’s endpoint title includes both, but the posted results presented in this outcome are participant counts. The record reports no efficacy data.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
In the AFQ056 total category, 7 participants were reported with serious adverse events, among 148 at risk, and 117 participants were reported with other adverse events, also among 148 at risk. The dose-period counts are recorded separately: at 25 mg twice daily, 1 participant was reported with a serious adverse event and 26 with other adverse events, among 147 at risk; at 50 mg twice daily, the corresponding counts were 0 and 28, among 148 at risk; at 75 mg twice daily, they were 1 and 36, among 141 at risk; and at 100 mg twice daily, they were 6 and 88, among 135 at risk. Before the first extension dose, 0 participants were reported with serious adverse events and 6 with other adverse events, among 40 at risk.
These figures describe the registry’s recorded participant counts. The dose categories are treatment periods within a titration scheme, not separate randomized groups. The event description assigns an event to the last AFQ056 dose taken on or before its onset. Participants could move through dose levels, so the counts across dose periods should not be interpreted as independent groups or added to create a count of unique participants. The AFQ056 total is the posted total category, not a comparison against a control group.
The reported serious-event terms include Aggression (2.0%), Agitation (1.5%), Hepatic enzyme increased (0.7%), Epilepsy (0.7%), Hallucination, auditory (0.7%) and Hallucination, visual (0.7%). These are listed as the top serious terms; the record does not provide additional detail about timing, duration, recurrence or participant-level overlap among terms. The percentages are reported as listed and should not be treated as evidence of a causal relationship.
There is no concurrent control group, and no inferential analysis is reported. Consequently, the counts cannot quantify a treatment effect relative to placebo or another intervention, and they do not establish whether an event was caused by AFQ056. The registry record also presents no efficacy results because the study was terminated. Interpretation is therefore limited to a descriptive account of recorded safety events in the analyzed population and treatment periods, rather than a comparative estimate of benefit or harm.
9. Statistical Methods Explained
The posted results are descriptive counts of participants with adverse events. The registry record identifies the outcome unit as participants and defines the safety set as participants who received at least one dose of extension-study medication and had at least one safety assessment after the first dose. The at-risk counts differ across some dose periods, and the event counts should be read alongside their matching at-risk counts rather than as standalone numbers.
What does a participant count represent?
General: a participant count indicates how many people in a defined analysis group were recorded as having an event meeting the outcome definition. It is not necessarily a count of every event episode. A participant can experience more than one event, and a person-level count does not reveal how many episodes occurred, how long they lasted or whether they recurred. The registry outcome reports participants with events, not a full event-by-event history.
The posted AFQ056 total reports 7 participants with serious adverse events and 117 with other adverse events, each among 148 at risk. The dose-period entries report counts for particular periods and their at-risk populations. Those entries should not be summed across dose levels: this was a titration study, and the same participant could contribute during more than one dose period. The registry’s event-assignment rule uses the last dose taken on or before the event’s onset, which defines how an event is placed into a dose category; it does not make the dose categories independent comparison groups.
What does the open-label design allow?
General: a descriptive, open-label safety record can show what events were reported during treatment, but without a concurrent comparator it cannot separate treatment effects from other explanations for events. Such explanations may include the underlying condition, background circumstances or other factors; the record does not evaluate their contribution. The single-group design and lack of masking also mean that the posted counts are not a randomized estimate of differences between treatments.
The study description allows dose increases and decreases to manage tolerability. The registry record does not provide a dose-by-dose analysis adjusted for how long participants spent at each dose, nor does it report an analysis accounting for changes in dose over time. Thus, a larger count in a dose category cannot be interpreted as a higher risk at that dose without considering exposure and the way participants entered that period. A participant count is not an exposure-adjusted event rate.
How should uncertainty be understood?
General: a confidence interval is a range of values compatible with the data and a stated statistical procedure. It helps communicate the precision of an estimate; narrower intervals generally indicate greater precision, while wider intervals indicate more uncertainty. The registry record does not report confidence intervals or other inferential estimates for this primary outcome. It therefore offers no interval-based precision assessment for the adverse-event counts.
General: when observations vary more than a simple statistical model assumes, over-dispersion can make conventional uncertainty estimates too small if the model does not account for that extra variation. No model-based analysis or over-dispersion assessment is reported in the registry record, so this is a general consideration rather than a description of an analysis used in this study.
The registry record lists no analyses for the outcome and no efficacy data. It does not report a statistical analysis plan, a method for handling repeated events, an adjustment for exposure time, or a model relating dose to adverse events. The study’s termination reason and any planned interim analyses are not reported in the registry record. No sample-size justification is reported in the registry record. As a result, interpretation should remain descriptive and should not imply a formal test of treatment differences or a dose-response relationship.
10. Multiplicity, Missing Data and Analysis Populations
The registry record identifies one outcome measure, focused on the incidence and severity of adverse events and serious adverse events, and reports no analyses for it. A multiplicity strategy—how statistical testing would account for more than one outcome, comparison or analysis—is not reported in the registry record. Because no inferential analyses are posted, the record does not establish a formal family of tests or describe any adjustment for multiple testing.
Methods for missing data are not reported in the registry record. It does not describe how missing safety assessments, incomplete follow-up or withdrawals were handled in the outcome summaries. The safety-set definition requires at least one dose and at least one post-dose safety assessment, but that definition alone does not explain how participants with less complete observation were handled or how much follow-up each participant contributed.
The record does not report an analysis population for efficacy, and no efficacy data are presented because the study was terminated. The safety set is defined in the outcome description, but the full detail of the population-description text is incomplete in the registry record. The reason for termination and whether any planned analyses were not completed are not reported in the registry record. These omissions limit assessment of the intended analysis plan, the effect of missing information and the completeness of outcome reporting.
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 |
|---|---|---|---|
| Prior to Ext.First Dose | 0 | 40 | 0.0% |
| AFQ056 25 mg Bid | 1 | 147 | 0.7% |
| AFQ056 50 mg Bid | 0 | 148 | 0.0% |
| AFQ056 75 mg Bid | 1 | 141 | 0.7% |
| AFQ056 100 mg Bid | 6 | 135 | 4.4% |
| AFQ056 Total | 7 | 148 | 4.7% |
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 |
|---|---|
| Prior to Ext.First Dose | 6 of 40 |
| AFQ056 25 mg Bid | 26 of 147 |
| AFQ056 50 mg Bid | 28 of 148 |
| AFQ056 75 mg Bid | 36 of 141 |
| AFQ056 100 mg Bid | 88 of 135 |
| AFQ056 Total | 117 of 148 |
Most frequent serious adverse event terms
| Event term | Organ system | Prior to Ext.First Dose | AFQ056 25 mg Bid | AFQ056 50 mg Bid | AFQ056 75 mg Bid | AFQ056 100 mg Bid | AFQ056 Total |
|---|---|---|---|---|---|---|---|
| Aggression | Psychiatric disorders | 0 of 40 | 0 of 147 | 0 of 148 | 1 of 141 | 2 of 135 | 3 of 148 |
| Agitation | Psychiatric disorders | 0 of 40 | 0 of 147 | 0 of 148 | 0 of 141 | 2 of 135 | 2 of 148 |
| Hallucination, visual | Psychiatric disorders | 0 of 40 | 1 of 147 | 0 of 148 | 0 of 141 | 1 of 135 | 1 of 148 |
| Hepatic enzyme increased | Investigations | 0 of 40 | 0 of 147 | 0 of 148 | 0 of 141 | 1 of 135 | 1 of 148 |
| Epilepsy | Nervous system disorders | 0 of 40 | 0 of 147 | 0 of 148 | 0 of 141 | 1 of 135 | 1 of 148 |
| Hallucination, auditory | Psychiatric disorders | 0 of 40 | 0 of 147 | 0 of 148 | 0 of 141 | 1 of 135 | 1 of 148 |
| Panic attack | Psychiatric disorders | 0 of 40 | 0 of 147 | 0 of 148 | 0 of 141 | 1 of 135 | 1 of 148 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Prior to Ext.First Dose | AFQ056 25 mg Bid | AFQ056 50 mg Bid | AFQ056 75 mg Bid | AFQ056 100 mg Bid | AFQ056 Total |
|---|---|---|---|---|---|---|---|
| Nasopharyngitis | Infections and infestations | 3 of 40 | 2 of 147 | 4 of 148 | 3 of 141 | 21 of 135 | 27 of 148 |
| Aggression | Psychiatric disorders | 0 of 40 | 6 of 147 | 8 of 148 | 5 of 141 | 11 of 135 | 22 of 148 |
| Insomnia | Psychiatric disorders | 1 of 40 | 4 of 147 | 3 of 148 | 7 of 141 | 12 of 135 | 23 of 148 |
| Headache | Nervous system disorders | 0 of 40 | 4 of 147 | 3 of 148 | 7 of 141 | 14 of 135 | 21 of 148 |
| Upper respiratory tract infection | Infections and infestations | 0 of 40 | 4 of 147 | 1 of 148 | 3 of 141 | 16 of 135 | 24 of 148 |
| Vomiting | Gastrointestinal disorders | 0 of 40 | 1 of 147 | 2 of 148 | 2 of 141 | 14 of 135 | 18 of 148 |
| Anxiety | Psychiatric disorders | 0 of 40 | 1 of 147 | 3 of 148 | 3 of 141 | 10 of 135 | 16 of 148 |
| Irritability | Psychiatric disorders | 1 of 40 | 0 of 147 | 7 of 148 | 4 of 141 | 6 of 135 | 15 of 148 |
| Cough | Respiratory, thoracic and mediastinal disorders | 1 of 40 | 4 of 147 | 0 of 148 | 2 of 141 | 9 of 135 | 16 of 148 |
| Dizziness | Nervous system disorders | 1 of 40 | 5 of 147 | 4 of 148 | 1 of 141 | 5 of 135 | 13 of 148 |
Serious events with the highest arm-level rate: aggression (2.0%), agitation (1.5%), hepatic enzyme increased (0.7%), epilepsy (0.7%), hallucination, auditory (0.7%).
The serious adverse-event counts describe participants recorded with at least one serious event in each reported period. For the AFQ056 total, the record reports 7 participants with serious adverse events among 148 at risk. The dose-period entries report 1 among 147 at 25 mg twice daily, 0 among 148 at 50 mg twice daily, 1 among 141 at 75 mg twice daily, and 6 among 135 at 100 mg twice daily. Before the first extension dose, the record reports 0 among 40 at risk.
These are counts by period, not results from separate randomized arms. Participants were titrated through dose levels, and the event description assigns events by the last dose taken on or before onset. The counts across dose periods should not be added or treated as independent participant groups. The total category is the registry’s separate AFQ056 total.
General: a count of zero means no participant in that recorded group was listed with the event category; it does not prove that the event is impossible or that there is no risk. The registry record does not provide confidence intervals, event timing details or a comparison group for these counts. It also does not report detailed seriousness criteria or graded severity categories.
12. What the Result Does, and Does Not, Mean
The posted results provide a descriptive safety account for participants in an open-label AFQ056 extension study. They show the numbers of participants recorded with serious and other adverse events in the reported periods, including a pre-extension-dose category and treatment periods assigned by dose at event onset. The AFQ056 total category reports 7 participants with serious adverse events and 117 with other adverse events among 148 at risk.
These results do not establish that AFQ056 caused an event. The study had a single group, no randomized allocation and no concurrent control. The dose-period counts are not direct comparisons between treatment groups because the study used titration and the same participant could contribute to successive dose periods. The registry record does not provide an exposure-adjusted analysis, inferential estimates or confidence intervals for the safety counts.
The outcome title includes both incidence and severity, but the posted results are participant counts; detailed severity grades and event-level information are not reported in the registry record. The listed serious-event terms provide some information on the types of events recorded, but do not show individual clinical courses or establish attribution.
No efficacy data are presented because the study was terminated. The registry record does not report why it was terminated, and the safety results cannot be used to infer efficacy. The findings therefore describe reported events in the analyzed safety set during the recorded periods. They do not provide a comparative estimate of treatment benefit, a causal safety estimate, or a basis for conclusions about outcomes beyond the registry record.
13. Why This Trial Matters Statistically
This study is statistically informative as an example of how a safety outcome is presented in a single-group extension study. The registry record distinguishes the period before the first extension dose from events during open-label AFQ056 treatment, and it assigns treatment-period events according to the last dose taken on or before onset. Those details matter because a dose-specific count depends on the study’s classification rule, not simply on an assignment to a fixed parallel treatment group.
General: interpretation of safety counts depends on the analysis population, the period at risk and the event definition. A count without its denominator is hard to contextualize, while a count with a denominator still does not account for differences in exposure duration. Here, the record reports at-risk counts for each period, but it does not report an exposure-time analysis. Differences between period counts therefore cannot be treated as dose-specific risk estimates.
The study also illustrates why design and reporting context are essential. An open-label, single-group record can describe what was observed, but without a concurrent randomized comparator it cannot estimate a treatment difference. The registry’s report of no efficacy data, alongside the terminated status, further limits the scope of conclusions to the posted safety descriptions.
For statistical interpretation, the key distinction is between observed counts and causal or comparative claims. The counts are useful for understanding what the registry reports in this extension study; missing analysis details, absent inferential estimates and the lack of a control group constrain what can be concluded from them.
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 study was open-label and single-group, with no randomized allocation or concurrent control. The adverse-event counts therefore cannot establish treatment effects or support direct treatment comparisons. Dose-period results are especially easy to overinterpret: participants were titrated across dose levels, and events were assigned according to the last dose before onset. The registry record does not report exposure-adjusted rates or an analysis accounting for time at each dose.
The registry reports participant counts, not detailed event histories. It does not give event duration, recurrence, timing for each participant, or a complete account of severity grading. The criteria for classifying serious events are not reported in the registry record. The safety-set definition is available, but methods for missing assessments, incomplete follow-up and withdrawals are not reported.
No confidence intervals, inferential analyses or efficacy data are reported. The study is listed as terminated, but the reason and implications for planned analyses are not reported in the registry record. The sample-size justification, statistical analysis plan and any interim analyses are also not reported in the registry record. These limitations mean the results should be read as descriptive safety counts for the recorded analysis population and periods, not as definitive comparative or causal estimates.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Long-term, Safety, Tolerability and Efficacy Study of AFQ056 in Adult Patients With Fragile X Syndrome — NCT01348087.
- Registry record last updated 2016-05-25; status last verified 2016-04.
- Results first posted 2016-05-25.
- 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.
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 phase 2 study evaluated long-term safety, tolerability and efficacy of AFQ056 in eligible adults with Fragile X Syndrome who had participated in earlier studies. It was open-label, single-group and terminated. The registry lists enrollment of 148, a start date of 2011-08 and primary completion in 2014-09.
The primary outcome concerned adverse events and serious adverse events. The safety set required at least one dose of extension-study medication and at least one post-dose safety assessment. The AFQ056 total category reports 7 participants with serious adverse events and 117 with other adverse events among 148 at risk. No efficacy data were presented because the study was terminated.
The registry record does not report the reason for termination, efficacy findings, inferential analyses, confidence intervals or methods for missing data.