An Adaptive First in Man Dose-Escalation Study of NGX267: Statistical, Clinical, and Operational Considerations

The primary objective of the dose-escalation trial for NGX267 was to estimate the maximally tolerated dose (MTD) and to gather detailed clinical and pharmacokinetic observations near the MTD. The MTD was defined based on the weighted average of moderate and severe adverse events. An adaptive design was employed to concentrate dosage assignments at or near the MTD. Favoring the acquisition of data near the MTD, at the expense of information at lower dosage levels, resulted in a shorter trial and no loss of the type of information required to inform subsequent studies where larger normal volunteer or patient samples are evaluated.