The search strategy described provides a comprehensive and broad search selecting relevant studies. However most of the available literature is case reports. The submission contained the following clinical information: 10 clinical studies have been conducted to evaluate the pharmacokinetic parameters of fomepizole in healthy volunteers and in patients with ethylene glycol and methanol poisoning to determine optimum dosing recommendation, interactions with ethanol, and the effects of renal dialysis on fomepizole plasma levels, since dialysis is commonly used as a component of the treatment for both EG and methanol poisonings. Three pivotal efficacy/safety studies conducted by the manufacturer: Studies S7 S8 (OMC-4MP-1) and S13 (OMC-4MP-2). Other efficacy/safety studies: these include many published studies and case reports. 272 literature references Paediatric data The submission did not include any paediatric clinical studies (conducted by the manufacturer). However, some case reports and case series of use of fomepizole in treatment of EG and methanol poisoning in infants and children were provided. Good clinical practice (GCP) The 3 main studies submitted by the manufacturer were conducted according to GCP ICH guidelines. Most of the other published studies were conducted with ethics approval from the investigating centre. Pharmacokinetics Studies providing pharmacokinetic data Table 2 below shows the studies submitted relating to each pharmacokinetic topic. Table 2: Submitted pharmacokinetic studies PK Subtopic Study ID PK in healthy General PK- Single dose S-2 adults S-3 Maraffa, 2008 Jacobsen, 1996 - Multi-dose McMartin , 2012 Bioequivalence† - Single dose S-2 - Multi-dose S-3 Food effect Not applicable. PK in special Target population - Single dose S1 populations S11
The search strategy described provides a comprehensive and broad search selecting relevant studies. However most of the available literature is case reports. The submission contained the following clinical information: 10 clinical studies have been conducted to evaluate the pharmacokinetic parameters of fomepizole in healthy volunteers and in patients with ethylene glycol and methanol poisoning to determine optimum dosing recommendation, interactions with ethanol, and the effects of renal dialysis on fomepizole plasma levels, since dialysis is commonly used as a component of the treatment for both EG and methanol poisonings. Three pivotal efficacy/safety studies conducted by the manufacturer: Studies S7 S8 (OMC-4MP-1) and S13 (OMC-4MP-2). Other efficacy/safety studies: these include many published studies and case reports. 272 literature references Paediatric data The submission did not include any paediatric clinical studies (conducted by the manufacturer). However, some case reports and case series of use of fomepizole in treatment of EG and methanol poisoning in infants and children were provided. Good clinical practice (GCP) The 3 main studies submitted by the manufacturer were conducted according to GCP ICH guidelines. Most of the other published studies were conducted with ethics approval from the investigating centre. Pharmacokinetics Studies providing pharmacokinetic data Table 2 below shows the studies submitted relating to each pharmacokinetic topic. Table 2: Submitted pharmacokinetic studies PK Subtopic Study ID PK in healthy adults General PK- Single dose S-2 S-3 Maraffa, 2008 Jacobsen, 1996 - Multi-dose McMartin , 2012 Bioequivalence† - Single dose S-2 - Multi-dose S-3 Food effect Not applicable. PK in special populations Target population - Single dose S1 S11
auspar-fomepizole-170817.docx