singleascendingdose

Single ascending dose (SAD) is a phase I clinical trial design used to evaluate the safety, tolerability, pharmacokinetics, and sometimes pharmacodynamics of a drug after a single administration across increasing dose levels. The goal is to characterize the initial dose-exposure and dose-response relationships and to help identify a safe starting point and dose range for subsequent studies.

In a typical SAD study, cohorts of healthy volunteers or patients receive a single dose at a predefined level. Doses escalate in successive cohorts after safety data from earlier cohorts are reviewed by a data monitoring committee or sponsor. Sentinel dosing may be employed, in which the first subject in a cohort receives the dose and is observed before others are dosed. Dose levels are selected based on preclinical data and safety margins, and routes of administration can include oral, intravenous, subcutaneous, or other methods.

Pharmacokinetic sampling is performed to determine parameters such as Cmax, Tmax, area under the curve (AUC), half-life, clearance, and volume of distribution. Safety monitoring includes recording adverse events, vital signs, electrocardiograms, and laboratory tests. Pharmacodynamic assessments may be included if measurable biomarkers are available to indicate target engagement or biological effect.

SAD is contrasted with multiple ascending dose (MAD) studies, where multiple administrations are given over days or weeks. SAD helps establish a maximum tolerated dose, identify dose-limiting toxicities, and provide initial exposure-response information for planning MAD studies and regulatory submissions. Trials are conducted under Good Clinical Practice with appropriate regulatory oversight and risk management.