Ascending Multiple-Doses of Erenumab (AMG 334) in Healthy Adults and in Migraine Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Ascending Multiple-Doses of Erenumab (AMG 334) in Healthy Adults and in Migraine Patients (NCT01723514), a randomized phase 1 study. The primary outcome is Number of Participants With Adverse Events.

2. Clinical Question

This was a Phase 1 study, not a trial whose primary endpoint was a clinical measure of migraine benefit. Its primary focus was safety and tolerability after multiple doses. The registry also describes secondary objectives: characterizing erenumab’s pharmacokinetic profile and assessing its effect on capsaicin-induced dermal blood flow.

The groups were small: individual group sizes at risk for serious adverse events ranged from 4 to 8 participants. Counts in groups of this size describe what was observed among enrolled participants, but offer limited precision for comparing uncommon events. The record does not report eligibility criteria in enough detail to characterize how closely these participants represent a broader population.

3. Trial Design

This completed Phase 1 study was randomized, quadruple-masked, placebo-controlled and parallel-group. It enrolled 48 participants and included both healthy adults and participants with migraine. The sponsor was Amgen. The registry lists a start date of 2012-11-14 and a primary completion date of 2014-07-10.

Participants received multiple subcutaneous doses on days 1, 29 and 57. The registry lists placebo and erenumab groups separately within healthy participants and participants with migraine. In healthy participants, the erenumab dose groups were 21 mg, 70 mg, 140 mg and 280/210 mg. In participants with migraine, the listed erenumab groups were 21 mg and 140 mg. The group descriptions do not explain the 280/210 mg dose notation, and further details about dose escalation or assignment are not reported in the registry record.

Randomization means that assignment to study groups was intended to be determined by chance; masking means that specified people involved in the study were kept unaware of assigned treatment. The record does not identify which four groups of people were masked or describe how randomization and masking were implemented. The parallel-group model indicates that participants were assigned to groups rather than all participants receiving each treatment in sequence.

The study’s stated primary purpose was to assess safety and tolerability. Secondary objectives concerned serum concentration measures, including maximum observed concentration and exposure over specified periods, as well as the ratio of dermal blood flow after and before capsaicin. The registry lists 8 outcome measures and 22 analyses. A detailed protocol, allocation ratio, sample-size justification, and statistical analysis plan 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: Healthy participants were randomized to 1 of 4 cohorts and migraine patients were randomized to 1 of 2 cohorts. Within each cohort participants were assigned to erenumab or placebo in a 3:1 ratio.

Only the first 6 of 8 groups are shown.

Overall Study

Analysis population for the primary outcome, as defined in the registry: All participants who received at least 1 dose of study drug.

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 9 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Adverse Events, measured over From first dose of study drug until a maximum of 168 days after last dose (225 days).

The primary endpoint was the number of participants with adverse events. An adverse event was defined as any untoward medical occurrence during a clinical trial, whether or not it was considered causally related to study treatment. The definition also included worsening of a pre-existing medical condition. Laboratory value changes that required treatment or an adjustment in current therapy counted as adverse events.

The endpoint used a participant count rather than measuring symptom change or treatment benefit. Its purpose in this study was to describe how many participants experienced an adverse event during exposure and follow-up. Treatment-related adverse events were those the investigator assessed as possibly related to study drug. Serious adverse events were defined using criteria such as death, immediate risk of death, hospitalization, persistent or significant disability, congenital anomaly or another medically important event.

The observation period ran from the first dose until a maximum of 168 days after the last dose, stated as 225 days. The primary population comprised participants who received at least one dose of study drug. This definition focuses the endpoint on participants exposed to study treatment, rather than everyone who may have enrolled.

Counting participants is useful for a broad safety summary because it records whether each person experienced an event, without treating multiple events in one person as multiple affected participants. It does not, by itself, convey event severity, duration, recurrence, or causal certainty. Those details are not reported for the primary endpoint in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study is described as randomized, quadruple-masked, placebo-controlled and parallel-group. Randomization is a design approach that uses chance to assign participants to groups. In general, it can help balance characteristics across groups, but the registry record does not describe the randomization procedure, allocation ratio or how assignment was concealed. Quadruple masking indicates that four categories of people were intended to be unaware of assignment; which categories and how masking was maintained are not reported in the registry record.

The primary endpoint is a count of participants with adverse events, rather than a continuous measurement or a time-to-event outcome. The registry gives the numbers at risk and affected for adverse events and serious adverse events for each listed group. These counts are direct descriptions of observed participants. The record does not give an inferential analysis for the primary endpoint, such as a test of a difference, an estimate of relative or absolute effect, or uncertainty intervals.

What does a participant count capture?

A participant count records whether a person experienced at least one event during the defined period. It does not indicate how many events each affected person had. Nor does the count alone describe event duration, severity, timing, or whether the event was judged related to treatment. Those are distinct aspects of safety assessment. The registry defines treatment-related events as those the investigator assessed as possibly related to study drug, but does not provide those counts in the registry record reported for this endpoint.

How should small groups be interpreted?

General statistical explanation: small groups tend to yield estimates with substantial sampling uncertainty. A single participant’s outcome can make a noticeable difference to a group’s observed count, and uncommon outcomes may not appear during a limited study even if they can occur. These principles are relevant to the group sizes, which range from 4 to 8 participants at risk for serious adverse events. The registry does not report confidence intervals that would quantify uncertainty for the event counts.

The groups also represent different populations and doses. Healthy participants and participants with migraine are listed separately, and the dose groups differ between those populations. Combining groups or comparing a dose group with a placebo group would require a specified analysis and a clear rationale. Such a pooled analysis is not reported in the registry record. The record identifies that the primary outcome has several categories or time points and is not reduced to one comparison.

What do the secondary measures address?

The listed secondary outcomes include maximum observed serum concentration, time to maximum concentration, area under the serum concentration-time curve from 0 to 28 days, area under the serum curve from time zero to the last quantifiable concentration, and the ratio of post-capsaicin dermal blood flow to pre-capsaicin dermal blood flow. These address pharmacokinetic exposure and a pharmacodynamic measure, rather than the primary safety count. The registry lists 8 outcome measures and 22 analyses, but detailed analysis specifications and results for these measures are not reported in the record.

What does the planning information mean?

General statistical explanation: sample-size planning uses assumptions about the effect to be detected, the variability or event frequency, the significance level, and the desired probability of detecting that effect under the assumed model. A planning calculation is not a result from observed participants and is not “observed power.” The registry describes a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and planning for stated fractions of the observed effect. The reported details do not include the resulting sample-size values or a trial-specific sample-size justification. The illustration therefore should not be read as the design rationale for this study.

For binary outcomes, methods generally compare event counts or proportions. General statistical explanation: the validity and interpretation of a comparison depend on the analysis population, outcome definition, treatment groups, and prespecified method. The registry identifies the primary population as all participants who received at least one dose, but does not report a complete statistical analysis plan, handling of missing data, or interim analyses. A recalculated comparison is not reported, and no sponsor analysis is available in the registry record to take precedence over a recalculation.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple outcome measures and analyses: 8 outcome measures and 22 analyses. It does not report how the analyses were organized, which were prespecified as primary or secondary beyond the stated primary outcome and secondary objectives, or whether any adjustment for multiple testing was planned. Multiplicity arises when many outcomes, groups, time points or statistical tests are considered; without a stated approach, the chance of at least one apparently unusual result across analyses can be difficult to interpret. No correction method is reported in the registry record.

The primary outcome is not reduced to one comparison because it has several categories or time points. The registry does not report a single prespecified contrast between erenumab and placebo, nor a pooled primary estimate. The group-specific adverse-event counts can therefore be read descriptively, but they do not establish a formal treatment comparison.

The primary population includes participants who received at least one dose of study drug. Further analysis-population definitions are not reported in the registry record. The record also does not describe missing outcome data, exclusions after randomization, withdrawals, or the method used to handle missing observations. Those details matter because analyses based on different participant sets can produce different estimates, especially if missingness is related to treatment or outcomes.

Interim analyses, stopping rules and any adjustments to the analysis plan are not reported in the registry record. These omissions mean that the listed counts cannot be used to infer whether analyses were monitored or modified during the study. They also limit assessment of whether all planned outcomes and comparisons are represented in the reported results.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: polyarthritis (16.7%), depression (16.7%), suicidal ideation (16.7%).

The serious adverse event figures count affected participants, with the at-risk group size shown for each treatment group. In healthy participants, serious adverse events affected 0 of 8 receiving placebo, 0 of 6 receiving erenumab 21 mg, 1 of 6 receiving erenumab 70 mg, 0 of 6 receiving erenumab 140 mg and 0 of 6 receiving erenumab 280/210 mg. In participants with migraine, the counts were 0 of 4 for placebo, 0 of 6 for erenumab 21 mg and 1 of 6 for erenumab 140 mg.

These figures describe the number of participants with at least one serious event, not the total number of serious events. The record defines serious events by criteria including fatality, immediate risk of death, hospitalization, significant disability, congenital anomaly or another medically important event. The registry lists Polyarthritis, Depression and Suicidal ideation as serious-event terms, each at 16.7%. The context and denominators for those term percentages are not reported in the registry record.

Death counts are not reported in the registry record. A zero count in an event category means no affected participants were recorded for that group; it does not demonstrate that the event is impossible. The small groups also make these counts unsuitable for precise comparisons. Seriousness is a classification of the event’s consequences or importance, not proof that study drug caused it.

12. What the Result Does, and Does Not, Mean

The results describe adverse events observed among participants in a small Phase 1 study with multiple dose groups, two participant populations and a placebo group. The counts show that adverse events were reported in every listed group, while serious adverse events were reported for one participant in the healthy erenumab 70 mg group and one participant in the migraine erenumab 140 mg group. The registry does not provide a single comparative estimate for the primary endpoint.

These observations can inform a descriptive account of safety during the study’s specified exposure and follow-up period. They cannot, on their own, quantify how much the chance of an event differs between erenumab and placebo. The lack of reported uncertainty estimates, formal comparisons and detailed event-level information limits the precision and interpretation of between-group patterns. Because adverse events do not necessarily have a causal relationship with treatment, their occurrence should not be equated with a treatment-caused effect.

The record also describes secondary pharmacokinetic and pharmacodynamic objectives. Those objectives concern drug concentration and a capsaicin-induced dermal blood-flow measure; they are distinct from the primary adverse-event endpoint. Their presence does not turn this study into a trial with a primary clinical migraine outcome. Results for those secondary measures are not included in the registry record.

General statistical explanation: evidence from a trial is strongest for the specific participants, interventions, outcomes and follow-up actually studied. A small early-phase study can characterize observed events and support further investigation, but it cannot by itself establish the frequency of uncommon events in a broader population. Here, the registry record does not report a sample-size justification or comparative safety analysis that would support stronger claims about differences across groups.

The findings also do not establish safety beyond the maximum follow-up described, or answer questions about outcomes that were not measured or reported. They should be read as a record of what was observed in this study, not as a definitive estimate of risk for other populations or settings.

13. Why This Trial Matters Statistically

This trial is statistically useful as an example of how early-phase safety evidence differs from a definitive comparative estimate. Its randomized, masked, placebo-controlled design provides a framework for describing outcomes across assigned groups. At the same time, the small group sizes and the separation of healthy participants from participants with migraine make the observed counts primarily descriptive.

The primary endpoint is a participant count for adverse events, and the record includes distinct dose groups and populations. That structure matters: a reader should not treat all erenumab participants as one group or assume that a single pooled comparison was planned. The registry explicitly does not reduce the primary outcome to one comparison. A formal estimate would require a defined contrast, analysis method and treatment of the several categories or time points.

The record also illustrates why statistical reporting should include uncertainty and methods alongside event counts. Counts show what happened in the enrolled groups; confidence intervals or other uncertainty measures would help convey how precisely those results estimate an underlying frequency or difference. Such comparative estimates are not reported in the registry record.

Finally, the study’s multiple objectives span safety, pharmacokinetics and a pharmacodynamic measure. These objectives answer different questions and may involve multiple analyses. The registry lists 8 outcome measures and 22 analyses, but does not report a multiplicity strategy or complete statistical analysis plan. Recognizing those limits helps keep the interpretation aligned with what the design and posted results can support, without turning descriptive observations into broader claims.

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 detailed eligibility criteria, so the enrolled population cannot be fully characterized beyond healthy participants and participants with migraine. Group sizes are small, and the separate populations and dose groups complicate any simple treatment-wide comparison. Allocation ratios and the randomization procedure are not reported.

The registry does not identify the four masked groups or explain how masking was maintained. The notation for the healthy erenumab 280/210 mg group is not explained. Detailed dose-escalation procedures, if any, are not reported in the registry record.

The primary outcome is reported as counts, without a single comparative analysis, confidence intervals or a statistical test. The record does not report detailed event-level information, including timing, duration or severity for each event, or the count of treatment-related adverse events. Death counts are not reported. The serious-event terms are listed with percentages, but their denominators and relationship to treatment groups are not specified.

The record lists secondary objectives and outcome measures but does not report their analysis details or results in the registry record. It also does not report a sample-size justification, a full statistical analysis plan, missing-data methods, interim analyses, stopping rules, or a multiplicity approach. These gaps limit assessment of how the analyses were planned and how complete the reported results are.

Follow-up was described as extending from first dose until a maximum of 168 days after the last dose, stated as 225 days. The findings therefore pertain to the study’s observation period and cannot answer questions about outcomes beyond it. The registry’s counts should be interpreted as observations in this study, not as precise estimates for broader populations.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Ascending Multiple-Doses of Erenumab (AMG 334) in Healthy Adults and in Migraine Patients — NCT01723514.
• Registry record last updated 2019-01-18; status last verified 2018-08.
• Results first posted 2019-01-18.
• 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.

18. Record Summary

NCT01723514 is a completed Phase 1 randomized, quadruple-masked, placebo-controlled, parallel-group study sponsored by Amgen. It enrolled 48 participants, including healthy adults and participants with migraine, and evaluated multiple subcutaneous doses of erenumab against placebo. Doses were administered on days 1, 29 and 57.

The primary outcome was the number of participants with adverse events among those who received at least one dose, assessed from first dose until a maximum of 168 days after the last dose (225 days). The registry reports group-specific counts for adverse events and serious adverse events, but does not reduce the primary outcome to one comparison. Secondary objectives concerned pharmacokinetics and capsaicin-induced dermal blood flow.

The record lists 8 outcome measures and 22 analyses. A sample-size justification, detailed statistical analysis plan, missing-data methods and multiplicity approach are not reported in the registry record. The posted adverse-event counts are descriptive and are not accompanied by comparative estimates or uncertainty intervals.