A previous blog from Attentive Science provided an overview of the core battery Safety Pharmacology assessments required prior to first administration of new drugs to humans. In this issue we will discuss assessments of the potential impacts of a new drug on the central nervous system (CNS).
CNS studies are conducted in a controlled environment (e.g., limiting extraneous noise, excessive entering and exiting the room, etc.) with a limited number of test systems to allow the observer time to make a number of post dose observations during the day. Each test system acts as its own control and is usually observed for around 3 minutes at each post dose time point. This permits us to determine the onset, duration and disappearance of any changes in a particular parameter. Finally, the same experienced Attentive scientist conducts the observations to reduce inter-observer variability.
The ICH S7A Safety Pharmacology (Studies for Human Pharmaceuticals) guidance document states that motor activity, behavioral changes, coordination, sensory/motor reflex responses and body temperature should be evaluated. For example, a Functional Observation Battery (FOB), modified Irwin’s or other appropriate industry-standard test can be used. Follow up studies, such as behavioral pharmacology, learning and memory, ligand-specific binding, neurochemistry, visual, auditory, and/or electrophysiology examinations can be conducted to further evaluate CNS effects if required.
The principal core battery CNS test should allow for the assessment of multiple behavioral, neurological and autonomic parameters in the same test system. The Irwin Test is an observational method that allows for multi-parameter assessment of nervous system function and is typically performed in rodents. There are approximately 40 different parameters that are assessed during the course of the study. Each individual parameter (grouped indicative of autonomic, neuromuscular, sensorimotor and behavioral) is assigned a score by a trained observer (who is blinded as to treatment group) dependent on the severity of the observed indicator.
The Attentive Science team has individuals who have been conducting observational studies for at least 2 decades and can use their knowledge to assist you in the elucidation of potential effects and avoidance of unwanted drug effects on the CNS as you approach your Phase I clinical trial.