Cardiovascular safety risk assessment for new candidate drugs from functional and pathological data: Conference report

Klein, Stéphanie; Redfern, William S.

doi:10.1016/j.vascn.2015.06.003

Cited by 4 publications

(1 citation statement)

References 44 publications

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“…Although non-clinical cardiac SP assessment models and testing strategies have been extensively evaluated (Porsolt et al, 2002;Pugsley et al, 2009;Valentin et al, 2010;Authier et al, 2010;Vargas et al, 2015;Klein & Redfern, 2015), only limited information is available with respect to CNS adverse effect testing strategy and practices. At the more granular level, there are comprehensive reviews of non-clinical CNS models for seizure (Bassett et al, 2014;Easter et al, 2009;Metea et al, 2015;Fonck et al, 2015) and drug abuse liabilities (Kallman, 2015;Moser et al, 2010;Porsolt et al, 2002" O"Connor et al, 2011, with consideration of specific screening models for seizure (Authier et al, 2009;Koseki et al, 2014), sleep (Authier et al, 2014) and peripheral nerve function (Zotova & Arezzo, 2013).…”

Section: Introductionmentioning

confidence: 99%

Safety pharmacology investigations on the nervous system: An industry survey

Authier¹,

Arezzo

Delatte

et al. 2016

Journal of Pharmacological and Toxicological Methods

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The Safety Pharmacology Society (SPS) conducted an industry survey in 2015 to identify industry practices as they relate to central, peripheral and autonomic nervous system ('CNS') drug safety testing. One hundred fifty-eight (158) participants from Asia (16%), Europe (20%) and North America (56%) responded to the survey. 52% of participants were from pharmaceutical companies (>1000 employees). Oncology (67%) and neurology/psychiatry (66%) were the most frequent target indications pursued by companies followed by inflammation (48%), cardiovascular (43%), metabolic (39%), infectious (37%), orphan (32%) and respiratory (29%) diseases. Seizures (67% of participants), gait abnormalities (67%), tremors (65%), emesis (56%), sedation (52%) and salivation (47%) were the most commonly encountered CNS issues in pre-clinical drug development while headache (65%), emesis/nausea (60%), fatigue (51%) and dizziness (49%) were the most frequent issues encountered in Phase I clinical trials. 54% of respondents reported that a standard battery of tests applied to screen drug candidates was the approach most commonly used to address non-clinical CNS safety testing. A minority (14% of all participants) reported using electroencephalography (EEG) screening prior to animal inclusion on toxicology studies. The most frequent group size was n=8 for functional observation battery (FOB), polysomnography and seizure liability studies. FOB evaluations were conducted in a dedicated room (78%) by blinded personnel (66%) with control for circadian cycle (55%) effects (e.g., dosing at a standardized time; balancing time of day across treatment groups). The rat was reported as the most common species used for seizure liability, nerve conduction and drug-abuse liability testing.

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