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 Safety and Pharmacology Study of VP 20629 in Adults With Friedreich's Ataxia (NCT01898884), a randomized phase 1 study. The primary outcome is Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01898884 |
| Phase | Phase 1 |
| Condition | Friedreich's Ataxia |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 46 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Shire |
| Results posted | Yes |
2. Clinical Question
Population
Adults with Friedreich's ataxia were eligible for the study. The registry describes the safety population as randomly assigned participants who received at least a partial or complete dose of investigational product. The record lists enrollment as 46, but the safety denominators vary across dose groups; the reasons for those differences are not reported in the registry record.
Intervention
VP 20629 was studied as an oral drug in both single-dose and multiple-dose groups. The single-dose groups were assigned 150 mg, 450 mg, 900 mg, or 1200 mg. The multiple-dose groups were assigned total daily doses of 300 mg, 600 mg, or 900 mg, administered every 8 hours for 7 days, followed by a single morning dose on Day 8.
Comparator
Participants in the placebo groups received placebo in place of VP 20629. The registry describes four single-dose groups and three multiple-dose groups, each planned to include 8 subjects. The actual safety denominators reported for individual groups are not all the same as those planned group sizes.
Primary question
The primary objective was to evaluate safety and tolerability of single and multiple oral doses. The primary endpoint counts participants with treatment-emergent adverse events and treatment-emergent serious adverse events from the start of study treatment up to Day 19. Pharmacokinetics were secondary objectives, while specified plasma and urinary biomarkers were exploratory objectives.
3. Trial Design
This was a Phase 1 randomized, double-blind, placebo-controlled, multicenter study with parallel groups. It evaluated both single and multiple oral doses of VP 20629 in adults with Friedreich's ataxia. The registry lists the study as completed, with enrollment of 46. The recorded study start was 2013-08-13, and primary completion was 2015-06-18.
The single-dose plan included four dose groups: 150 mg, 450 mg, 900 mg, and 1200 mg. The multiple-dose plan included total daily doses of 300 mg, 600 mg, and 900 mg, administered every 8 hours for 7 days and then as a single morning dose on Day 8. The registry describes each planned dose group as having 8 subjects and states that placebo was also used. Actual safety denominators in the results differ by group; the record does not explain the differences.
Randomization and double blinding are features of the design intended to reduce the influence of participant and investigator expectations on treatment assignment and outcome assessment. In general, a parallel-group design assigns participants to a group that receives its assigned treatment rather than crossing participants between treatments. These design features do not by themselves establish that groups were comparable in every respect or that the study can answer questions beyond its stated objectives.
The primary objective concerned safety and tolerability. The secondary objectives concerned plasma concentration-time profiles for VP 20629 and its metabolite, VP 20631. Exploratory objectives concerned plasma 8-isoprostane and malondialdehyde and urinary 8-hydroxydeoxyguanosine concentrations after multiple doses. The registry lists pharmacokinetic outcomes but does not report numerical outcome results in the information available for this analysis.
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 46 participants were enrolled to the study, of which 32 were randomly assigned to single-dose group and 24 were randomly assigned to multiple-dose group. Participants who received investigational product in a single-dose group and completed the post-treatment safety assessment were allowed to enrol in a multiple-dose group.
Only the first 6 of 9 groups are shown.
Single Dose Period
| Stage | Single Dose Placebo | Single Dose VP 20629 150 mg | Single Dose VP 20629 450 mg | Single Dose VP 20629 900 mg | Single Dose VP 20629 1200 mg | Multiple Dose Placebo |
|---|---|---|---|---|---|---|
| STARTED | 8 | 6 | 6 | 6 | 6 | 0 |
| COMPLETED | 8 | 6 | 6 | 6 | 6 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
Multiple Dose Period
| Stage | Single Dose Placebo | Single Dose VP 20629 150 mg | Single Dose VP 20629 450 mg | Single Dose VP 20629 900 mg | Single Dose VP 20629 1200 mg | Multiple Dose Placebo |
|---|---|---|---|---|---|---|
| STARTED | 0 | 0 | 0 | 0 | 0 | 6 |
| Treated | 0 | 0 | 0 | 0 | 0 | 6 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 6 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
Reasons for not completing this period:
| Reason | Single Dose Placebo | Single Dose VP 20629 150 mg | Single Dose VP 20629 450 mg | Single Dose VP 20629 900 mg | Single Dose VP 20629 1200 mg | Multiple Dose Placebo |
|---|---|---|---|---|---|---|
| Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 |
| Randomized Not Treated | 0 | 0 | 0 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: The ITT-safety (ITT-S) set consisted of all participants who were randomly assigned to an investigational product treatment group and who received at least 1 partial or complete dose of investigational product.
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.
Population: The intent-to-treat (ITT) set consisted of all participants who were randomly assigned to an investigational product treatment group. The baseline data for 14 participants who were randomised directly to multiple dose groups, was not summarised and not reported.
| Characteristic | Unit | Single Dose Placebo | Single Dose VP 20629 150 mg | Single Dose VP 20629 450 mg | Single Dose VP 20629 900 mg | Single Dose VP 20629 1200 mg | Total |
|---|---|---|---|---|---|---|---|
| Participants analysed | 8 | 6 | 6 | 6 | 6 | 32 | |
| Age, Continuous | years | 25.1 (SD 7.04) | 22.7 (SD 1.97) | 27.8 (SD 4.45) | 28.0 (SD 6.90) | 26.8 (SD 8.86) | 26.0 (SD 6.27) |
| Sex: Female, Male: Female | Participants | 5 | 3 | 2 | 3 | 4 | 17 |
| Sex: Female, Male: Male | Participants | 3 | 3 | 4 | 3 | 2 | 15 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs), measured over From Start of Study Treatment up to Day 19.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of participants with treatment-emergent adverse events and treatment-emergent serious adverse events. An adverse event is defined in the record as an untoward medical occurrence after receiving study drug, without requiring a judgment that the drug caused it. A serious adverse event is an event with specified serious consequences, such as death, hospitalization, a life-threatening experience, persistent or significant disability, or a congenital anomaly, or an event judged significant for another reason.
Treatment-emergent events are those that begin during study treatment and up to 7 days after the last dose, and were absent at baseline or increased in frequency or severity compared with baseline. The recorded observation timeframe is from the start of study treatment up to Day 19. This endpoint is used to describe the occurrence of safety events during and shortly after exposure; it is not, on its own, proof that treatment caused an event.
Counting participants with at least one event is a straightforward way to summarize how many people experienced an event in each group. It does not describe every event's duration, severity, recurrence, or relationship to treatment. The primary outcome includes both TEAEs and TESAEs, and the registry reports those categories separately in the safety results. A single summary count would therefore leave out important distinctions between non-serious and serious events.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted safety results show variation in the number of participants with other treatment-emergent adverse events across the dose groups. In the single-dose groups, the reported counts were 3 of 8 for placebo, 0 of 6 for VP 20629 150mg, 4 of 6 for 450mg, 5 of 6 for 900mg, and 6 of 6 for 1200mg. In the multiple-dose groups, the counts were 4 of 6 for placebo, 3 of 6 for VP 20629 300mg, 6 of 6 for 600mg, and 3 of 5 for 900mg. These are descriptive counts; they do not establish that a dose caused an event or that differences between groups are statistically reliable.
For treatment-emergent serious adverse events, the registry reports 1 of 6 participants in the multiple-dose VP 20629 300mg group and 0 in each of the other listed groups. These group counts are sparse, so a difference of even a small number of participants can substantially affect the impression created by a proportion. The counts should be read as observations in this study, not as precise estimates of the frequency of events in a broader population.
The record identifies angina pectoris as a serious adverse event term and lists 16.7%. That term is a description of a reported event, not evidence that VP 20629 caused it. The available record does not provide enough detail to assign the term to a particular treatment group or to assess individual participants' clinical circumstances. Death counts are not reported in the registry record.
The study's primary objective was safety and tolerability, not a test of clinical benefit. The record describes secondary pharmacokinetic objectives and exploratory biomarker objectives, but numerical results for those objectives are not reported in the registry record. A formal statistical comparison of the safety groups, including confidence intervals or hypothesis-test results, is also not reported in the registry record. The available counts therefore support a descriptive account only.
The planned group sizes and actual safety denominators are not identical in every group. The registry does not explain why. As a general statistical consideration, unequal denominators make direct comparisons less intuitive, especially when the groups are small. The data should be interpreted within the context of this early-phase study and its limited reported outcomes, rather than used to infer a stable pattern across doses or to make conclusions about efficacy.
9. Statistical Methods Explained
What does randomization contribute?
Randomization assigns participants to treatment groups using a chance-based process. In general, it helps reduce systematic differences between groups at the start of a study, including differences that investigators may not have measured. It does not guarantee identical groups, particularly in a study with small groups. The registry identifies the study as randomized and double-blind, but the method used to generate or conceal the random assignment is not reported in the registry record.
Double blinding means that treatment assignment is masked for two parties, but the registry information does not identify those parties or describe how masking was maintained. In general, masking can reduce the influence of treatment expectations on participant reports and outcome assessment. It cannot remove all sources of bias, and the record does not report whether masking was assessed.
What do the event counts describe?
The reported safety figures count participants with events, rather than counting every event occurrence. A participant with more than one event remains one participant in a count of participants affected. This form of summary communicates how many participants experienced at least one event, but does not show the total number of events or their recurrence. In general, those are different quantities and should not be treated as interchangeable.
The primary endpoint distinguishes treatment-emergent adverse events from treatment-emergent serious adverse events. An adverse event does not need to be judged related to treatment to be recorded. Seriousness is defined by outcomes or clinical significance, not by how likely an event is to have been caused by the study drug. In general, seriousness and severity are related but distinct concepts; the registry definition focuses on serious outcomes and significance.
Why are the group denominators important?
The group-specific denominators indicate the number of participants at risk in the posted safety summaries. They vary across the groups, including between the planned group sizes described in the design and the actual safety denominators. The registry does not report the reasons for these differences. In general, a proportion is interpreted in relation to its denominator: the same event count can imply a different observed proportion in groups of different sizes. No additional proportions or comparisons should be inferred from the counts without an explicit analysis.
Small groups also make estimates imprecise. In general, a confidence interval expresses a range of values compatible with the observed data under a statistical model. Wider intervals indicate greater uncertainty. Confidence intervals and formal comparisons are not reported in the registry record, so the posted counts cannot establish the precision of an estimated treatment difference.
What is the role of dose groups?
The study includes several single-dose and multiple-dose groups, as well as placebo groups. These groups allow the study to observe safety and pharmacology under different dosing schedules. In general, a pattern across dose groups may motivate further investigation, but a descriptive pattern is not by itself evidence of a dose-response relationship. Such a conclusion requires an appropriate analysis and careful consideration of the small group sizes, exposure schedules, and other possible explanations. A formal dose-response analysis is not reported in the registry record.
The single-dose and multiple-dose regimens are not interchangeable exposures. The multiple-dose schedule involved repeated administration over 7 days with a morning dose on Day 8, whereas the other groups received a single dose. General comparisons between those parts of the study should account for the different exposure patterns rather than treating them as one continuous dose scale.
What can be said about the planned analyses?
The registry identifies pharmacokinetic measures including maximum observed concentration, time to maximum concentration, areas under the concentration-time curve, terminal half-life, volume of distribution, and clearance. These measures describe different aspects of drug exposure and disposition. The registry also identifies exploratory biomarker measures. Numerical results and analysis details for these outcomes are not reported in the registry record.
The statistical analysis plan, including methods for handling missing observations, is not reported in the registry record. The record does not report a sample-size justification, interim analyses, or a specified statistical model for the primary endpoint. In general, these details help readers understand how an analysis was planned, what assumptions it uses, and how uncertainty is handled. Their absence means the posted event counts should be interpreted descriptively rather than as the outcome of a documented comparative test.
10. Multiplicity, Missing Data and Analysis Populations
The study includes multiple dose groups, two dosing schedules, a primary safety objective, secondary pharmacokinetic objectives, and exploratory biomarker objectives. When many outcomes or group comparisons are examined, the chance of finding an apparently notable result by chance can increase. General approaches to multiplicity include adjusting statistical thresholds, defining a testing sequence, or treating analyses as exploratory. The multiplicity strategy for this study is not reported in the registry record.
The registry identifies the primary endpoint as counts of participants with TEAEs and TESAEs, but the handling of multiple comparisons among dose groups is not reported in the registry record. The available record also does not report a statistical analysis plan or formal hypothesis tests for these results. Accordingly, the event counts should not be interpreted as evidence from a prespecified significant-versus-not-significant comparison.
The ITT-safety population is defined as all participants randomly assigned to an investigational product group who received at least a partial or complete dose of investigational product. This definition focuses on participants exposed to study product. The registry does not report a separate analysis population for pharmacokinetic or biomarker outcomes, or explain how participants with incomplete observations were handled.
Missing-data methods, reasons for missing observations, and the extent of missingness for the outcomes are not reported in the registry record. In general, missing-data handling matters because participants with unavailable measurements may differ from those with observed measurements. Without those details, readers cannot assess whether missing observations could have affected the reported summaries. No imputation or other missing-data procedure should be assumed.
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 |
|---|---|---|---|
| Single Dose Placebo | 0 | 8 | 0.0% |
| Single Dose VP 20629 150mg | 0 | 6 | 0.0% |
| Single Dose VP 20629 450mg | 0 | 6 | 0.0% |
| Single Dose VP 20629 900mg | 0 | 6 | 0.0% |
| Single Dose VP 20629 1200mg | 0 | 6 | 0.0% |
| Multiple Dose Placebo | 0 | 6 | 0.0% |
| Multiple Dose VP 20629 300mg | 1 | 6 | 16.7% |
| Multiple Dose VP 20629 600mg | 0 | 6 | 0.0% |
| Multiple Dose VP 20629 900mg | 0 | 5 | 0.0% |
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 |
|---|---|
| Single Dose Placebo | 3 of 8 |
| Single Dose VP 20629 150mg | 0 of 6 |
| Single Dose VP 20629 450mg | 4 of 6 |
| Single Dose VP 20629 900mg | 5 of 6 |
| Single Dose VP 20629 1200mg | 6 of 6 |
| Multiple Dose Placebo | 4 of 6 |
Most frequent serious adverse event terms
| Event term | Organ system | Single Dose Placebo | Single Dose VP 20629 150mg | Single Dose VP 20629 450mg | Single Dose VP 20629 900mg | Single Dose VP 20629 1200mg | Multiple Dose Placebo |
|---|---|---|---|---|---|---|---|
| Angina pectoris | Cardiac disorders | 0 of 8 | 0 of 6 | 0 of 6 | 0 of 6 | 0 of 6 | 0 of 6 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Single Dose Placebo | Single Dose VP 20629 150mg | Single Dose VP 20629 450mg | Single Dose VP 20629 900mg | Single Dose VP 20629 1200mg | Multiple Dose Placebo |
|---|---|---|---|---|---|---|---|
| Headache | Nervous system disorders | 1 of 8 | 0 of 6 | 0 of 6 | 3 of 6 | 0 of 6 | 2 of 6 |
| Fatigue | General disorders | 1 of 8 | 0 of 6 | 0 of 6 | 1 of 6 | 2 of 6 | 0 of 6 |
| Diarrhoea | Gastrointestinal disorders | 0 of 8 | 0 of 6 | 0 of 6 | 0 of 6 | 1 of 6 | 1 of 6 |
| Flatulence | Gastrointestinal disorders | 1 of 8 | 0 of 6 | 0 of 6 | 0 of 6 | 0 of 6 | 1 of 6 |
| Nausea | Gastrointestinal disorders | 0 of 8 | 0 of 6 | 1 of 6 | 1 of 6 | 0 of 6 | 0 of 6 |
| Back pain | Musculoskeletal and connective tissue disorders | 1 of 8 | 0 of 6 | 0 of 6 | 0 of 6 | 1 of 6 | 0 of 6 |
| Dizziness | Nervous system disorders | 1 of 8 | 0 of 6 | 0 of 6 | 1 of 6 | 0 of 6 | 0 of 6 |
| Angina pectoris | Cardiac disorders | 0 of 8 | 0 of 6 | 0 of 6 | 0 of 6 | 0 of 6 | 1 of 6 |
| Palpitations | Cardiac disorders | 0 of 8 | 0 of 6 | 0 of 6 | 1 of 6 | 0 of 6 | 0 of 6 |
| Vision blurred | Eye disorders | 0 of 8 | 0 of 6 | 0 of 6 | 1 of 6 | 0 of 6 | 0 of 6 |
Serious events with the highest arm-level rate: angina pectoris (16.7%).
The serious-event results are counts of participants, not rates per unit of treatment time. The registry reports one participant with a treatment-emergent serious adverse event in the multiple-dose VP 20629 300mg group, whose safety denominator is 6. It reports zero participants with such events in the other listed groups. These figures describe what was recorded during the stated timeframe; they do not show whether the event was caused by treatment.
The registry lists angina pectoris as a serious adverse event term and gives 16.7%. The record does not provide enough information in this summary to connect that term to a particular group or to describe its clinical course. Death counts are not reported in the registry record. A zero count means no participant with the event was recorded in that group during the reported period; it does not establish that the underlying risk is absent.
Because the groups are small, the counts are inherently limited in how precisely they describe uncommon serious events. A serious event in one group, or no recorded serious events in another, is not by itself a reliable basis for ranking treatments. The registry counts should be read alongside the study's early-phase safety purpose and the limited duration of observation.
12. What the Result Does, and Does Not, Mean
The results provide a descriptive account of treatment-emergent adverse events and serious adverse events in adults with Friedreich's ataxia who received study product. They show that other treatment-emergent adverse events were reported in several groups, with the posted participant counts varying across groups. The serious-event results include one affected participant in the multiple-dose VP 20629 300mg group and zero in the other listed groups. These observations are relevant to the stated safety and tolerability objective.
They do not establish that VP 20629 caused any particular adverse event. The adverse-event definition does not require causal attribution, and the registry information does not report a formal comparative analysis. The counts also do not establish that one dose is safer than another: groups are small, their safety denominators vary, and the single-dose and multiple-dose schedules differ.
The results do not answer whether VP 20629 changes Friedreich's ataxia or improves a clinical outcome. The primary endpoint is safety-focused, and numerical results for the secondary pharmacokinetic and exploratory biomarker objectives are not reported in the registry record. No conclusion about clinical benefit should be drawn from these safety counts.
In general, early-phase studies are used to characterize safety, tolerability, and drug exposure in the studied setting. Their observations can inform questions for later research, but the study record does not report a sample-size justification or a statistical plan that would support precise comparative conclusions. The available information should therefore be treated as a limited description of events among participants in this trial, not as a definitive estimate of risk or a prediction for other populations.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of the distinction between a safety description and a comparative treatment-effect analysis. Its primary endpoint counts participants with treatment-emergent events, an outcome suited to recording safety observations in an early-phase study. Those counts can be useful even when they do not support a formal claim about differences between groups.
The design has multiple dose groups and two exposure schedules. That structure makes it important to keep group-specific denominators and dosing patterns in view. The safety denominators reported in the results vary, while the design description specifies planned groups of 8 subjects. The registry does not explain why the observed denominators differ. This limits interpretation of apparent differences and underlines why simple comparisons across groups can be misleading.
The study also illustrates why event counts need context. A count of participants with an event does not convey the number of events, recurrence, severity beyond the serious-event classification, or causal relationship to treatment. The serious-event count is particularly sparse, so it offers limited precision about uncommon outcomes.
Finally, the study's stated aims extend beyond safety to pharmacokinetics and exploratory biomarkers, but numerical results for those objectives are not reported in the registry record. Statistical interpretation is constrained not only by group size, but also by what analyses and outcome details are available. Readers can identify the study's objectives and observed safety counts, while recognizing that the record does not document the comparative statistical methods needed for stronger conclusions.
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 safety denominators differ across the reported groups, and the registry does not explain why. This makes interpretation of group-to-group differences more difficult. The planned group descriptions specify 8 subjects in each group, while the safety results list smaller denominators for some groups. Reasons for any nonparticipation, nonexposure, or exclusion are not reported in the registry record and should not be inferred.
The event summaries are counts of participants with events. The registry information does not give a full account of event frequency, recurrence, duration, severity beyond the serious classification, or individual clinical context. The listed serious-event term angina pectoris and its reported 16.7% cannot, from this information alone, be assigned to a particular group or used to establish causation. Death counts are not reported in the registry record.
Formal statistical comparisons and confidence intervals are not reported in the registry record. Neither a sample-size justification nor the analysis methods for the primary outcome are reported. As a result, the precision of group-specific estimates and the reliability of apparent differences cannot be assessed from the posted information.
The registry describes secondary pharmacokinetic and exploratory biomarker objectives, but numerical results for these outcomes are not reported in the registry record. Missing-data handling, multiplicity procedures, and reasons for incomplete observations are also not reported. The observation timeframe for the primary safety endpoint ends at Day 19; longer-term safety findings are not described in this record. These limitations restrict the interpretation to the posted safety observations and study design details.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety and Pharmacology Study of VP 20629 in Adults With Friedreich's Ataxia — NCT01898884.
- Registry record last updated 2021-06-02; status last verified 2021-05.
- Results first posted 2016-10-06.
- 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
The registry record describes a completed Phase 1 randomized, double-blind, placebo-controlled, multicenter, parallel-group study of oral VP 20629 in adults with Friedreich's ataxia. Enrollment is listed as 46. The recorded study start was 2013-08-13, and primary completion was 2015-06-18.
The study evaluated single doses of 150 mg, 450 mg, 900 mg, or 1200 mg, and multiple total daily doses of 300 mg, 600 mg, or 900 mg. The primary objective was safety and tolerability, assessed through participant counts for treatment-emergent adverse events and serious adverse events from the start of treatment up to Day 19. Secondary objectives concerned pharmacokinetics; exploratory objectives concerned specified plasma and urinary biomarkers.
The registry reports group-specific safety counts but does not report formal statistical analyses, numerical pharmacokinetic results, or numerical biomarker results in the information available for this analysis. The results are therefore best understood as descriptive safety observations.