Multiple Ascending Dose Study of AMG 598 in Adults With Obesity: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Multiple Ascending Dose Study of AMG 598 in Adults With Obesity (NCT03757130), a randomized phase 1 study. The primary outcome is Number of Participants With Treatment-emergent Adverse Events.

2. Clinical Question

3. Trial Design

The registry describes a randomized, double-blind, placebo-controlled multiple ascending dose study. Its official title identifies it as phase 1b; the phase field classifies it as phase 1. The study model is listed as sequential. The registry does not explain the sequence used for dose escalation or provide further details about allocation procedures.

There were eight treatment groups: placebo, placebo with liraglutide, three AMG 598 dose groups, and three groups combining each AMG 598 dose with liraglutide. AMG 598 doses were 70 mg, 210 mg, and 420 mg. AMG 598 and placebo injections were scheduled once every 4 weeks for 3 doses. Combination groups also received daily liraglutide by subcutaneous injection for 12 weeks. Liraglutide began at 0.6 mg/day, with planned increases in increments of 0.6 mg/day every 7 days; the full titration description is not reported in the registry record.

The primary outcome was the number of participants with treatment-emergent adverse events. The registry defines its primary endpoint population as participants who received at least one dose of study drug on day 1. The outcome timeframe was 207 days. Secondary outcomes concerned AMG 598 pharmacokinetics, including maximum observed concentration, time to maximum observed concentration, concentration-time area measures, dose-normalized measures, and accumulation ratios on day 1 and day 57.

The registry reports 50 participants enrolled and a completed study status. It does not report the allocation ratio, the number screened, withdrawals by group, or details of who was masked. The posted results include adverse-event counts, but do not report a primary-outcome analysis or a specified treatment contrast.

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: Eligible participants were randomized to one of six treatment cohorts. Within each cohort participants were randomly assigned in a 3:1 ratio to receive either AMG 598 or placebo.

Only the first 6 of 8 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 at least 1 dose of study drug (AMG 598 or placebo) on day 1.

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 enrolled participants

Only the first 6 of 9 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Treatment-emergent Adverse Events, measured over 207 days.

The primary endpoint counts participants who experienced at least one treatment-emergent adverse event. The registry describes investigator assessment of each adverse event’s severity and whether it was related to study drug administration. Severity categories are mild, moderate, and severe, with descriptions based on symptom awareness, interference with usual activity, and inability to work or carry out usual activity. The investigator’s relatedness assessment was based on clinical judgment.

The endpoint also distinguishes serious adverse events. The registry defines these by criteria such as death, a life-threatening event, inpatient hospitalization or its prolongation, persistent or significant disability, a congenital anomaly or birth defect, or another medically important serious event. The primary outcome is expressed as a count of participants, rather than as a measure of symptom intensity or the total number of events each participant experienced.

Counting affected participants is useful for describing how many people in each group had an event during the stated follow-up timeframe. It does not, by itself, describe event duration, recurrence, severity distribution, or causal relationship to treatment. The registry reports the treatment-emergent adverse-event outcome over 207 days. It does not report a statistical comparison for this endpoint, and no single contrast is identified in the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The main statistical information available for interpretation is the number of participants with adverse events in each group. This is a binary participant-level outcome: a participant either had at least one event in the category being counted or did not. The posted counts do not show how many separate events occurred in each participant, and the record does not provide event-level summaries by type, severity, or relatedness.

What do the counts describe?

The serious-adverse-event count and the count for other adverse events are reported separately. The number at risk is given for each group, alongside the number affected. These values describe the enrolled study groups over the study follow-up; they are not a model-based estimate of risk. When group sizes are small, a change in the experience of a single participant can change the observed count noticeably. General statistical principle: small samples tend to leave substantial uncertainty about the range of outcomes that could occur in a larger population.

Counts are useful for understanding the observed data without implying a statistical test. A comparison of raw counts alone does not account for uncertainty, differences in exposure time, or other design and analysis considerations. In this record, the adverse-event timeframe is 207 days, but exposure-adjusted event rates are not reported. The posted results do not specify a primary treatment contrast or provide a formal comparison across all groups.

What would an inferential analysis add?

General statistical explanation: a confidence interval can express uncertainty around an estimated difference or rate, while a hypothesis test evaluates data against a stated null hypothesis using a specified analysis plan. Neither a confidence interval nor a primary-outcome test is reported in the registry record. Without those results and their underlying assumptions, the reported counts should not be interpreted as proving that groups are equivalent or that a difference between groups is statistically reliable.

For binary outcomes, different methods can be used to estimate treatment contrasts, and their suitability depends on the design, sample size, outcome frequency, and planned comparison. The registry record does not report which method, if any, was used for the primary endpoint. It also does not report whether analyses adjusted for study features or covariates. No method should be attributed to the study on the basis of the counts alone.

Why does the study structure matter?

The study used randomized allocation and double masking, with placebo control and a sequential model. Randomization is generally intended to reduce systematic differences between assigned groups, while masking is generally intended to reduce the influence of knowledge of assigned treatment on study conduct or assessment. These are general purposes of the design features; the registry does not provide enough detail to evaluate their implementation or success. In particular, allocation procedures, masking roles, and dose-escalation decision rules are not reported in the registry record.

The treatment groups combine different AMG 598 doses with the presence or absence of liraglutide. A comparison across all groups would need to specify which question is being tested—for example, a comparison between a particular dose and its placebo control, or an assessment of dose pattern. The posted results do not identify one such comparison for the primary safety endpoint. A difference between groups receiving different combinations could not, by itself, isolate the effect of one component.

How should missing information be handled?

The registry defines the primary endpoint population as participants who received at least one study-drug dose on day 1. This is a stated population definition, not a full description of the analysis population for every outcome. The record does not report the number of participants with incomplete follow-up, how missing adverse-event information was handled, or whether all participants were observed for the full timeframe. No assumptions about those procedures can be drawn from the counts.

The registry lists secondary pharmacokinetic outcomes such as maximum concentration, time to maximum concentration, area under the concentration-time curve, dose-normalized measures, and accumulation ratios. These are distinct from the primary safety outcome and require their own summaries and analysis methods. Their numerical results and statistical analyses are not reported in the registry record. General statistical principle: concentration data can have different distributions and analysis requirements from binary adverse-event counts, so a method for one outcome should not be presumed to apply to another.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary safety outcome and multiple secondary pharmacokinetic outcomes, including concentration, timing, area-under-the-curve, dose-normalized, and accumulation measures. It does not report a statistical plan describing how these outcomes were ordered, whether any were designated for confirmatory testing, or how multiplicity was handled. The number of planned comparisons and the approach to controlling the chance of false-positive findings are not reported in the registry record.

The posted results do not identify a single primary comparison among the eight treatment groups. They provide affected-participant counts by group but no reported test or confidence interval for the primary outcome. Accordingly, there is no basis in the record to determine whether any apparent differences were prespecified comparisons, exploratory observations, or subject to an adjustment for multiple testing.

The record specifies the primary endpoint population as participants who received at least one dose on day 1. It does not report how many participants were excluded from this population, whether the outcome was analyzed in other populations, or how missing follow-up was addressed. Missing-data methods, imputation procedures, and sensitivity analyses are not reported in the registry record.

These omissions limit interpretation of the posted counts. They do not establish that the study did or did not use a particular procedure; they mean the procedure is not reported in the registry record. The counts remain useful as descriptive observations, but the record does not support reconstructing a complete confirmatory analysis.

11. Safety Results

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

Deaths

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

The registry reports serious adverse events separately from other adverse events. No participants with serious adverse events are reported in any of the eight groups, and deaths are reported as 0 in each group. For other adverse events, the affected-participant counts are 1 of 6 with placebo, 6 of 6 with placebo and liraglutide, 4 of 6 with AMG 598 70 mg, 7 of 8 with AMG 598 70 mg and liraglutide, 5 of 6 with AMG 598 210 mg, 6 of 6 with AMG 598 210 mg and liraglutide, 0 of 6 with AMG 598 420 mg, and 4 of 6 with AMG 598 420 mg and liraglutide.

These are participant counts, not counts of every event, and the groups are small. A zero serious-event count means no serious event was recorded in that group during the reported study period; it does not show that the true risk is zero. The registry describes investigator grading and relatedness assessment, but these group counts do not show the breakdown by severity, event term, or judged relationship to treatment. Those details are not reported in the registry record.

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

The registry record describes a randomized, double-blind, placebo-controlled phase 1b study of multiple AMG 598 doses, alone or with liraglutide, in adults with obesity. Its posted primary outcome is a count of participants with treatment-emergent adverse events over 207 days. The available group counts show that no serious adverse events or deaths were reported in any treatment group, while other adverse events were recorded in several groups.

These findings are descriptive. The study enrolled 50 participants across eight groups, and the individual groups were small. The counts cannot provide a precise estimate of event frequency beyond the enrolled participants, and no confidence intervals or formal statistical comparisons for the primary endpoint are reported. The record also does not report an analysis that separates the effects of AMG 598 and liraglutide in the combination groups.

The results do not establish that one dose or combination is safer than another, nor do the zero serious-event counts establish an absence of risk. They also do not show that a treatment is effective for obesity: the stated primary objective concerns safety and tolerability, and the registry record does not report a clinical efficacy outcome analysis. Pharmacokinetic outcomes are listed, but their numerical results are not reported in the registry record.

Interpretation is further limited by the absence of reported details about missing data, treatment comparisons, analysis methods, and multiplicity handling. The record is informative about the trial structure and the adverse-event counts it reports, but it does not provide the inferential evidence needed to quantify treatment differences or draw broader conclusions about outcomes in other populations.

13. Why This Trial Matters Statistically

This study illustrates a common statistical challenge in early-phase clinical research: several doses and treatment combinations can be studied while the principal aim is safety and tolerability. Here, the groups include placebo controls, three AMG 598 dose levels, and corresponding combinations with liraglutide. The posted safety outcome is a participant count, which is straightforward to describe but does not by itself resolve whether observed group differences reflect treatment effects or chance variation.

Small treatment groups make uncertainty especially important. Counts such as 0 of 6 and 6 of 6 describe the enrolled groups, but they do not precisely define the range of outcomes that could occur in a wider population. General statistical principle: estimates based on limited observations are typically less precise than estimates based on larger samples. The registry does not report confidence intervals or a formal model that would quantify uncertainty for these results.

The combination groups also raise a question of attribution. When two treatments are assigned together, an observed group count cannot isolate the contribution of each component without a specified comparison and analysis. The record gives no single primary contrast and does not report an analysis separating AMG 598 from liraglutide.

Finally, the registry lists multiple pharmacokinetic secondary outcomes alongside the safety endpoint. Without a reported analysis plan, readers cannot determine how those outcomes were prioritized or how multiple comparisons were handled. This record therefore highlights why descriptive results, prespecified comparisons, uncertainty estimates, and transparent reporting of analysis populations are all important for statistical interpretation.

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 principal limitation of the posted results is that they report adverse-event counts without a statistical comparison for the primary endpoint. There are eight treatment groups, but no single treatment contrast is identified. No confidence intervals, adjusted estimates, or hypothesis-test results are reported. The counts therefore support descriptive reading, not a precise estimate of differences between regimens.

Group sizes are small: the reported denominators range from 6 to 8 participants. The overall enrollment is 50. Results from groups of this size may be sensitive to the experience of individual participants, and the registry record does not report uncertainty estimates. The absence of a reported serious event in a group should not be interpreted as proof that the risk is absent.

Although the registry describes severity grading and investigator assessment of relatedness, the posted group-level results do not include event terms, severity distributions, or relatedness counts. The registry does not report exposure-adjusted rates, participant-level event histories, or the number of recurrent events. It is therefore not possible to characterize the clinical pattern of adverse events from these counts alone.

The record also does not report missing-data procedures, follow-up completeness, analysis methods, multiplicity handling, or detailed allocation and masking procedures. It lists pharmacokinetic outcomes but does not provide their numerical analyses in the record summarized by the posted results. These limitations constrain conclusions about treatment differences, dose patterns, pharmacokinetic findings, and generalizability beyond the enrolled study participants.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Multiple Ascending Dose Study of AMG 598 in Adults With Obesity — NCT03757130.
• Registry record last updated 2023-09-14; status last verified 2022-11.
• Results first posted 2023-09-14.
• 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

NCT03757130 is a completed randomized, double-blind, placebo-controlled multiple ascending dose study in adults with obesity. The official title identifies it as phase 1b. The registry reports 50 participants enrolled and eight groups receiving placebo, AMG 598 at 70 mg, 210 mg, or 420 mg, or these treatments in combination with liraglutide.

The primary outcome was the number of participants with treatment-emergent adverse events over 207 days. The posted results report zero serious adverse events and zero deaths in each group, along with group-specific counts for other adverse events. Secondary outcomes concern AMG 598 pharmacokinetics on day 1 and day 57. Statistical analyses of the primary outcome and numerical results for the listed pharmacokinetic outcomes are not reported in the registry record.