Being involved in early phase clinical research, safety and tolerability of the investigated compounds are a major focus of our research. Safety data often are at least as important as efficacy results, particularly in first-in-human (FIH) and first-in-patient (FIP) studies. Having performed more than fifty of these trials we are very experienced in safe-guarding study participants as much as possible from undesired side effects and in eliciting important data on safety and tolerability for our clients.
FIH-studies are usually performed as single ascending dose (SAD) studies, i.e. subjects are dosed with a single dose of the study drug or placebo in a double-blind fashion. To minimise potential risks the first cohort of study participants start with very low doses which then are escalated in further cohorts step by step to the maximum tolerated dose or to the pre-defined maximum exposure. First-in patient studies are often designed as multiple ascending dose (MAD) studies with a very similar approach as SAD studies, however, study participants receive multiple rather than just single administrations of the study drug or placebo.
At Profil Germany we perform FIH/FIP-studies in full compliance with regulatory requirements as outlined in the ICH guideline M3(R2) on "non-clinical safety studies for the conduct of human clinical trials and marketing authorisation for pharmaceuticals" and the EMA "guideline on strategies to identify and mitigate risks for first-in human clinical trials with investigational medicinal products". Study participants are carefully selected for these studies to avoid any unnecessary risks, e.g. through concomitant diseases or medication. During the studies, the participants are very closely supervised with frequent examinations, adverse event questioning, and measurements of vital signs, ECG, and safety laboratory. For FIH/FIP-studies subjects are usually connected to our state-of-the-art telemetry device allowing a continuous supervision of ECG and oxygen saturation. Our telemetry set-up allows supervising up to 28 people simultaneously in our whole clinic including the clamp facilities. If needed, the telemetric recordings can be downloaded and be made available to our clients.
In later phase studies (when safety information in humans and patients is already available) safety precautions might be a bit less stringent, but the well-being of study participants still is the top priority in all studies at Profil Germany. Safety measures will strongly depend on a study drug's mechanism of action and available safety data, but might include very frequent blood glucose measurements or even continuous glucose measurements in case of expected strong hypoglycemic effects, holter monitoring of blood pressure and/or ECG, or the assessment of particular laboratory parameters. For injectable drugs, a highly standardized assessment of potential local side reactions has been implemented that also includes the assessment of the subjects' sensation during and after injection using our electronic visual analogue scale (eVAS) system.
While safety data are of utmost importance in particular in early phase trials, it is often feasible to also obtain first data on the pharmacodynamic effect of a study drug already in SAD-studies, e.g. by using the glucose clamp technique. At Profil Germany, we are specialized in optimizing the design of these early studies in a way that allows getting as much information as possible on a study drug's efficacy without compromising the well-being of our study participants.
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