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

1. Trial at a Glance

This page covers the registry results for Ascending Single Doses of Erenumab (AMG 334) in Healthy Adults and Migraine Patients (NCT01688739), a randomized phase 1 study. The primary outcome is Number of Participants With Adverse Events.

2. Clinical Question

The study also aimed to characterize erenumab’s pharmacokinetic profile after single subcutaneous or intravenous doses and its effect on capsaicin-induced changes in dermal blood flow. Those are secondary objectives, not the primary safety question. The listed secondary measures include maximum observed concentration, time to maximum observed concentration, areas under the concentration-time curve, and the ratio of post-capsaicin to pre-capsaicin dermal blood flow.

The central statistical question is descriptive: what adverse-event counts were recorded in each dose, route, and participant group? The posted results give counts of participants with serious and other adverse events, but do not provide one combined estimate comparing erenumab with placebo. Because dose and route vary across the groups, the separate counts should be read as dose-specific observations rather than as a single pooled treatment contrast.

3. Trial Design

This was a randomized, double-blind, placebo-controlled, sequential, phase I study. The registry record lists quadruple masking. It enrolled 61 participants and studied healthy adults as well as migraine patients. The trial status is completed; the recorded study start was 2012-03-13 and primary completion was 2013-03-27.

Participants received a single dose of erenumab or matching placebo. Erenumab was administered subcutaneously at 1 mg, 7 mg, 21 mg, 70 mg, 140 mg, or 210 mg, or intravenously at 140 mg. Placebo was administered by subcutaneous or intravenous injection. Safety results distinguish healthy and migraine groups and separate the erenumab dose and route groups.

The sequential, ascending-dose structure means the registry record presents several dose-specific groups rather than one erenumab group at a single dose. The posted safety counts include healthy participants receiving placebo and each listed erenumab regimen, and migraine patients receiving placebo or erenumab 140 mg subcutaneously. These group-specific counts are the relevant descriptive units for reading the safety results.

The primary outcome is the number of participants with adverse events, in the population of participants who received study drug, over the period from the initial dose up to 155 days. The registry record does not report the allocation ratio, the sequence rules for dose escalation, or a detailed protocol for how dose groups were assigned. It also does not report whether participants or investigators were unmasked at any point.

The trial’s stated primary purpose was to evaluate safety and tolerability. Its secondary objectives addressed pharmacokinetics and capsaicin-induced dermal blood flow. The record lists seven outcome measures and three analyses, but does not provide enough information to reconstruct a complete analysis plan or the results for the secondary outcomes.

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 in a 3:1 ratio to erenumab or placebo within each dose cohort. Migraine participants were randomized in a 1:1 ratio to erenumab or placebo.

Only the first 6 of 10 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All participants who received 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.

Population: All participants who received study drug.

Only the first 6 of 11 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Adverse Events, measured over From the initial dose of study drug up to 155 days..

The primary endpoint counts participants who experienced an adverse event after receiving study drug, from the initial dose up to 155 days. It is a participant-level count: the endpoint concerns how many people had an event, not how many separate event episodes occurred. The registry record defines an adverse event as an untoward medical occurrence during a clinical trial. An event can qualify even when it is not considered caused by the study treatment; worsening of a pre-existing medical condition is included. Laboratory changes requiring treatment or adjustment of current therapy also count as adverse events.

This endpoint is used to describe safety and tolerability during the recorded follow-up period. Reporting participants with an event makes it possible to see the observed burden in each dose and participant group, while retaining the distinction between serious and other adverse events in the posted results. Treatment-related adverse events are a narrower category: the investigator had to assess them as possibly related to study drug.

The endpoint does not by itself establish whether treatment caused an event. Nor does a participant count describe the event’s severity, duration, or recurrence unless those details are reported separately. The record defines serious adverse events using criteria that include fatal or life-threatening events, hospitalization, persistent or significant disability, congenital anomaly or birth defect, and other medically important events. The posted figures therefore need to be interpreted as safety counts with these definitions and the stated follow-up window in mind.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

For a binary safety endpoint, each participant is classified according to whether an event occurred during the defined observation period. The posted results give the number at risk and the number affected in each group. This makes the counts interpretable at the participant level, but it does not show how many total event episodes occurred or how events were distributed by type, timing, duration, or severity beyond the serious-event classification.

What does a zero count tell us?

A zero observed count means that no participant in that particular group was recorded as having the specified event category in the registry results. It is not a claim that the true probability is zero. In general, estimates from small groups are imprecise, especially when events are uncommon. A confidence interval, when reported, expresses a range of values compatible with the data under the method used; it can make that uncertainty more visible than the count alone. The registry record does not report confidence intervals for these safety counts.

Why keep the groups separate?

The trial includes distinct populations, doses, and routes. Keeping those categories separate preserves the information recorded for healthy participants and migraine patients, and for subcutaneous and intravenous administration. Pooling groups could conceal differences across dose or population, while a single pooled number could imply a comparison that was not reported. The posted record does not supply a pooling rule or a prespecified contrast for combining these groups.

What does the comparison require?

A treatment comparison usually needs a defined contrast, an effect measure, and an uncertainty estimate. For example, an analysis might compare event risks between groups, but the registry record does not post such an estimate for the primary safety outcome. It also does not report a statistical test or model for that outcome. It is therefore appropriate to describe the group counts without treating them as a statistically established treatment difference.

How should adverse-event categories be understood?

The endpoint’s broad adverse-event definition includes occurrences that do not necessarily have a causal relationship to treatment. The related-event definition depends on the investigator’s assessment that an event was possibly related to study drug. Seriousness is classified using the registry’s stated criteria, which include clinical consequences such as hospitalization and other medically important events. These are different concepts: an event can be an adverse event without being treatment-related, and seriousness is not the same as causation.

The group results distinguish serious adverse events from other adverse events. The record does not provide a definition for the “other” category beyond its presentation alongside serious events, so that label should not be expanded into an assumption about event severity or relationship to treatment. The counts also do not describe treatment-related adverse events separately.

What can planning calculations establish?

Sample-size calculations are planning illustrations, not observed power. The registry record does not report the trial’s sample-size justification. The planning assumptions described for illustrations use a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. Such assumptions do not establish that the trial was designed to detect a particular effect, and they do not turn the observed results into evidence of adequate or inadequate power. The primary outcome is not reduced to a single comparison in the posted analysis.

More generally, over-dispersion matters when count data vary more than a chosen statistical model expects: a model that understates variation can produce uncertainty estimates that are too narrow. That general issue does not establish that over-dispersion applies to these participant-level binary safety counts. The registry record does not report a model or dispersion estimate for the primary outcome.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists seven outcome measures and three analyses. It identifies the number of participants with adverse events as the primary outcome and lists pharmacokinetic and dermal blood-flow measures among the secondary outcomes. However, it does not report a complete statistical analysis plan, a hierarchy among secondary outcomes, or a method for controlling multiplicity across outcomes or dose groups. No adjustment for multiple comparisons is reported.

The primary safety result is presented through several categories and time points rather than as one posted comparison. The record does not provide a single treatment-effect estimate, confidence interval, or test for the primary outcome. It also does not report whether analyses were prespecified, exploratory, adjusted, or based on any particular model.

Missing-data procedures are not reported in the registry record. The record does not state how participants with incomplete follow-up, missing outcome assessments, or incomplete adverse-event information were handled. The primary population is described as all participants who received study drug, but the record does not explain whether every such participant contributed complete data through the stated follow-up period.

The registry record does not report an interim-analysis plan or stopping rules. It also does not describe a detailed analysis population for each secondary measure. These omissions limit assessment of how multiplicity, incomplete data, and analysis choices may affect interpretation. No method should be inferred from the posted counts alone.

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 non-serious adverse event terms

Serious adverse events are reported as participants affected among participants at risk. The serious-event count is 0 in every listed group: the healthy placebo group, each healthy erenumab dose and route group, the migraine placebo group, and the migraine erenumab group. The group sizes are small, ranging from 3 to 12 participants in the posted safety data. A zero count in these groups describes what was recorded; it does not show that the underlying risk is zero or rule out events that could occur in a larger population or longer observation.

The serious-event definition includes fatal events, life-threatening events, events requiring inpatient hospitalization or prolongation of hospitalization, persistent or significant disability or incapacity, congenital anomaly or birth defect, and other medically important serious events. The record lists no serious-event terms. It does not report deaths in the group data, so that field should not be interpreted as a recorded zero.

Other adverse events are reported separately and are more common in the posted counts. The record does not provide comparative uncertainty estimates or identify a statistically tested contrast. These counts therefore support a descriptive reading by group, not a conclusion that one regimen is safer than another.

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

The posted results describe adverse events observed after single doses of erenumab or placebo in healthy adults and migraine patients. They show no serious adverse events recorded in the listed groups and provide counts of participants with other adverse events for each group. Those counts preserve distinctions by population, dose, and route, which is important in a sequential, ascending-dose study.

The counts do not establish that erenumab caused or prevented any event. The registry’s broad adverse-event definition explicitly does not require a causal relationship to study treatment. Although the record defines treatment-related adverse events by investigator assessment, it does not give separate group counts for that category. Nor do the posted figures give event-level details that would establish severity, recurrence, or timing for the other adverse events.

The results also do not establish equivalence between erenumab and placebo, or demonstrate that the groups have the same underlying event risk. A lack of a reported comparative estimate is not evidence of no difference. With small groups and no reported confidence intervals or hypothesis tests, the precision of any between-group difference cannot be assessed from the registry record.

The trial’s objectives included pharmacokinetic and pharmacodynamic characterization, but the registry entries described for this analysis do not include numerical results for those measures. No conclusion about drug concentration or capsaicin-induced dermal blood flow can be drawn from the safety counts. The registry record also does not report a full analysis plan, missing-data approach, or sample-size justification.

In general, a phase I single-dose study can provide early descriptive information about tolerability and guide questions for later research. That general role does not replace evidence from other studies or establish clinical benefit. The record supports a narrow interpretation of the recorded safety observations within the stated groups and follow-up period, not broader conclusions about treatment effects.

13. Why This Trial Matters Statistically

This trial is statistically notable for the way its safety question is represented. The primary outcome concerns participants with adverse events, but the registry reports results across multiple dose, route, and participant groups rather than as a single treatment contrast. That structure makes careful descriptive reading more appropriate than collapsing the groups into an unreported pooled comparison.

The setting also makes the size and composition of groups important. The study enrolled 61 participants overall, while the listed safety groups contain small numbers of participants. Counts can be clinically legible, but they do not by themselves express uncertainty. A zero serious-event count is informative as an observation, yet it does not precisely characterize the possible frequency of rare events.

The record distinguishes serious events from other adverse events and defines adverse events broadly, including events without an assumed treatment relationship. This emphasizes an important statistical and interpretive distinction: recording an event is not the same as attributing it to a study drug. The related-event category requires an investigator judgment, but corresponding counts are not reported in the posted results.

Finally, the record illustrates the limits of registry outcome summaries. It specifies objectives and endpoint definitions, but does not provide a complete analysis plan, inferential results for the primary outcome, multiplicity procedures, or missing-data methods. Those details matter when interpreting how much evidence a set of counts offers. The posted data are useful as a record of observed safety categories, while leaving the strength and precision of between-group comparisons unresolved.

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 groups are small and separated across participant type, dose, and administration route. The resulting counts are descriptive and do not include comparative effect estimates or uncertainty intervals. This limits conclusions about differences between erenumab and placebo and about variation across doses or routes.

The registry record does not report detailed event-level information for the other adverse events, including event types, timing, duration, recurrence, or investigator attribution. It does not give separate treatment-related adverse-event counts. The absence of listed serious-event terms and the unreported death data also mean that these details cannot be reconstructed from the group summaries.

The observation window is described as extending from the initial dose up to 155 days, but the record does not explain completeness of follow-up or how missing outcome information was handled. The analysis population is described as participants who received study drug; further analysis-population definitions are not reported.

The trial’s allocation, masking, and sequential model are identified, but the allocation ratio, dose-escalation rules, and detailed protocol are not reported in the registry record. A complete statistical analysis plan, multiplicity approach, interim-analysis plan, and sample-size justification are also not reported. The record therefore does not establish how analyses were selected or whether the reported categories were prespecified.

These limitations are specific to interpreting this registry record. They do not negate the value of the posted counts, but they constrain the conclusions that can be drawn about treatment comparisons, rare events, and the precision or generalizability of the safety observations.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Ascending Single Doses of Erenumab (AMG 334) in Healthy Adults and Migraine Patients — NCT01688739.
• 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

NCT01688739 is a completed, randomized, double-blind, placebo-controlled, sequential phase I study of single ascending doses of erenumab in healthy adults and migraine patients. The registry record lists quadruple masking and 61 participants enrolled. Erenumab was given subcutaneously at 1 mg, 7 mg, 21 mg, 70 mg, 140 mg, or 210 mg, or intravenously at 140 mg; matching placebo was given by either route.

The primary outcome was the number of participants with adverse events from the initial dose up to 155 days, among participants who received study drug. The posted safety data list zero serious adverse events in every group and report group-specific counts for other adverse events. The record does not report a single comparative estimate for the primary outcome, confidence intervals, or a complete statistical analysis plan. Its results are best read as descriptive safety observations by group.