Studies in early clinical development
2. Single Dose/Multiple Dose Escalation Studies (SAD and MAD)
Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) studies are typically the First-in-Human study (or studies). These are performed as randomised, placebo-controlled trials in healthy volunteers (though, as described above, sometimes in patients). The starting dose is determined by non-clinical toxicology studies and is based on algorithms found in regulatory guidance documents. Common escalation schemes include: 2x, 3.3x (half-long, and modified Fibonacci series). Some stopping rules are: toxicity, absent toxicity (maximised exposure, maximised pharmacodynamics, others).
The information gained from SAD/MAD studies is: